Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
Mais filtros

Base de dados
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Aesthetic Plast Surg ; 48(9): 1679-1687, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38379008

RESUMO

OBJECTIVES: Recently, radial cartilage incision (first-stage) at an early age combined with free auricular composite tissue grafting (second-stage) can effectively correct the concha-type microtia with the moderate or severe folded cartilage in the middle and upper third auricle, but radial cartilage incision's effects on the growth of the ear remain to be determined. The authors aimed to evaluate the effects of radial cartilage incision in young rabbits model. METHODS: Ten New Zealand white rabbits were included in our experiment. Two ears of each rabbit were divided randomly into two groups. The experimental group was operated with radial cartilage incision, and no intervention was given to the control group. The ear width, length, and perimeter were noted every two weeks. Auricular surface area was noted at 4 and 22 weeks old. The repeated measures ANOVA was used to describe ears' growth trend. A paired-sample's t test is conducted to test whether there are significant differences among the variables through the SPSS25.0 software. RESULTS: The growth tendencies of the ear length, width, and perimeter were observed and analyzed. The growth curves of the experimental ears were similar to that of the control. There was no significant difference in the increased ratio of surface area among the two groups. The cartilage of the experimental ears showed no change in biomechanical properties compared to that of control group. CONCLUSION: This study shows that radial cartilage incision at an early age does not influence the growth of rabbit ear length, width, perimeter, and surface area and also does not change the biomechanical properties of the cartilage. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .


Assuntos
Cartilagem da Orelha , Animais , Coelhos , Cartilagem da Orelha/cirurgia , Distribuição Aleatória , Orelha Externa/cirurgia , Microtia Congênita/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Feminino , Modelos Animais de Doenças
2.
Circ Res ; 124(1): 66-78, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30582453

RESUMO

RATIONALE: Short QT syndrome (SQT) is a rare but arrhythmogenic disorder featured by shortened ventricular repolarization and a propensity toward life-threatening ventricular arrhythmias and sudden cardiac death. OBJECTIVE: This study aimed to investigate the single-cell mechanism of SQT using patient-specific and gene-corrected induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). METHODS AND RESULTS: One SQT patient carrying missense mutation T618I in potassium voltage-gated channel subfamily H member 2 ( KCNH2) was recruited as well as 2 healthy control subjects in this study. Control and SQT patient-specific iPSCs were generated from skin fibroblasts using nonintegrated Sendai virus. The KCNH2 T618I mutation was corrected by genome editing in SQT iPSC lines to generate isogenic controls. All iPSCs were differentiated into iPSC-CMs using monolayer-based differentiation protocol. SQT iPSC-CMs exhibited abnormal action potential phenotype featured by shortened action potential duration and increased beat-beat interval variability, when compared with control and gene-corrected iPSC-CMs. Furthermore, SQT iPSC-CMs showed KCNH2 gain-of-function with increased rapid delayed rectifying potassium current (IKr) density and enhanced membrane expression. Gene expression profiling of iPSC-CMs exhibited a differential cardiac ion-channel gene expression profile of SQT. Moreover, QTc of SQT patient and action potential durations of SQT iPSC-CMs were both normalized by quinidine, indicating that quinidine is beneficial to KCNH2 T618I of SQT. Importantly, shortened action potential duration phenotype observed in SQT iPSC-CMs was effectively rescued by a short-peptide scorpion toxin BmKKx2 with a mechanism of targeting KCNH2. CONCLUSIONS: We demonstrate that patient-specific and gene-corrected iPSC-CMs are able to recapitulate single-cell phenotype of SQT, which is caused by the gain-of-function mutation KCNH2 T618I. These findings will help elucidate the mechanisms underlying SQT and discover therapeutic drugs for treating the disease by using peptide toxins as lead compounds.


Assuntos
Potenciais de Ação/genética , Arritmias Cardíacas/genética , Canal de Potássio ERG1/genética , Mutação com Ganho de Função , Edição de Genes/métodos , Frequência Cardíaca/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação de Sentido Incorreto , Miócitos Cardíacos/metabolismo , Análise de Célula Única/métodos , Adulto , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Sistemas CRISPR-Cas , Estudos de Casos e Controles , Linhagem Celular , Linhagem da Célula , Canal de Potássio ERG1/metabolismo , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Tempo
3.
Cardiol Young ; 31(2): 260-263, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33198842

RESUMO

BACKGROUND: The objective of this study was to delineate the characteristics and incidence of congenital heart disease (CHD) in patients with isolated microtia and to determine whether the prevalence of CHD among patients with isolated microtia increases with the severity of microtia. METHODS: A total of 804 consecutive patients had a pre-operative colour Doppler echocardiographic examination. A retrospective study was performed with the clinical and imaging data from November, 2017 to January, 2019. The χ2 test was performed to analyse the interaction between isolated microtia and CHD. RESULTS: With the colour Doppler echocardiographic examination's data from 804 consecutive isolated microtia patients, we found CHD, including atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus, and others, occurred in 52 of 804 patients (6.5%). Atrial septal defect prevalence in patients with isolated microtia was significantly higher than ventricular septal defect (24/804 versus 11/804, p < 0.05) and patent ductus arteriosus (24/804 versus 2/804, p < 0.001). Ventricular septal defect prevalence in patients with isolated microtia was significantly higher than patent ductus arteriosus (11/804 versus 2/804, p < 0.05). All four types of microtia (concha-type microtia, small concha-type microtia, lobule-type microtia, and anotia) had similar incidences of CHD with no difference in the incidences among these types (p > 0.05 respectively). Furthermore, there was no significant difference in the incidence of the atrial septal defect among the four subtypes (p > 0.05 respectively). Similarly, ventricular septal defect and patent ductus arteriosus also showed no differences (p > 0.05 respectively). CONCLUSIONS: The overall incidences of CHD and three most common CHD subtypes (atrial septal defect, ventricular septal defect, and patent ductus arteriosus) in patients with isolated microtia are higher than general population. The prevalence of CHD among patients with isolated microtia does not increase with the severity of microtia. According to our experience in this study, we suggest colour Doppler echocardiographic imaging should be performed for isolated microtia patients soon after birth if possible. Furthermore, for the plastic surgeon and anaesthesiologist, it is important to take pre-operative colour Doppler echocardiographic images which can help evaluate heart function to ensure the safety of the peri-operative period. Future studies when investigating CHDs associated with isolated microtia could focus on genetic and molecular mechanisms.


Assuntos
Microtia Congênita , Permeabilidade do Canal Arterial , Cardiopatias Congênitas , Comunicação Interatrial , Cor , Microtia Congênita/epidemiologia , Ecocardiografia Doppler em Cores , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/epidemiologia , Humanos , Estudos Retrospectivos
4.
J Mol Cell Cardiol ; 142: 53-64, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32251671

RESUMO

Diabetes mellitus is a serious metabolic condition associated with a multitude of cardiovascular complications. Moreover, the prevalence of diabetes in heart failure populations is higher than that in control populations. However, the role of cardiomyocyte alterations in type 2 diabetes mellitus (T2DM) has not been well characterized and the underlying mechanisms remain elusive. In this study, two patients who were diagnosed as T2DM were recruited and patient-specific induced pluripotent stem cells (iPSCs) were generated from urine epithelial cells using nonintegrated Sendai virus. The iPSC lines derived from five healthy subjects were used as controls. All iPSCs were differentiated into cardiomyocytes (iPSC-CMs) using the monolayer-based differentiation protocol. T2DM iPSC-CMs exhibited various disease phenotypes, including cellular hypertrophy and lipid accumulation. Moreover, T2DM iPSC-CMs exhibited higher susceptibility to high-glucose/high-lipid challenge than control iPSC-CMs, manifesting an increase in apoptosis. RNA-Sequencing analysis revealed a differential transcriptome profile and abnormal activation of TGFß signaling pathway in T2DM iPSC-CMs. We went on to show that inhibition of TGFß significantly rescued the hypertrophic phenotype in T2DM iPSC-CMs. In conclusion, we demonstrate that the iPSC-CM model is able to recapitulate cellular phenotype of T2DM. Our results indicate that iPSC-CMs can therefore serve as a suitable model for investigating molecular mechanisms underlying diabetic cardiomyopathies and for screening therapeutic drugs.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Apoptose/genética , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Biomarcadores , Estudos de Casos e Controles , Diferenciação Celular/genética , Células Cultivadas , Diabetes Mellitus Tipo 2/etiologia , Células Epiteliais/metabolismo , Glucose/metabolismo , Humanos , Imunofenotipagem , Células-Tronco Pluripotentes Induzidas/citologia , Metabolismo dos Lipídeos , Miócitos Cardíacos/citologia , Transcriptoma
5.
J Mol Cell Cardiol ; 126: 143-154, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30423318

RESUMO

Cardiac hypertrophy is an adaptive response against increased workload featuring by an increase in left ventricular mass and a thickening left ventricle wall. Here, we showed the expression of transient receptor potential canonical 1 (TRPC1) is higher in hearts of patients with hypertrophic cardiomyopathy (HCM) or heart failure (HF) than that of normal hearts. To better understand the mechanisms of TRPC1 in regulating cellular hypertrophy of human-based cardiomyocytes, we generated human pluripotent stem cell lines of TRPC1 knockout by CRISPR/Cas9. We demonstrated that knockout of TRPC1 significantly attenuated cardiomyocyte hypertrophy phenotype induced by phorbol 12-myristate 13-acetate, which was associated with abnormal activation of NF-κB. In contrast, overexpression of TRPC1 induced cardiomyocyte hypertrophy, which can be reversed by inhibition of NF-κB. Taken together, we established a stable human-based cardiomyocyte hypertrophy model and highlighted molecular mechanisms underlying TRPC1-mediated hypertrophy, aiding the development of therapeutic drugs for HCM and HF by targeting TRPC1.


Assuntos
Cardiomegalia/metabolismo , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Células-Tronco Pluripotentes/metabolismo , Transdução de Sinais , Canais de Cátion TRPC/antagonistas & inibidores , Sequência de Bases , Cardiomegalia/genética , Cardiomegalia/patologia , Humanos , Canais de Cátion TRPC/metabolismo
6.
J Craniofac Surg ; 30(1): e28-e32, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30444766

RESUMO

Autogenous rib cartilage graft procedure for microtia reconstruction has been adopted as the most standardized current method. But calcification would make it difficult for cartilage harvesting and ear framework sculpting. The objective of this study was to explore the rate, degree, and pattern of rib cartilage calcification in microtia and to guide rib cartilage harvesting and the optimal timing of auricular reconstruction. A retrospective study was performed with the imaging data from 320 consecutive patients who received a preoperative 3-dimensional chest computed tomography (CT). Overall, calcification rate of cartilages in female patients was higher than male's (P < 0.05). In 6 to 15 years group, calcification rates of male and female had a similar rate, while female's were higher than male's in other 3 groups. Furthermore, the moderate-to-severe calcification rate was higher in female than in male patients (P < 0.001). Therefore, girls who are over 15 years should be paid more attention regarding the possibility of moderate-to-severe calcification; these patients should take CT examinations if necessary. Calcification rate of the youngest group (6-15 years) was the lowest of all groups, while other 3 groups showed no statistical significance (P > 0.05). So merely the age increasing is not the contradiction for cartilage harvesting, as long as the authors effectively evaluate the condition of rib cartilage before operation. Rib cartilages serve as the key material in auricular framework sculpting and determine the feasibility and outcomes of the surgery. So CT examinations for preoperative evaluation of rib cartilage could be a useful method for planning microtia reconstruction.


Assuntos
Calcinose/diagnóstico por imagem , Microtia Congênita/cirurgia , Cartilagem Costal/diagnóstico por imagem , Cartilagem Costal/transplante , Adolescente , Adulto , Autoenxertos , Criança , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , Fatores Sexuais , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
Arch Virol ; 162(5): 1349-1353, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28116526

RESUMO

In this study, we analyzed the genome of a H10N5 influenza virus from wild birds. This virus was identified as a novel reassortant virus with internal genes from multiple subtypes and of distinct origins. After sequential passage in mice, mouse-adapted viruses bearing mutations PB2-E627K and HA-G218E were generated. These viruses caused dramatic body weight loss and death, and also replicated in mouse brain, suggesting that the pathogenicity of low pathogenic H10N5 in chickens can be enhanced after passage in mammals. Our data imply that H10N5 viruses might be a potential risk to human health therefore it is important to undertake continued surveillance and biosecurity evaluation of these viruses.


Assuntos
Doenças das Aves/virologia , Aves/virologia , Hemaglutininas Virais/genética , Influenza Aviária/virologia , Vírus Reordenados/classificação , Vírus Reordenados/genética , Animais , Animais Selvagens/virologia , Embrião de Galinha , Feminino , Marcadores Genéticos/genética , Camundongos , Camundongos Endogâmicos BALB C , Vírus Reordenados/isolamento & purificação
8.
Chemistry ; 20(4): 979-82, 2014 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-24403091

RESUMO

A highly enantioselective Michael addition of nitroacetates to ß,γ-unsaturated α-ketoesters was developed by using chiral copper catalysts. The Michael addition products can be obtained in high yields with up to 99 % ee. With these densely functionalized products, the chiral cyclic nitrones, which are important synthetic intermediates, can be obtained in one step.

9.
J Plast Reconstr Aesthet Surg ; 95: 87-91, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38879938

RESUMO

BACKGROUND: Chin prosthesis implantation, a cosmetic procedure to correct chin asymmetry, depression, or retraction, is generally safe and simple. However, its long-term effects on surrounding tissues are a concern. This study aimed to use three-dimensional (3D) scanning to classify the mentalis muscle shapes and assess the impact of prosthesis implantation on these muscles. METHOD: This study evaluated 450 eligible female participants. Using three-dimensional imaging, data on the types, thickness, width, and length of the left and right mentalis muscles were collected and summarized. The impact of chin prosthesis on these muscle dimensions was assessed using analysis of variance, and the effect on muscle type was determined using χ2 test. RESULTS: Chin implant placement affected the mentalis muscles, resulting in increased length, thickness, and width. The subjects' mentalis muscles were categorized into 3 types and divided into 7 subtypes. χ2 test results indicated that implantation influences the classification of these muscles. CONCLUSION: Recognizing how implant placement affects the mentalis muscle can guide the development of treatments to mitigate these changes. Additionally, understanding the muscle's morphology enables more precise treatment approaches for patients.

10.
Acta Biomater ; 181: 161-175, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38679405

RESUMO

Diabetic wound management remains a significant challenge in clinical care due to bacterial infections, excessive inflammation, presence of excessive reactive oxygen species (ROS), and impaired angiogenesis. The use of multifunctional wound dressings has several advantages in diabetic wound healing. Moreover, the balance of macrophage polarization plays a crucial role in promoting skin regeneration. However, few studies have focused on the development of multifunctional wound dressings that can regulate the inflammatory microenvironment and promote diabetic wound healing. In this study, an extracellular matrix-inspired glycopeptide hydrogel composed of glucomannan and polypeptide was proposed for regulating the local microenvironment of diabetic wound sites. The hydrogel network, which was formed via Schiff base and hydrogen bonding interactions, effectively inhibited inflammation and promoted angiogenesis during wound healing. The hydrogels exhibited sufficient self-healing ability and had the potential to scavenge ROS and to activate the mannose receptor (MR), thereby inducing macrophage polarization toward the M2 phenotype. The experimental results confirm that the glycopeptide hydrogel is an effective tool for managing diabetic wounds by showing antibacterial, ROS scavenging, and anti-inflammatory effects, and promoting angiogenesis to facilitate wound repair and skin regeneration in vivo. STATEMENT OF SIGNIFICANCE: •The designed wound dressing combines the advantage of natural polysaccharide and polypeptide. •The hydrogel promotes M2-polarized macrophages, antibacterial, scavenges ROS, and angiogenesis. •The multifunctional glycopeptide hydrogel dressing could accelerating diabetic wound healing in vivo.


Assuntos
Glicopeptídeos , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Nanofibras , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Nanofibras/química , Camundongos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Glicopeptídeos/farmacologia , Glicopeptídeos/química , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Células RAW 264.7 , Masculino , Mananas/química , Mananas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Espécies Reativas de Oxigênio/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Ratos Sprague-Dawley , Complicações do Diabetes/patologia
11.
Org Biomol Chem ; 11(39): 6691-4, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-23995231

RESUMO

A cobalt-catalyzed oxidative [3 + 2] cycloaddition cascades of dihydroisoquinoline esters with nitroolefins or N-sulfuryl aldimines were developed at room temperature. A multi-component reaction for the synthesis of 5,6-dihydroimidazo[2,1-a]isoquinolines were also realized under almost identical conditions. This method is particularly suitable for the synthesis of tricyclic nitrogen heterocycles due to its simple manipulation, wide scope of the reaction substrates and excellent regioselectivity.

12.
Stem Cell Res Ther ; 14(1): 92, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-37061738

RESUMO

BACKGROUND: Although human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising cell resource for cardiovascular research, these cells exhibit an immature phenotype that hampers their potential applications. The inwardly rectifying potassium channel Kir2.1, encoded by the KCNJ2 gene, has been thought as an important target for promoting electrical maturation of iPSC-CMs. However, a comprehensive characterization of morphological and functional changes in iPSC-CMs overexpressing KCNJ2 (KCNJ2 OE) is still lacking. METHODS: iPSC-CMs were generated using a 2D in vitro monolayer differentiation protocol. Human KCNJ2 construct with green fluorescent protein (GFP) tag was created and overexpressed in iPSC-CMs via lentiviral transduction. The mixture of iPSC-CMs and mesenchymal cells was cocultured with decellularized natural heart matrix for generation of 3D human engineered heart tissues (EHTs). RESULTS: We showed that mRNA expression level of KCNJ2 in iPSC-CMs was dramatically lower than that in human left ventricular tissues. KCNJ2 OE iPSC-CMs yielded significantly increased protein expression of Kir2.1 and current density of Kir2.1-encoded IK1. The larger IK1 linked to a quiescent phenotype that required pacing to elicit action potentials in KCNJ2 OE iPSC-CMs, which can be reversed by IK1 blocker BaCl2. KCNJ2 OE also led to significantly hyperpolarized maximal diastolic potential (MDP), shortened action potential duration (APD) and increased maximal upstroke velocity. The enhanced electrophysiological maturation in KCNJ2 OE iPSC-CMs was accompanied by improvements in Ca2+ signaling, mitochondrial energy metabolism and transcriptomic profile. Notably, KCNJ2 OE iPSC-CMs exhibited enlarged cell size and more elongated and stretched shape, indicating a morphological phenotype toward structural maturation. Drug testing using hERG blocker E-4031 revealed that a more stable MDP in KCNJ2 OE iPSC-CMs allowed for obtaining significant drug response of APD prolongation in a concentration-dependent manner. Moreover, KCNJ2 OE iPSC-CMs formed more mature human EHTs with better tissue structure and cell junction. CONCLUSIONS: Overexpression of KCNJ2 can robustly enhance maturation of iPSC-CMs in electrophysiology, Ca2+ signaling, metabolism, transcriptomic profile, cardiomyocyte structure and tissue engineering, thus providing more accurate cellular model for elucidating cellular and molecular mechanisms of cardiovascular diseases, screening drug-induced cardiotoxicity, and developing personalized and precision cardiovascular medicine.


Assuntos
Células-Tronco Pluripotentes Induzidas , Canais de Potássio Corretores do Fluxo de Internalização , Humanos , Miócitos Cardíacos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Diferenciação Celular/genética , Técnicas de Cocultura , Cardiotoxicidade , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo
13.
EBioMedicine ; 95: 104741, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37544203

RESUMO

BACKGROUND: Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the genotype-phenotype correlations are not completely matched. Clinical phenotypes of a particular SCN5A variant may range from asymptomatic to SCD. Here, we used comparison of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from a SCN5A mutation-positive (D356Y) BrS family with severely affected proband, asymptomatic mutation carriers (AMCs) and healthy controls to investigate this variation. METHODS: 26 iPSC lines were generated from skin fibroblasts using nonintegrated Sendai virus. The generated iPSCs were differentiated into cardiomyocytes using a monolayer-based differentiation protocol. FINDINGS: D356Y iPSC-CMs exhibited increased beat interval variability, slower depolarization, cardiac arrhythmias, defects of Na+ channel function and irregular Ca2+ signaling, when compared to controls. Importantly, the phenotype severity observed in AMC iPSC-CMs was milder than that of proband iPSC-CMs, an observation exacerbated by flecainide. Interestingly, the iPSC-CMs of the proband exhibited markedly decreased Ca2+ currents in comparison with control and AMC iPSC-CMs. CRISPR/Cas9-mediated genome editing to correct D356Y in proband iPSC-CMs effectively rescued the arrhythmic phenotype and restored Na+ and Ca2+ currents. Moreover, drug screening using established BrS iPSC-CM models demonstrated that quinidine and sotalol possessed antiarrhythmic effects in an individual-dependent manner. Clinically, venous and oral administration of calcium partially reduced the malignant arrhythmic events of the proband in mid-term follow-up. INTERPRETATION: Patient-specific and genome-edited iPSC-CMs can recapitulate the varying phenotypic severity of BrS. Our findings suggest that preservation of the Ca2+ currents might be a compensatory mechanism to resist arrhythmogenesis in BrS AMCs. FUNDING: National Key R&D Program of China (2017YFA0103700), National Natural Science Foundation of China (81922006, 81870175), Natural Science Foundation of Zhejiang Province (LD21H020001, LR15H020001), National Natural Science Foundation of China (81970269), Key Research and Development Program of Zhejiang Province (2019C03022) and Natural Science Foundation of Zhejiang Province (LY16H020002).


Assuntos
Síndrome de Brugada , Células-Tronco Pluripotentes Induzidas , Humanos , Síndrome de Brugada/genética , Síndrome de Brugada/patologia , Miócitos Cardíacos , Arritmias Cardíacas/patologia , Mutação , Morte Súbita Cardíaca/patologia
14.
J Clin Invest ; 133(14)2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37200096

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most prominent cause of sudden cardiac death in young people. Due to heterogeneity in clinical manifestations, conventional HCM drugs have limitations for mitochondrial hypertrophic cardiomyopathy. Discovering more effective compounds would be of substantial benefit for further elucidating the pathogenic mechanisms of HCM and treating patients with this condition. We previously reported the MT-RNR2 variant associated with HCM that results in mitochondrial dysfunction. Here, we screened a mitochondria-associated compound library by quantifying the mitochondrial membrane potential of HCM cybrids and the survival rate of HCM-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in galactose media. 1-Deoxynojirimycin (DNJ) was identified to rescue mitochondrial function by targeting optic atrophy protein 1 (OPA1) to promote its oligomerization, leading to reconstruction of the mitochondrial cristae. DNJ treatment further recovered the physiological properties of HCM iPSC-CMs by improving Ca2+ homeostasis and electrophysiological properties. An angiotensin II-induced cardiac hypertrophy mouse model further verified the efficacy of DNJ in promoting cardiac mitochondrial function and alleviating cardiac hypertrophy in vivo. These results demonstrated that DNJ could be a potential mitochondrial rescue agent for mitochondrial hypertrophic cardiomyopathy. Our findings will help elucidate the mechanism of HCM and provide a potential therapeutic strategy.


Assuntos
1-Desoxinojirimicina , Cardiomiopatia Hipertrófica , Animais , Camundongos , 1-Desoxinojirimicina/farmacologia , 1-Desoxinojirimicina/metabolismo , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/metabolismo , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Cardiomegalia/tratamento farmacológico , Cardiomegalia/genética , Cardiomegalia/metabolismo
15.
J Org Chem ; 77(7): 3563-9, 2012 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-22390283

RESUMO

A regioselective oxyalkylation reaction of vinylarenes with cyclic ethers was developed under the catalysis of a new heterogeneous catalyst, the diatomite-supported Mn(3)O(4) nanoparticles (SMONP-1). The use of this heterogeneous catalyst provided a novel approach for the synthesis of α-carbonyled ß-alkylated aryl derivatives via a sp(3) C-H bond functionalization under mild aerobic conditions.


Assuntos
Compostos de Manganês/química , Nanopartículas/química , Óxidos/química , Compostos de Vinila/química , Alquilação , Catálise , Estrutura Molecular , Estereoisomerismo
16.
J Org Chem ; 77(24): 11161-6, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23181828

RESUMO

A facile iodine-mediated decarboxylative cyclization from α-amino acids and N-heterocyclic carbaldehydes was developed. By virtue of this method, a series of imidazo[1,5-a]N-heterocycles can be synthesized efficiently under mild conditions. A tentative reaction mechanism was proposed based on the experimental results and previous reports.


Assuntos
Aminoácidos/química , Produtos Biológicos/química , Imidazóis/química , Imidazóis/síntese química , Técnicas de Química Sintética
17.
Stem Cell Res ; 62: 102813, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35569348

RESUMO

Long QT syndrome (LQT) is an inherited primary arrhythmic disorder characterized by prolonged QT interval on the surface electrocardiogram and life-threatening arrhythmia. In this study, a skin biopsy was obtained from an LQT type 2 (LQT2) patient, who carried a nonsense mutation (c.1956C > A; p.Y652X) in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. The skin fibroblasts were reprogrammed by non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical embryonic stem cell-like morphology, exhibited normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.


Assuntos
Células-Tronco Pluripotentes Induzidas , Síndrome do QT Longo , Arritmias Cardíacas/metabolismo , Canal de Potássio ERG1/genética , Canal de Potássio ERG1/metabolismo , Fibroblastos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Síndrome do QT Longo/metabolismo , Mutação/genética
18.
Stem Cell Res ; 64: 102883, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35944310

RESUMO

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited cardiovascular disease characterized by left ventricular hypertrophy and cardiomyocyte disarray. In this study, a skin biopsy was obtained from a HCM patient, who carried a missense mutation (c.4384G > A; p.E1462K) in the myosin heavy chain 7 (MYH7) gene. The skin fibroblasts were subsequently reprogrammed with a non-integrated Sendai viral method to generate a patient-specific induced pluripotent stem cell (iPSC) line. The generated iPSC line showed typical morphology and normal karyotype, expressed pluripotency markers, and was capable to differentiate into three germ layers.


Assuntos
Cardiomiopatia Hipertrófica , Células-Tronco Pluripotentes Induzidas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Cadeias Pesadas de Miosina/genética , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Mutação/genética , Mutação de Sentido Incorreto , Miosinas Cardíacas/genética
19.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(5): 656-659, 2020 May 15.
Artigo em Zh | MEDLINE | ID: mdl-32410436

RESUMO

OBJECTIVE: To summarize the current progress of clinical therapy for concha-type microtia. METHODS: The domestic and overseas literature about the treatment of concha-type microtia was reviewed and the contents of operative timing, operation selection, and complications were analyzed. RESULTS: The unified therapeutic schedule of the concha-type microtia has not yet been determined due to its complicated various therapeutic methods and unknown etiology. The operation methods commonly used in clinic are partial ear reconstruction with autologous costal cartilage framework and free composite tissue transplantation. The timing of the partial ear reconstruction depends on the development of costal cartilage and children's psychological healthy. The timing of free composite tissue transplantation depends on the severity. It is recommended to perform the operation at about 10 years old for mild patients. For moderate patients, ear cartilage stretching should be performed at 1-2 years old and free composite tissue transplantation would be performed at about 10 years old. The complications of partial ear reconstruction with autologous costal cartilage framework for concha-type microtia mainly include framework exposure, deformation, infection, cartilage absorption, and skin necrosis. The complications of free composite tissue transplantation have not been reported. CONCLUSION: Etiology and elaborated classifications with individualized treatment are the future research directions.


Assuntos
Microtia Congênita/cirurgia , Pavilhão Auricular/cirurgia , Procedimentos de Cirurgia Plástica , Criança , Pré-Escolar , Cartilagem da Orelha/cirurgia , Orelha Externa/cirurgia , Humanos , Lactente , Costelas
20.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(4): 501-504, 2020 Apr 15.
Artigo em Zh | MEDLINE | ID: mdl-32291989

RESUMO

OBJECTIVE: To explore the anthropometric changes of the auricle after auricular cartilage unfolding in moderate concha-type microtia patients, so as to provide the basis to help evaluate surgical timing and prognostic. METHODS: A total of 33 children with moderate concha-type microtia, who were treated with auricular cartilage unfolding between October 2016 and September 2018 and met the inclusive criteria, were included in the study. There were 24 boys and 9 girls with an average age of 1.4 years (range, 1-3 years). Sixteen cases were left ears and 17 cases were right ears. The follow-up time was 12-23 months (mean, 17.5 months). The affected auricular detailed structures were observed and quantitatively analyzed before operation and at immediate after operation. The width, length, and perimeter of auricle before operation and at immediate after operation and at last follow-up were noted with three dimensional-scanning technology. The normal auricle was noted as control. RESULTS: There were (7.5±1.0) and (11.3±0.8) structures of the affected auricle at pre- and post-operation, respectively, showing significant difference between pre- and post-operation ( t=23.279, P=0.000). The length, width, and perimeter of the affected auricle constantly increased after operation, and there were significant differences between pre-operation and immediately after operation and between immediately after operation and last follow-up ( P<0.05). The differences of length, width, and perimeter of the affected auricle between immediately after operation and last follow-up were (3.13±1.44), (2.44±0.92), and (8.50±3.76) mm, respectively. And the differences of length, width, and perimeter of the normal auricle between pre-operation and last follow-up were (3.16±1.54), (2.35±0.86), and (9.79±4.60) mm, respectively. There was no significant difference in the differences of length, width, and perimeter between the affected auricle and the normal auricle ( P>0.05). CONCLUSION: The auricular cartilage unfolding in treatment of the moderate concha-type microtia can receive more ear structures and increase auricle sizes, which make it possible for free composite tissue transplantation. In addition, the affected and the contralateral normal auricles have a very similar growth rate and it offers the theoretical foundation for the early treatment for moderate concha-type microtia.


Assuntos
Microtia Congênita/cirurgia , Pavilhão Auricular/anatomia & histologia , Cartilagem da Orelha/anatomia & histologia , Procedimentos de Cirurgia Plástica , Antropometria , Pré-Escolar , Microtia Congênita/patologia , Feminino , Humanos , Lactente , Masculino
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa