Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
Org Lett ; 25(15): 2611-2615, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37027142

RESUMEN

The direct dehydrogenative C-H cleaving carbonylative lactamization of 2-arylanilines promoted by visible light and potassium bases is reported. Solvent DMF acts as the sole carbonyl source in the absence of an oxidant. The irreversible release of hydrogen gas drags this reaction to the stable phenanthridinone products. This work provides a direct conversion of a broad range of 2-arylanilines to various phenanthridinones. This method could be applied in the synthesis of bioactive molecules and organic optoelectronic materials.

2.
Exp Physiol ; 107(6): 562-574, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35365954

RESUMEN

NEW FINDINGS: What is the central question of this study? What are the cardioprotective effects of different aerobic exercises on chronic heart failure with different aetiologies, and is mitophagy involved? What is the main finding and its importance? Moderate-intensity continuous training may be the 'optimum' modality for improving cardiac structure and function in ischaemic heart failure, while both moderate-intensity continuous training and high-intensity interval training were suitable for pressure-overload heart failure. Various mitophagy pathways, especially parkin-dependent pathways, participated in the protective effects of exercise on heart failure. ABSTRACT: The cardioprotective effects of different aerobic exercises on chronic heart failure with different aetiologies and whether mitophagy is involved remain elusive. In the current research, left anterior descending ligation and transverse aortic constriction surgeries were used to establish mouse models of heart failure, followed by 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). The results showed that for ischaemic heart failure MICT significantly improved ejection fraction (P < 0.05) and fractional shortening (P < 0.05), mitigated left ventricular end-systolic dimension (P < 0.01), decreased brain natriuretic peptide (P < 0.0001) and mitigated fibrosis (P < 0.0001), while HIIT only decreased brain natriuretic peptide (P < 0.0001) and fibrosis (P < 0.0001). For pressure-overload heart failure, both MICT and HIIT significantly increased ejection fraction (P < 0.0001) and fractional shortening (MICT: P < 0.001, HIIT: P < 0.0001), and reduced left ventricular end-diastolic and end-systolic dimensions, brain natriuretic peptide (P < 0.0001), and fibrosis (MICT: P < 0.01, HIIT: P < 0.0001); HIIT was even better in reducing brain natriuretic peptide. Myocardial autophagy and mitophagy were compromised in heart failure, and the exercises improved myocardial autophagic flux and mitophagy inconsistently in heart failure with different aetiologies. Significant correlations were found between multiple mitophagy pathways and the cardioprotection of the exercises. Collectively, MICT may be the 'optimum' modality for ischaemic heart failure, while both MICT and HIIT (especially HIIT) were suitable for pressure-overload heart failure. Exercises differently improved myocardial autophagy/mitophagy, and multiple mitophagy-related pathways were closely implicated in cardioprotection of exercises for chronic heart failure.


Asunto(s)
Insuficiencia Cardíaca , Entrenamiento de Intervalos de Alta Intensidad , Animales , Enfermedad Crónica , Fibrosis , Entrenamiento de Intervalos de Alta Intensidad/métodos , Ratones , Mitofagia , Péptido Natriurético Encefálico
3.
Angew Chem Int Ed Engl ; 61(4): e202112638, 2022 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-34863045

RESUMEN

Polycyclic aromatic molecules are promising functional materials for a wide range of applications, especially in organic electronics. However, their largely hydrophobic nature has impeded further applications. As such, imparting high solubility/hydrophilicity to polycyclic aromatic molecules leads to a breakthrough in this research field. Herein, we report the synthesis of diazapentabenzocorannulenium, a cationic nitrogen-embedded buckybowl bearing a central imidazolium core, by a bottom-up strategy from polycyclic aromatic azomethine ylide. X-ray crystallography analyses have revealed a bowl-shaped molecular structure that is capable of forming charge-segregated one-dimensional columns by bowl-in-bowl packing. In addition to its fluorescence capabilities and high dispersibility in water, the molecule was found to selectively localize in the mitochondria of various tumor cells, showing potential as viable mitochondria-selective fluorescent probes.

4.
Platelets ; 33(5): 679-686, 2022 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-34472997

RESUMEN

Crushed or chewed potent P2Y12 inhibitors are commonly used in the hope of bridging the gap of platelet inhibition in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). The study aimed to investigate the efficacy and safety of this alternative oral administration strategy by performing a meta-analysis of available randomized clinical trials (RCTs). PubMed, Embase, the Cochrane Library and Web of Science medical literature databases were searched for RCTs comparing crushed/chewed vs. integral administration of loading dose potent P2Y12 inhibitors in patients with STEMI undergoing pPCI with no language restrictions from inception to January 20th, 2021. The primary efficacy endpoints of high on treatment platelet reactivity (HPR) and P2Y12 reaction units (PRU) at 1 hour together with safety and additional clinical endpoints were evaluated by pooled odds ratio (OR) or mean differences (MD) with 95% confidence intervals (95% CI). A total of 973 patents in six RCTs were eligible for analysis, while 876 patients present baseline and procedural characteristics. HPR and PRU at 1 hour were significantly reduced in the group receiving crushed/chewed P2Y12 inhibitors compared with integral tablets (OR 0.28, 95% CI 0.16 to 0.49, P < .0001; MD -60.62, 95% CI -97.06 to -24.19, P = .001, respectively). Safety endpoints of major bleeding (OR 0.54, 95% CI 0.11 to 2.73, P = .46) and any bleeding (OR 0.84, 95% CI 0.43 to 1.64, P = .61), as well as additional clinical endpoints of cardiovascular death, myocardial infarction, and stroke were not affected by the oral administration strategy. In STEMI patients undergoing pPCI, crushed or chewed administration of potent P2Y12 inhibitors are associated with enhanced early platelet inhibition and appear to be safe. The clinical profile transformed from this pharmacodynamic benefit need to be determined by further researches.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio/tratamiento farmacológico , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y/farmacología , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Resultado del Tratamiento
5.
Adv Mater ; 33(9): e2006711, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33491810

RESUMEN

Heterogeneous noble-metal-based catalysis plays an essential role in the production of fine chemicals. Rh-based catalysts are one of the most active candidates for indole synthesis. However, it is still highly desired to develop heterogeneous Rh-based catalysts with high activity and selectivity. In this work, a general, facile wet-chemical method is reported to synthesize ultrathin amorphous/crystalline heterophase Rh and Rh-based bimetallic alloy nanosheets (NSs), including RhCu, RhZn, and RhRu. Impressively, the amorphous/crystalline heterophase Rh NSs exhibit enhanced catalytic activity toward the direct synthesis of indole compared to the crystalline counterpart. Importantly, the obtained amorphous/crystalline heterophase RhCu alloy NSs can further enhance the selectivity to indole of >99.9% and the conversion is 100%. This work demonstrates the importance of phase engineering and metal alloying in the rational design and synthesis of tandem heterogeneous catalysts toward fine chemical synthesis.

6.
Medicine (Baltimore) ; 99(50): e23517, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33327296

RESUMEN

BACKGROUND: Symptoms of hand osteoarthritis result in activity limitations and lower quality of life. Hydroxychloroquine, which has been used successfully in the treatment of many autoimmune diseases, can suppress inflammation and might also be beneficial in hand osteoarthritis. METHODS: We plan to perform a systematic review and meta-analysis of randomized clinical trial to determine the symptom-modifying effect of hydroxychloroquine in hand osteoarthritis. We will search PubMed, EMBASE, Cochrane Library, and Web of Science using a comprehensive strategy. The related conference proceedings and reference lists of the included studies will also be checked to identify additional studies. Two reviewers will screen retrieved records, extract information and assess the risk of bias independently. Stata v15.1 software will be used to conduct data synthesis. RESULTS: This study will be submitted to a peer-reviewed journal for publication. CONCLUSION: We hope it will provide a relatively comprehensive reference for clinical practice and future relevant clinical trials. INPLASY REGISTRATION NUMBER: INPLASY2020110005.


Asunto(s)
Antirreumáticos , Articulaciones de la Mano , Hidroxicloroquina , Osteoartritis , Humanos , Antirreumáticos/uso terapéutico , Hidroxicloroquina/uso terapéutico , Osteoartritis/tratamiento farmacológico , Osteoartritis/psicología , Calidad de Vida , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto
7.
Org Lett ; 22(15): 6132-6137, 2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32663016

RESUMEN

Here we report the 1,3-dipolar cycloaddition of polycyclic aromatic azomethine ylides with nitriles to produce highly fused imidazole derivatives, that is, tribenzo[b,g,ij]imidazo[2,1,5-de]quinolizine. The advantages of this transformation are the broad substrate scope and the good functional group compatibility. The subsequent palladium-catalyzed intramolecular cyclization provides an efficient approach to further π-extended imidazoles, that is, 14b1,15-diazadibenzo[fg,ij]cyclopenta[rst]pentaphene.

8.
J Am Chem Soc ; 142(26): 11363-11369, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32413264

RESUMEN

Heterocyclic [8]circulenes are an important class of polycyclic aromatic hydrocarbon molecules because of their unique structural properties and promising applications. However, the synthesis of heterocyclic [8]circulenes is still limited and thus is an important synthetic challenge. Here we describe the first example of a π-extended diaza[8]circulene surrounded by and fused with six hexagons and two pentagons, which was successfully synthesized only by a combined in-solution and on-surface synthetic strategy. State-of-the-art scanning tunneling microscopy with a CO-functionalized tip and density functional theory calculations revealed its planar conformation and unique electronic structure.

9.
Mol Med Rep ; 21(3): 1011-1020, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31922242

RESUMEN

Increasing evidence has indicated that miR­155 is closely associated with apoptosis, which may protect the myocardium and diminish the infarct area in myocardial ischemia reperfusion injury (IRI). In addition, studies have revealed that miR­155 serves a leading role in promoting fibroblast inflammation, cardiac dysfunction and other aspects of myocardial injury. The present study aimed to uncover the function and potential biological mechanism of miR­155 in myocardial IRI. The rat H9c2 myocardial cells was treated with hypoxia/reoxygenation (H/R) to simulate IRI in vitro. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to detect the expression levels of miR­155 mRNA. Cell Counting Kit­8 and flow cytometry assays and western blot analysis were applied to determine the biological behaviors of the H/R­treated cells. The association between miR­155 and BAG family molecular chaperone regulator 5 (BAG5) was predicted by bioinformatics software and was confirmed by dual luciferase assay. RT­qPCR and western blot analysis were used to analyze the expression of BAG5. The key proteins involved in mitogen­activated protein kinase (MAPK)/JNK signaling pathway were detected by western blot analysis. The data from the RT­qPCR assay indicated that the expression of miR­155 was markedly upregulated in the H/R model, and that downregulation of miR­155 may promote cell proliferation and inhibit cell apoptosis, and vice versa. BAG5, which was downregulated in the H/R model, was confirmed as a target of miR­155 and negatively modulated by miR­155. The key proteins involved in MAPK/JNK signaling, which were highly expressed in the H/R model, were suppressed by treatment with the miR­155 inhibitor, and overexpression of BAG5 promoted the protective effect of miR­155 inhibition on cell injury caused by H/R. In addition, the expression patterns of hypoxia­inducible factor 1­α and von Hippel­Lindau were altered following different treatments. Taken together, the data from the present study indicated that miR­155 inhibition represented a potential treatment strategy to improve myocardial H/R injury, which may be associated with targeting BAG5 and inhibition of the MAPK/JNK pathway.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Sistema de Señalización de MAP Quinasas , MicroARNs/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Animales , Hipoxia de la Célula , Línea Celular , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/prevención & control , Ratas
10.
J Biochem Mol Toxicol ; 34(2): e22426, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31777165

RESUMEN

The purpose of this study was to investigate the biological effect of miR-16 on myocarditis and the underlying molecular mechanism. H9c2 cells were treated with 10 µg/mL lipopolysaccharide (LPS) for 12 hours to form a myocarditis injury model. We observed that LPS treatment distinctly decreased the level of miR-16 in H9c2 cells. Upregulation of miR-16 increased cell proliferation and reduced cell apoptosis. Then, CD40 was predicted and verified as a target gene of miR-16 by TargetScan and luciferase reporter assay, respectively. Furthermore, the messenger RNA and protein expression of CD40 are negatively regulated by miR-16. The relative expression of inflammatory factors was dramatically decreased by the miR-16 mimic. Cells cotransfected with miR-16 mimic and si-CD40 could significantly abolish the injury of cardiomyocytes caused by myocarditis. Our study illustrated that the upregulation of miR-16 has a protective effect on LPS-damaged H9c2 cells, which may be achieved by regulating CD40 and the nuclear factor kappa B pathway.


Asunto(s)
Antígenos CD40/metabolismo , Lipopolisacáridos/farmacología , MicroARNs/metabolismo , Miocarditis/inducido químicamente , Miocarditis/metabolismo , FN-kappa B/metabolismo , Regulación hacia Arriba/genética , Regiones no Traducidas 3'/genética , Animales , Apoptosis/genética , Sitios de Unión , Biomarcadores/metabolismo , Antígenos CD40/genética , Línea Celular , Técnicas de Silenciamiento del Gen , Lipopolisacáridos/efectos adversos , MicroARNs/genética , Miocitos Cardíacos/metabolismo , Ratas , Transducción de Señal/genética , Transfección
11.
Can J Cardiol ; 35(12): 1851-1856, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31813511

RESUMEN

BACKGROUND: The relationship between clinical outcomes and gene mutations in Chinese pediatric patients with idiopathic and heritable pulmonary arterial hypertension (PAH) is unclear. METHODS: We retrospectively studied the clinical characteristics and outcomes of pediatric patients who visited Beijing Anzhen Hospital from September 2008 to December 2018. RESULTS: Eighty-two pediatric patients were included. Forty-two gene mutations were identified in 41 patients (50%), including 25 mutations in BMPR2, 5 mutations in ACVRL1, 3 mutations each in ABCA3 and NOTCH3, 2 mutations each in KCNK3 and HTR2B, 1 mutation in ENG, and 1 mutation in EIF2AK4. The mean age at diagnosis of PAH was 86.4 ± 55.1 months. Forty-eight patients (twenty-eight mutation carriers) underwent cardiac catheterization examinations, with acute vasodilator testing performed simultaneously. Results showed that mutation carriers demonstrated a higher pulmonary vascular resistance index (P = 0.037). Patients with gene mutations responded poorly to vasodilators (P = 0.001). The 1-, 2-, and 3-year survival rates of mutation noncarriers were 95.1%, 87.8%, and 82.5% respectively; while for mutation carriers, the proportions were 86.6% (P = 0.216), 63.8% (P = 0.021), and 52.2% (P = 0.010), respectively. Cardiac index was an independent predictor of death (P = 0.005; odds ratio [OR] 2.16, 95% confidence interval [CI] 1.258-3.704), as well as RAP (P = 0.01; OR 1.26, 95% CI 1.056-1.503). CONCLUSIONS: In our cohort of Chinese pediatric patients, those with an identified gene mutation demonstrated worse clinical outcomes. Therefore, early gene screening for pediatric patients with idiopathic and heritable PAH is recommended, and more aggressive treatment for mutation carriers may be advisable.


Asunto(s)
Causas de Muerte , Hipertensión Pulmonar Primaria Familiar/epidemiología , Hipertensión Pulmonar Primaria Familiar/genética , Predisposición Genética a la Enfermedad/epidemiología , Hipertensión Arterial Pulmonar/epidemiología , Hipertensión Arterial Pulmonar/genética , Niño , Preescolar , China , Estudios de Cohortes , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/tratamiento farmacológico , Femenino , Regulación de la Expresión Génica , Pruebas Genéticas/métodos , Genotipo , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Pediatría , Fenotipo , Prevalencia , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Vasodilatadores/uso terapéutico
12.
J Org Chem ; 83(1): 296-302, 2018 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-29188712

RESUMEN

A base-promoted transition metal-free approach to substituted alkenes using alcohols under aerobic conditions using air as the inexpensive and clean oxidant is described. Aldehydes are relatively difficult to handle compared to corresponding alcohols due to their volatility and penchant to polymerize and autoxidize. Wittig ylides are easily oxidized to aldehydes and consequently form homo-olefination products. By the strategy of simultaneously in situ generation of ylides and aldehydes, for the first time, alcohols are directly transferred to olefins with no need of prepreparation of either aldehydes or ylides. Thus, the di/monocontrollable olefination of diols is accomplished. This synthetically practical method has been applied in the gram-scale synthesis of pharmaceuticals, such as DMU-212 and resveratrol from alcohols.

13.
Org Lett ; 17(24): 6102-5, 2015 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-26618248

RESUMEN

Phenanthroline and tert-butoxide have been established as powerful radical initiators in reactions such as the SRN1-type coupling reactions due to the cooperation of large heteroarenes and a special feature of tert-butoxide. The first phenanthroline-tert-butoxide-catalyzed transition-metal-free allylic isomerization is described. The resulting ketones are key intermediates for indenes. The control experiments rule out the base-promoted allylic anion pathway. The radical pathway is supported by experimental evidence that includes kinetic study, kinetic isotope effect, isotope-labeling experiments, trapping experiments, and EPR experiments.

14.
Org Lett ; 17(21): 5328-31, 2015 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-26473336

RESUMEN

A base-catalyzed/promoted transition-metal-free direct alkylation of amines with alcohols has been developed, giving the desired amines in generally high yields from either aromatic or aliphatic alcohols. On the basis of the (1)H NMR and in situ IR (React-IR) monitoring experiments, isotope-labeling experiments, as well as control experiments, a novel "hemiaminal" model is proposed to understand the mechanism, which explains the formation of the "extra" aldehyde in the reaction.

15.
Chem Commun (Camb) ; 51(36): 7729-32, 2015 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-25850736

RESUMEN

An unprecedented base-promoted direct olefination of aryl alcohols with sulfones via a Julia-type reaction has been described. No extra reductants are needed for Julia reaction since alcohols work as double sources of aldehydes and the hydride. Generally high yields were given for both terminal and highly (E)-selective internal olefins.

16.
Zhonghua Wai Ke Za Zhi ; 48(10): 727-30, 2010 May 15.
Artículo en Chino | MEDLINE | ID: mdl-20646485

RESUMEN

OBJECTIVE: To evaluate the efficacy of iloprost in acute vasodilatation test during cardiac catheterization and to explore a useful hemodynamic indication regarding operability in the patients with severe pulmonary hypertension (PH) related to congenital heart disease (CHD). METHODS: The clinical data of 46 patients [mean age (12 ± 9) years] with severe PH related to CHD from June 2006 to December 2008 was retrospectively analyzed. All patients underwent standard right and left cardiac catheterization and a trial of inhaled iloprost test during cardiac catheterization. The mean pulmonary arterial pressure was (80 ± 13) mm Hg (1 mm Hg = 0.133 kPa) and pulmonary vascular resistance index was (17 ± 10) wood.m². A positive response to inhaled iloprost was defined as a decrease of at least 20% in pulmonary vascular resistance index (PVRI) without changes on systemic artery pressure. Patients with positive response to iloprost underwent cardiac surgical repair. The pulmonary artery pressure and PVRI was monitored by Swan-Ganz catheter postoperatively. RESULTS: Of the 46 patients, 29 (63.1%) showed a positive response after iloprost inhalation, defined by a significant reduction in PVRI from (15 ± 6) wood.m(2) at baseline to (9 ± 4) wood.m² in response to iloprost inhalation therapy (P < 0.05). The ratio of pulmonary to systemic resistance (Rp/Rs) decreased from 0.7 ± 0.2 to 0.4 ± 0.2 (P < 0.05). Seventeen patients (36.9%) didn't respond to iloprost displayed only little changes in PVRI [from (21 ± 10) wood.m(2) to (19 ± 9) wood.m²] and Rp/Rs (from 1.0 ± 0.5 to 0.9 ± 0.5). Out of 29 positive patients, 21 (72%) underwent successful cardiac surgical repair with a reduction of mean pulmonary arterial pressure (mPAP) to an average of (27 ± 10) mm Hg after the operation. Only 2 patients out of the 17 patients from the negative group were referred to surgery. Their mPAP was greater than 45 mm Hg. CONCLUSIONS: A significant reduction in pulmonary artery pressure after cardiac surgery was observed in patients with positive response to inhaled iloprost. Inhaled iloprost may be a valuable tool in the preoperative evaluation of patients with severe PH related to CHD.


Asunto(s)
Cardiopatías Congénitas/fisiopatología , Hipertensión Pulmonar/fisiopatología , Iloprost/farmacología , Pulmón/irrigación sanguínea , Administración por Inhalación , Adolescente , Niño , Preescolar , Femenino , Cardiopatías Congénitas/cirugía , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión Pulmonar/cirugía , Lactante , Masculino , Cuidados Preoperatorios , Estudios Retrospectivos , Vasodilatadores/farmacología , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA