Morphological and Morphometric Analysis, Apoptosis and Oxidative Stress Study in Hep 2 Cells Treated by Resveratrol or Quercetine / Análisis Morfológico y Morfométrico, Estudio de Apoptosis y Estrés Oxidativo en Células Hep 2 Tratadas con Resveratrol o Quercetina

SUMMARY: Resveratrol (RES) and quercetine (QRC), is a promising agent relevant for both cancer chemoprevention and treatment via several signaling pathways, involved in their anticancer activity related to its chemotherapeutic potential, associated with the induction of ROS generation in cancer cells, leading to apoptosis. In our study, we have summarized the mechanisms of action of RES and QRC, and their pharmacological implications and potential therapeutic applications in cancer therapy. After treatment of Hep 2 cells with QRC or RES, the death pathways such as the cytochrome c release, ERK1/2 and IRS-1 pathways were upregulated, while cell survival pathway, including PI3K/AKT were downregulated. The RES and QRC caused oncosis, cells hypertrophy, hypercondensatin of chromatin, rupture of the plasma membrane and nuclear membrane, and formation of apoptotic bodies. Morphometric measurements of some cellular and nuclear parameters showed that RES and QRC induced an increase in cells and nuclear size, the nucleocytoplasmic ratio remained below 1 (N-Cyt R < 1), sign of low nuclear activity. The RES and QRC induced apoptosis of Hep2 cells by increasing of oxidative stress markers, MDA, and by modulating detoxifying enzymes, CAT and SOD. Our study results prove antiproliferative and proapoptotic properties of quercetin and resveratrol with regard to larynx cancer.

Resveratrol (RES) y quercetina (QRC), es un agente prometedor y relevante tanto para la quimioprevención como para el tratamiento del cáncer a través de varias vías de señalización, involucrado en su actividad anticancerígena relacionada con su potencial quimioterapéutico, asociado con la inducción de la generación de especies reactivas del oxígeno (ROS) en células cancerosas, lo que lleva a apoptosis. En nuestro estudio, hemos resumido los mecanismos de acción de RES y QRC, y sus implicaciones farmacológicas y posibles aplicaciones terapéuticas en la terapia del cáncer. Después del tratamiento de las células Hep 2 con QRC o RES, las vías de muerte, tal como la liberación de citocromo c, las vías ERK1/2 e IRS-1, se regulaban positivamente, mientras que la vía de supervivencia celular, incluida PI3K/AKT, se regulaba negativamente. El RES y el QRC provocaron oncosis, hipertrofia celular, hipercondensación de la cromatina, rotura de la membrana plasmática y nuclear y formación de cuerpos apoptóticos. Las mediciones morfométricas de algunos parámetros celulares y nucleares mostraron que RES y QRC indujeron un aumento en las células y el tamaño nuclear, la proporción nucleocitoplasmática se mantuvo por debajo de 1 (N- Cyt R <1), signo de baja actividad nuclear. RES y QRC indujeron la apoptosis de las células Hep2 aumentando los marcadores de estrés oxidativo, MDA, y modulando las enzimas desintoxicantes, CAT y SOD. Los resultados de nuestro estudio demuestran las propiedades antiproliferativas y proapoptóticas de la quercetina y el resveratrol con respecto al cáncer de laringe.

Left ventricular hypertrophy: hypertensive or hypertrophic cardiomyopathy? What a dilemma! A case report / Hipertrofia ventricular izquierda: ¿cardiopatía hipertensiva o miocardiopatía hipertrófica? ¡Vaya dilema! Reporte de caso

Abstract In the presence of the left ventricle hypertrophy (LVH), the differential diagnosis with hypertrophic cardiomyopathy (HCM) or some phenocopy must be always considered, which can be easily suspected when the hypertrophy is markedly asymmetric. However, when the hypertrophy is homogeneous, especially if the patient has concomitant hypertension, it may be a challenge to distinguish between hypertensive and HCM, although some clinical features may help us to suspect it. In addition, patients with HCM may present with exertional angina due to microcirculation involvement in the setting of the hypertrophy itself or dynamic obstruction in the left ventricular outflow tract, but in some cases, the presence of concomitant coronary artery disease must be suspected as the cause of angina, especially if the patient has an intermediate or high-risk probability of having ischemic heart disease. We present the case of a 46-year-old Afro-American man with poorly controlled hypertension who was found to have severe LVH, and who presented with symptoms of exertional angina during follow-up. We will review the clinical features that can help us in the differential diagnosis in this context.

Resumen Ante la presencia de hipertrofia del ventrículo izquierdo (HVI), siempre se debe considerar el diagnóstico diferencial con la miocardiopatía hipertrófica (MCH) o alguna fenocopia, que puede sospecharse fácilmente cuando la hipertrofia es marcadamente asimétrica. Además, los pacientes con MCH pueden presentar angina de esfuerzo debido a la afectación de la microcirculación en el contexto de la propia hipertrofia o si ésta condiciona obstrucción dinámica al tracto de salida del ventrículo izquierdo, pero en algunos casos debe sospecharse la presencia de enfermedad coronaria concomitante como causa de la angina, especialmente si el paciente tiene una probabilidad de riesgo intermedio o alto de padecer cardiopatía isquémica. Presentamos el caso de un varón de 46 años de afroamericana con hipertensión arterial mal controlada a quien se le detectó una HVI severa, y que durante el seguimiento presentó síntomas de angina de esfuerzo. Revisaremos las características clínicas que nos pueden ayudar en el diagnóstico diferencial en este contexto.

Efectos del entrenamiento cluster sobre la hipertrofia muscular: una revisión sistemática / Effects of cluster training on muscle hypertrophy: a systematic review / Efeitos do treinamento em cluster na hipertrofia muscular: uma revisão sistemática

Resumen Objetivo: El objetivo de la presente revisión sistemática fue determinar los efectos del entrenamiento cluster sobre la hipertrofia muscular. Metodología: Se realizó una búsqueda bibliográfica en las bases de datos electrónicas Pubmed, Scopus y Web of Science, utilizando las siguientes palabras clave: 'cluster training', 'rest Interval', 'rest pause', 'hypertrophy', 'resistance training' y 'cross sectional area'. Se incluyeron ensayos clínicos que utilizaron el entrenamiento cluster como intervención en personas mayores de 18 años de ambos sexos. Resultados: La revisión sistemática obtenida durante la búsqueda de las bases de datos consultadas arrojó un total de 23 artículos, potencialmente elegibles, de los cuales se tomó una muestra de 9, con los que se podían obtener resultados que respondían al objetivo de esta revisión. La cantidad de participantes de los 9 artículos elegibles fue de 172 sujetos. Los entrenamientos cluster permiten aumentar el volumen de entrenamiento y la intensidad sin provocar elevados niveles de fatiga, favoreciendo así el desarrollo de la hipertrofia muscular. Conclusiones: Los resultados de esta revisión sistemática sugieren que los entrenamientos cluster pueden ser una herramienta eficaz para el desarrollo de la hipertrofia muscular.

Abstract Objective: The aim of this systematic review was to determine the effects of cluster training on muscle hypertrophy. Methodology: A literature search was performed in the electronic databases Pubmed, Scopus and Web of Science, using the following keywords: 'cluster training', 'rest interval', 'rest pause', 'hypertrophy', 'resistance training' and 'cross sectional area'. We included clinical trials that used cluster training as an intervention in people over 18 years of age of both sexes. Results: The systematic review obtained during the search of the databases consulted yielded a total of 23 potentially eligible articles, of which a sample of 9 was taken from which results could be obtained that responded to the objective of this review. The number of participants from the 9 eligible articles was 172 subjects. Cluster workouts allow for increased training volume and intensity without causing high levels of fatigue, thus favoring the development of muscle hypertrophy. Conclusions: The results of this systematic review suggest that cluster training can be an effective tool for the development of muscle hypertrophy.

Resumo Objetivo: O objetivo desta revisão sistemática foi determinar os efeitos do treinamento em cluster na hipertrofia muscular. Metodologia: Realizou-se uma busca na literatura nas bases de dados eletrônicas Pubmed, Scopus e Web of Science, utilizando as seguintes palavras-chave: 'cluster training', 'rest interval', 'rest pause', 'hypertrophy', 'resistance training' e 'cross sectional area'. Foram incluídos ensaios clínicos que utilizaram o treinamento em cluster como intervenção em pessoas com mais de 18 anos de ambos os sexos. Resultados: A revisão sistemática realizada durante a busca nas bases de dados consultadas resultou em um total de 23 artigos potencialmente elegíveis, dos quais uma amostra de 9 foi selecionada para obter resultados que respondessem ao objetivo desta revisão. O número de participantes nos 9 artigos elegíveis foi de 172 indivíduos. Os treinos em cluster permitem um aumento no volume e na intensidade do treinamento sem causar altos níveis de fadiga, favorecendo assim o desenvolvimento da hipertrofia muscular. Conclusões: Os resultados desta revisão sistemática sugerem que o treinamento em cluster pode ser uma ferramenta eficaz para o desenvolvimento da hipertrofia muscular.

Diferenças entre Duas Condições Cardíacas Hipertróficas Distintas: Doença de Fabry Versus Cardiomiopatia Hipertrófica / Differences Between Two Distinct Hypertrophic Cardiac Conditions: Fabry Disease versus Hypertrophic Cardiomyopathy

Resumo Fundamento A cardiomiopatia hipertrófica (CMH) e a doença de Fabry (DF) são doenças herdadas geneticamente com características fenotípicas de hipertrofia ventricular esquerda (HVE) que causam resultados cardíacos adversos. Objetivos Investigar as diferenças demográficas, clínicas, bioquímicas, eletrocardiográficas (ECG) e ecocardiográficas (ECO) entre CMH e DF. Métodos 60 pacientes com CMH e 40 pacientes com DF foram analisados retrospectivamente como uma subanálise do "estudo LVH-TR" após exclusão de pacientes com fibrilação atrial, ritmo de estimulação, bloqueios de ramo e bloqueios atrioventriculares (AV) de segundo e terceiro graus. O nível de significância foi aceito como <0,05. Resultados O sexo masculino (p=0,048) e a creatinina (p=0,010) são significativamente maiores a favor da DF; entretanto, infradesnivelamento do segmento ST (p=0,028), duração do QT (p=0,041), espessura do septo interventricular (SIVd) (p=0,003), espessura da parede posterior (PWd) (p=0,009), insuficiência mitral moderada a grave (IM) (p=0,013) e o índice de massa ventricular esquerda (IMVE) (p=0,041) são significativamente maiores a favor da CMH nas análises univariadas. Na análise multivariada, a significância estatística apenas permanece na creatinina (p=0,018) e na duração do intervalo QT (0,045). A DF foi positivamente correlacionada com a creatinina (rho=0,287, p=0,004) e a CMH foi positivamente correlacionada com o PWd (rho=0,306, p=0,002), IVSd (rho=0,395, p<0,001), IM moderada-grave (rho= 0,276, p<0,005), IMVE (rho=0,300, p=0,002), espessura relativa da parede (ERP) (rho=0,271, p=0,006), duração do QT (rho=0,213, p=0,034) e depressão do segmento ST (rho =0,222, p=0,026). Conclusão Características bioquímicas, ECG e ECO específicas podem auxiliar na diferenciação e no diagnóstico precoce da CMH e da DF.

Abstract Background Hypertrophic cardiomyopathy (HCM) and Fabry disease (FD) are genetically inherited diseases with left ventricular hypertrophy (LVH) phenotype characteristics that cause adverse cardiac outcomes. Objectives To investigate the demographic, clinical, biochemical, electrocardiographic (ECG), and echocardiographic (ECHO) differences between HCM and FD. Methods 60 HCM and 40 FD patients were analyzed retrospectively as a subanalysis of the 'LVH-TR study' after excluding patients with atrial fibrillation, pace rhythm, bundle branch blocks, and second and third-degree atrioventricular (AV) blocks. The significance level was accepted as <0.05. Results Male gender (p=0.048) and creatinine (p=0.010) are significantly higher in favor of FD; however, ST depression (p=0.028), QT duration (p=0.041), interventricular septum thickness (IVSd) (p=0.003), posterior wall thickness (PWd) (p=0.009), moderate-severe mitral regurgitation (MR) (p=0.013), and LV mass index (LVMI) (p=0.041) are significantly higher in favor of HCM in the univariate analyses. In multivariate analysis, statistical significance only continues in creatinine (p=0.018) and QT duration (0.045). FD was positively correlated with creatinine (rho=0.287, p=0.004) and HCM was positively correlated with PWd (rho=0.306, p=0.002), IVSd (rho=0.395, p<0.001), moderate-severe MR (rho=0.276, p<0.005), LVMI (rho=0.300, p=0.002), relative wall thickness (RWT) (rho=0.271, p=0.006), QT duration (rho=0.213, p=0.034) and ST depression (rho=0.222, p=0.026). Conclusion Specific biochemical, ECG, and ECHO characteristics can aid in the differentiation and early diagnosis of HCM and FD.

Research progress on the roles of angiopoietin-like protein 8 in the pathogenesis of cardiovascular diseases / 基础医学与临床

Angiopoietin-like protein 8(ANGPTL8)secreted by liver and adipose tissue,is a glycoprotein exerting paramount effects on facilitation of vascular remodeling and regulation of inflammatory response;ANGPTL8 is in-volved in the initiation and progression of cardiovascular diseases including coronary artery disease,hypertension,aortic aneurysm and pathological cardiac hypertrophy,and holds promise for being a new target for the prevention and treatment of cardiovascular diseases.

Relationship between left ventricular hypertrophy diagnosed by Peguero-Lo-Presti index and recurrence after radiofrequency catheter ablation of paroxysmal atrial fibrillation / 天津医药

Objective To investigate the relationship between left ventricular hypertrophy(LVH)diagnosed by Peguero-Lo-Presti index and recurrence of paroxysmal atrial fibrillation(AF)after radiofrequency ablation.Methods A total of 652 patients with paroxysmal atrial fibrillation who underwent radiofrequency ablation were selected.According to Peguero-Lo-Presti index,patients were divided into the LVH group(167 cases)and the normal left ventricle group(485 cases).Baseline data were collected,and regular follow-up was performed at 3,6 and 12 months after radiofrequency catheter ablation.The recurrence of AF was assessed.Kaplan-Meier survival curve was used to analyze the recurrence rate of AF in the two groups.Cox proportional hazard model was used to assess risk factors for recurrent atrial fibrillation.Results The median follow-up time was 20.5(15.0,26.0)months.A total of 155 patients(23.8%)developed recurrence of AF,including 95 patients in the LVH group and 60 patients in the LVN group.The recurrence rate without AF was significantly lower in the LVH group than that in the LVN group(64.1%vs.80.4%,Log-rank χ2=26.361,P＜0.01).After adjusting for age,sex,body mass index,hypertension,diabetes,coronary heart disease,cardiac dysfunction,left anteroposterior and posterior atrial diameter,left ventricular end-diastolic diameter,and left ventricular ejection fraction,LVH diagnosed by Peguero-Lo-Presti index was still a risk factor for recurrent AF[HR(95%CI):2.359(1.663-3.345),P＜0.01].Conclusion In patients with paroxysmal AF,LVH diagnosed by Peguero-Lo-Presti index is a risk factor of AF recurrence after radiofrequency catheter ablation.

miR-20a regulates pressure overload-induced cardiac hypertrophy / 中国组织工程研究

BACKGROUND:Cardiac hypertrophy is an adaptive response of the heart to physiological and pathological stimuli such as pressure overload.It is of compensatory significance in the early stage,but if the stimulation continues,it can cause cardiomyopathy leading to heart failure.MicroRNAs are involved in the regulation of cardiac hypertrophy.However,the role of miR-20a in pressure overload-induced cardiac hypertrophy has not been reported. OBJECTIVE:To investigate the role of miR-20a in pressure overload-induced cardiac hypertrophy and the underlying mechanisms. METHODS:Transverse aortic constriction was used to induce cardiac hypertrophy in vivo and angiotensin Ⅱ was used to induce H9c2 cell models of cardiac hypertrophy in vitro.MiR-20a was overexpressed in vivo by intramyocardial injection of miR-20a overexpressing adenovirus and in vitro by transfecting miR-20a mimic into H9c2 cells.Cardiac hypertrophy was assessed by measuring heart weight/body weight ratio,cell surface area,and myocardial fibrosis.The expression levels of atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain and miR-20a were detected by real-time fluorescence quantitative PCR.Mitochondrial fission was detected by MitoTracker.The downstream target genes of miR-20a were predicted by RNAhybrid software. RESULTS AND CONCLUSION:(1)The expression level of miR-20a was significantly decreased in both hypertrophic cardiomyocytes and hearts(P<0.05).(2)At the animal level,overexpression of miR-20a significantly inhibited transverse aortic constriction-induced cardiac hypertrophy,including decreasing the upregulated expression level of hypertrophic marker genes(P<0.05),reduced the enlarged heart volume,reducing the increased heart weight/body weight ratio(P<0.01),reducing the increased myocardial cross-sectional area(P<0.05),and attenuating fibrosis(P<0.01).(3)At the cellular level,overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced cardiomyocyte hypertrophy,including decreasing the upregulated expression levels of atrial natriuretic peptide(P<0.05),brain natriuretic peptide(P<0.01)and β-myosin heavy chain(P<0.05),reducing the increased protein/DNA ratio(P<0.01),and suppressing the increased cell surface area(P<0.05).(4)Overexpression of miR-20a significantly inhibited angiotensin Ⅱ-induced mitochondrial fission(P<0.05).(5)The results of RNAhybrid software analysis showed that miR-20a and the mRNA 3'untranslated region of cAMP-dependent protein kinase inhibitor alpha were well complementary and the predicted binding sites were highly conserved.(6)In conclusion,miR-20a is significantly down-regulated in pressure overload-induced cardiac hypertrophy.Overexpression of miR-20a inhibits cardiac hypertrophy at both the cellular level and animal level and attenuates angiotensin Ⅱ-induced mitochondrial fission.

Regulation of N6-methyladenosine on non-coding RNAs in pathological cardiac remodeling / 中国组织工程研究

BACKGROUND:N6-methyladenosine(m6A)is a hot research topic in the mechanism of pathological cardiac remodeling and plays an important role in the development of cardiovascular diseases. OBJECTIVE:To summarize the possible mechanism by which m6A modification in non-coding RNAs regulates the main processes of pathological cardiac remodeling,such as pathological cardiac hypertrophy,cardiomyocyte death,myocardial fibrosis and vascular remodeling. METHODS:"m6A,non-coding RNA,pathological cardiac hypertrophy,cardiomyocyte apoptosis,cardiomyocyte pyroptosis,cardiomyocyte ferroptosis,myocardial fibrosis,vascular remodeling"were used as search terms in Chinese and English.Relevant literature from CNKI,PubMed and Web of Science databases published from January 1974 to April 2023 was retrieved,and finally 86 eligible articles were reviewed. RESULTS AND CONCLUSION:m6A modification is a highly dynamic and reversible modification.Pathological cardiac remodeling mainly involves pathological cardiac hypertrophy,cardiomyocyte apoptosis,cardiomyocyte pyroptosis,cardiomyocyte ferroptosis,myocardial fibrosis and vascular remodeling.m6A-related enzymes can regulate pathological cardiac remodeling processes through various non-coding RNAs and different signaling pathways,which can be used as a new potential intervention for cardiovascular diseases.In pathological cardiac remodeling,research on the regulatory relationship between m6A modification and non-coding RNAs is still in its infancy.With the development of epigenetics,m6A modification in non-coding RNAs is expected to have a new development in the regulation of pathological cardiac remodeling.

circMYO9A_006 inhibits expression of cardiac hypertrophy-related pro-teins in cardiomyocytes by translating protein MYO9A-208aa / 中国病理生理杂志

AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

Spermidine alleviates pressure overload-induced heart failure in mice via improving cardiac mitochondrial energy metabolism / 中国病理生理杂志

AIM:To investigate the effect of spermidine(SPD)on pressure overload-induced cardiac hyper-trophy and heart failure model in mice and its underlying mechanisms.METHODS:(1)Eight-week-old male C57BL/6J mice were randomly divided into 4 groups:sham group,sham+SPD group,transverse aortic constriction(TAC)group,and TAC+SPD group.After TAC,the mice in sham+SPD group and TAC+SPD group were fed with 3 mmol/L SPD via drinking water,and the mice in other groups were fed with normal water.Western blot was used to detect the protein ex-pression levels of silent information regulator 6(SIRT6),peroxisome proliferator-activated receptor γ coactivator-1(PGC-1)and mitofusin 2(MFN2).Adult mouse cardiomyocytes were isolated to detect cell length and width.Wheat germ agglu-tinin staining was used to detect the cardiac cell size.Masson staining was used to detect the extent of fibrosis.Echocar-diography was used to detect cardiac function and myocardial hypertrophy.Transmission electron microscopy was used to analyze mitochondrial morphology.Oxygraph-2k high-resolution respirometer was used to detect cardiac mitochondrial oxy-gen consumption.(2)In vitro,primary rat ventricular cardiomyocytes were cultured and treated with angiotensin II(Ang II;1 μmol/L)to construct a hypertrophy model of cardiomyocytes.These cardiomyocytes were divided into control(Con)group,Con+SPD(1 mmol/L)group,Ang II group,Ang II+SPD group and Ang II+SPD+SIRT6 siRNA(siSIRT6)group.Confocal microscopy was used to detect cardiomyocytes area and mitochondrial.RESULTS:(1)Compared with sham group,cardiac function of the mice in TAC group was significantly decreased(P＜0.05),the degree of myocardial hyper-trophy was significantly increased(P＜0.05),and the expression levels of SIRT6,PGC-1 and MFN2 in the myocardial tis-sue were significantly decreased(P＜0.05).Compared with TAC group,the expression levels of SIRT6,PGC-1 and MFN2 in mouse myocardial tissues of TAC+SPD group were significantly increased(P＜0.05),pathological myocardial hy-pertrophy was reduced(P＜0.05),the numbers of mitochondria and mitochondrial cristae were increased(P＜0.05),mito-chondrial function was restored(P＜0.05),myocardial fibrosis was alleviated(P＜0.05),and cardiac function was im-proved(P＜0.05).(2)In vitro,compared with Con group,the expression levels of SIRT6,PGC-1 and MFN2 in cardio-myocytes of Ang II group were decreased(P＜0.05),and the degree of cardiomyocyte hypertrophy was significantly in-creased(P＜0.05).Treatment with SPD increased the expression levels of SIRT6,PGC-1 and MFN2 in cardiomyocytes of Ang II group(P＜0.05),reversed myocardial hypertrophy and improved mitochondrial dynamics(P＜0.05).Compared with Ang II group,the expression levels of SIRT6,PGC-1 and MFN2 in Ang II+SPD+siSIRT6 group showed no significant changes,and the degree of cardiomyocyte hypertrophy and mitochondrial dynamics also had no statistically significant changes.CONCLUSION:Spermidine promotes the expression of SIRT6,PGC-1 and MFN2,thus improving mitochon-drial function,reducing myocardial hypertrophy and alleviating heart failure in mice with pressure overload.

Visual Analysis of Research Trends and Hotspots in Animal Models of Chronic Heart Failure / 中药新药与临床药理

Objective To understand the research situation of animal model of chronic heart failure(CHF)based on visualization software and bibliometrics methods,and to explore the research hotspots of animal models of CHF and guide the design of animal experiments and scientific research.Methods Literature related to animal model of CHF included in Web of Science core collection from January 1,2001 to October 10,2022 were retrieved.After reading the full text and obtaining the final included literature,VOSviewer and CiteSpace software were used to analyze the contents of institutions,journals and co-cited journals,authors and co-cited authors,keywords.Results A total of 961 papers were included,and the number of published papers increased steadily.The United States and China are the main research countries.Johns Hopkins University and Harvard University are major research institutions.The most frequently published and cited journals are AM J PHYSIOL-HEART C and CIRCULATION,etc..Schultz Harold D and Sabbah Hani N are more influential in author selection."Myocardial infarction","cardiac hypertrophy",and"rat"are the most frequent keywords,10 clusters and 18 emergent words were formed.Conclusion The research in this field is numerous,high quality but scattered.Commonly used animal models are rodents and dogs.The main modeling methods are surgery and drugs.The main pathological mechanisms are mainly myocardial hypertrophy,oxidative stress,and myocardial fibrosis.

Effects of Modified Shenling Baizhu Powder （参苓白术散）and Xiaoluo Pills（消瘰丸）on Quality of Life and Serum Inflammatory Factors in Children with Adenoid Hypertrophy due to Spleen Deficiency and Phlegm Accumulation / 中医杂志

ObjectiveTo investigate the clinical effect and possible mechanism of modified Shenling Baizhu Powder （参苓白术散） and Xiaoluo Pill （消瘰丸） in the treatment of children with adenoid hypertrophy due to spleen deficiency and phlegm accumulation. MethodsOne hundred and thirty children with adenoid hyperplasia due to spleen deficiency and phlegm accumulation were randomly divided into 65 cases each in the observation group and control group. The control group was given mometasone furoate nasal spray， one spray into each nostril， once a day， while the observation group was given modified Shenling Baizhu Powder and Xiaoluo Pill orally， one dose per day， and both groups were treated for 8 months. The pre- and after-treatment electronic nasopharyngoscope scores， specific quality of life survey scale （OSA-18） scores， total TCM symptom scores， serum cysteine leukotrienes （CysLTs）， interleukin 2 （IL-2）， tumor necrosis factor α （TNF-α）， and interleukin 10 （IL-10） levels were compared to determine the clinical efficacy after treatment. ResultsAfter treatment， the electronic nasopharyngoscope scores， OSA-18 scores， total TCM symptom scores， serum CysLTs， IL-2 and TNF-α levels significantly decreased， while IL-10 levels increased in both groups （P＜0.01）. Compared between the two groups after treatment， the electronic nasopharyngoscope score， OSA-18 score， total TCM symptom score， serum CysLTs， IL-2 and TNF-α levels were significantly lower， and the IL-10 level was higher in the observation group than in the control group （P＜0.01）. The total effective rate of the observation group was 95.38% （62/65）， superior to 81.54% （53/65） of the control group （P＜0.05）. ConclusionFor children with adenoid hypertrophy due to spleen deficiency and phlegm accumulation， modified Shenling Baizhu Powder and Xiaoluo Pill can help to improve symptoms， increase quality of life and clinical efficacy， and its mechanism may be related to reducing the inflammatory response.

Hyperthyroidism Induces Ventricular Remodeling via Activating β-catenin/FoxO1 in Rat Cardiomyocytes / 中山大学学报(医学科学版)

ObjectiveTo explore how hyperthyroidism induces ventricular remodeling via activating β-catenin/FoxO1 in rat cardiomyocytes. MethodsHyperthyroidism-induced ventricular remodeling rat models were established by intraperitoneal injection of levothyroxine （T4） at 0.1 mg/kg for 30 days. β-catenin inhibitor MSAB （14 mg/kg） was administrated for 30 days. We used western blot to detect the expression of myocardial hypertrophy marker ANP， β-catenin and FoxO1； immunofluorescence to examine the expression and intracellular distribution of β-catenin and FoxO1. Hyperthyroidism-induced cardiomyocyte hypertrophy rat models were established by treatment of triiodothyronine （T3） into cultured primary neonatal rat cardiomyocytes for 24 hours. β-catenin siRNA （30 nmol/L） was used to down-regulate β-catenin expression in cardiomyocytes. Western blot and immunofluorescence were used to analyze the effects of β-catenin inhibition on the hyperthyroidism-induced cardiomyocyte hypertrophy. ResultsFollowing Wnt/β-catenin activation， β-catenin was found increased nuclear expression， to bind to the nuclear transcriptional factors and regulate the gene expression. β-catenin nuclear expression was significantly increased in the hyperthyroidism-induced ventricular remodeling rats， but no change was found in the expression of typical transcriptional factor TCF7l2. Our results revealed that inhibiting β-catenin by MSAB attenuated the hyperthyroidism-induced rat ventricular remodeling. Further analysis indicated that β-catenin/FoxO1 expression was significantly increased in hyperthyroidism-induced myocardial hypertrophy which could be attenuated by suppressing β-catenin/FoxO1 in cardiomyocytes. Conclusionsβ-catenin/FoxO1 is activated in hyperthyroidism-induced myocardial hypertrophy and β-catenin/FoxO1 inhibition attenuates hyperthyroidism-induced cardiomyocyte hypertrophy.

Function of Cortactin/N-cadherin signal axis in pathological myocardial hypertrophy / 中国药理学通报

Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.

Establishment of a rat model of myocardial hypertrophy by a modified abdominal aortic coarctation method / 解剖学报

Objective To compare effectiveness between the modified and traditional pressure-overload myocardial hypertrophy(POMH) model by abdominal aorta coarctation (AAC) method. Methods Totally 45 rats were divided into three groups(n = 15 per group), sham group, traditional group, and modified group. In the traditional group, the diameter ol the abdominal aorta was narrowed to 0. 70 mm through a midline incision for 4 weeks; in the modified group, the diameter of the abdominal aorta was narrowed above the left kidney to 0. 45 mm for 1 week, and then the narrowing was lifted postoperatively. The cardiac index, heart weight (HW) /body weight (BW) and left ventricular index, left ventricular weight (LVW)/BW were measured from the heart specimens, and the cross-sectional area of cardiac myocytes, myocardial collagen area, and myocardial collagen area Iraction were measured in the pathological sections by HE staining and Masson staining. Results Compared with the sham group, the differences in end-systolic interventricular septum thickness (IVSs), left ventricular end-systolic posterior wall thickness (LVPWs), HW/BW, LVW/BW, cardiomyocyte cross-sectional area, myocardial collagen area, myocardial collagen area fraction, and brain natriuretic peptide (BNP) expression levels were statistically significant (P0. 05). Conclusion The modified abdominal aortic constriction method used in this experiment is time-saving, stable, homogeneous and easy to replicate, and is a more ideal approach to establish a rat model of POMH.

Effect of microparticles derived from bone marrow mesenchymal stem cells on cardiomyocyte hypertrophy and its mechanism / 中国生物制品学杂志

@#Objective To investigate the effect of microparticles(MPs)derived from bone marrow mesenchymal stem cells(BMSCs) on myocardial hypertrophy and its mechanism.Methods The osteogenic differentiation and adipogenic differentiation of mesenchymal stem cells(MSCs) were induced. After isolation and purification,the morphological characteristics were observed by transmission electron microscope,and the MPs surface antigen was identified by flow cytometry. Myocardial hypertrophy model was induced by using isoprenaline(ISO)in rats,which were measured for the cardiac structure and function by echocardiography,and then detected for various indexes of the heart and isolated left ventricle. Single ventricular myocytes of rats were acutely isolated and divided into control group(Control group),cardiomyocyte hypertrophy group(ISO group),MPs group(MPs group),and MPs supernatant group(Supernatant group). The mRNA expressions of atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)were detected by qRTPCR. The expression levels of calmodulin-dependent protein kinaseⅡ（CaMKⅡ）and phosphorylated calmodulin-dependent protein kinaseⅡ（p-CaMKⅡ）were detected by ELISA. The L-type calcium current(LCa-L)in single ventricular myocyte of various groups was recorded by whole-cell patch clamp.Results The bone nodules of MSCs osteogenic differentiation turned red after alizarin red staining,and lipid droplets of adipogenic differentiation turned red after oil red O staining;Under transmission electron microscope,MPs membrane had a complete structure,a clear outline and a diameter of about200 nm;The positive rates of CD29 and CD90 on the surface of MPs were(98. 24 ± 0. 82)% and(97. 69 ± 1. 83)%,respectively. Compared with Control group,the left ventricular end diastolic dimension(LVEDD)reduced signifi-cantly(t =5. 065,P < 0. 05),while the interventricular septum end-diastolic dimension(IVSd),left ventricular posterior wall dimension(LVPWd),heart weight to body weight ratio(HW/BW),and heart weight to tibial length ratio(HW/Tibia)significantly increased in ISO group(t = 4. 013,2. 368,4. 392,5. 043 and 6. 120,respectively,each P < 0. 05),indicating that the hypertrophic model was successfully established. The expression levels of ANP and BNP mRNA in hypertrophic cardiomyocytes of rats in ISO group were significantly higher than those in Control group(t = 25. 120 and18. 261,respectively,each P < 0. 01);While the expression levels of ANP and BNP mRNA in MPs group significantly reduced after incubation with 48 μg/mL MPs for 48 h compared with ISO group(t = 12. 110 and 3. 526,respectively,each P < 0. 05);The expression levels of CaMK Ⅱand p-CaMKⅡ in ISO group were significantly higher than those in Control group(t = 3. 278 and 4. 181,respectively,each P < 0. 05),while the expression of p-CaMK Ⅱ in MPs group decreased significantly(t = 5. 420,P < 0. 05);The calcium current density in ISO group was significantly higher than that in Control group(t = 15. 261,P < 0. 01),while that in MPs group was significantly lower than that in ISO group(t =6. 216,P < 0. 05).Conclusion MSC-MPs can significantly inhibit ISO-induced cardiomyocyte hypertrophy in rats,which is related to its down-regulation of cardiomyocyte CaMKⅡ and inhibition of L-type calcium channel.

Mediating effects of metabolic related indicators on the association between childhood overweight/obesity and left ventricular hypertrophy / 中国学校卫生

Objective@#To examine the mediating effects of blood pressure, glucose, lipids, and serum uric acid on the association between childhood overweight/obesity and left ventricular hypertrophy (LVH), and to provide scientific evidence for the prevention and control of cardiovascular diseases during childhood.@*Methods@#One public school in Huantai County, Zibo City was selected to conduct the baseline survey from November 2017 to January 2018 using a convenient cluster sampling method. A total of 1 400 children aged 6 to 11 were included in the study. According to the classification criteria based on body mass index (BMI), participants were divided into the non overweight/obese group ( n =787) and the overweight/obese group ( n =613). The mediating effects of metabolic variables on the association between childhood overweight/obesity and left ventricular hypertrophy (LVH) were analyzed using the "mediation" package in R software.@*Results@#Children who were overweight/obese had higher levels of BMI- Z score (2.0±0.8), systolic blood pressure (SBP) (109.1±8.9 mmHg), diastolic blood pressure (DBP) (65.4±6.8 mmHg), fasting plasma glucose (FPG) (4.8±0.5 mmol/L), insulin (INS) (11.3±7.6 μU/mL), apolipoprotein B (ApoB) (0.7±0.2 g/L), lowdensity lipoprotein cholesterol (LDL-C) (2.4±0.7 mmol/L), total cholesterol (TC) (4.2±0.9 mmol/L), triglycerides (TG) (0.9±0.4 mmol/L), and serum uric acid (SUA) (321.2±91.4 μmol/L) compared to those who were non-overweight/obese [the corresponding values were (-0.2±0.7),(104.3±8.8) mmHg, (62.2±6.2) mmHg, (4.7±0.6) mmol/L, (6.1±4.2) μU/mL, (0.6±0.2) g/L, (2.2±0.6) mmol/L, (4.1±0.7) mmol/L, (0.7±0.2) mmol/L, and (278.6±74.7) μmol/L, respectively], whereas the levels of high density lipoprotein cholesterol (HDL-C) were lower in overweight/obese children (1.5±0.3 mmol/L) than in non-overweight/obese children (1.7±0.4 mmol/L). All differences were statistically significant ( t =53.66, 9.88, 9.19, 3.60, 16.32, 7.36, 5.11, 2.55, 11.08, 9.58, -10.31, P <0.05). After adjusting for potential covariates, overweight/obese children had 8.72 times increased risk of developing LVH compared to the non-overweight/obese children ( OR=8.72, 95%CI =5.45-14.66， P <0.01). Mediation analysis showed that INS, HDL-C, LDL-C, TG, ApoB, and SUA partially mediated the association between childhood overweight/obesity and LVH, and among these, INS and TG had relatively strong mediating effects, accounting for 28.05% and 13.71% of the total effects, respectively.@*Conclusions@#INS, HDL-C, LDL-C, TG, ApoB, and SUA are intermediate risk factors on the association between childhood overweight/obesity and LVH. Keeping metabolic indicators (especially INS and TG) at healthy levels is particularly important for reducing the burden of cardiovascular diseases in overweight/obese children.

Characteristics of Early Cardiac Involvement in 45 Patients With Fabry Disease Monitored by Ultrasonic Cardiogram / 中山大学学报(医学科学版)

ObjectiveTo evaluate the changes in cardiac structure and ventricular function in patients with Anderson-Fabry Disease （AFD） by two-dimensional speckle tracking echocardiography （2D-STE） and to explore the characteristics of their early cardiac involvement. MethodsAll 45 patients diagnosed with AFD in this observational study underwent routine ultrasonic cardiogram （UCG） examination and 2D-STE. The patients were divided into 2 groups based on UCG measurements： with left ventricular hypertrophy （interventricular septum or posterior left ventricular wall thickness ≥12 mm） and without left ventricular hypertrophy. TomTec software was used to analyze the echocardiographic images， then the baseline data， UCG routine parameters and myocardial strain of the two groups were compared. ResultsThe study included 27 males （60.0%） and 18 females （40.0%）， with an average age of （32.33±16.11）， 17 cases （37.78%） with left ventricular hypertrophy and 28 cases （62.22%） without left ventricular hypertrophy. All patients had normal left ventricular ejection fraction （LVEF） （> 50%）. Compared with those without left ventricular hypertrophy， patients with left ventricular hypertrophy had significantly more target organ involvement， significantly higher E/A and average E/E' ratios （P < 0.05）. No statistical difference was found in global and segmental longitudinal strain （LS）， circumferential strain （CS） and radial strain （RS） of the endocardium and myocardium between the two groups （all P > 0.05）. There were lower absolute values of global and segmental LS and CS in the myocardium than in the endocardium （all P < 0.05）， and higher absolute values of LS and RS in the mid segment than in the basal and apical segments （all P < 0.05）. ConclusionsThere is no significant association between early systolic dysfunction and left ventricular wall thickness. 2D-STE strain can be used to detect AFD in the early stage. Ventricular wall myocardium exhibits more serious involvement than endocardium and mid segment was less involved than the apical and basal segments.

Progression,Imaging Characteristics of Left Ventricular Remodeling and the Clinical Value on Decision-making of Intervention in Patients With Aortic Stenosis / 中国循环杂志

Aortic stenosis is a valve disease characterized by dynamic and continuous changes in structure and function of left ventricle.Left ventricular remodeling,which embodies pathological changes in myocardial cellular and ventricular geometry,is an important prognostic factor of patients with aortic stenosis.Aortic valve replacement is the only effective treatment for severe aortic stenosis.Current guideline recommendations for interventions are based on symptoms and left ventricular ejection fraction.With the improvements of modern imaging technology,different patterns of remodeling,including hypertrophy and fibrosis,could be identified now.Studies also explored the close association between left ventricular remodeling and function in the setting of aortic stenosis.In this review,we aim to elucidate the characteristic imaging features and potential mechanisms of left ventricular remodeling,and further,we highlight the clinical value of specific imaging features and clinical application of modern imaging methods in the evaluation,risk stratification,and intervention decision-making for patients with aortic stenosis.