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1.
Circulation ; 148(18): 1395-1409, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37732466

RESUMEN

BACKGROUND: Remuscularization of the mammalian heart can be achieved after cell transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). However, several hurdles remain before implementation into clinical practice. Poor survival of the implanted cells is related to insufficient vascularization, and the potential for fatal arrhythmogenesis is associated with the fetal cell-like nature of immature CMs. METHODS: We generated 3 lines of hiPSC-derived endothelial cells (ECs) and hiPSC-CMs from 3 independent donors and tested hiPSC-CM sarcomeric length, gap junction protein, and calcium-handling ability in coculture with ECs. Next, we examined the therapeutic effect of the cotransplantation of hiPSC-ECs and hiPSC-CMs in nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice undergoing myocardial infarction (n≥4). Cardiac function was assessed by echocardiography, whereas arrhythmic events were recorded using 3-lead ECGs. We further used healthy non-human primates (n=4) with cell injection to study the cell engraftment, maturation, and integration of transplanted hiPSC-CMs, alone or along with hiPSC-ECs, by histological analysis. Last, we tested the cell therapy in ischemic reperfusion injury in non-human primates (n=4, 3, and 4 for EC+CM, CM, and control, respectively). Cardiac function was evaluated by echocardiography and cardiac MRI, whereas arrhythmic events were monitored by telemetric ECG recorders. Cell engraftment, angiogenesis, and host-graft integration of human grafts were also investigated. RESULTS: We demonstrated that human iPSC-ECs promote the maturity and function of hiPSC-CMs in vitro and in vivo. When cocultured with ECs, CMs showed more mature phenotypes in cellular structure and function. In the mouse model, cotransplantation augmented the EC-accompanied vascularization in the grafts, promoted the maturity of CMs at the infarct area, and improved cardiac function after myocardial infarction. Furthermore, in non-human primates, transplantation of ECs and CMs significantly enhanced graft size and vasculature and improved cardiac function after ischemic reperfusion. CONCLUSIONS: These results demonstrate the synergistic effect of combining iPSC-derived ECs and CMs for therapy in the postmyocardial infarction heart, enabling a promising strategy toward clinical translation.


Asunto(s)
Células Madre Pluripotentes Inducidas , Infarto del Miocardio , Humanos , Ratones , Animales , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Células Endoteliales/metabolismo , Ratones SCID , Ratones Endogámicos NOD , Infarto del Miocardio/patología , Primates , Diferenciación Celular , Mamíferos
2.
Nurs Res ; 73(2): 158-165, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38193910

RESUMEN

BACKGROUND: The outbreak of COVID-19 caused severe damage to public health globally and served as a stark reminder of the potential for future pandemics. Promoting protective behaviors to prevent the spread of any contagious disease thus remains a priority. Although research has shown that health beliefs can affect protective behaviors, few studies have examined the role of information-seeking in this relationship. OBJECTIVES: On the basis of the health belief model, this research focused on whether health beliefs affect personal protective behaviors through health information-seeking behaviors. METHODS: This cross-sectional study with a causal-comparative design used an online questionnaire to investigate the Taiwanese public's health beliefs, protective behaviors, and information-seeking behaviors during the COVID-19 pandemic. Data were analyzed using descriptive statistics and multiple regression analysis. RESULTS: Between September 2021 and January 2022, 322 valid questionnaires were collected. The results revealed that the effects of two health beliefs-self-efficacy and perceived benefits-on handwashing, social distancing, practicing good cough etiquette, and keeping one's environment clean and well ventilated were partially mediated by the frequency of official information-seeking. DISCUSSION: Results of this study support the regular and timely promotion of pandemic prevention measures through official sites. Promoting official information-seeking can help enhance protective behaviors.


Asunto(s)
COVID-19 , Pandemias , Humanos , Pandemias/prevención & control , Conducta en la Búsqueda de Información , Estudios Transversales , COVID-19/prevención & control , Encuestas y Cuestionarios , Conductas Relacionadas con la Salud
3.
BMC Geriatr ; 23(1): 443, 2023 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-37468836

RESUMEN

BACKGROUND: The second-and third-generation drug-eluting stents (DESs) in-stent restenosis (ISR) genetic risk score (GRS) model has been previously validated. However, the model has not been validated in geriatric patients. Therefore, we conducted this study to test the feasibility of the DES-ISR GRS model in geriatric patients with coronary artery disease (CAD) in Taiwan. METHODS: We conducted a retrospective, single-center cohort study and included geriatric patients (age ≥ 65 years) with CAD and second-or third-generation DES(s) deployment. Patients undergoing maintenance dialysis were excluded. ISR was defined as ≥ 50% luminal narrowing on the follow-up coronary arteriography. The DES-ISR GRS model included five selected exonic single-nucleotide polymorphisms (SNPs): CAMLG, GALNT2, C11orf84, THOC5, and SAMD11. The GRS was defined as the sum of the five selected SNPs for the risk allele. RESULTS: We enrolled 298 geriatric patients from January 2010 and December 2019 in this study. After propensity score matching, there were 192 geriatric patients with CAD in the final analysis, of which 32 patients had ISR. Patients were divided into two groups based on their GRS values: low (0-2) and high (≥ 3) GRS. A high GRS was significantly associated with DES-ISR in geriatric patients. CONCLUSION: Those geriatric patients with a high GRS had significantly higher second-or third-generation DES ISR rates. The five SNP-derived DES-ISR GRS model could provide genetic information for interventional cardiologists to treat geriatric patients with CAD. TRIAL REGISTRATION: The primary study protocol was registered with clinicaltrials.org. with registration number: NCT03877614; on March 15, 2019. ( http://clinicaltrials.gov/ct2/show/NCT03877614 ).


Asunto(s)
Enfermedad de la Arteria Coronaria , Reestenosis Coronaria , Stents Liberadores de Fármacos , Humanos , Anciano , Estudios Retrospectivos , Estudios de Cohortes , Reestenosis Coronaria/terapia , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/terapia , Factores de Riesgo , Proteínas Nucleares
4.
Rev Cardiovasc Med ; 23(7): 242, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39076927

RESUMEN

Background: Atrial fibrillation (AF) is associated with an increased risk of heart failure, death and thromboembolism. AF is prevalent in patients with cancer. Although current guidelines suggest the application of oral anticoagulants (OACs) for thromboembolic event prevention in high-risk AF patients, owing to the high thromboembolic and bleeding risks of active-cancer patients, there is no consensus on the use of OACs in such a population. Therefore, we conducted this retrospective cohort study to investigate the applicability of the CHA 2 DS 2 -VASc score and to evaluate the efficacy and safety outcomes of OAC therapy in active-cancer patients with AF. Methods: This retrospective cohort study enrolled patients diagnosed with cancer at National Cheng Kung University Hospital between November 2012 and August 2019. The primary outcomes included all-cause mortality, thromboembolic events (stroke/transient ischemic attack and systemic emboli), acute myocardial infarction (AMI), hospitalization for HF and major bleeding events. Results: We enrolled 2429 patients with active cancer. Among these patients, 1060 patients (43.6%) had AF. After 1:2 propensity score matching, 690 cancer patients with AF were enrolled for the final analysis, grouped as follows: 225 patients taking OACs and 465 patients without OAC treatment. The OAC-treated group had lower all-cause mortality than the patients without OAC treatment (all-cause mortality rate in OAC treatment vs. non-OAC treatment: 24.4% vs. 37.4%, hazard ratio 0.58 [95% confidence interval (CI) 0.43-0.78], p < 0.001). However, there was no difference in thromboembolic events, myocardial infarction or heart failure hospitalization between the OAC-treated and non-OAC-treated groups. Importantly, the risk of major bleeding composition (i.e., major gastrointestinal bleeding and intracranial hemorrhage) was similar between these two groups. Moreover, the CHA 2 DS 2 -VASc score could not predict thromboembolic events in the enrolled active-cancer patients with AF (OR 1.23, 95% CI 0.98-1.56). Conclusions: OAC treatment may significantly reduce the risk of death, without safety concerns, in active-cancer patients with AF. OAC treatment may not prevent thromboembolic events in patients with active cancer and AF. However, we found that OAC treatment is associated with improved prognosis without increasing the risks of major bleeding, despite several limitations in this study. Further studies are required to determine the optimal use of anticoagulation therapy in this high-risk population.

5.
Acta Cardiol Sin ; 38(1): 1-12, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35068877

RESUMEN

Advances in cancer management have significantly improved survival in patients with cancers. Cardiovascular complications of cancer treatment are becoming significant competing causes of death in these patients. Radiotherapy is an indispensable component of cancer treatment, and irradiation of the heart and vasculature during cancer radiotherapy is now recognized as a new risk factor for cardiovascular diseases. It is important to involve multidisciplinary expertise and provide practical recommendations to promote awareness, recognize risks, and provide adequate interventions without jeopardizing cancer control. In this consensus paper, experts from the Taiwan Society for Therapeutic Radiology and Oncology and Taiwan Society of Cardiology provide a focused update on the clinical practice for risk stratification and management of radiation-induced cardiovascular disease (RICVD). We believe that implementing RICVD care under a collaborative cardio-oncology program will significantly improve cancer treatment outcomes and will facilitate high quality clinical investigations.

6.
Nature ; 510(7504): 273-7, 2014 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-24776797

RESUMEN

Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure by providing human cardiomyocytes to support heart regeneration. Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment. However, it remains unknown whether clinical-scale hESC-CM transplantation is feasible, safe or can provide sufficient myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (more than one billion cells per batch) and cryopreserved with good viability. Using a non-human primate model of myocardial ischaemia followed by reperfusion, we show that cryopreservation and intra-myocardial delivery of one billion hESC-CMs generates extensive remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a 3-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small-animal models, non-fatal ventricular arrhythmias were observed in hESC-CM-engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome.


Asunto(s)
Células Madre Embrionarias/citología , Corazón , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Miocitos Cardíacos/citología , Regeneración , Animales , Arritmias Cardíacas/fisiopatología , Calcio/metabolismo , Supervivencia Celular , Vasos Coronarios/fisiología , Criopreservación , Modelos Animales de Enfermedad , Electrocardiografía , Humanos , Macaca nemestrina , Masculino , Ratones , Medicina Regenerativa/métodos
7.
Int J Mol Sci ; 22(1)2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33374215

RESUMEN

Cardiovascular disease is the leading cause of deaths worldwide, claiming an estimated total of 17.9 million lives each year, of which one-third of the people are under the age of 70 years. Since adult cardiomyocytes fail to regenerate, the heart loses the ability to repair itself after an injury, making patients with heart disease suffer from poor prognosis. Pluripotent stem cells have the ability to differentiate into cardiomyocytes in vitro through a well-established process, which is a new advancement in cardiac regeneration therapy. However, pluripotent stem cell-derived cardiomyocytes have certain drawbacks, such as the risk of arrhythmia and immune incompatibility. Thus, amniotic fluid stem cells (AFSCs), a relatively novel source of stem cells, have been exploited for their ability of pluripotent differentiation. In addition, since AFSCs are weakly positive for the major histocompatibility class II molecules, they may have high immune tolerance. In summary, the possibility of development of cardiomyocytes from AFSCs, as well as their transplantation in host cells to produce mechanical contraction, has been discussed. Thus, this review article highlights the progress of AFSC therapy and its application in the treatment of heart diseases in recent years.


Asunto(s)
Líquido Amniótico/metabolismo , Isquemia Miocárdica , Miocardio/metabolismo , Miocitos Cardíacos , Células Madre Pluripotentes/metabolismo , Regeneración , Anciano , Diferenciación Celular , Humanos , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/terapia , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/trasplante
8.
Int J Mol Sci ; 21(7)2020 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-32244307

RESUMEN

AIM: Immunological checkpoint therapy is considered a powerful method for cancer therapy and acts by re-activating autologous T cells to kill the cancer cell. Myocarditis cases have been reported in cancer patients after immunological therapy; for example, nivolumab treatment is a monoclonal antibody that blocks programmed cell death-1/programmed cell death ligand-1 ligand interaction. This project provided insight into the inflammatory response as a benchmark to investigate the potential cardiotoxic effect of T cell response to the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis in regulating cardiomyocyte injury in vitro. METHODS AND RESULTS: We investigated cardiomyopathy resulted from the PD-1/PD-L1 axis blockade using the anti-PD-1 antibody in Rockefeller University embryonic stem cells-derived cardiomyocytes (RUES2-CMs) and a melanoma tumor-bearing murine model. We found that nivolumab alone did not induce inflammatory-related proteins, including PD-L1 expression, and did not induce apoptosis, which was contrary to doxorubicin, a cardiotoxic chemotherapy drug. However, nivolumab was able to exacerbate the immune response by increasing cytokine and inflammatory gene expression in RUES2-CMs when co-cultured with CD4+ T lymphocytes and induced apoptosis. This effect was not observed when RUES2-CMs were co-cultured with CD8+ T lymphocytes. The in vivo model showed that the heart function of tumor-bearing mice was decreased after treatment with anti-PD-1 antibody and demonstrated a dilated left ventricle histological examination. The dilated left ventricle was associated with an infiltration of CD4+ and CD8+ T lymphocytes into the myocardium. PD-L1 and inflammatory-associated gene expression were significantly increased in anti-PD-1-treated tumor-bearing mice. Cleaved caspase-3 and mouse plasma cardiac troponin I expressions were increased significantly. CONCLUSION: PD-L1 expression on cardiomyocytes suppressed T-cell function. Blockade of PD-1 by nivolumab enhanced cardiomyocyte inflammation and apoptosis through the enhancement of T-cell response towards cardiomyocytes.


Asunto(s)
Apoptosis/fisiología , Antígeno B7-H1/metabolismo , Inflamación/metabolismo , Miocitos Cardíacos/metabolismo , Linfocitos T/metabolismo , Animales , Anticuerpos Monoclonales/farmacología , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Humanos , Inmunoterapia/métodos , Masculino , Melanoma/metabolismo , Ratones , Ratones Endogámicos BALB C , Miocitos Cardíacos/patología , Nivolumab/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Int J Mol Sci ; 21(7)2020 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-32235313

RESUMEN

Mature mammalian hearts possess very limited regenerative potential. The irreversible cardiomyocyte loss after heart injury can lead to heart failure and death. Pluripotent stem cells (PSCs) can differentiate into cardiomyocytes for cardiac repair, but there are obstacles to their clinical application. Among these obstacles is their potential for post-transplant rejection. Although human amniotic fluid-derived stem cells (hAFSCs) are immune privileged, they cannot induce cardiac differentiation. Thus, we generated hAFSC-derived induced PSCs (hAFSC-iPSCs) and used a Wnt-modulating differentiation protocol for the cardiac differentiation of hAFSC-iPSCs. In vitro studies using flow cytometry, immunofluorescence staining, and patch-clamp electrophysiological study, were performed to identify the characteristics of hAFSC-iPSC-derived cardiomyocytes (hAFSC-iPSC-CMs). We injected hAFSC-iPSC-CMs intramuscularly into rat infarcted hearts to evaluate the therapeutic potential of hAFSC-iPSC-CM transplantation. At day 21 of differentiation, the hAFSC-iPSC-CMs expressed cardiac-specific marker (cardiac troponin T), presented cardiomyocyte-specific electrophysiological properties, and contracted spontaneously. Importantly, these hAFSC-iPSC-CMs demonstrated low major histocompatibility complex (MHC) class I antigen expression and the absence of MHC class II antigens, indicating their low immunogenicity. The intramyocardial transplantation of hAFSC-iPSC-CMs restored cardiac function, partially remuscularized the injured region, and reduced fibrosis in the rat infarcted hearts. Therefore, hAFSC-iPSCs are potential candidates for the repair of infarcted myocardium.


Asunto(s)
Líquido Amniótico/citología , Diferenciación Celular , Células Madre Embrionarias/citología , Privilegio Inmunológico , Células Madre Pluripotentes Inducidas/citología , Desarrollo de Músculos , Miocitos Cardíacos/citología , Animales , Biomarcadores , Modelos Animales de Enfermedad , Fenómenos Electrofisiológicos , Humanos , Inmunohistoquímica , Células Madre Pluripotentes Inducidas/inmunología , Células Madre Pluripotentes Inducidas/metabolismo , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Miocitos Cardíacos/metabolismo , Fenotipo , Ratas , Regeneración , Trasplante de Células Madre/métodos , Resultado del Tratamiento , Función Ventricular Izquierda
10.
Acta Cardiol Sin ; 36(6): 588-594, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33235414

RESUMEN

Despite enormous advances in the treatment of cardiovascular disease (CVD), heart disease remains the leading cause of mortality and morbidity worldwide. Thus, there is a need for novel CVD therapeutics. CVD appears to be a custom-made scenario for applying stem cell therapy. Although human pluripotent stem cells can differentiate into cardiomyocytes to regenerate injured heart tissue and restore post-myocardial infarction cardiac function, several obstacles need to be overcome before cell therapy can be applied in CVD patients. One of these major hurdles is the immunological barrier. Currently, long-term immunosuppressant treatment is necessary for allogenic stem cell or organ transplantation to prevent rejection. However, the long-term use of immunosuppressants may cause serious adverse events such as nephrotoxicity, severe infections and malignancy. Thus, overcoming this immunological hurdle is crucial for the clinical application of stem cell therapy in cardiac regeneration. This review summarizes the recent advances and challenges of immunogenicity in relation to stem cell therapy.

11.
Int Heart J ; 57(5): 541-6, 2016 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-27581671

RESUMEN

It is unknown whether there has been any change in the causes of death for acute ST-segment elevation myocardial infarction (STEMI) in the era of aggressive reperfusion. We analyzed the direct causes of in-hospital death in patients with STEMI treated with primary percutaneous coronary intervention (PCI) in a tertiary referral center over the past 10 years.We retrospectively analyzed 878 STEMI patients treated with primary PCI in our hospital between January 2005 and December 2014. There were no significant changes in the age and sex of patients, but the prevalence of hypertension and smoking decreased. STEMI severity increased with more patients in Killip classification > 2. The number of out-ofhospital cardiac arrest events also increased over the 10 years. Symptom onset-to-door time did not change in the 10year study period. The care quality was improved with shorter door-to-balloon time for primary PCI and increased use of dual antiplatelet therapy. The all-cause in-hospital mortality was 9.1%, which did not vary over the 10 years. Multivariable analysis showed that Killip classification > 2 was the most important determinant of death. Cardiogenic shock was the major cause of cardiovascular death. There was an increase in non-cardiovascular causes of death in the most recent 3 years, with infection being a major problem.Despite improvement in care quality for STEMI, the in-hospital mortality did not decrease in this tertiary referral center over these 10 years due to increased disease severity and non-cardiovascular causes of death.


Asunto(s)
Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/cirugía , Anciano , Causas de Muerte , Manejo de la Enfermedad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/complicaciones , Taiwán , Centros de Atención Terciaria , Tiempo de Tratamiento
12.
J Formos Med Assoc ; 114(9): 797-805, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26188763

RESUMEN

Despite the recent enormous advances in medicine, high mortality and morbidity rates among the chronic kidney disease (CKD) patients remain an important but unresolved issue. Cardiovascular disease is a major cause of mortality and morbidity in patients with CKD. Abnormal left ventricular geometry and functions are common in this patient group and have been proven to be correlated with a high cardiovascular mortality/morbidity and all-cause mortality. For this reason, echocardiographic study plays an important role in evaluating cardiac structure and functions as well as in stratifying prognostic risk. We here summarize the reported findings on the usefulness of echocardiographic methodologies and identify their roles in diagnostic and prognostic clinical approaches.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Ecocardiografía , Ventrículos Cardíacos/diagnóstico por imagen , Insuficiencia Renal Crónica/complicaciones , Ventrículos Cardíacos/fisiopatología , Humanos , Pronóstico , Medición de Riesgo , Factores de Riesgo
13.
Biomed Pharmacother ; 176: 116759, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38788603

RESUMEN

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors, such as empagliflozin, are pivotal therapies for heart failure. However, the effect of empagliflozin on doxorubicin-related cardiac dysfunction remains unclear. METHODS: Human induced pluripotent stem cell- and embryonic stem cell-derived cardiomyocytes were used to investigate the direct effect of empagliflozin on human cardiomyocytes. Then, the c-Jun amino-terminal kinases (JNK) inhibitor SP600125 was administered to the doxorubicin cardiotoxicity model in vitro and in vivo to investigate the role of JNK in empagliflozin. RESULTS: In human stem cell-derived cardiomyocytes, pretreatment with empagliflozin attenuated doxorubicin-induced cleavage of caspase 3 and other apoptosis markers. Empagliflozin significantly attenuated doxorubicin-induced phosphorylation of JNK and p38. Inhibiting the phosphorylation of JNK (SP600125) or STAT3 attenuated doxorubicin-induced apoptosis, but inhibiting the phosphorylation of p38 did not. SP600125 inhibits the phosphorylation of STAT3 (S727), and a STAT3 (Y705) inhibitor also inhibits the phosphorylation of JNK. Empagliflozin and SP600125 attenuated doxorubicin-induced increases in reactive oxygen species (ROS) and decreases in oxidized nicotinamide adenine dinucleotide (NAD+). In animal studies, empagliflozin and SP600125 attenuated doxorubicin-induced cardiac dysfunction and fibrosis. CONCLUSIONS: Empagliflozin attenuated doxorubicin-induced apoptosis by inhibiting the phosphorylation of JNK and its downstream signaling pathways, including ROS and NAD+.


Asunto(s)
Apoptosis , Compuestos de Bencidrilo , Cardiotoxicidad , Doxorrubicina , Glucósidos , Miocitos Cardíacos , Glucósidos/farmacología , Compuestos de Bencidrilo/farmacología , Doxorrubicina/toxicidad , Doxorrubicina/efectos adversos , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Humanos , Animales , Apoptosis/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Masculino , Especies Reactivas de Oxígeno/metabolismo , Antracenos/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Ratones , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Ratones Endogámicos C57BL
14.
Echocardiography ; 30(7): 812-9, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23432461

RESUMEN

BACKGROUND: Right ventricular (RV) pacing is associated with left ventricular (LV) dysfunction. However, the effects of RV pacing at different sites on both LV and RV function have rarely been studied before. We want to determine whether different RV pacing sites differentially affect LV and RV deformation by using speckle tracking echocardiography (STE). METHODS: The subjects were 73 patients who had undergone dual-chamber permanent pacemaker implantation and did not have structural heart diseases. LV and RV global longitudinal strains (GLS) were measured using STE to determine subtle changes in LV function. Twenty-three patients without pacing after pacemaker implantation served as controls; 14 and 36 patients showed apical and septal pacing, respectively. RESULTS: There were no significant intergroup demographic differences. LV biplane ejection fractions in the septal- and apical-pacing groups were significantly lower than those in the controls. The GLS LV values were similar between the control and septal-pacing groups, but they were lower in the apical-pacing group. Multivariate analysis revealed that cumulative pacing loads and apical pacing were independent factors associated with lower GLS LV values. The GLS RV values were similar between the control and apical-pacing groups; however, they were lower in the septal-pacing group. CONCLUSION: We concluded that patients with septal pacing have significantly higher GLS LV and more modest decreases in GLS RV values than patients with apical pacing. Thus, septal pacing may be not necessarily preferable in patients without significant heart disease undergoing dual-chamber permanent pacemaker implantation.


Asunto(s)
Bloqueo Atrioventricular/epidemiología , Bloqueo Atrioventricular/prevención & control , Dispositivos de Terapia de Resincronización Cardíaca/estadística & datos numéricos , Síndrome del Seno Enfermo/epidemiología , Síndrome del Seno Enfermo/prevención & control , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Derecha/epidemiología , Anciano , Bloqueo Atrioventricular/diagnóstico por imagen , Causalidad , Comorbilidad , Femenino , Atrios Cardíacos , Tabiques Cardíacos , Humanos , Estudios Longitudinales , Masculino , Implantación de Prótesis/estadística & datos numéricos , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Síndrome del Seno Enfermo/diagnóstico por imagen , Volumen Sistólico , Taiwán/epidemiología , Resultado del Tratamiento , Ultrasonografía , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Derecha/diagnóstico por imagen
15.
J Chin Med Assoc ; 86(2): 176-182, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36306389

RESUMEN

BACKGROUND: Moderate to severe tricuspid regurgitation (TR) is known to cause right ventricular (RV) failure and death. Although TR is traditionally classified as primary or secondary, recently, a new class of TR called idiopathic TR has been proposed, with varying definitions among different studies. METHODS: The data were retrospectively collected for the period of January to June 2018 for 8711 patients from the patient cohort of the National Cheng Kung University Hospital echocardiography laboratory. A total of 670 patients (7.7%) with moderate-to-severe TR were included. Idiopathic TR was diagnosed strictly using a new systematic approach. RESULTS: The distribution of significant TR included 74 (11.0%) primary TR cases, 48 (7.2%) with pacemaker-related TR, 267 (39.9%) with left heart disease, 24 (3.6%) with congenital heart disease, 6 (0.9%) with RV myopathy, 105 (15.7%) with pulmonary hypertension, and 146 (21.8%) with idiopathic TR. The mean age in primary and idiopathic TR groups was older ( p = 0.004), with lower estimated pulmonary pressure ( p < 0.001), higher RV fraction area change (FAC, p < 0.001), and tricuspid annulus systolic velocity (S', p = 0.004) compared with functional TR group. Multivariate analysis showed that idiopathic TR ( p = 0.002) and primary TR ( p = 0.008) had better RV FAC than functional TR. CONCLUSION: Idiopathic TR was associated with better RV function than the other secondary TRs. Thus, idiopathic TR should be strictly defined and regarded as a distinct type of TR.


Asunto(s)
Insuficiencia de la Válvula Tricúspide , Humanos , Ecocardiografía , Estudios Retrospectivos , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/etiología , Insuficiencia de la Válvula Tricúspide/fisiopatología , Función Ventricular Derecha
16.
Biomed Pharmacother ; 157: 113962, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36370523

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) patients suffer varying degrees of heart dysfunction after tyrosine kinase inhibitor (TKI) treatment. Interestingly, HCC patients often have higher levels of pentraxin 3 (PTX3), and PTX3 inhibition was found to improve left ventricular dysfunction in animal models. OBJECTIVES: We sought to assess the therapeutic potential of PTX3 inhibition on TKI-associated cardiotoxicity. METHODS: We used a human embryonic stem cell line, RUES2, to generate cardiomyocyte cultures (RUES2-CM) for functional testing. We also assessed heart function and PTX3 expression levels in 16 HCC patients who received TKI treatment, 3 HCC patients who did not receive TKIs, and 7 healthy volunteers. RESULTS: Significantly higher PTX3 expression was noted in HCC patients with TKI treatment versus those without, and 38% of male and 33% of female patients had QTc prolongation after TKI treatment. Treatment of cardiomyocyte cultures with sorafenib also increased PTX3 expression and induced cytoskeletal remodelling, contraction reduction, sodium current inhibition, and mitochondrial respiratory dysfunction. PTX3 colocalised with CD44 in cardiomyocytes, and cardiomyocyte contraction, mitochondrial respiratory function, and regular cytoskeletal and apoptotic protein expression were restored with PTX3 inhibition. CD44 knockdown confirmed PTX3/CD44 signalling. These results suggest a possible mechanism in which sorafenib treatment increases PTX3 expression, thereby resulting in reduced extracellular signal-regulated kinase (ERK) 1/2 expression that affects cardiomyocyte contraction, while also activating c-Jun N-terminal kinase (JNK) downstream pathways to disrupt mitochondrial respiration and trigger apoptosis. CONCLUSIONS: TKI-induced cardiotoxicity may be partly mediated by the upregulation of PTX3, and thus PTX3 inhibition has potential as a therapeutic strategy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Humanos , Masculino , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Proteína C-Reactiva/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Sorafenib/uso terapéutico , Cardiotoxicidad , Mitocondrias/metabolismo
17.
Adv Healthc Mater ; 12(29): e2301186, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37672681

RESUMEN

Although human pluripotent stem cells (hPSCs)-derived cardiomyocytes (hPSC-CMs) can remuscularize infarcted hearts and restore post-infarct cardiac function, post-transplant rejection resulting from human leukocyte antigen (HLA) mismatching is an enormous obstacle. It is crucial to identify hypoimmunogenic hPSCs for allogeneic cell therapy. This study is conducted to demonstrate the immune privilege of HLA-Ehigh /HLA-Ghigh /HLA-IIlow human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs). Ischemia-reperfusion surgery is done to create transmural myocardial infarction in rats. At post-infarct 4 days, hPSC-CMs (1.0×107 cells per kg), including human embryonic stem cell-derived cardiomyocytes (hESC-CMs), HLA-Elow/HLA-Glow/HLA-IIhigh hiPSC-CMs, and HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs, are injected into the infarcted myocardium. Under the treatment of very low dose cyclosporine A (CsA), only HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs survive in vivo and improved post-infarct cardiac function with infarct size reduction. HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs activate the SHP-1 signaling pathway of natural killer (NK) cells and cytotoxic T cells to evade attack by NK cells and cytotoxic T cells. Herein, it is demonstrated that using a clinically relevant CsA dose, HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSC-CMs repair the infarcted myocardium and restore the post-infarct heart function. HLA-Ehigh /HLA-Ghigh /HLA-IIlow hiPSCs are less immunogenic and may serve as platforms for regeneration medicine.


Asunto(s)
Células Madre Pluripotentes Inducidas , Infarto del Miocardio , Humanos , Ratas , Animales , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Antígenos HLA-G/metabolismo , Infarto del Miocardio/terapia , Regeneración , Diferenciación Celular , Antígenos HLA-E
18.
Nat Commun ; 14(1): 7249, 2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37945565

RESUMEN

The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.


Asunto(s)
Infarto del Miocardio , Infarto del Miocardio con Elevación del ST , Humanos , Animales , Ratones , Butiratos/metabolismo , Corazón , Cuerpos Cetónicos
19.
Analyst ; 137(22): 5201-3, 2012 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-23014158

RESUMEN

A simple 2-hydroxy-1-naphthaldehyde (receptor 1) serves as a selective chemosensor for Al(3+) based on chelation-enhanced fluorescence (CHEF). The receptor 1 exhibited a high association constant with micromolar detection for Al(3+) in EtOH-H(2)O solution.

20.
Biomedicines ; 10(11)2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-36359284

RESUMEN

The progress of medical technology and scientific advances in the field of anticancer treatment have increased the survival probabilities and duration of life of patients. However, cancer-therapy-induced cardiac dysfunction remains a clinically salient problem. Effective anticancer therapies may eventually induce cardiomyopathy. To date, several studies have focused on the mechanisms underlying cancer-treatment-related cardiotoxicity. Cardiomyocyte cell lines with no contractile physiological characteristics cannot adequately model "true" human cardiomyocytes. However, applying "true" human cardiomyocytes for research is fraught with many obstacles (e.g., invasiveness of the procedure), and there is a proliferative limitation for rodent primary cultures. Human-induced pluripotent stem-cell-differentiated cardiomyocytes (hiPSC-CMs), which can be produced efficiently, are viable candidates for mimicking human cardiomyocytes in vitro. We successfully performed cardiac differentiation of human iPSCs to obtain hiPSC-CMs. These hiPSC-CMs can be used to investigate the pathophysiological basis and molecular mechanism of cancer-treatment-related cardiotoxicity and to develop novel strategies to prevent and rescue such cardiotoxicity. We propose that hiPSC-CMs can be used as an in vitro drug screening platform to study targeted cancer-therapy-related cardiotoxicity.

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