RESUMEN
Ischemia-reperfusion injury (IRI) results in irreversible metabolic dysfunction and structural damage to tissues or organs, posing a formidable challenge in the field of organ implantation, cardiothoracic surgery, and general surgery. Glycogen synthase kinase-3ß (GSK-3ß) a multifunctional serine/threonine kinase, is involved in a variety of biological processes, including cell proliferation, apoptosis, and immune response. Phosphorylation of its tyrosine 216 and serine 9 sites positively and negatively regulates the activation and inactivation of the enzyme. Significantly, inhibition or inactivation of GSK-3ß provides protection against IRI, making it a viable target for drug development. Though numerous GSK-3ß inhibitors have been identified to date, the development of therapeutic treatments remains a considerable distance away. In light of this, this review summarizes the complicated network of GSK-3ß roles in IRI. First, we provide an overview of GSK-3ß's basic background. Subsequently, we briefly review the pathological mechanisms of GSK-3ß in accelerating IRI, and highlight the latest progress of GSK-3ß in multiorgan IRI, encompassing heart, brain, kidney, liver, and intestine. Finally, we discuss the current development of GSK-3ß inhibitors in various organ IRI, offering a thorough and insightful reference for GSK-3ß as a potential target for future IRI therapy.
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Integrin ß6 (ITGB6), a member of the integrin family of proteins, is only present in epithelial tissues and frequently associates with integrin subunit αv to form transmembrane heterodimers named integrin αvß6. Importantly, ITGB6 determines αvß6 expression and availability. In addition to being engaged in organ fibrosis, ITGB6 is also directly linked to the emergence of cancer, periodontitis, and several potential genetic diseases. Therefore, it is of great significance to study the molecular-biological mechanism of ITGB6, which could provide novel insights for future clinical diagnosis and therapy. This review introduces the structure, distribution, and biological function of ITGB6. This review also expounds on ITGB6-related diseases, detailing the known biological effects of ITGB6.
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Antígenos de Neoplasias , Fibrosis , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Fibrosis/genética , Fibrosis/metabolismo , Animales , Cadenas beta de Integrinas/metabolismo , Cadenas beta de Integrinas/genética , Integrinas/metabolismo , Integrinas/genética , Periodontitis/genética , Periodontitis/metabolismo , Periodontitis/patologíaRESUMEN
Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury in vitro. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy.
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Cardiomiopatías , Doxorrubicina , Proteínas Relacionadas con la Folistatina , Mitofagia , Miocitos Cardíacos , Mitofagia/efectos de los fármacos , Animales , Doxorrubicina/efectos adversos , Cardiomiopatías/inducido químicamente , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Cardiomiopatías/prevención & control , Ratas , Proteínas Relacionadas con la Folistatina/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Masculino , Línea Celular , Apoptosis/efectos de los fármacosRESUMEN
G protein-coupled receptors (GPCRs) are currently the most widely focused drug targets in the clinic, exerting their biological functions by binding to chemicals and activating a series of intracellular signaling pathways. Formyl-peptide receptor 1 (FPR1) has a typical seven-transmembrane structure of GPCRs and can be stimulated by a large number of endogenous or exogenous ligands with different chemical properties, the first of which was identified as formyl-methionine-leucyl-phenylalanine (fMLF). Through receptor-ligand interactions, FPR1 is involved in inflammatory response, immune cell recruitment, and cellular signaling regulation in key cell types, including neutrophils, neural stem cells (NSCs), and microglia. This review outlines the critical roles of FPR1 in a variety of heart and brain diseases, including myocardial infarction (MI), ischemia/reperfusion (I/R) injury, neurodegenerative diseases, and neurological tumors, with particular emphasis on the milestones of FPR1 agonists and antagonists. Therefore, an in-depth study of FPR1 contributes to the research of innovative biomarkers, therapeutic targets for heart and brain diseases, and clinical applications.
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Encefalopatías , Receptores de Formil Péptido , Humanos , N-Formilmetionina Leucil-Fenilalanina/metabolismo , Receptores de Formil Péptido/metabolismo , Encéfalo/metabolismoRESUMEN
Xylitol is a hygroscopic compound known to protect nasal cavity against bacteria. It has also been developed into nasal spray and evaluated as a potential candidate drug for respiratory diseases. Consequently, it is necessary to study its inhalation toxicity. Based on our previous study on its subacute inhalation toxicity, this study aimed to investigate the safety of xylitol inhalation for long-term use. According to the OECD Test Guideline 413, Sprague-Dawley rats were randomly divided into six groups and exposed with different concentrations of xylitol aerosol or air. After exposure for 90-day, the recovery groups were continued to observe for a recovery period of 28-day. No significant changes in body weight were observed between sham and xylitol groups. Several significant differences in hematological, clinical chemistry, bronchoalveolar lavage fluid were observed, which either had no dose-effect relationship for both male and female rats or were restored during the recovery period. Finally, except for high dose group of xylitol, two rats showed a small amount of inflammatory exudate in alveolar and bronchial cavities, which was restored in the recovery period. The rest of rats showed no obvious difference. For the recovery groups, no significant difference was observed between these two groups. In conclusion, the no observable adverse effect level (NOAEL) of xylitol in our subchronic inhalation toxicological experiments was 2.9 mg/L, which indicated that xylitol for rats' long-time inhalation is tolerant and safe.
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Exposición por Inhalación , Xilitol , Administración por Inhalación , Aerosoles/toxicidad , Animales , Líquido del Lavado Bronquioalveolar/química , Femenino , Exposición por Inhalación/efectos adversos , Masculino , Ratas , Ratas Sprague-Dawley , Xilitol/toxicidadRESUMEN
OBJECTIVES: The purpose of this study was to review the experiences with transcatheter closure of mitral PVL after surgical valve replacement. BACKGROUND: Transcatheter closure of paravalvular leak (PVL) is an intricate alternative to surgical closure. But it represents one of the most intricate procedures in the field of structural heart interventions, especially for patients with mitral PVL. METHODS: From January 2015 through January 2019, 35 patients with mitral PVL after valve replacement underwent transcatheter closure. We reviewed the catheter techniques, perioperative characteristics, and prognosis. The median follow-up was 26 (3-48) months. RESULTS: Acute procedural success was achieved in 33/35 (94.3%) patients. Twenty-five patients had single mitral prosthetic valve replacements; 10 had combined aortic and mitral prosthetic valve replacements previously; 28 had mechanical valves; and 7 had bioprosthetic valves. All percutaneous procedures were performed with local anesthesia except for seven transapical cases with general anesthesia. Multiple approaches were used: transfemoral, transapical, and transseptal via an arteriovenous loop. Multiple devices were deployed. There were no hospital deaths. The procedural time was 67-300 (124 ± 62) minutes. Fluoroscopic time was 17-50 (23.6 ± 12.1) minutes. The hospital stay was 5-17 (8.3 ± 3.2) days. Complications included recurrent hemolysis, residual regurgitation, acute renal insufficiency, and anemia. Twenty-seven (77.1%) patients improved by ≥1 New York Heart Association functional class at the 1-year follow-up. CONCLUSIONS: Transcatheter mitral PVL closure requires complex catheter techniques. However, this minimally invasive treatment could provide reliable outcomes and shorter hospital stays in selected patients. This trial is registered with NCT02917980.
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Cateterismo Cardíaco/métodos , Prótesis Valvulares Cardíacas/efectos adversos , Válvula Mitral/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Impresión Tridimensional , Reoperación/métodos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Our goal was to determine the accuracy of 3-dimensional transesophageal echocardiography (3D-TEE) compared with that of computed tomography (CT) in the preoperative evaluation for transcatheter aortic valve replacement (TAVR) when the errors caused by inconsistent software and method have been eliminated and the representativeness of the sample has been improved. We also investigated the influence of aortic root calcification on the accuracy of 3D-TEE in aortic annulus evaluations. METHODS: Part I: 45 of 233 patients who underwent TAVR in the department of cardiovascular surgery at the Xijing hospital from January 2016 to August 2019 were studied retrospectively. Materialise Mimics software and the multiplanar reconstruction method were used for evaluation, based on 3D-TEE and CT. The annulus area-derived diameter, the annulus perimeter-derived diameter (Dp), the annulus mean diameter, the left ventricular outflow tract Dp diameter, the sinotubular junction (STJ) diameter-Dp, and the aortic sinus diameter were compared and analyzed. Part II: 31 of 233 patients whose 3D-TEE and CT data were well preserved and in the required format were included. HU450 and HU850 were used as indicators to measure the severity of calcification. The Spearman rank correlation and Linear regression were used to analyze the correlation between aortic root calcification and the accuracy of 3D-TEE in aortic annulus measurement. RESULTS: The measurement results based on 3D-TEE were significantly lower than those obtained using CT (P < 0.05), except for the STJ diameter-Dp in diastole (P = 0.11). The correlation coefficient of the two groups was 0.699-0.954 (P < 0.01), which also indicated a significant correlation between the two groups. A Bland-Altman plot showed that the ordinate values were mostly within the 95% consistency limit; the consistency of the two groups was good. By establishing the linear regression equation, the two groups can be inferred from each other. The Spearman rank correlation analysis and the Linear regression analysis showed that the influence of aortic calcification on the accuracy of the 3D-TEE annulus evaluation was limited. CONCLUSIONS: Although an evaluation based on 3D-TEE underestimated the results, we can deduce CT results from 3D-TEE because the two methods exhibit considerable correlation and consistency. TRIAL REGISTRATION: Name: Surgery and Transcatheter Intervention for Structural Heart Diseases. Number: NCT02917980. URL: https://clinicaltrials.gov/ct2/results?term=NCT02917980 .
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Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Calcinosis/diagnóstico por imagen , Ecocardiografía Tridimensional , Ecocardiografía Transesofágica , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Válvula Aórtica/fisiopatología , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/fisiopatología , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/cirugía , Calcinosis/fisiopatología , Calcinosis/cirugía , Toma de Decisiones Clínicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos XRESUMEN
Streptococcus iniae has become one the most serious aquatic pathogens causing invasive diseases in farmed marine and freshwater fish worldwide, and orally attenuated vaccine is still the best option in protecting these invasive diseases. In this study, the safety, stability, immunogenicity of the S. iniae attenuated strain YM011 were evaluated, and comprehensively analyzed its virulence weakening mechanism at whole genome level. The results shown that attenuated S. iniae strain YM011 completely lost its pathogenicity to tilapia and had good immunogenicity with relative percent survival being 93.25% at 15 days and 90.31% at 30 days via IP injection, respectively, and 76.81% at 15 days and 56.69% at 30 days via oral gavage, respectively. Back-passage safety assay indicated that YM011 did not cause diseases or death in tilapia after 100 generations of serial passaging. Comparative genome-wide sequencing shown that YM011 had a 0.4 M large inversion fragment compared with its parental strain virulent strain GX005, which encoded 372 genes including drug resistance genes pbp2A and tet, as well as known virulence factors including hemolysin transport system gene, recA, and mutator family transposase. The attenuated S. iniae strain YM011 is an ideal attenuated oral vaccine candidate with good immunogenicity, safety and stability. Abnormal expression of important drug resistance genes as well as known virulence factors due to inversion of a 0.4 M large fragment is the leading mechanism underlying its attenuated virulence.
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Vacunas Bacterianas/inmunología , Cíclidos/inmunología , Enfermedades de los Peces/inmunología , Estudio de Asociación del Genoma Completo/veterinaria , Infecciones Estreptocócicas/veterinaria , Animales , Enfermedades de los Peces/microbiología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Streptococcus iniae , Vacunas Atenuadas/inmunología , Virulencia , Factores de Virulencia/inmunologíaRESUMEN
OBJECTIVE: Paravalvular leak (PVL) after valve replacement remains clinically challenging. Percutaneous closure is an effective therapy for patients with PVLs because reoperation is associated with high rates of morbidity and mortality. The purpose of this study was to retrospectively compare the clinical outcome of transcatheter closure and surgical repair in patients with a PVL. METHODS: From January 2000 to May 2016, 131 patients with PVL were treated at three major medical centers in China. Perioperative characteristics and outcomes of the procedure were reviewed. RESULTS: Sixty-eight (51.9%) patients with PVLs were treated with percutaneous transcatheter closure (group I). The procedure was successful in 67 (98%) with no hospital deaths. Sixty-three (48.1%) patients with PVLs had a reoperation (group II). Five of the surgical patients had a third open-heart operation for residual regurgitation, and one underwent successful percutaneous closure. Six patients died in the hospital postoperatively. All patients in group II but only 11 in group I needed perioperative blood transfusions. The procedural time and hospital stay after the procedure were significantly shorter in group I than in group II. At the 1-year follow-up, cardiac function improved by ≥ 1 New York Heart Association functional class in 55 (82%) patients in group I and in 39 (68%) patients in group II. CONCLUSIONS: Transcatheter closure was shown to be a safe, effective therapeutic option in patients with PVL. It was associated with a lower hospital mortality rate, shorter procedural time, and fewer blood transfusions than surgical treatment in selected patients.
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Cateterismo Cardíaco , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Válvulas Cardíacas/cirugía , Complicaciones Cognitivas Postoperatorias/cirugía , Adulto , Anciano , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/mortalidad , China , Femenino , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/mortalidad , Enfermedades de las Válvulas Cardíacas/fisiopatología , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Válvulas Cardíacas/diagnóstico por imagen , Válvulas Cardíacas/fisiopatología , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Cognitivas Postoperatorias/diagnóstico por imagen , Complicaciones Cognitivas Postoperatorias/mortalidad , Complicaciones Cognitivas Postoperatorias/fisiopatología , Recuperación de la Función , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Resultado del TratamientoRESUMEN
AIM: To evaluate the effects of quercetin to improve ischemia/reperfusion-induced cardiomyocyte apoptosis in vitro and in vivo study. METHODS: The cells were divided into five groups: model control (MC) group was ischemia/reperfusion (I/R) model group; DL group was treated with 25 mL/L quercetin based on MC group; DM group was treated with 50 ml/L quercetin based on MC group; DH group was treated with 100 mL/L quercetin based on MC group; Meto group was treated with metoprolol based on MC group. In the in vivo study, the rats were divided into five groups: MC group was I/R model group; DL group was treated with 25 mg/kg quercetin; DM group was treated with 50 mg/kg quercetin; DM group was treated with 100 mg/kg quercetin; Meto group was treated with Meto as positive drug. RESULTS: The cell apoptosis rates of quercetin treated groups (DL, DM, and DH groups) were significantly suppressed compared with the MC group. The silent information regulatory factor 1 (SIRT1), peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), and Bcl-2 proteins expression of quercetin treated were significantly upregulation compared with MC group (P < 0.05, respectively), and Bax protein expression of quercetin treated group was significantly downregulation compared with MC group ( P < 0.05, respectively). In the vivo study, the myocardial pathological morphology of quercetin treated groups was improved. The cell apoptosis number of quercetin treated group were significantly suppressed compared with MC group by terminal deoxynucleotidyl transferase dUTP nick end labeling assay ( P < 0.05, respectively). SIRT1, PGC-1a, Bcl-2, and Bax proteins expressions of quercetin treated groups were significant differences compared with MC group in myocardial tissue ( P < 0.05, respectively). CONCLUSION: Quercetin had improved the myocardial ischemia/reperfusion-induced cardiomyocyte apoptosis via SIRT1/PGC-1α signaling.
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Apoptosis/efectos de los fármacos , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Quercetina/farmacología , Sirtuina 1/metabolismo , Animales , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas , Ratas Sprague-DawleyRESUMEN
In this study, the tilapia was orally vaccinated by the attenuated Streptococcus agalactiae(S. agalactiae) strain YM001, and the distribution and the pathological effect of strain YM001 in different intestinal segments of tilapia were evaluated by real-time PCR(qPCR), immunohistochemistry(IHC) and histomorphology. The qPCR results showed that the number of bacteria was the highest in the intestinal tracts at 12â¯h post oral gavage in the YM001 group, then began to decrease sharply and eliminated at 7â¯d. And the number of bacteria was highest in the foregut, hindgut, and rectum at 12â¯h, 24â¯h, and 3â¯d, respectively. IHC indicated that bacteria mainly distributed in the margin epithelium and the goblet cells at 12â¯h - 24â¯h, and in the submucosa and muscle layer in the YM001 group in 3â¯d post gavage, then almost disappeared at 7â¯d. Histological examination of intestines post gavage displayed that an inflammation was observed at 7â¯d in the YM001 group and the intestinal structure was fully recovered at 15â¯d. and the intestinal structure was fully recovered at 15â¯d. Conclusion: The attenuated S. agalactiae vaccine strain YM001 could enter the intestinal tissue after oral gavage and had a strong spatial and temporal selectivity in the intestinal tract, which could cause obvious mucosal immune response and mild pathological reaction, but the pathological change could be gradually repaired with the extinction of bacteria in the body.
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Vacunas Bacterianas/inmunología , Cíclidos/inmunología , Enfermedades de los Peces/inmunología , Intestinos/inmunología , Administración Oral , Animales , Mucosa Intestinal/anatomía & histología , Mucosa Intestinal/inmunología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/veterinaria , Streptococcus agalactiae/fisiología , Distribución Tisular , Vacunas Atenuadas/inmunologíaRESUMEN
Forkhead box P3 (FOXP3)-positive Treg cells are crucial for maintaining immune homeostasis. FOXP3 cooperates with its binding partners to elicit Treg cells' signature and function, but the molecular mechanisms underlying the modulation of the FOXP3 complex remain unclear. Here we report that Deleted in breast cancer 1 (DBC1) is a key subunit of the FOXP3 complex. We found that DBC1 interacts physically with FOXP3, and depletion of DBC1 attenuates FOXP3 degradation in inflammatory conditions. Treg cells from Dbc1-deficient mice were more resistant to inflammation-mediated abrogation of Foxp3 expression and function and delayed the onset and severity of experimental autoimmune encephalomyelitis and colitis in mice. These findings establish a previously unidentified mechanism regulating FOXP3 stability during inflammation and reveal a pathway for potential therapeutic modulation and intervention in inflammatory diseases.
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Proteínas Adaptadoras Transductoras de Señales/fisiología , Factores de Transcripción Forkhead/fisiología , Linfocitos T Reguladores/inmunología , Animales , Encefalomielitis Autoinmune Experimental/inmunología , Ratones , Ratones Endogámicos C57BLRESUMEN
Naringenin, a flavanone mainly derived from grapes and citrus fruits, has been reported to exhibit cardioprotective effects. Accumulating evidence has confirmed that endoplasmic reticulum (ER) stress-mediated apoptosis participates in the process of myocardial ischemia/reperfusion injury and inhibiting ER stress is a potential therapeutic target/strategy in preventing cardiovascular diseases. Herein, the current study was designed to investigate whether naringenin protects H9c2 myocardial cells against hypoxia/reoxygenation (H/R) injury via attenuating ER stress or ER stress-mediated apoptosis. Our results showed that naringenin treatment resulted in obvious increases in the viability of H9c2 cells and the expression of Bcl-2 (anti-apoptotic protein), and decreases in the morphological changes of apoptotic cells, the activity of caspase-3 and the expression of Bax (pro-apoptotic protein) in H/R-treated H9c2 cells, implying the protective effects of naringenin against H/R-induced injury. In addition, naringenin also significantly reversed H/R-induced ER stress as evidenced by the up-regulation of Glucose-regulated protein 78, C/EBP homologous protein and Cleaved caspase-12 proteins. Meanwhile, naringenin remarkably reversed H/R-induced the increases in the expression of cleaved activating transcription factor 6 (ATF6) and phosphorylation levels of phospho-extracellular regulated protein kinases (PERK) and inositol-requiring enzyme-1α (IRE1α) in H9c2 cells. Finally, we found that ATF6 siRNA, PERK siRNA or IRE1α siRNA abolished H/R-induced cytotoxicity and apoptosis in H9c2 cells. In conclusion, these results confirmed that ER stress-mediated apoptosis contributes to the protection effects of naringenin against H/R injury, which is potentially involved in ATF6, IRE1α and PERK signaling activation.
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Factor de Transcripción Activador 6/metabolismo , Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Endorribonucleasas/metabolismo , Flavanonas/farmacología , Complejos Multienzimáticos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , eIF-2 Quinasa/metabolismo , Animales , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Miocitos Cardíacos , RatasRESUMEN
Cardiovascular disease (CVD) is the primary global cause of death, and inflammation is a crucial factor in the development of CVDs. The acute phase inflammatory protein pentraxin 3 (PTX3) is a biomarker reflecting the immune response. Recent research indicates that PTX3 plays a vital role in CVDs and has been investigated as a possible biomarker for CVD in clinical trials. PTX3 is implicated in the progression of CVDs through mechanisms such as exacerbating vascular endothelial dysfunction, affecting angiogenesis, and regulating inflammation and oxidative stress. This review summarized the structure and function of PTX3, focusing on its multifaceted effects on CVDs, such as atherosclerosis, myocardial infarction, and hypertension. This may help in explaining the varying PTX3 functions and usage, as well as in utilizing target organs to manage diseases. Moreover, elucidating the opposite role of PTX3 in the cardiovascular system will demonstrate the therapeutic and predictive potential in human diseases.
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Enfermedades Cardiovasculares , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Inflamación/metabolismo , BiomarcadoresRESUMEN
In a previous study, we used metabolomic techniques to identify a new metabolite of Danshen Dripping Pills called isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP), which has potential as a drug candidate for cardiovascular diseases. This study aimed to explore the protective effects of IDHP against septic myocardial injury, as well as its molecular mechanism. Wild type or GAS6 knockout mice injured by cecal ligation and puncture (CLP) were used to observe the effect of IDHP. Here, we found that a specific concentration of IDHP (60 mg/kg) significantly increased the survival rate of septic mice to about 75 % at 72 h post CLP, and showed improvements in sepsis score, blood biochemistry parameters, cardiac function, and myocardial tissue damage. Furthermore, IDHP inhibited myocardial oxidative stress, inflammatory response, apoptosis, and mitochondrial dysfunction. Molecularly, we discovered that IDHP treatment reversed the CLP-induced downregulation of GAS6, Axl, and p-AMPK/AMPK expression. In addition, GAS6 knockout reversed the positive effect of IDHP in septic mice, indicated by more severe myocardial tissue damage, oxidative stress, inflammatory response, and mitochondrial dysfunction. GAS6 knockout also resulted in decreased levels of GAS6, Axl, and p-AMPK/AMPK. Taken together, our study provides evidence that IDHP has significant cardioprotective effects against sepsis by regulating the GAS6/Axl-AMPK signaling pathway. This finding has important therapeutic potential for treating sepsis.
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Enfermedades Mitocondriales , Sepsis , Infección de Heridas , Animales , Ratones , Proteínas Quinasas Activadas por AMP , Miocardio , Transducción de Señal , Ratones Noqueados , Sepsis/tratamiento farmacológicoRESUMEN
Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, the role of cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling and pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine the impact of irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), and cGAS/STING signaling in DCM-induced cardiac dysfunction and the effect of gasdermin D (GSDMD)-dependent pyroptosis. High-fat diet-induced mice and H9c2 cells were used for cardiac geometry and function or pyroptosis-related biomarker assessment at the end of the experiments. Here, we show that DCM impairs cardiac function by increasing cardiac fibrosis and GSDMD-dependent pyroptosis, including the activation of MITOL and cGAS/STING signaling. Our results confirmed that the protective role of irisin and MITOL was partially offset by the activation of cGAS/STING signaling. We also demonstrated that GSDMD-dependent pyroptosis plays a pivotal role in the pathological process of DCM pathogenesis. Our results indicate that irisin treatment protects against DCM injury, mitochondrial homeostasis, and pyroptosis through MITOL upregulation.
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Diabetes Mellitus , Cardiomiopatías Diabéticas , Animales , Ratones , Cardiomiopatías Diabéticas/patología , Fibronectinas , Nucleotidiltransferasas , Piroptosis , Remodelación Ventricular , RatasRESUMEN
Rationale: Despite recent studies indicating a crucial role of ecto-5'-nucleotidase (CD73) on T cells in cardiac injury after ischemia/reperfusion, the involvement of CD73+ regulatory T cells (Tregs) in cardiac repair post-myocardial infarction (MI) remains unclear. We sought to investigate the contribution of CD73 on Tregs to the resolution of cardiac inflammation and remodeling after MI. Methods: Cardiac function, tissue injury, Tregs percentage in injured hearts, and purinergic signaling changes in cardiac FoxP3+ Tregs were analyzed after permanent descending coronary artery ligation. CD73 knockout Tregs were used to determine the function of CD73 on Tregs. Peripheral blood mononuclear cells (PBMCs) from acute myocardial infarction (AMI) patients and matched non-MI subjects were assessed via flow cytometry. Results: Cardiac Tregs exhibited distinction of purinergic signaling post MI with dramatically high level of CD73 compared to the sham Tregs. CD73 deficiency decreased the tissue tropism, and impaired the immunosuppressive and protective function of Tregs in cardiac healing. Administration of low-dose of IL-2/anti-IL-2 complex resulted in FoxP3+CD73+Tregs expansion in the heart and contributed to the recovery of cardiac function. CD73 derived from FoxP3+Tregs could bind to FoxP3- effector T-cells and inhibit the production of multiple inflammatory cytokines. In AMI patients, CD73 expressions on both CD4+ cells and FoxP3+Tregs decreased in PBMCs. Moreover, CD73 expressions on CD4+ T cells were negatively correlated with the levels of NT pro-BNP and myocardial zymogram in serum. Conclusions: Our findings indicated the importance of FoxP3+CD73+Tregs in inflammation resolution and cardiac healing post-MI.
Asunto(s)
Infarto del Miocardio , Linfocitos T Reguladores , 5'-Nucleotidasa/metabolismo , Factores de Transcripción Forkhead/metabolismo , Humanos , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , Infarto del Miocardio/metabolismo , Linfocitos T Reguladores/metabolismoRESUMEN
Heart diseases remain the top threat to human health, and the treatment of heart diseases changes with each passing day. Convincing evidence shows that three-dimensional (3D) printing allows for a more precise understanding of the complex anatomy associated with various heart diseases. In addition, 3D-printed models of cardiac diseases may serve as effective educational tools and for hands-on simulation of surgical interventions. We introduce examples of the clinical applications of different types of 3D printing based on specific cases and clinical application scenarios of 3D printing in treating heart diseases. We also discuss the limitations and clinically unmet needs of 3D printing in this context.
RESUMEN
OBJECT: Our goal was to assess the implant depth of a Venus-A prosthesis during transcatheter aortic valve replacement (TAVR) when the areas of eccentric calcification were distributed in different sections of the aortic valve. METHODS: A total of 53 patients with eccentric calcification of the aortic valve who underwent TAVR with a Venus-A prosthesis from January 2018 to November 2019 were retrospectively analyzed. The patients were divided into three groups (A, B, and C) according to the location of the eccentric calcification, which was determined by preprocedural computerized tomography angiography (CTA) images. The prosthesis release process and position were evaluated by contrast aortography during TAVR, and the differences in valve implant depths were compared among the three groups. The effects of different aortic root structures and procedural strategies on prosthesis implant depth were analyzed. RESULTS: Eleven patients had eccentric calcification in region A; 19 patients, in region B; and 23 patients, in region C. The patients with eccentric calcification in region B had a higher risk of prosthesis migration (10.5% upward and 21.1% downward), and the position of the prosthesis after TAVR in group B was the deepest among the three groups. When eccentric calcification was located in region A or C, the prosthesis was released at the standard position with more stability, and the location of the prosthesis was less deep after TAVR (region A: 4.12 ± 3.4 mm; region B: 10.2 ± 5.3 mm; region C: 8.4 ± 4.0 mm; region A vs. region B, P = 0.0004; region C vs. region B; and P = 0.0360). In addition, the left ventricular outflow tract (LVOT) (P = 0.0213) and aortic root angulation (P = 0.0263) also had a significant effect on implant depth in the aortic root structure of the patients. The prosthesis size was 28.3 ± 2.4 in the deep implant group and 26.4 ± 2.0 in the appropriate implant group (P = 0.0068). CONCLUSION: The implant depth of the Venus-A prosthesis is closely related to the distribution of eccentric calcification in the aortic valve during TAVR. Surgeons should adjust the surgical strategy according to aortic root morphology to prevent prosthesis migration.
RESUMEN
Xylitol has reported to decrease gingival inflammation and nasopharyngeal pneumonia, which indicated that xylitol may have potential application in respiratory diseases. Although some studies have reported the inhalation toxicity of xylitol, however, the longest period tested was only for 14 days. The inhalation toxicity of xylitol is insufficient. This work investigated the potential subacute toxicity of xylitol according to the OECD TG 412. Rats were randomly divided into a control group and different dosage groups (2 g/m3, 3 g/m3, 5 g/m3), and exposed for 6 hours/day, 5 days/week for 28 days. At the end of the exposure or recovery period, clinical signs, mortality, body weight, food consumption, hematology, blood biochemistry, gross pathology, organ weight, and histopathology were examined. Compared with the control group, rats of both sexes in the exposure groups exhibited no significant changes in body weight, organ mass, and food uptake. After the xylitol exposure, aspartate aminotransferase activity in the xylitol group (3 g/m3) was significantly higher than that in the control group, while other blood indicators and pathological changes of liver and the analysis of the recovery group showed no changes, suggesting that xylitol exerted no observable toxic effect on the liver. Finally, other observations including the histopathology of target organs and hematology also showed no alterations. These results indicated that xylitol had no significant inhalation toxicity at doses up to 5 g/m3. These subacute inhalation toxicity results of xylitol showed that its no-observed-adverse-effect concentration (NOAEC) in rats was determined to 5 g/m3.