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1.
N Engl J Med ; 383(19): 1838-1847, 2020 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-32865380

RESUMEN

BACKGROUND: Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited. METHODS: In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke. RESULTS: A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31). CONCLUSIONS: In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).


Asunto(s)
Antiinflamatorios/uso terapéutico , Colchicina/uso terapéutico , Enfermedad Coronaria/tratamiento farmacológico , Anciano , Antiinflamatorios/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Enfermedad Crónica , Colchicina/efectos adversos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales
2.
Appl Opt ; 61(5): 1254-1260, 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35201178

RESUMEN

We propose an all-media photonic crystal (PC) composed of isosceles triangle dielectric cylinders that realizes the topological phase transition by simply rotating the isosceles triangular dielectric cylinders. Additionally, the topological phase transition is closely linked with the size parameters and rotation angle of the isosceles triangle. The topological boundary states with lossless transmission are constructed on the interface of two different topological structures, and the optical quantum spin Hall effect is simulated. Further, we verified that the boundary state is unidirectional and immune to disorder, cavity, and sharp bend defects. By rotating the angle of the triangle to control the transmission path of the pseudo-spin state, we realize diverse transport pathways of light, such as the "straight line" shape, "Z" shape, "U" shape, and "Y" shape. This topological system shows a higher degree of freedom, which can promote the research on topological boundary states and the development of topological insulators in practical applications.

3.
Angew Chem Int Ed Engl ; 61(38): e202208570, 2022 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-35900359

RESUMEN

Targeting metabolic reprogramming to treat cancer could increase overall survival and reduce side effects. Here, we put forward a strategy using arene-ruthenium(II)/osmium(II) complexes to potentiate the anticancer effect of metformin (Met.) via glucose metabolism reprogramming. Complexes 1-6 with oxoglaucine derivatives as ligands were synthesized and their anti-tumor activities were tested under hypoglycemia. Results indicated that 2 and 5 potentiated the anticancer effects of Met. under hypoglycemia, exhibiting lower toxicity, slower blood glucose decline and inhibition of early tumor liver metastasis. Combination of 5 with Met. could be used as a new strategy to treat cancer under hypoglycemia through glucose metabolism reprogramming.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Hipoglucemia , Metformina , Compuestos Organometálicos , Rutenio , Antineoplásicos/farmacología , Línea Celular Tumoral , Complejos de Coordinación/farmacología , Glucosa , Humanos , Metformina/farmacología , Osmio , Rutenio/farmacología
4.
Microb Pathog ; 148: 104414, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32771657

RESUMEN

Biofilm formation and virulence factor secretion in opportunistic pathogen Pseudomonas aeruginosa are essential for establishment of chronic and recurrent infection, which are regulated by quorum sensing (QS) system. In this study, a set of cajaninstilbene acid analogues were designed and synthesized, and their abilities to inhibit QS and biofilm formation were investigated. Among all the compounds, compounds 3g, 3m and 3o showed potent anti-biofilm activity, especially 3o exhibited promising biofilm inhibitory activity with biofilm inhibition ratio of 49.50 ± 1.35% at 50 µM. Three lacZ reporter strains were constructed to identify the effects of compound 3o on different QS systems. Compound 3o showed the suppression on the expression of lasB-lacZ and pqsA-lacZ as well as on the production of their corresponding virulence factors. Therefore, compound 3o is expected to be generated as a lead compound with inhibition of biofilm formation and QS of Pseudomonas aeruginosa.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Percepción de Quorum , Salicilatos/farmacología , Estilbenos/farmacología , Proteínas Bacterianas/genética , Percepción de Quorum/efectos de los fármacos , Factores de Virulencia
5.
Drug Dev Res ; 80(6): 750-757, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31169945

RESUMEN

The prevalence of multidrug resistance among clinically significant bacterial pathogens underlines a critical need for the development of new classes of antibacterial agents with novel structural scaffolds. Cajaninstilbene acid (CSA), which is isolated from pigeonpea leaves, has shown potent antibacterial activity. In this study, a series of 2-hydroxyl-4-methoxyl-3-(3-methylbut-2-en-1-yl)-6-(4-phenylbenzoylamino)benzoic acid derivatives derived from CSA were designed and synthesized, and their antibacterial activities were evaluated. Several synthesized compounds exhibit better antibacterial activity than CSA against Staphylococcus aureus, Staphylococcus epidermidis, and two strains of methicillin-resistant S. aureus. Meanwhile, the results of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays illustrate the good selectivity between bacteria and normal cells of the most active compounds 6u and 6v. Furthermore, well combinations with bacterial RNA polymerase of 6u arising from docking study imply the possible mechanism of antibacterial activity of these synthetic compounds.


Asunto(s)
Antibacterianos , Benzoatos , Salicilatos , Estilbenos , Animales , Antibacterianos/química , Antibacterianos/farmacología , Benzoatos/química , Benzoatos/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Pruebas de Sensibilidad Microbiana , Salicilatos/química , Salicilatos/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Estilbenos/química , Estilbenos/farmacología
6.
J Nat Prod ; 81(12): 2621-2629, 2018 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-30444360

RESUMEN

The quorum sensing (QS) system inhibitors of Pseudomonas aeruginosa are thought to attenuate bacterial pathogenicity and drug resistance by inhibiting biofilm formation and the production of virulence factors. In this study, a synthetic approach to the natural products cajaninstilbene acid (1) and amorfrutins A (2) and B (3) has been developed and was characterized by the Heck reaction, which was used to obtain the stilbene core and a Pinick oxidation to give the O-hydroxybenzoic acid. The biological activities of these compounds against the P. aeruginosa quorum sensing systems were evaluated. Amorfrutin B (3) showed promising antibiofilm activity against P. aeruginosa PAO1 with a biofilm inhibition ratio of 50.3 ± 2.7. Three lacZ reporter strains were constructed to identify the effects of compound 3 on different QS systems. Suppression efficacy of compound 3 on the expression of lasB-lacZ and pqsA-lacZ as well as on the production of their corresponding virulence factors elastase and pyocyanin was observed.


Asunto(s)
Pseudomonas aeruginosa/efectos de los fármacos , Salicilatos/farmacología , Estilbenos/farmacología , Expresión Génica/efectos de los fármacos , Genes Bacterianos/efectos de los fármacos , Estructura Molecular , Pseudomonas aeruginosa/genética , Percepción de Quorum/efectos de los fármacos , Salicilatos/síntesis química , Salicilatos/química , Estilbenos/síntesis química , Estilbenos/química , Factores de Virulencia/biosíntesis , Factores de Virulencia/genética
7.
Zhongguo Zhong Yao Za Zhi ; 43(24): 4746-4752, 2018 Dec.
Artículo en Zh | MEDLINE | ID: mdl-30717513

RESUMEN

A questionnaire survey of 1 000 clinicians having experience in treating uncomplicated lower urinary tract infections from different levels of hospitals was conducted to mainly evaluate the applicability and effectiveness of clinical application of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for uncomplicated lower urinary tract infection(hereinafter referred to as Guideline). The research was conducted with the three-level quality control strictly throughout the process, and the data was real and reliable. The survey's results showed that: most clinicians considered that the Guideline had good clinical applicability. The availability and price of the recommended medicine were moderate. Traditional Chinese medicine had obvious features and advantages in treating lower urinary tract infection for it could reduce the usage of antibiotics and shorten the course of antibiotic application. In the recommendation section, clinicians proposed increasing medication guidance, updating the Guideline timely, as well as increasing treating methods and techniques, strengthen propaganda and promotion, and improve the use of evidence-based methods. In the evaluation of effectiveness, the majority of clinicians agreed that the definition in both traditional Chinese medicine (TCM) and Western medicine and differential diagnosis in the Guideline were accurately described and the basic principle of treatment as well as the treating method of TCM were recommended appropriately. The TCM formulas and Chinese patent medicine had good effect. Some clinicians suggested refining the syndrome differentiation of stranguria. Some clinicians considered that the formulas and herbs recommended in Guideline didn't have obvious effect and some had doubts about the manipulation of fumigation and washing in the part of other methods recommended in Guideline. Moreover, specification and procedure of manipulation of fumigation and washing using herbs and the acupuncture included in characteristic TCM therapy treating uncomplicated lower urinary tract infection remained to be developed.


Asunto(s)
Medicamentos Herbarios Chinos , Infecciones Urinarias , Terapia por Acupuntura , Antibacterianos , Diagnóstico Diferencial , Humanos , Medicina Tradicional China
8.
Heart Lung Circ ; 24(12): e210-3, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26304799

RESUMEN

A 36-year-old woman presented to hospital after a penetrating chest injury. She was haemodynamically stable. Echocardiography revealed left ventricular thrombus, with minimal pericardial effusion and no associated cardiac injuries. Intravenous anticoagulation was commenced for her intracardiac thrombus and her pericardial effusion was monitored with serial echocardiography. She remained well, was converted to warfarin and discharged home day 12 post admission, with cautious follow-up given her risk of late effusion and tamponade. Follow-up imaging revealed resolution of her intracardiac thrombus. She remains well to date.


Asunto(s)
Lesiones Cardíacas/tratamiento farmacológico , Heparina/administración & dosificación , Derrame Pericárdico/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Heridas Penetrantes/tratamiento farmacológico , Adulto , Femenino , Humanos
9.
Tumour Biol ; 35(11): 11183-91, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25106409

RESUMEN

The cytochrome CYP1A1 gene has been implicated in the etiology of oral cancer. However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in CYP1A1 gene with oral cancer risk. Published literatures from PubMed, MEDLINE, EMBASE, and China National Knowledge infrastructure (CNKI) databases were retrieved. A total of 12 studies were included in this meta-analysis. We found that significant positive associations between CYP1A1*2A polymorphism and oral cancer risk in recessive model (CC vs. TC + TT, OR = 1.93), dominant model (CC + TC vs. TT, OR = 1.33), and additive model (CC vs. TT, OR = 1.97). In subgroup analysis based on the ethnicity of study population, significant associations were found in all three genetic models for Asians (recessive OR = 2.29, 95% CI = .42-3.71; dominant OR = 1.54, 95% CI = 1.03-2.31; additive OR 2.39, 95% CI = 1.47-3.88) but not non-Asians. For the smoking stratification, the result indicated a significant association between CYP1A1*2A polymorphism and oral cancer among the smoking subjects (OR = 1.83, 95% CI = 1.47-2.26). This meta-analysis indicated a marked association of CYP1A1*2A polymorphisms with oral cancer risk, particularly among Asians, whereas there were significant interactions between the polymorphisms and cigarette smoking on oral cancer risk.


Asunto(s)
Citocromo P-450 CYP1A1/genética , Predisposición Genética a la Enfermedad , Neoplasias de la Boca/etiología , Polimorfismo Genético/genética , Fumar/efectos adversos , Estudios de Casos y Controles , Humanos , Pronóstico , Factores de Riesgo
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 43(1): 109-14, 2014 01.
Artículo en Zh | MEDLINE | ID: mdl-24616469

RESUMEN

Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme for synthesis of nicotinamide adenine dinucleotide in mammalian cells. Recent studies show that Nampt also works as a cytokine that exerts insulin-mimetic effects by binding to the insulin receptor, induces B-cell differentiation, inhibits neutrophil apoptosis, and affects immune and inflammatory functions. This review is focused on current knowledge regarding the structure and function of Nampt and its roles in carcinogenesis.


Asunto(s)
Neoplasias/enzimología , Nicotinamida Fosforribosiltransferasa/metabolismo , Humanos , Nicotinamida Fosforribosiltransferasa/fisiología
11.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 43(3): 281-6, 2014 05.
Artículo en Zh | MEDLINE | ID: mdl-24998650

RESUMEN

OBJECTIVE: To evaluate the effect of water channel aquaporin 4 (AQP4) on bleomycin-induced lung fibrosis in mice. METHODS: In wild type and AQP4 gene knockout (AQP4-/-) mice, lung fibrosis was induced by injection of bleomycin (3 mg/kg) into the trachea and saline injection was used as a control. At d3, 7, 14, 28 after bleomycin-treatment, mice were randomly sacrificed in batch and the lung coefficient was determined. Serum levels of TGF-ß1 and TNF-α were measured by ELISA and hydroxyproline contents in lung tissue were determined by Alkaline hydrolysis method. H-E staining and Masson's staining were performed to examine the pathological changes of lung tissues after bleomycin-treatment. RESULTS: On d14 after bleomycin-treatment, the lung coefficients in wild type mice and AQP4-/- mice were 1.9-fold (12.69 ± 6.05 vs 6.80 ± 0.82, q=4.204, P<0.05) and 2.3-fold (14.05 ± 5.82 vs 6.05± 0.58, q=5.172, P<0.01) of that in control, respectively, but no significant difference was found between wild type and AQP4-/- mice in the lung coefficient value (P>0.05). The hydroxyproline contents in the lung increased after bleomycin-treatment; on d28, the lung hydroxyproline contents in wild type and in AQP4-/- mice were 1.55-fold (0.85 ± 0.22 g/mg vs 0.55 ± 0.14 µg/mg, q=4.313, P<0.05) and 1.4-fold (0.84 ± 0.13 µg/mg vs 0.60 ± 0.14µg/mg, q=4.595,P<0.05) of that in control, respectively, but no significant difference was noticed between wild type and AQP4-/- mice in lung hydroxyproline contents. There was a tendency that serum TGF-ß1 and TNF-α levels increased in bleomycin-treated mice, but no significant difference was found between wild type and AQP4-/- mice. AQP4-knockout showed no effects on pathological changes of lung tissues with H-E staining and Masson's staining in mice with bleomycin-induced lung fibrosis. CONCLUSION: AQP4 might not be involved in bleomycin-induced lung fibrosis in mice.


Asunto(s)
Acuaporina 4/genética , Bleomicina/toxicidad , Fibrosis Pulmonar/inducido químicamente , Animales , Masculino , Ratones , Ratones Noqueados , Fibrosis Pulmonar/genética
12.
BMC Complement Altern Med ; 13: 322, 2013 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-24256941

RESUMEN

BACKGROUND: Ardisia pusilla A. DC., family Myrsinaceae, is a traditional Chinese medicine named Jiu Jie Long with a variety of pharmacological functions including anti-cancer activities. In this study, we purified a natural triterpenoid saponin, ardipusilloside I, from Ardisia pusilla, and show that it exhibits inhibitory activities in human mucoepidermoid carcinoma Mc3 cells. We also investigated the underlying mechanisms of proliferation inhibition that ardipusilloside I exerts on Mc3 cells. METHODS: MTT test was used to detect cell proliferation. Cell apoptosis was detected by transmission electron microscopy, Hoechst-33342 staining, DNA fragmentation detection, and flow cytometry. We also used western blot analysis to detect the potential mechanisms of apoptosis. RESULTS: Ardipusilloside I affected the viability of Mc3 cells in a dose- and time-dependent manner. The IC50 of ardipusilloside I was approximately 9.98 µg/ml at 48 h of treatment. Characteristic morphological changes of apoptosis, including nuclear condensation, boundary aggregation and splitting, and DNA fragmentation, were seen after treatment with 10 µg/ml ardipusilloside I for 48 h. Western blots demonstrated that ardipusilloside I caused Mc3 cell death through the induction of apoptosis by downregulation of Bcl-2 protein levels and upregulation of Bax and caspase-3 protein levels. CONCLUSIONS: Our results revealed that ardipusilloside I could be a new active substance for mucoepidermoid carcinoma treatment. We demonstrated that the potential mechanism of inhibition might be through the induction of apoptosis by regulation of Bcl-2 family protein levels. This suggests a further rationale for the development of ardipusilloside I as an anti-cancer agent.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Ardisia/química , Carcinoma Mucoepidermoide/fisiopatología , Ácido Oleanólico/análogos & derivados , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Saponinas/farmacología , Carcinoma Mucoepidermoide/tratamiento farmacológico , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Humanos , Ácido Oleanólico/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(12): 3278-81, 2013 Dec.
Artículo en Zh | MEDLINE | ID: mdl-24611386

RESUMEN

In the present paper, cobalt films, chromium and cobalt double layer films, and silver and cobalt double layer films were deposited by magnetron sputtering technique. The transient reflectivity response in cobalt thin films and their double layer films was studied by using femtosecond laser pump-probe transient reflection experimental technology. The result shows that, under the condition of the cobalt films of the same thickness, when the pump power increases, the heating time of the electrons in cobalt thin films is independent of the pump power, and is 0. 134 4 ps. And for the cobalt films of different thickness, the electron thermalization time is directly related to the film thickness. In addition, when the laser pulse power is high enough, two or three transient reflectivity decline signals on glass substrate films are found which is different with previous researches, when the cobalt films were thin, there are three times of transient reflectivity abruptly decline signals, and when the cobalt films were thick, there are two times of transient reflectivity abruptly decline signals, so the thickness of the cobalt films determines the times of the changes of the ultrafast dynamics in cobalt films.

14.
Zhongguo Zhong Yao Za Zhi ; 38(11): 1760-5, 2013 Jun.
Artículo en Zh | MEDLINE | ID: mdl-24010292

RESUMEN

This experiment was performed to establish a qualitative analysis on chemical composition in water extract of Paeoniae Radix Alba by HPLC-ESI-Q-TOF-MS. The analysis was conducted on a C18 (Hanbon Lichrospher, 4.6 mm x 250 mm, 5 microm) column with methanol-0.1% formic acid as the mobile phase for gradient elution; ESI ion source was used for mass spectra, and data were collected in both positive and negative modes. The results showed that eleven compounds from water extract of Paeoniae Radix Alba had been identified by analyzing positive and negative ion mass data including element composition and by comparing with data from literatures. Since efficient separation of HPLC and the high sensitive detection of MS was used, this experiment, it will provide evidences for elucidation of the effective substance in the water extract of Paeoniae Radix Alba.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Paeonia/química , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/aislamiento & purificación , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray/métodos
15.
World J Gastroenterol ; 29(22): 3422-3439, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37389234

RESUMEN

BACKGROUND: Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes, which can progress to cirrhosis. AIM: To evaluate the effect and mechanism of action annexin (Anx)A1 in liver fibrosis and how this could be targeted therapeutically. METHODS: CCl4 (20%) and active N-terminal peptide of AnxA1 (Ac2-26) and N-formylpeptide receptor antagonist N-Boc-Phe-Leu-Phe-Leu-Phe (Boc2) were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice, and to detect expression of inflammatory factors, collagen deposition, and the role of the Wnt/ß-catenin pathway in hepatic fibrosis. RESULTS: Compared with the control group, AnxA1, transforming growth factor (TGF)-ß1, interleukin (IL)-1ß and IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased, which promoted collagen deposition and expression of α-smooth muscle actin (α-SMA), collagen type I and connective tissue growth factor (CTGF), and increased progressively with time. CCl4 induced an increase in TGF-ß1, IL-1ß and IL-6 in liver tissue of AnxA1 knockout mice, and the degree of liver inflammation and fibrosis and expression of α-SMA, collagen I and CTGF were significantly increased compared with in wild-type mice. After treatment with Ac2-26, expression of liver inflammatory factors, degree of collagen deposition and expression of a-SMA, collagen I and CTGF were decreased compared with before treatment. Boc2 inhibited the anti-inflammatory and antifibrotic effects of Ac2-26. AnxA1 downregulated expression of the Wnt/ß-catenin pathway in CCl4-induced hepatic fibrosis. In vitro, lipopolysaccharide (LPS) induced hepatocyte and hepatic stellate cell (HSC) expression of AnxA1. Ac2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation, decreased expression of α-SMA, collagen I and CTGF in HSCs, and inhibited expression of the Wnt/ß-catenin pathway after HSC activation. These therapeutic effects were inhibited by Boc2. CONCLUSION: AnxA1 inhibited liver fibrosis in mice, and its mechanism may be related to inhibition of HSC Wnt/ß-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.


Asunto(s)
Anexina A1 , beta Catenina , Animales , Ratones , Anexina A1/genética , Células Estrelladas Hepáticas , Interleucina-6 , Lipopolisacáridos , Macrófagos , Cirrosis Hepática/inducido químicamente , Colágeno Tipo I
16.
Exp Lung Res ; 38(8): 427-33, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23030646

RESUMEN

To investigate the effects of phospholipase D (PLD) on low-concentration hydrogen peroxide (H(2)O(2))-induced growth and migration in alveolar epithelial A549 cells, the cells were exposed to H(2)O(2) (3-100 µM) for 12-48 hours, cell proliferation was determined by MTT assay and cell migration was tested by a modified epithelial wound healing assay. We found that one bolus of H(2)O(2) (10-100 µM) did not affect proliferation, but significantly stimulated migration (143-161% of control) after a 12-hour exposure. Pretreatment with the antioxidants catalase (1000 U/ml), N-acetyl-cysteine (2 mM), or edaravone (10 µM) abolished the migration induced by 30 µM H(2)O(2); the PLD inhibitor 1-butanol (0.5%) also attenuated H(2)O(2)-induced migration to the control level; while exogenous phosphatidic acid (PA) (10(-7)-10(-4) M) mimicked the effects of PLD activation and induced migration in a dose-dependent manner. We suggest that the alveolar epithelial cell migration induced by exposure to low concentrations of H(2)O(2) benefits tissue repair during acute lung injury (ALI) and PLD is involved in the underlying mechanism.


Asunto(s)
Células Epiteliales Alveolares/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Neoplasias Pulmonares/tratamiento farmacológico , Oxidantes/toxicidad , Fosfolipasa D/metabolismo , 1-Butanol/farmacología , Células Epiteliales Alveolares/enzimología , Antioxidantes/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colorantes/metabolismo , Relación Dosis-Respuesta a Droga , Antagonismo de Drogas , Humanos , Peróxido de Hidrógeno/antagonistas & inhibidores , Neoplasias Pulmonares/enzimología , Oxidantes/antagonistas & inhibidores , Ácidos Fosfatidicos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismo
17.
BMC Cardiovasc Disord ; 12: 8, 2012 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-22340728

RESUMEN

BACKGROUND: Acute Decompensated Cardiac Failure (ADCF) is frequently associated with deterioration in renal function. Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We aimed to determine if NGAL measured at admission predicts in-hospital acute kidney injury (AKI) in ADCF. METHODS: A prospective observational study measured NGAL and B-natriuretic peptide (BNP) from patients with ADCF presenting to two tertiary hospitals. Patients received standard care and were followed up daily as inpatients. ADCF was defined by PRIDE score ≥ 6 and AKI by RIFLE criteria. RESULTS: One hundred and two patients (median age 80, IQR 69-84 years, 52% male) were enrolled. AKI developed in 22 (25%) of 90 for whom outcome data was available. Seven patients died. NGAL was significantly elevated in those who developed AKI versus those who did not (median 130 ng/ml vs 69 ng/ml, p = 0.002). NGAL was also higher in those who died (median 136 ng/ml vs 68 ng/ml, p = 0.005). AKI was significantly associated with risk of death (5/22 (23%) vs 1/68 (1.5%), p = 0.001), but not length of hospital stay. NGAL significantly correlated with admission eGFR but not BNP. For prediction of AKI, NGAL > 89 ng/ml had sensitivity of 68% and specificity of 70% with area under the receiver operator characteristic (ROC) curve of 0.71 (0.58-0.84). After adjustment for baseline renal function, the odds ratio (OR) for AKI was 3.73 (1.26-11.01) if admission NGAL > 89 ng/ml. CONCLUSIONS: Elevated NGAL at admission is associated with in-hospital AKI and mortality in patients with ADCF. However, it has only moderate diagnostic accuracy in this setting.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Insuficiencia Cardíaca/mortalidad , Lipocalinas/sangre , Proteínas Proto-Oncogénicas/sangre , Lesión Renal Aguda/etiología , Proteínas de Fase Aguda , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Creatinina/sangre , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Lipocalina 2 , Masculino , Estudios Prospectivos , Medición de Riesgo , Sensibilidad y Especificidad
18.
Open Heart ; 9(1)2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35534092

RESUMEN

BACKGROUND: Despite rapid technological advances and growth, quality in imaging has not received the focus seen elsewhere in cardiovascular medicine, resulting in significant gaps between guidelines and practice. Contemporary echocardiography practice requires comprehensive real-time data collection to allow dynamic auditing and benchmarking of key performance indices. The American College of Cardiology (ACC) proposed additional data standardisation, structured reporting identifying key data elements and imaging registries. In the absence of an Australian echocardiography registry, we developed a national clinical quality registry (GenesisCare Cardiovascular Outcomes Echo Registry). We hypothesised that measurement and local reporting of data would improve compliance of echo studies with quality guidelines and hence their clinical value. METHODS AND RESULTS: We prospectively collected data on 4 099 281 echocardiographic studies entered directly into a central electronic database from 63 laboratories across four Australian states between 2010 and 2021. Real-time auditing of key data elements and introduction of quality improvement pathways were performed to maximise completeness and uniformity of data acquisition and reporting. We compared completeness of key data element acquisition (AV peak velocity, left ventricular ejection fraction, E/e', LA area, rhythm, RVSP) by time and state using de-identified data. Key performance outcomes benchmarked against the aggregated study cohort and international standards were reported to individual sites to drive quality improvement. Between 2010 and 2014 there were significant improvements in data completeness (72.0%+/-26.8% vs 86.8%+/-13.5%, p=0.02), which were maintained to 2020. In addition, interstate variability fell for both EF and E/e' (p<0.002). CONCLUSIONS: This large-scale collaboration provides a platform for the development of major quality improvement initiatives in echocardiography. Introduction of local quality assurance programmes via a unified national data set significantly improved the completeness of reporting of key echo quality measures. This in turn significantly improved the quality of, and reduced the interstate variability of, echo data. Developing a centralised database allowed rapid adoption nationally of local quality improvements.


Asunto(s)
Ecocardiografía , Función Ventricular Izquierda , Australia , Humanos , Sistema de Registros , Volumen Sistólico , Estados Unidos
19.
Case Rep Cardiol ; 2022: 5690844, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35958101

RESUMEN

A 63-year-old female presented late with anterior ST-elevation myocardial infarction and cardiogenic shock. This was complicated by acute ventricular septal defect with large left-to-right shunt. An Impella CP was inserted on day seven with rapid haemodynamic improvement. This facilitated bridge to cardiac transplant on day twelve post-MI.

20.
Invest New Drugs ; 29(4): 637-45, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20204673

RESUMEN

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor in salivary glands and high-grade MEC in particular demonstrates little response to chemotherapy which has been used largely for palliative treatment of metastatic disease. Baicalin, one of the main active compounds of Scutellaria baicalensis, possesses anti-inflammatory, antioxidant and antitumor properties. In the present study, we investigated the growth inhibiting and apoptosis-inducing effects of baicalin on a highly metastatic human mucoepidermoid carcinoma cell line Mc3 for the first time. Baicalin exerted dose- and time-dependent antiproliferative potential against Mc3 cells as assessed by MTT assay. Baicalin treatment of Mc3 cells resulted in an accumulation of cells at the G0/G1 and G2/M phase with a concomitant decrease in cells processing to S phase as assessed by flow cytometry. Furthermore, baicalin induced apoptosis of Mc3 cells as determined by annexin V binding and PI dual staining, DNA fragmentation, nuclear condensation and in vivo tumor inhabitation. Rhodamine 123 assay indicated that baicalin caused cytotoxicity and induced apoptosis through decreasing the mitochondrial membrane potential in Mc3 cells. Our results suggest that baicalin seems to be very attractive as a new anticancer drug and a potential chemotherapeutic agent against human high-grade mucoepidermoid carcinoma.


Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma Mucoepidermoide/patología , Flavonoides/farmacología , Animales , Carcinoma Mucoepidermoide/ultraestructura , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Flavonoides/química , Citometría de Flujo , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Desnudos , Scutellaria/química , Ensayos Antitumor por Modelo de Xenoinjerto
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