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1.
Cardiovasc Diabetol ; 22(1): 171, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37420232

RESUMEN

BACKGROUND: The triglyceride-glucose (TyG) index has been demonstrated to be a reliable surrogate marker of insulin resistance (IR) and an effective predictive index of cardiovascular (CV) disease risk. However, its long-term prognostic value in patients with chronic heart failure (CHF) remains uncertain. METHODS: A total of 6697 consecutive patients with CHF were enrolled in this study. Patients were divided into tertiles according to their TyG index. The incidence of primary outcomes, including all-cause death and CV death, was recorded. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. RESULTS: During a median follow-up of 3.9 years, a total of 2158 (32.2%) all-cause deaths and 1305 (19.5%) CV deaths were documented. The incidence of primary events from the lowest to the highest TyG index tertiles were 50.61, 64.64, and 92.25 per 1000 person-years for all-cause death and 29.05, 39.40, and 57.21 per 1000 person-years for CV death. The multivariate Cox hazards regression analysis revealed hazard ratios for all-cause and CV deaths of 1.84 (95% CI 1.61-2.10; P for trend < 0.001) and 1.94 (95% CI 1.63-2.30; P for trend < 0.001) when the highest and lowest TyG index tertiles were compared. In addition, the predictive ability of the TyG index against all-cause death was more prominent among patients with metabolic syndrome and those with heart failure with preserved ejection fraction phenotype (both P for interaction < 0.05). Furthermore, adding the TyG index to the established model for all-cause death improved the C­statistic value (0.710 for the established model vs. 0.723 for the established model + TyG index, P < 0.01), the integrated discrimination improvement value (0.011, P < 0.01), the net reclassification improvement value (0.273, P < 0.01), and the clinical net benefit (probability range, 0.07-0.36). CONCLUSIONS: The TyG index was significantly associated with the risk of mortality, suggesting that it may be a reliable and valuable predictor for risk stratification and an effective prognostic indicator in patients with CHF.


Asunto(s)
Glucosa , Insuficiencia Cardíaca , Humanos , Factores de Riesgo , Glucemia/metabolismo , Medición de Riesgo , Estudios Retrospectivos , Triglicéridos , Biomarcadores , China/epidemiología , Enfermedad Crónica , Insuficiencia Cardíaca/diagnóstico
2.
Int J Geriatr Psychiatry ; 38(10): e6010, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37794769

RESUMEN

OBJECTIVES: The proportion of older people with dementia in China is gradually increasing with the increase in the aging population over recent years. Hypertension and diabetes are common non-communicable diseases among rural populations in China. However, it remains unclear whether these conditions affect the occurrence and development of cognitive impairment as there is limited research on cognitive status and its risk factors among residents of rural areas. METHODS: A multi-stage stratified cluster random sampling method was used to select 5400 participants from rural permanent residents. A self-designed structured questionnaire was used to investigate demographic data of the participants. Cognitive function was assessed using the Montreal Cognitive Function Assessment Scale (MoCA). The results were analyzed using chi-square test, ANOVA and multiple linear regression analysis. RESULTS: A total of 5028 participants returned the survey, giving a response rate of 93.1%. Higher education (odds ratio (OR) = 3.2, 95% confidence interval (CI) 2.87-3.54, p < 0.001), higher income (OR = 1.61, 95% CI 1.16-2.07, p < 0.001), and dietary control (OR = 0.66, 95%CI 0.34-0.98, p < 0.001) were protective factors. A visual representation of the relationship between annual income and MoCA score showed an inverted U-curve, the group with an annual income of 6000-7999 RMB had a maximum OR of 1.93 (95%CI 0.12-2.74, p < 0.001). While difficulty in maintaining sleep were risk factors for cognitive impairment (OR = -2.28, 95% CI-4.18-0.39, p = 0.018). CONCLUSIONS: Participants with middle incomes had better cognitive status than those with the highest incomes. Higher education, proper diet control and good sleep are beneficial to the cognitive status of residents in rural areas.


Asunto(s)
Diabetes Mellitus , Hipertensión , Humanos , Anciano , Estudios Transversales , Población Rural , Factores de Riesgo , Hipertensión/epidemiología , Cognición , China/epidemiología
3.
Toxicol Ind Health ; 39(2): 104-114, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36617730

RESUMEN

Aluminum (Al) is a common neurotoxic element that can exacerbate intracellular ß-amyloid (Aß) deposition. Reelin is a highly conserved extracellular glycoprotein that is involved in intracellular Aß deposition. However, the action of Reelin on aluminum-induced Aß deposition is not fully understood. Here, we investigated the effects of the Reelin-Dab1 signaling pathway on Aß deposition in aluminum maltol (Al(mal)3) exposure in rat pheochromocytoma-derived cells (PC12). Our results showed that Al(mal)3 exposure decreased activity of PC12, increased expression of Aß42, and decreased expression of Aß40. Moreover, Al(mal)3 exposure in PC12 induced Reelin-Dab1 signaling pathway-associated proteins changed, decreased expression of Reelin and Dab1, and increased expression of pdab1. Moreover, the expression of Reelin, Dab1, and Aß40 was found to be elevated in PC12 exposed to Al(mal)3 and corticosterone compared to those exposed to Al(mal)3. Also, the expression of Reelin, Dab1, and Aß40 was found to be depressed in PC12 exposed to Al(mal)3 and streptozotocin compared with cells exposed to Al(mal)3 alone. These results suggested that Al(mal)3 inhibits the expression of the Reelin-Dab1 signaling pathway, promoting Aß deposition. Thus, our findings provided important evidence to better understand how the Reelin-Dab1 signaling pathway may be a potential mechanism of Aß deposition induced by aluminum.


Asunto(s)
Aluminio , Proteínas de la Matriz Extracelular , Animales , Ratas , Aluminio/toxicidad , Moléculas de Adhesión Celular Neuronal/genética , Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Transducción de Señal , Péptidos beta-Amiloides/metabolismo
4.
Artículo en Inglés | MEDLINE | ID: mdl-36350487

RESUMEN

PURPOSE: Doxorubicin is an important cancer chemotherapeutic agent with severe cardiotoxic effects that eventually lead to dilated cardiomyopathy (DCM). Calsyntenin-1(CLSTN1) plays a critical role in the nervous system, but its relevance in cardiovascular diseases is unknown. We investigated the significance of CLSTN1 in doxorubicin-induced DCM. METHODS: CLSTN1 expression in doxorubicin-induced DCM rats and H9c2 cells was determined using western blotting. To further explore the functions of CLSTN1, a cardiac-specific CLSTN1 overexpression rat model was constructed. The rats were subjected to analysis using echocardiographic, hemodynamic, and electrocardiographic parameters. Potential downstream molecules in CLSTN1 overexpression heart tissue were investigated using proteomics and western blotting. Finally, a knockdown of CLSTN1 was constructed to investigate the rescue function on doxorubicin-induced cell toxicity. RESULTS: CLSTN1 protein expression increased drastically in doxorubicin-induced DCM rats and H9c2 cells. Under doxorubicin treatment, CLSTN1 protein-specific overexpression in the heart muscle promoted cardiac chamber enlargement and heart failure, while the knockdown of CLSTN1 reduced doxorubicin-induced cardiomyocyte toxicity in vitro. At the mechanistic level, overexpression of CLSTN1 downregulated SERCA2 expression and increased the phosphorylation levels of PI3K-Akt and CaMK2. CONCLUSION: Our findings demonstrated that CLSTN1 promotes the pathogenesis of doxorubicin-induced DCM. CLSTN1 could be a therapeutic target to prevent the development of doxorubicin-induced DCM.

5.
BMC Vet Res ; 18(1): 279, 2022 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-35842618

RESUMEN

BACKGROUND: Flagellin elicits potent immune response and may serve as a vaccine adjuvant. We previously reported that the N-terminus of flagellin (residues 1-99, nFliC) is sufficient for vaccine efficacy enhancement against Pasteurella multocida challenge in chickens. In this study, we futher tested the adjuvancy of nFliC in a subunit vaccine against the pig pathogen Actinobacillus pleuropneumoniae in a mice model. For vaccine formulation, the antigen ApxIIPF (the pore-forming region of the exotoxin ApxII) was combined with nFliC, either through genetic fusion or simple admixture. RESULTS: Immune analysis showed that nFliC, introduced through genetic fusion or admixture, enhanced both humoral (antibody levels) and cellular (T cell response and cytokine production) immunity. In a challenge test, nFliC increased vaccine protective efficacy to 60-80%, vs. 20% for the antigen-only group. Further analysis showed that, even without a supplemental adjuvant such as mineral salt or oil emulsion, genetically linked nFliC still provided significant immune enhancement. CONCLUSIONS: We conclude that nFliC is a versatile and potent adjuvant for vaccine formulation.


Asunto(s)
Infecciones por Actinobacillus , Actinobacillus pleuropneumoniae , Enfermedades de los Roedores , Enfermedades de los Porcinos , Infecciones por Actinobacillus/prevención & control , Infecciones por Actinobacillus/veterinaria , Animales , Anticuerpos Antibacterianos , Vacunas Bacterianas , Pollos , Flagelina , Ratones , Porcinos , Enfermedades de los Porcinos/prevención & control , Eficacia de las Vacunas
6.
Toxicol Mech Methods ; 32(7): 530-541, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35313783

RESUMEN

Aluminum (Al), a neurotoxic element, can induce Alzheimer's disease-like (AD-like) changes by triggering neuronal death. Iron homeostasis disturbance has also been implicated in Alzheimer's disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of neuronal death induced by aluminum maltolate (Al(mal)3) in the pathogenesis of AD remains elusive. In this study, the results of three different behavioral experiments suggested that the learning and memory ability deteriorated and autonomous activity declined of these rats that exposed Al(mal)3 were alleviated by deferoxamine (DFO). Transmission electron microscope observations showed that the membrane was ruptured, and the membrane density increased and ridge disappearance (the most prominent characteristic of ferroptosis) in the perinuclear and cytoplasmic compartments of the hippocampal neurons were perceived in the exposure group, while the DFO group and 18 µM/kg Al(mal)3+DFO group were alleviated compared with 18 µM/kg Al(mal)3. In addition, DFO prevented oxidative stress, such as increased glutathione (GSH) and decreased malondialdehyde (MDA) and reactive oxygen species (ROS), while the latter two indexes had the same changing tendency as the total iron of brain tissue. These data indicated that Al(mal)3 could cause ferroptosis in Sprague-Dawley (SD) rat neurons, which was inhibited by DFO via reducing the content of iron and increasing the ability of cells to resist oxidative damage.


Asunto(s)
Enfermedad de Alzheimer , Ferroptosis , Aluminio/toxicidad , Animales , Encéfalo/metabolismo , Deferoxamina/metabolismo , Deferoxamina/farmacología , Hierro/metabolismo , Hierro/toxicidad , Quelantes del Hierro/metabolismo , Quelantes del Hierro/farmacología , Neuronas/metabolismo , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley
7.
J Cell Physiol ; 236(11): 7405-7420, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33959974

RESUMEN

Tuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. Macrophage polarization is crucial for the innate immunity against M. tuberculosis. However, how M. tuberculosis interferes with macrophage polarization is elusive. We demonstrated here that M. tuberculosis PPE36 (Rv2108) blocked macrophage M1 polarization, preventing the cytokine storm, and alleviating inflammatory damage to mouse immune organs. PPE36 inhibited the polarization of THP-1 cell differentiation to M1 macrophages, reduced mitochondrial dehydrogenase activity, inhibited the expression of CD16, and repressed the expression of pro-inflammatory cytokines IL-6 and TNF-α, as well as chemokines CXCL9, CXCL10, CCL3, and CCL5. Intriguingly, in the mouse infection model, PPE36 significantly alleviated the inflammatory damage of immune organs caused by a cytokine storm. Furthermore, we found that PPE36 inhibited the polarization of macrophages into mature M1 macrophages by suppressing the ERK signaling. The study provided novel insights into the function and mechanism of action of M. tuberculosis effector PPE36 both at the cellular and animal level.


Asunto(s)
Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Síndrome de Liberación de Citoquinas/prevención & control , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Macrófagos/microbiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium smegmatis/metabolismo , Animales , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/metabolismo , Síndrome de Liberación de Citoquinas/microbiología , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Interacciones Huésped-Patógeno , Humanos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Infecciones por Mycobacterium no Tuberculosas/inmunología , Infecciones por Mycobacterium no Tuberculosas/metabolismo , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/inmunología , Fenotipo , Transducción de Señal , Células THP-1
8.
Cancer Sci ; 112(2): 781-791, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33315285

RESUMEN

Malignant pleural effusion is a common complication in metastatic breast cancer (MBC); however, changes in the pleural microenvironment are poorly characterized, especially with respect to estrogen receptor status. Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer-associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple-negative breast cancer (TNBC) is much more aggressive than that of hormone receptor-positive breast cancer (HPBC). However, BAPF from HPBC (BAPF-HP) and TNBC (BAPF-TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial-mesenchymal transition. Both BAPF-HP and BAPF-TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF-TN. The distinct contribution of p-JNK to endothelial angiogenesis was consequently thought to be induced by BAPF-HP and BAPF-TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF-HP and BAPF-TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p-JNK/VEGFR2 signaling. Distinct responses to blocking p-JNK and VEGFR2 in HUVECs cultured with BAPF-HP or BAPF-TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status.


Asunto(s)
Neoplasias de la Mama/patología , Sistema de Señalización de MAP Quinasas/fisiología , Neovascularización Patológica/metabolismo , Derrame Pleural Maligno/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Anciano , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Neovascularización Patológica/patología , Derrame Pleural Maligno/patología
9.
Mol Pharm ; 18(7): 2622-2633, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-34165313

RESUMEN

Cancer metastasis is the major cause of cancer-related death; therefore, achieving suppression of tumor metastasis is a long-sought goal in cancer therapy. As the premetastatic niche acts as a prerequisite for tumor metastasis, it serves as an effective target for metastasis suppression. This study tests the feasibility of inhalable porous microspheres loaded with two premetastatic niche modulation agents, metformin and docosahexaenoic acid, as orthotopic delivery carriers for the reversion of lung premetastatic microenvironments and targeted suppression of tumor lung metastasis. The microspheres were prepared via an improved emulsion-solvent evaporation method and exhibit an excellent lung deposition, leading to significant inhibition of circulating tumor cells (CTCs)-endothelial cells adhesion, reduction of vascular permeability, and suppression of adhesion protein expression in lung premetastatic microenvironments. As a result, inhalable microspheres can prevent tumor lung metastasis formation excellently in vivo. Overall, this study proved that the encapsulation of metformin and docosahexaenoic acid in inhalable microspheres could be a promising strategy for tumor lung metastasis inhibition via orthotopically modulating premetastatic niche in the lungs.


Asunto(s)
Neoplasias de la Mama/prevención & control , Ácidos Docosahexaenoicos/química , Hipoglucemiantes/farmacología , Neoplasias Pulmonares/prevención & control , Metformina/farmacología , Microesferas , Administración por Inhalación , Animales , Apoptosis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Metformina/administración & dosificación , Metformina/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ratas Sprague-Dawley , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Pacing Clin Electrophysiol ; 44(10): 1691-1700, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33734464

RESUMEN

BACKGROUND: Left atrial posterior wall isolation (PWI) is commonly used with persistent atrial fibrillation (AF) ablation. However, potentials are often still recorded in the posterior wall after pulmonary vein isolation (PVI), roof linear ablation, and bottom linear ablation in clinical practice. We aimed to explore the methodological approach and electrophysiological characteristics of PWI. METHODS: A total of 36 patients who attended our center with long-standing persistent AF were retrospectively analyzed. After routine PVI and roof and bottom linear ablation, complete PWI was confirmed in sinus rhythm by voltage mapping and high-output pacing. Otherwise, activation mapping and voltage mapping were used to guide ablation on the line or inside the posterior wall until bidirectional block was achieved. RESULTS: The first-pass success rate of PWI was 39%. In the remaining 61% of patients with posterior wall electrograms, activation mapping in sinus rhythm showed that the earliest activation point was not on the ablation line but in a relatively dispersed focal area, possibly related to epicardial muscular sleeve insertion. Voltage mapping revealed a focal high-voltage area in the posterior wall matching the relatively dispersed earliest activation site, in which an average of five points of ablation achieved complete PWI without serious esophageal injury. The middle zone contained 80% of the additional posterior wall ablation points. CONCLUSIONS: PWI was performed safely and effectively with an average of five additional ablation points in the posterior wall in 61% of patients under the guidance of voltage mapping.


Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Fibrilación Atrial/fisiopatología , Técnicas Electrofisiológicas Cardíacas , Femenino , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/cirugía , Humanos , Masculino , Persona de Mediana Edad , Venas Pulmonares/cirugía , Estudios Retrospectivos
11.
Ann Noninvasive Electrocardiol ; 26(6): e12898, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34550625

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of left bundle branch area pacing (LBBaP) in patients with heart failure and left bundle branch block (LBBB), and to compare the clinical effects with traditional cardiac resynchronization therapy (CRT). METHODS: Thirty-two patients with dilated cardiomyopathy complicated by cardiac insufficiency and left bundle branch block were divided into CRT group and LBBaP group. Parameters including pacing threshold, R-wave amplitude, pacing impedance and operation time, and X-ray exposure time were recorded. The left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD) were examined by echocardiography. The changes of QRS complex before and after operation were compared. RESULTS: Compared with CRT group, the LBBaP group spent less time on total operation time and X-ray exposure time and had stable electrode parameters including pacing threshold, R-wave amplitude, and lead impedance after 12-month follow-up. In addition, LBBaP can achieve narrow QRS complex (117.15 ± 9.91) ms immediately than that in CRT group (130.32 ± 12.41) ms. The change of QRS between LBBaP is (50.30 ± 23.79) ms and CRT group is (33.15 ± 20.22) ms. After 6 months' follow-up in LBBaP group, EF was higher than that before operation. Followed up for 12 months after operation, EF and LVEDD in LBBaP group were significantly improved compared with those before operation. CONCLUSION: Left bundle branch area pacing is a safe and effective resynchronization method for patients with cardiac insufficiency and asynchronization, which can achieve same clinical effects to CRT.


Asunto(s)
Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Bloqueo de Rama/complicaciones , Bloqueo de Rama/terapia , Electrocardiografía , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/terapia , Humanos , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda
12.
Toxicol Mech Methods ; 31(1): 33-42, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32900247

RESUMEN

Aluminum (Al), a neurotoxic element, can induce Alzheimer's disease (AD) via triggering neuronal death. Ferroptosis is a new type of programmed cell death related to neurological diseases. Unfortunately, its role in aluminum-induced neuronal death remains completely unclear. This study aimed to investigate whether ferroptosis is involved in neuronal death in response to aluminum exposure as well as its underlying mechanism. In this study, rat adrenal pheochromocytoma (PC12) cells were treated with 200 µM aluminum maltolate (Al(mal)3) for 24 h, and related biochemical indicators were assessed to determine whether ferroptosis was induced by aluminum in neurons. Then, the potential mechanism was explored by detecting of these genes and proteins associated with ferroptosis after adding ferroptosis-specific agonist Erastin (5 µM) and antagonist Ferrostatin-1 (Fer-1) (5 µM). The experimental results demonstrated that aluminum exposure significantly increased the death of PC12 cells and caused specific mitochondrial pathological changes of ferroptosis in PC12 cells. Further research confirmed that ferroptosis was triggered by aluminum in PC12 cells by means of activating the oxidative damage signaling pathway, which was displayed as inhibition of the cysteine/glutamate antiporter system (system Xc-), causing the depletion of cellular glutathione (GSH) and inactivation of glutathione peroxidase (GSH-PX) eventually lead to accumulation of reactive oxygen species (ROS). Taken together, ferroptosis was a means of neuronal death induced by aluminum and oxidative damage may be its underlying mechanism, which also provided some new clues to potential target for the intervention and therapy of AD.


Asunto(s)
Ferroptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Neuronas/efectos de los fármacos , Compuestos Organometálicos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Pironas/toxicidad , Animales , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Neuronas/metabolismo , Neuronas/ultraestructura , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
13.
Org Biomol Chem ; 18(32): 6247-6252, 2020 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-32735638

RESUMEN

Incorporation of water has been revealed to successfully facilitate visible-light photoredox catalysis of indole leading to increased production of C2-quaternary indolinone. The water-promoted photoreaction of indole under catalyst-free conditions by a household compact fluorescence light was also demonstrated. The antiproliferative activity of the synthesized indolinones was evaluated against three human cancer cell lines.


Asunto(s)
Antineoplásicos/farmacología , Indoles/farmacología , Luz , Agua/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Catálisis , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indoles/síntesis química , Indoles/química , Estructura Molecular , Oxidación-Reducción , Procesos Fotoquímicos , Relación Estructura-Actividad
14.
Ann Noninvasive Electrocardiol ; 25(6): e12757, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32335984

RESUMEN

A 51-year-old woman presented with a 5-year history of a bypass tract of a left posterior septal ablation for atrioventricular reentrant tachycardia (AVRT). Following the procedure, while swallowing even without any water or food, she felt a new onset of palpitations, and swallowing-induced atrial tachycardia was diagnosed. We report on this patient with tachycardia induced by swallowing who received a comprehensive assessment. The swallowing-induced atrial tachycardia deriving from the right pulmonary vein was cured by catheter ablation. In our case, the swallowing-induced atrial tachycardia was connected with the activation of the sympathetic nervous system, which differs from typical reports of a vagal nerve reflex association.


Asunto(s)
Fibrilación Atrial/diagnóstico , Fibrilación Atrial/etiología , Ablación por Catéter/métodos , Deglución/fisiología , Electrocardiografía/métodos , Venas Pulmonares/cirugía , Fibrilación Atrial/cirugía , Femenino , Humanos , Persona de Mediana Edad , Venas Pulmonares/fisiopatología
15.
Med Sci Monit ; 26: e926221, 2020 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-32898129

RESUMEN

BACKGROUND Paroxysmal atrial fibrillation (pAF) recurrence after radiofrequency catheter ablation (RFCA) is linked to low-voltage zone (LVZ). This study explored whether serum soluble ST2 (sST2) levels can predict the size of LVZs in patients with pAF. MATERIAL AND METHODS A total of 177 patients with pAF treated with RFCA were consecutively enrolled in this study. One hundred twenty-five patients (70.6%) with <20% LVZ were assigned to Group A, and 52 patients (29.4%) with a LVZ >20% were assigned to Group B. Levels of soluble ST2 (sST2), growth and differentiation factor (GDF-15) and tissue inhibitor of MMP1 (TIMP-1) were measured. RESULTS The sST2 levels were higher in Group B than in Group A (23.9±3.3 vs. 30.9±5.0 ng/mL, P<0.000). In multivariable logistic regression analysis, sST2 was the only independent parameter for predicting left atrial LVZ (odds ratio, 1.611 [1.379-1.882]; P<0.001). The cut-off value of sST2 obtained by receiver operating characteristic (ROC) analysis was 26.65 ng/mL for prediction of LVZ (sensitivity: 86.5%, specificity: 84.8%). The under-curve area was 0.895 (0.842-0.948) (P<0.001). At 12-month follow-up, patients with sST2 <26.65 ng/mL had more patients free from atrial arrhythmias compared to patients with sST2 >26.65 ng/mL (88.6% vs. 69.8%, P<0.01). CONCLUSIONS We demonstrated that sST2 levels are higher in pAF patients with LVZ >20% compared to those with a smaller LVZ. Also increased sST2 levels can serve as a novel predictor of AF recurrence rate in patients who have undergone RFCA.


Asunto(s)
Fibrilación Atrial/sangre , Fibrilación Atrial/fisiopatología , Biomarcadores/sangre , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Anciano , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Femenino , Atrios Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia
16.
BMC Vet Res ; 15(1): 313, 2019 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-31477093

RESUMEN

BACKGROUND: Bovine ephemeral fever virus (BEFV) causes fever and muscle stiffness in cattle, resulting in negative economic impact for cattle and dairy farms. During the manufacturing process of inactivated vaccine for virus control, it is important to determine the virus titer, but traditional methods such as plaque assay and TCID50 assay require days of waiting time. We sought to develop a quick dot blot assay for BEFV titering. RESULTS: Three different kinds of BEFV antigens were prepared to raise primary antibodies for BEFV detection in dot blot assays: 1) purified BEFV particles, 2) Escherichia coli (E. coli)-expressed BEFV G1 region, and 3) E. coli-expressed BEFV N protein. Results showed that antibodies raised against purified BEFV particles can detect BEFV particles, but it also showed a high background level from the proteins of BHK-21 cells. Antibodies raised against E.coli-expressed BEFV G1 region could not detect BEFV particles in dot blot assays. Finally, antibodies raised against E.coli-expressed BEFV N protein detected BEFV particles with a high signal-to-noise ratio in dot blot assays. CONCLUSIONS: E.coli-expressed N protein is a suitable antigen for the production of antiserum that can detect BEFV particles with a high signal-to-noise ratio. A dot blot assay kit using this antiserum can be developed as a quick and economical way for BEFV titering.


Asunto(s)
Virus de la Fiebre Efímera Bovina/aislamiento & purificación , Fiebre Efímera/virología , Immunoblotting/veterinaria , Animales , Anticuerpos Antivirales , Bovinos , Línea Celular , Cricetinae , Regulación Viral de la Expresión Génica , Immunoblotting/métodos , Conejos , Proteínas Virales/genética , Proteínas Virales/metabolismo
17.
Nano Lett ; 18(10): 6207-6213, 2018 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-30260652

RESUMEN

Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformans and a typical biomaterial for improving drug oral absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic- co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral absorption barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformans and increased survival of model mice. Currently, targeted drug delivery is mainly performed intravenously; however, the system described in our study may provide a universal means to facilitate drug targeting to specific tissues and disease sites by oral administration and may be especially powerful in the fight against increasingly severe fungal infections.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas/administración & dosificación , Neumonía Bacteriana/tratamiento farmacológico , Poliésteres/administración & dosificación , Administración Oral , Animales , Quitosano/administración & dosificación , Quitosano/química , Cryptococcus/efectos de los fármacos , Cryptococcus/patogenicidad , Humanos , Ligandos , Ratones , Nanopartículas/química , Péptidos/administración & dosificación , Péptidos/química , Neumonía Bacteriana/microbiología , Poliésteres/química
19.
BMC Vet Res ; 14(1): 194, 2018 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-29940938

RESUMEN

BACKGROUND: Inactivated and subunit bovine viral diarrhea virus (BVDV) vaccines have shown limited protective efficacy. This study aimed to evaluate the effectiveness of a vaccine containing both inactivated BVDV (iBVDV) and baculovirus-expressed recombinant E2 (rE2), an important BVDV antigen with strongly neutralizing epitopes. RESULTS: Four groups of goats were immunized twice with one of four vaccine preparations: 1) iBVDV+rE2, 2) rE2, 3) iBVDV, and 4) saline, and challenged with BVDV. For goats vaccinated with the iBVDV+rE2 vaccine, no viremia was observed after challenge, and clinical signs, pyrexia, and leukopenia were reduced compared to the saline group. In contrast, for goats vaccinated with either iBVDV or rE2 alone, viremia was still detectable. CONCLUSION: The combination of iBVDV and rE2 elicited stronger protective immune responses against BVDV than iBVDV or rE2 alone.


Asunto(s)
Virus de la Diarrea Viral Bovina Tipo 2/inmunología , Enfermedades de las Cabras/prevención & control , Infecciones por Pestivirus/prevención & control , Vacunas Virales/uso terapéutico , Animales , Anticuerpos Antivirales/inmunología , Clonación Molecular , Enfermedades de las Cabras/inmunología , Enfermedades de las Cabras/virología , Cabras/inmunología , Cabras/virología , Infecciones por Pestivirus/inmunología , Linfocitos T/inmunología , Vacunas de Productos Inactivados/inmunología , Vacunas Sintéticas/inmunología , Proteínas Virales/inmunología , Vacunas Virales/inmunología
20.
BMC Vet Res ; 13(1): 15, 2017 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-28061775

RESUMEN

BACKGROUND: Streptococcus suis (S. suis) causes arthritis, meningitis, septicemia, and sudden death in pigs and is also an zoonotic agent for humans. The present study demonstrated that immunization with recombinant Sao-L (surface antigen one-L, rSao-L) protein from a strain of S. suis serotype 2 in pigs was able to increase cross-serotype protection against S. suis serotype 1 and 2 challenge. Since weaning piglets are more susceptible to S. suis infections due to the stresses associated with weaning, prepartum immunization in sows may convey passive immunity to piglets and provide protection. RESULTS: Pregnant sows were immunized with a vaccine containing inactivated S. suis serotype 2 plus rSao as the antigens. Blood samples were collected from their piglets after birth for analysis of antigen-specific antibody titers and levels of various cytokines. Results demonstrated that the titers of S. suis and rSao-specific antibodies were significantly (p < 0.05) higher in the vaccinated piglets in comparison with that of piglets in the control group. The serum levels of interferon (IFN)-γ, interleukin (IL)-4, IL-6, and IL-12 were significantly (p < 0.05) increased in piglets born from vaccinated sows when compared to piglets from unvaccinated sows. In addition, piglets were challenged by heterologous and homologous S. suis. All piglets from unvaccinated sows developed severe symptoms of bacteremia, fever, anorexia, depression, and arthritis. On the other hand, piglets from vaccinated sows had significantly (p < 0.05) reduced clinical symptoms and lesion score (by 75 and 81%). CONCLUSIONS: Our results revealed that immunizing pregnant sows with the vaccine containing inactivated S. suis bacterin plus rSao as the antigens is able to enhance passive immunity against heterologous and homologous S. suis challenge in their piglets.


Asunto(s)
Proteínas Bacterianas/inmunología , Vacunas Bacterianas/inmunología , Inmunidad Materno-Adquirida , Streptococcus suis/inmunología , Enfermedades de los Porcinos/prevención & control , Envejecimiento , Animales , Citocinas/sangre , Citocinas/genética , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica/inmunología , Inmunización , Inmunización Pasiva/veterinaria , Embarazo , Proteínas Recombinantes , Streptococcus suis/metabolismo , Porcinos , Enfermedades de los Porcinos/microbiología
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