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Liriogerphines A-D (1-4, respectively), an unprecedented class of hybrids of germacranolide-type sesquiterpenoids and aporphine-type alkaloids, were isolated from the rare medicinal plant Liriodendron chinense. Their structures were elucidated by comprehensive spectroscopic analyses combined with electronic circular dichroism calculations and X-ray crystallographic data. Biosynthetically, an aza-Michael addition reaction is proposed to be involved in the assemblies of this class of hybrids. Compound 4 exhibited cytotoxicity against leukemia cells via inducing apoptosis and inhibiting Bcl-2 expression.
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Alcaloides , Antineoplásicos , Liriodendron , Sesquiterpenos , Alcaloides/química , Alcaloides/farmacología , China , Estructura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacología , ÁrbolesRESUMEN
BACKGROUND: To determine the change in refractive error and the incidence of myopia among school-aged children in the Yongchuan District of Chongqing City, Western China. METHODS: A population-based cross-sectional survey was initially conducted in 2006 among 3070 children aged 6 to 15 years. A longitudinal follow-up study was then conducted 5 years later between November 2011 and March 2012. Refractive error was measured under cycloplegia with autorefraction. Age, sex, and baseline refractive error were evaluated as risk factors for progression of refractive error and incidence of myopia. RESULTS: Longitudinal data were available for 1858 children (60.5%). The cumulative mean change in refractive error was -2.21 (standard deviation [SD], 1.87) diopters (D) for the entire study population, with an annual progression of refraction in a myopic direction of -0.43 D. Myopic progression of refractive error was associated with younger age, female sex, and higher myopic or hyperopic refractive error at baseline. The cumulative incidence of myopia, defined as a spherical equivalent refractive error of -0.50 D or more, among initial emmetropes and hyperopes was 54.9% (95% confidence interval [CI], 45.2%-63.5%), with an annual incidence of 10.6% (95% CI, 8.7%-13.1%). Myopia was found more likely to happen in female and older children. CONCLUSIONS: In Western China, both myopic progression and incidence of myopia were higher than those of children from most other locations in China and from the European Caucasian population. Compared with a previous study in China, there was a relative increase in annual myopia progression and annual myopia incidence, a finding which is consistent with the increasing trend on prevalence of myopia in China.
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Miopía/epidemiología , Errores de Refracción/patología , Adolescente , Niño , China/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Factores de RiesgoRESUMEN
Cardiomyocyte progenitor cells play essential roles in early heart development, which requires highly controlled cellular organization. microRNAs (miRs) are involved in various cell behaviors by post-transcriptional regulation of target genes. However, the roles of miRNAs in human cardiomyocyte progenitor cells (hCMPCs) remain to be elucidated. Our previous study showed that miR-134 was significantly downregulated in heart tissue suffering from congenital heart disease, underlying the potential role of miR-134 in cardiogenesis. In the present work, we showed that the upregulation of miR-134 reduced the proliferation of hCMPCs, as determined by EdU assay and Ki-67 immunostaining, while the inhibition of miR-134 exhibited an opposite effect. Both up- and downregulation of miR-134 expression altered the transcriptional level of cell-cycle genes. We identified Meis2 as the target of miR-134 in the regulation of hCMPC proliferation through bioinformatic prediction, luciferase reporter assay and western blot. The over-expression of Meis2 mitigated the effect of miR-134 on hCMPC proliferation. Moreover, miR-134 did not change the degree of hCMPC differentiation into cardiomyocytes in our model, suggesting that miR-134 is not required in this process. These findings reveal an essential role for miR-134 in cardiomyocyte progenitor cell biology and provide new insights into the physiology and pathology of cardiogenesis.
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Proliferación Celular , Proteínas de Homeodominio/metabolismo , MicroARNs/genética , Mioblastos Cardíacos/metabolismo , Miocitos Cardíacos/metabolismo , Factores de Transcripción/metabolismo , Células Cultivadas , Proteínas de Homeodominio/genética , Humanos , Mioblastos Cardíacos/fisiología , Miocitos Cardíacos/fisiología , Factores de Transcripción/genéticaRESUMEN
This study examined the prevalence of primary open-angle glaucoma (POAG) among residents aged ≥50 years living in Yongchuan district of Chongqing. Stratified cluster sampling was employed in random selection to estimate the prevalence of glaucoma from April to June, 2005. Twenty-nine villages or neighborhood communities were randomly selected in urban area (Zhongshan Road), suburban area (Shanjiao Town) and exurban area (Zhutuo Town) of this district. All the respondents underwent detailed ophthalmic examinations. The examinations included questionnaire investigation, visual acuity test, naked-eye examination, measurement of peripheral anterior chamber depth (Van Herrick's technique), detection of intraocluar pressure (IOP) with a Perkins hand-held applanation tonometer (HA-2) and examination of the optic disc by using a 78 diopters (D) lens (including the cup-disc ratio, cup/disc ratio asymmetries, horizontal and vertical diameter, notching and optic disc hemorrhages). A total of 5938 residents were actually examined, and the response rate was 85.19%. The crude prevalence of POAG was 0.86% (n=51/5938, 95% CI 0.64%-1.11%). There were 24 males and 27 females in the glaucoma group. The glaucoma prevalence was not significant different in case number between the male and female subjects (P=0.4900). Furthermore, no association between age or schooling and POAG was noted (P=0.8030, 0.0734). Out of 51 subjects with POAG, unilateral glaucoma-related blindness occurred in 38 subjects (74.5%) and bilateral glaucoma-related blindness was found in 7 subjects (13.7%). This study exhibited that the prevalence of POAG was 0.86% among residents aged ≥50 years living in Yongchuan District of Chongqing. The vision loss caused by POAG in this population was obviously higher than that previously reported in other studies. Glaucoma management, detection of affected persons and handling of the burden of glaucoma should be the priorities of the agenda of local health authorities of Western China.
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Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/epidemiología , Anciano , Ceguera/diagnóstico , Ceguera/epidemiología , China/epidemiología , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Gonioscopía/métodos , Encuestas Epidemiológicas/métodos , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/epidemiologíaRESUMEN
An extensive phytochemical investigation on the rare medicinal plant Semiliquidambar cathayensis (family: Hamamelidaceae) led to the isolation of four new (1-4, named semiliquidacids A-D, respectively) and 25 related known pentacyclic triterpenoids. The new structures with absolute configurations were elucidated by spectroscopic methods, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 represents the first naturally occurring ursane-type triterpenoid featuring an uncommon C-25 formyl group. Compound 4 and oleanolic acid (13) exhibited remarkable inhibitory effects against the ATP-citrate lyase (ACL, an emerging drug target for hyperlipidemia and related metabolic disorders) with IC50 values of 6.5 and 11.9 µM, respectively. The molecular interaction and binding mode between the bioactive triterpenoids and ACL were elaborated by conducting a molecular docking study. Meanwhile, the chemotaxonomic significance of the isolated triterpenoids has been briefly discussed.
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ATP Citrato (pro-S)-Liasa , Simulación del Acoplamiento Molecular , Triterpenos Pentacíclicos , Plantas Medicinales , Estructura Molecular , Plantas Medicinales/química , Triterpenos Pentacíclicos/farmacología , Triterpenos Pentacíclicos/aislamiento & purificación , Triterpenos Pentacíclicos/química , ATP Citrato (pro-S)-Liasa/antagonistas & inhibidores , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/química , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , China , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/químicaRESUMEN
Seventeen undescribed sesquiterpene-alkaloid hybrids (liriogerphines E-U, 1-17) were isolated and identified during a further phytochemical investigation on the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. These unique heterodimers are conjugates of germacranolide-type sesquiterpenoids with structurally diverse alkaloids [i.e., aporphine- (1-15), proaporphine- (16), and benzyltetrahydroisoquinoline-type (17)] via the formation of a C-N bond. The previously undescribed structures were elucidated by comprehensive spectroscopic data analyses and electronic circular dichroism calculations. Such a class of sesquiterpene-alkaloid hybrids presumably biosynthesized via an aza-Michael addition is quite rare from terrestrial plants. In particular, the sesquiterpene-benzyltetrahydroisoquinoline hybrid skeleton has never been reported until the present study. All the isolates were evaluated for their cytotoxic effects against a small panel of leukemia cell lines (Raji, Jeko-1, Daudi, Jurkat, MV-4-11 and HL-60), and some of them exhibited considerable activities.
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Alcaloides , Antineoplásicos , Liriodendron , Sesquiterpenos , Liriodendron/química , Alcaloides/química , Hojas de la Planta/química , Sesquiterpenos/química , Estructura MolecularRESUMEN
Rhodium-catalyzed three-component C-H bond activation of aromatics with amides and aldehydes to synthesize amines was established. The addition of copper was found to be essential to ensure the high reactivity. The mechanistic studies indicated that key intermediates formed by the transmetallization between rhodium and copper could further promote the addition between 2-(pyridin-2-yl)-phenyl-metal species and imines. A series of densely substituted amines could be conveniently prepared by this one-step, three-component procedure from commercially available substrates via C-H bond activation with water as the only by-product.
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Fiber-reinforced polymers (FRPs) provide promising prospects for replacing steel bars in traditional reinforced concrete structures. However, the use of FRP as tension bars in concrete beams leads to insufficient ductility because of its elastic characteristics. A newly developed compression-yielding (CY) beam has successfully solved this issue. Instead of tensile reinforcement yield, the ductile deformation of a CY beam is realized by the compression yield of a CY block in the compressive region. Another important feature is that the CY block is also the fuse of the beam, where material damage to the beam is concentrated in the CY block region and can be easily replaced. As a load-bearing recoverable and ductile structure, it is necessary to conduct a reliability-based design analysis and recommend reduction factors for this new structure. In this study, the function for calculating the failure probability of CY beams is proposed, semi-probabilistic design recommendations are presented, and Monte Carlo simulation (MCS) is adopted as a reliability analysis method. This study discusses the influence of the possible characteristics of the critical variables on reliability and provides the reliability index with different reduction factors to guide the design of the CY beam. These analyses indicate that the reliability index can be improved from the material design of the CY block in greater strength fb, smaller depth, smaller coefficient of variation of fb, and yield modulus ratio ξ. This study also shows that compared with the design of FRP concrete beams, the ductile failure mode of the CY beams allows a lower safety factor to meet safety requirements, which significantly reduces construction costs and avoids over-designing the load-bearing capacity.
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Exosomes are membranous structures secreted by nearly all cell types. As critical messengers for intercellular communication, exosomes deliver bioactive cargoes to recipient cells and are involved in multiple physiopathological processes, including immunoregulation. Our pioneering study revealed that cancer cells release programmed death-ligand 1-positive exosomes into the circulation to counter antitumor immunity systemically via T cells. Tumor cell-derived exosomes (TDEs) also play an immunosuppressive role in other immunocytes, including dendritic cells (DCs), macrophages, natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs). Moreover, exosomes secreted by nontumor cells in the tumor microenvironments (TMEs) also exert immunosuppressive effects. This review systematically provides a summary of the immunosuppression induced by exosomes in tumor microenvironments, which modulates tumor growth, invasion, metastasis, and immunotherapeutic resistance. Additionally, therapeutic strategies targeting the molecular mechanism of exosome-mediated tumor development, which may help overcome several obstacles, such as immune tolerance in oncotherapy, are also discussed. Detailed knowledge of the specific functions of exosomes in antitumor immunity may contribute to the development of innovative treatments.
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Exosomas , Neoplasias , Exosomas/metabolismo , Humanos , Tolerancia Inmunológica , Terapia de Inmunosupresión , Neoplasias/metabolismo , Microambiente TumoralRESUMEN
This paper presents an experimental program that includes 78 fiber reinforced polymer (FRP)-confined square concrete columns subjected to eccentric loading. The degradation of the axial strength of FRP-confined short concrete columns due to the load eccentricity is investigated in this work. A larger load eccentricity leads to a greater decrease in the axial strength. From the test results, it is found that FRP confinement can cause less strength degradation compared with that of unconfined concrete specimens. For FRP-confined square concrete specimens, the strength enhancement due to FRP confinement increases with increasing load eccentricity. However, the increasing load eccentricity decreases the confinement efficiency for FRP-confined circular concrete specimens. The relationship between the strength of eccentrically loaded FRP-confined square columns and their corner radii is evaluated.
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The stress-strain behavior of concrete can be improved by providing a lateral passive confining pressure, such as fiber-reinforced polymer (FRP) wrapping. Many axial stress-strain models have been proposed for FRP-confined concrete columns. However, few models can predict the stress-strain behavior of confined concrete columns with more than two specified cross-sections. A stress-strain model of FRP-confined concrete columns with cross-sectional unification was developed in this paper based on a database from the existing literature that includes circular, square, rectangular and elliptical concrete columns that are highly confined by FRP jackets. Using the database, the existing theoretical models were evaluated. In addition, the ultimate stress and strain models with cross-sectional unification were proposed using two parameters: the cross-sectional aspect ratio and corner radius ratio. The elliptical cross-section can be considered as a rectangular one with a special corner radius for the model calculations. A simple and accurate model of the equivalent corner radius ratio for elliptical columns was proposed. Compared to the other existing models and experimental data, the proposed models show good performance.
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OBJECTIVE: To compare the effects and pharmacoeconomics of single-dose of ceftriaxone versus 3-day cefuroxime prophylaxis in patients undergoing gastric or colorectal resection. METHODS: Three hundred and five consecutive patients with gastric or colorectal cancer from 5 medical centers were randomly divided into ceftriaxone group (n = 153, receiving intravenously 1 g ceftriaxone 0.5 - 1 h prior to operation only) and cefuroxime group (n = 152, receiving 0.75 g cefuroxime preoperatively and the same dose q8h for 3 d). The patients' intra- and postoperative status, adverse responses and infectious complications were observed and documented, and pharmacoeconomic parameters were analyzed. RESULTS: The disease distribution, operative procedures and patients' conditions in the 2 groups were comparable. No adverse responses to the test antibiotics were observed. Postoperative infectious complications occurred in 7 cases in the ceftriaxone group (4.58%) and 14 cases in the cefuroxime group (9.21%), respectively (P = 0.992), among which, 12 cases were surgical site infections (incisional, intra-abdominal): 2 cases in the ceftriaxone group (1.31%), and 10 cases in the cefuroxime group (6.58%), (chi(2) = 5.607, P = 0.018). The direct cost related to prevention and treatment of surgical site infections was 283.5 RMB in the ceftriaxone group and 811.1 RMB in the cefuroxime group (Z = 14.51, P = 0.000). CONCLUSION: Both ceftriaxone and cefuroxime are safe and effective for prevention of surgical site infections. Single-dose ceftriaxone prophylaxis is sufficient for gastric and colorectal operations, with a better cost-effectiveness ratio.
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Profilaxis Antibiótica/economía , Ceftriaxona/uso terapéutico , Cefuroxima/uso terapéutico , Infección de la Herida Quirúrgica/prevención & control , Adolescente , Adulto , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/economía , Antibacterianos/uso terapéutico , Ceftriaxona/administración & dosificación , Ceftriaxona/economía , Cefuroxima/administración & dosificación , Cefuroxima/economía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Study of the chemical constituents of ethanol extract from the aerial parts of Atalantia buxifolia led to the identification of a new acridone alkaloid named as buxifoliadine (1), along with known compounds citrusinine--I (2), N-methylatalaphylline (3), Severinolid (4) and cycloseverinolide (5). Structural elucidation of compound 1 was carried out by a combination of mass spectrometry and (1)H and (13)C NMR spectroscopy analyses.