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1.
Stem Cells ; 41(1): 77-92, 2023 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-36208284

RESUMEN

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.


Asunto(s)
Proteínas de la Membrana , Células-Madre Neurales , Humanos , Proteínas de la Membrana/genética , Hipoxia de la Célula , Hipoxia/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Autofagia , Células-Madre Neurales/metabolismo , Proliferación Celular , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo
2.
Environ Sci Technol ; 58(6): 2598-2614, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38291652

RESUMEN

The widespread application of nanotechnology inevitably leads to an increased release of engineered nanoparticles (ENPs) into the environment. Due to their specific physicochemical properties, ENPs may interact with other contaminants and exert combined effects on the microbial community and metabolism of anaerobic digestion (AD), an important process for organic waste reduction, stabilization, and bioenergy recovery. However, the complicated interactions between ENPs and other contaminants as well as their combined effects on AD are often overlooked. This review therefore focuses on the co-occurrence of ENPs and cocontaminants in the AD process. The key interactions between ENPs and cocontaminants and their combined influences on AD are summarized from the available literature, including the critical mechanisms and influencing factors. Some sulfides, coagulants, and chelating agents have a dramatic "detoxification" effect on the inhibition effect of ENPs on AD. However, some antibiotics and surfactants increase the inhibition of ENPs on AD. The reasons for these differences may be related to the interactive effects between ENPs and cocontaminants, changes of key enzyme activities, adenosine triphosphate (ATP) levels, reactive oxygen species (ROS) production, and microbial communities. New scientific opportunities for a better understanding of the coexistence in real world situations are converging on the scale of nanoparticles.


Asunto(s)
Nanopartículas , Anaerobiosis , Nanopartículas/química , Nanotecnología , Especies Reactivas de Oxígeno
3.
Mol Pharmacol ; 103(3): 188-198, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36456191

RESUMEN

A dopamine D2 receptor mutation was recently identified in a family with a novel hyperkinetic movement disorder. That allelic variant D2-I212F is a constitutively active and G protein-biased receptor. We now describe mice engineered using CRISPR-Cas9-mediated gene editing technology to carry the D2-I212F variant. Drd2I212F mice exhibited gait abnormalities resembling those in other mouse models of chorea and/or dystonia and had striatal D2 receptor expression that was decreased approximately 30% per Drd2I212F allele. Electrically evoked inhibitory postsynaptic conductances in midbrain dopamine neurons and striatum from Drd2I212F mice, caused by G protein activation of potassium channels, exhibited slow kinetics (e.g., approximately four- to sixfold slower decay) compared with Drd2 +/+ mice. Current decay initiated by photolytic release of the D2 antagonist sulpiride from CyHQ-sulpiride was also ∼fourfold slower in midbrain slices from Drd2I212F mice than Drd2 +/+ mice. Furthermore, in contrast to Drd2 +/+ mice, in which dopamine is several-fold more potent at neurons in the nucleus accumbens than in the dorsal striatum, reflecting activation of Gα o versus Gα i, dopamine had similar potencies in those two brain regions of Drd2I212F mice. Repeated cocaine treatment, which decreases dopamine potency in the nucleus accumbens of Drd2 +/+ mice, had no effect on dopamine potency in Drd2 I212F mice. The results demonstrate the pathogenicity of the D2-I212F mutation and the utility of this mouse model for investigating the role of pathogenic DRD2 variants in early-onset hyperkinetic movement disorders. SIGNIFICANCE STATEMENT: The first dopamine receptor mutation to cause a movement disorder, D2-I212F, was recently identified. The mutation makes receptor activation of G protein-mediated signaling more efficient. To confirm the pathogenesis of D2-I212F, this study reports that mice carrying this mutation have gait abnormalities consistent with the clinical phenotype. The mutation also profoundly alters D2 receptor expression and function in vivo. This mouse model will be useful for further characterization of the mutant receptor and for evaluation of potential therapeutic drugs.


Asunto(s)
Dopamina , Trastornos del Movimiento , Receptores de Dopamina D2 , Animales , Humanos , Ratones , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Marcha/genética , Hipercinesia , Mutación , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Sulpirida
4.
Anal Bioanal Chem ; 415(2): 345-356, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36350342

RESUMEN

Bear bile powder (BBP) is one of the most famous traditional Chinese medicines derived from animals. It has a long history of medicinal use and is widely used in the treatment of hepatobiliary and ophthalmic diseases. Due to its similar morphological characterizations and chemical composition compared with other bile powders, it is difficult to accurately identify its authenticity. In addition, there are very few methods that could analyze the geographical origins of BBP. In this study, elemental analysis isotope ratio mass spectrometry (EA-IRMS) and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine stable isotope ratios and elemental contents, respectively. Combined these variables with chemometrics, the discrimination models were established successfully for identifying the authenticity and geographical origins of BBP. Meanwhile, the discrimination markers were identified by calculating the variable importance for the projection (VIP) value of each variable. A total of 13 discrimination markers (δ13C, δ15N, C, Li, Mg, K, Ca, Cr, Ni, Zn, As, Se, and Sr) were used to further establish the fingerprint of BBP. According to similarity analysis, the authenticity and geographical origins of BBP could be identified without chemometrics. In conclusion, the present study established a reliable method for authenticity identification and origin traceability of BBP, which will provide references for the quality control of bile medicines.


Asunto(s)
Ursidae , Animales , Polvos , Bilis , Isótopos/química , Espectrometría de Masas/métodos
5.
Nanotechnology ; 32(46)2021 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-34371488

RESUMEN

The exfoliation of bulk raw graphitic carbon nitride (g-C3N4) by edible glucose syrup to produce ultrathing-C3N4nanosheets in concentrations of up to 0.2 mg ml-1was achieved. Detailed characterization through TEM, AFM, FT-IR, XRD, Raman and TGA confirmed the formation of ultrathin structure and improved properties. Compared to rawg-C3N4, the prepared thing-C3N4layers exhibited a 18-fold enhancement in Cr(VI) reduction and a 3-fold enhancement in tetracycline hydrochloride degradation, which is ascribed to their larger specific surface area and more exposed active sites. The layeredg-C3N4membrane was constructed via direct vacuum filtration. The layer-stackedg-C3N4nanosheet membrane exhibited an excellent and sustained photocatalytic performance as the prepared thing-C3N4layers could maintain a layered lamella after stacking in filtration process. The recyclable synthesis of ultrathing-C3N4layers and layer-stackedg-C3N4membrane by our method provides a sustainable strategy to pollution treatment by 2D materials.

6.
Bioorg Chem ; 104: 104295, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32987309

RESUMEN

Two synthesized resveratrol analogs from our laboratory, namely pinosylvin (3,5-dihydroxy-trans-stilbene, PIN) and 4,4'-dihydroxystilbene (DHS), have been carefully evaluated for treatment of oligoasthenospermia. Recent studies have demonstrated that PIN and DHS improved sperm quality in the mouse. However, the mechanism of action of PIN and DHS on oligoasthenospermia remains unknown. Herein, we investigated the mechanistic basis for improvements in sperm parameters by PIN and DHS in a mouse model of oligoasthenospermia induced by treatment with busulfan (BUS) at 6 mg/kg b.w.. Two weeks following busulfan treatment, mice were administered different concentrations of PIN or DHS daily for 2 consecutive weeks. Thereafter, epididymal sperm concentration and motility were determined, and histopathology of the testes was performed. Serum hormone levels including testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured using corresponding specific enzyme-linked immunosorbent assay (ELISA) kits. Testicular mRNA expression profiles were determined by RNA sequencing analysis. These findings were validated by quantitative real-time PCR, western blotting and ELISA. Both PIN and DHS improved the epididymal sperm concentration and motility, enhanced testosterone levels, and promoted testicular morphological recovery following BUS treatment. PIN treatment was found to significantly reduce oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE)-dependent antioxidant, glutathione peroxidase 3. DHS treatment significantly reduced oxidative stress via the Nrf2-ARE-dependent antioxidants glutathione S-transferase theta 2 and glutathione S-transferase omega 2. In summary, PIN and DHS ameliorated oligoasthenospermia in this mouse model by attenuating oxidative stress via the Nrf2-ARE pathway.


Asunto(s)
Elementos de Respuesta Antioxidante/efectos de los fármacos , Modelos Animales de Enfermedad , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Oligospermia/tratamiento farmacológico , Estilbenos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos ICR , Estructura Molecular , Factor 2 Relacionado con NF-E2/metabolismo , Oligospermia/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estilbenos/química , Relación Estructura-Actividad
7.
J Microencapsul ; 37(4): 297-304, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32096670

RESUMEN

For slow release of tea tree oil (TTO), TTO were encapsulated by urea-formaldehyde (UF) resin via in situ polymerisation. The effects of curing time and drying condition on particle size, and TTO loading of the TTO/UF microcapsules were investigated. The results indicated that TTO/UF resin microcapsules with curing time of 80 min had narrow size distribution and good wall cover. Drying at ambient was better to maintain the TTO content than drying at oven. The loading of TTO with curing time of 80 min can be up to 45 wt.% of the mass-proportion to the prepared microcapsules, and more than 90 wt.% of the loaded TTO could be sustainably released in about 5 days. Moreover, the release kinetics of TTO/UF microcapsules was well described by Ritger-Peppas model, revealing non-Fickian diffusion. Promisingly, TTO/UF microcapsules with good stability can be used as a slow release vehicle for antibacterial application.


Asunto(s)
Cápsulas/química , Formaldehído/química , Aceite de Árbol de Té/química , Urea/química , Antibacterianos/administración & dosificación , Preparaciones de Acción Retardada , Difusión , Composición de Medicamentos , Tamaño de la Partícula , Polimerizacion
8.
PLoS Comput Biol ; 14(11): e1006514, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30481171

RESUMEN

Quality assessment is essential for the computational prediction and design of RNA tertiary structures. To date, several knowledge-based statistical potentials have been proposed and proved to be effective in identifying native and near-native RNA structures. All these potentials are based on the inverse Boltzmann formula, while differing in the choice of the geometrical descriptor, reference state, and training dataset. Via an approach that diverges completely from the conventional statistical potentials, our work explored the power of a 3D convolutional neural network (CNN)-based approach as a quality evaluator for RNA 3D structures, which used a 3D grid representation of the structure as input without extracting features manually. The RNA structures were evaluated by examining each nucleotide, so our method can also provide local quality assessment. Two sets of training samples were built. The first one included 1 million samples generated by high-temperature molecular dynamics (MD) simulations and the second one included 1 million samples generated by Monte Carlo (MC) structure prediction. Both MD and MC procedures were performed for a non-redundant set of 414 RNAs. For two training datasets (one including only MD training samples and the other including both MD and MC training samples), we trained two neural networks, named RNA3DCNN_MD and RNA3DCNN_MDMC, respectively. The former is suitable for assessing near-native structures, while the latter is suitable for assessing structures covering large structural space. We tested the performance of our method and made comparisons with four other traditional scoring functions. On two of three test datasets, our method performed similarly to the state-of-the-art traditional scoring function, and on the third test dataset, our method was far superior to other scoring functions. Our method can be downloaded from https://github.com/lijunRNA/RNA3DCNN.


Asunto(s)
Redes Neurales de la Computación , Conformación de Ácido Nucleico , ARN/química , Conjuntos de Datos como Asunto , Calor , Simulación de Dinámica Molecular , Método de Montecarlo
9.
Int J Legal Med ; 133(1): 99-101, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29850923

RESUMEN

We analyzed Chinese Miao population samples (n = 268) from Guizhou province, Southwest China, with 19 X-chromosomal short tandem repeats (STRs) included in the AGCU X19 amplification kit. The combined PE is 0.999999922 and the combined PDs in males and females are 0.9999999999999999999994 and 0.9999999999998, respectively. The mean paternity exclusion change values are larger than 0.99999996. The HDs in seven linkage groups vary from 0.9324 to 0.9968. Subsequently, comparison among different Chinese populations shows that the substructures of Chinese were significantly influenced by ethno-linguistic rather than geographical boundaries, including most prominently Turkic-speaking and Tibeto-Burman-speaking populations.


Asunto(s)
Cromosomas Humanos X , Etnicidad/genética , Variación Genética , Genética de Población , Haplotipos , Repeticiones de Microsatélite , China , Dermatoglifia del ADN , Femenino , Frecuencia de los Genes , Humanos , Masculino
10.
Angew Chem Int Ed Engl ; 58(24): 8039-8043, 2019 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-30977261

RESUMEN

Enabling all-solid-state Li-ion batteries requires solid electrolytes with high Li ionic conductivity and good electrochemical stability. Following recent experimental reports of Li3 YCl6 and Li3 YBr6 as promising new solid electrolytes, we used first principles computation to investigate the Li-ion diffusion, electrochemical stability, and interface stability of chloride and bromide materials and elucidated the origin of their high ionic conductivities and good electrochemical stabilities. Chloride and bromide chemistries intrinsically exhibit low migration energy barriers, wide electrochemical windows, and are not constrained to previous design principles for sulfide and oxide Li-ion conductors, allowing for much greater freedom in structure, chemistry, composition, and Li sublattice for developing fast Li-ion conductors. Our study highlights chloride and bromide chemistries as a promising new research direction for solid electrolytes with high ionic conductivity and good stability.

12.
Anal Biochem ; 561-562: 52-58, 2018 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-30036498

RESUMEN

N-glycolylneuraminic acid (Neu5Gc) is a type of sialic acid that is not typically produced in healthy humans but detective in some visceral cancer cells. As a new carcinoma biomarker, the level change in the serum and urine from the patient could potentially have the relation to the disease progression. So the measurement of the Neu5Gc will help to take a better response to therapeutic schedule for the sufferers. A sensitive and rapid aptamer-nanoparticle immunochromatographic strip for the visual detection of Neu5Gc was developed. The assay is based on the competitive reaction of binding the DNA aptamer targeting the candidate molecule selected by SELEX between Neu5Gc and complementary DNA. The sensing results indicated that the aptamer-based strip was sufficiently sensitive to detect Neu5Gc. The visual limit of detection (LOD) for semi-quantitative detection was 30 ng/mL under the optimal conditions and a quantitative detection limit of 5.38 ng/mL could be obtained using a scanning strip reader. The average recovery of the spiked cancer cell samples was 88.86%, with a coefficient of variation (CV) of 5.27%. The detection could be performed in less than 15 min using a simple procedure without any complicated equipment, demonstrating that this aptamer-nanoparticle biosensor strip has great potential for use to Neu5Gc-related cancer diagnosis.


Asunto(s)
Aptámeros de Nucleótidos/química , Técnicas Biosensibles , Cromatografía de Afinidad , Oro/química , Nanopartículas del Metal/química , Ácidos Neuramínicos/análisis , Humanos , Células Tumorales Cultivadas
13.
Phys Chem Chem Phys ; 20(14): 9123-9129, 2018 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-29577157

RESUMEN

Despite the good progress made in materials fabrication, it remains a big challenge to synthesize 2D sheets by assembling nanoflakes that are usually produced in experiments, and few theoretical studies have explored this topic. Based on the recent experimental synthesis of pentagonal graphene nanoflakes and the novel properties of penta-graphene, we report a series of 2D assembled carbon allotropes (CG568-80, CG568-180 and CG568-320) that have the following unusual properties: different from most other 2D carbon allotropes, the assembled carbon sheets have negative Gaussian curvatures, and exhibit ultra-softness and better chemical reactivity due to the curvature-induced misalignment of π-orbitals as compared with pristine graphene; all three studied carbon sheets are highly stable with binding energies comparable to those of phagraphene and ψ-graphene, and are semiconductors with tunable band gaps, displaying size-dependent carrier mobilities: ∼105 cm2 V-1 s-1 (CG568-80 and CG568-320) and ∼104 cm2 V-1 s-1 (CG568-180). These features indicate that assembling nanoflakes can effectively tune the structural morphology and properties to expand the family of 2D carbon materials for future applications.

14.
Mol Med ; 23: 258-271, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-29387863

RESUMEN

The kidney is vulnerable to hypoxia-induced injury. One of the mechanisms underlying this phenomenon is cell apoptosis triggered by hypoxia-inducible factor-1-alpha (HIF-1α) activation. MicroRNA-210 (miR-210) is known to be induced by HIF-1α and can regulate various pathological processes, but its role in hypoxic kidney injury remains unclear. Here, in both kinds of rat systemic hypoxia and local kidney hypoxia models, we found miR-210 levels were upregulated significantly in injured kidney, especially in renal tubular cells. A similar increase was observed in hypoxia-treated human renal tubular HK-2 cells. We also verified that miR-210 can directly suppress HIF-1α expression by targeting the 3' untranslated region (UTR) of HIF-1α mRNA in HK-2 cells in severe hypoxia. Accordingly, miR-210 overexpression caused significant inhibition of the HIF-1α pathway and attenuated apoptosis caused by hypoxia, while miR-210 knockdown exerted the opposite effect. Taken together, our findings verify that miR-210 is involved in the molecular response in hypoxic kidney lesions in vivo and attenuates hypoxia-induced renal tubular cell apoptosis by targeting HIF-1α directly and suppressing HIF-1α pathway activation in vitro.


Asunto(s)
Lesión Renal Aguda/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Hipoxia/genética , Riñón/citología , MicroARNs , Lesión Renal Aguda/metabolismo , Animales , Apoptosis , Línea Celular , Humanos , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Riñón/metabolismo , Masculino , Ratas Sprague-Dawley
15.
J Sep Sci ; 40(8): 1755-1764, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28217859

RESUMEN

Aminosilanized magnetic carbon microspheres as a novel adsorbent were designed and fabricated. The adsorbent was used for the magnetic solid-phase extraction of bisphenols at trace levels from environmental water samples before liquid chromatography with tandem mass spectrometry analysis. The structure, surface, and magnetic behavior of the as-prepared aminosilanized magnetic carbon microspheres were characterized by elemental analysis, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, and vibrating sample magnetometry. The effects of the experimental parameters were investigated by the Plackett-Burman design, and then the parameters that were significant to the extraction efficiencies were optimized through a response surface methodology. The aminosilanized magnetic carbon microspheres exhibited high adsorption efficiency and selectivity for bisphenols. Under optimal conditions, low limits of detection (0.011-2.22 ng/L), and a wide linear range (2-3 orders of magnitude), good repeatability (4.7-7.8%, n = 5), and reproducibility (6.0-8.3%, n = 3) were achieved. The results demonstrate that the novel adsorbent possesses great potentials in the determination of trace levels of bisphenols in environmental water samples.

16.
Anal Bioanal Chem ; 407(29): 8673-9, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26302960

RESUMEN

In this paper, a novel and simple method for the sensitive determination of endocrine disrupter compounds octylphenol (OP) and nonylphenol (NP) in environmental water samples has been developed using solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry. Carboxylated carbon nano-spheres (CNSs-COOH) are used as a novel SPME coating via physical adhesion. The CNSs-COOH fiber possessed higher adsorption efficiency than 100 µm polydimethysiloxane (PDMS) fiber and was similar to 85 µm polyacrylate (PA) fiber for the two analytes. Important parameters, such as extraction time, pH, agitation speed, ionic strength, and desorption temperature and time, were investigated and optimized in detail. Under the optimal parameters, the developed method achieved low limits of detection of 0.13~0.14 ng·L(-1) and a wide linear range of 1~1000 ng·(-1) for OP and NP. The novel method was validated with several real environmental water samples, and satisfactory results were obtained.


Asunto(s)
Carbono/química , Disruptores Endocrinos/análisis , Nanosferas/química , Fenoles/análisis , Microextracción en Fase Sólida/métodos , Contaminantes Químicos del Agua/análisis , Disruptores Endocrinos/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas/métodos , Límite de Detección , Fenoles/aislamiento & purificación , Agua/análisis , Contaminantes Químicos del Agua/aislamiento & purificación
17.
Mar Drugs ; 13(12): 7433-45, 2015 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-26694424

RESUMEN

Okadaic acid (OA) is produced by Dinophysis and Prorocentrum dinoflagellates and primarily accumulates in bivalves, and this toxin has harmful effects on consumers and operators. In this work, we first report the use of aptamers as novel non-toxic probes capable of binding to a monoclonal antibody against OA (OA-mAb). Aptamers that mimic the OA toxin with high affinity and selectivity were generated by the magnetic bead-assisted systematic evolution of ligands by exponential enrichment (SELEX) strategy. After 12 selection rounds, cloning, sequencing and enzyme-linked immunosorbent assay (ELISA) analysis, four candidate aptamers (O24, O31, O39, O40) were selected that showed high affinity and specificity for OA-mAb. The affinity constants of O24, O31, O39 and O40 were 8.3 × 108 M(-1), 1.47 × 108 M(-1), 1.23 × 108 M(-1) and 1.05 × 108 M(-1), respectively. Indirect competitive ELISA was employed to determine the internal-image function of the aptamers. The results reveal that O31 has a similar competitive function as free OA toxin, whereas the other three aptamers did not bear the necessary internal-image function. Based on the derivation of the curvilinear equation for OA/O31, the equation that defined the relationship between the OA toxin content and O31 was Y = 2.185X - 1.78. The IC50 of O31 was 3.39 ng·mL(-1), which was close to the value predicted by the OA ELISA (IC50 = 4.4 ng·mL(-1)); the IC10 was 0.33 ng·mL(-1). The above data provides strong evidence that internal-image functional aptamers could be applicable as novel probes in a non-toxic assay.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Aptámeros de Nucleótidos/metabolismo , Ácido Ocadaico/metabolismo , Técnica SELEX de Producción de Aptámeros/métodos , Aptámeros de Nucleótidos/inmunología , Dinoflagelados/metabolismo , Ensayo de Inmunoadsorción Enzimática/métodos , Concentración 50 Inhibidora , Ácido Ocadaico/inmunología
18.
Pulm Pharmacol Ther ; 27(1): 1-9, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23796770

RESUMEN

BACKGROUND: Hypoxic pulmonary arterial hypertension (PAH) is a disabling disease with limited treatment options. Hypoxic pulmonary vascular remodeling is a major cause of hypoxic PAH. Pharmacological agents that can inhibit the remodeling process may have great therapeutic value. OBJECTIVE: To examine the effect of intermedin (IMD), a new calcitonin gene-related peptide family of peptide, on hypoxic pulmonary vascular remodeling. METHODS: Rats were exposed to normoxia or hypoxia (∼10% O(2)), or exposed to hypoxia and treated with IMD, administered by an implanted mini-osmotic pump (6.5 µg/rat/day), for 4 weeks. The effects of IMD infusion on the development of hypoxic PAH and right ventricle (RV) hypertrophy, on pulmonary vascular remodeling, on pulmonary artery smooth muscle cell (PASMC) proliferation and apoptosis, and on the activations of l-arginine nitric oxide (NO) pathway and endoplasmic reticulum stress apoptotic pathway were examined. RESULTS: Rats exposed to hypoxia developed PAH and RV hypertrophy. IMD treatment alleviated PAH and prevented RV hypertrophy. IMD inhibited hypoxic pulmonary vascular remodeling as indicated by reduced wall thickness and increased lumen diameter of pulmonary arterioles, and decreased muscularization of distal pulmonary vasculature in hypoxia-exposed rats. IMD treatment inhibited PASMC proliferation and promoted PASMC apoptosis. IMD treatment increased tissue level of constitutive NO synthase activity and tissue NO content in lungs, and enhanced l-arginine uptake into pulmonary vascular tissues. IMD treatment increased cellular levels of glucose-regulated protein (GRP) 78 and GRP94, two major markers of endoplasmic reticulum (ER) stress, and increased caspase-12 expression, the ER stress-specific caspase, in lungs and cultured PASMCs. CONCLUSIONS: These results demonstrate that IMD treatment attenuates hypoxic pulmonary vascular remodeling, and thereby hypoxic PAH mainly by inhibiting PASMC proliferation. Promotion of PASMC apoptosis may also contribute to the inhibitory effect of IMD. Activations l-arginine-NO pathway and of ER stress-specific apoptosis pathway could be the mechanisms mediating the anti-proliferative and pro-apoptotic effects of IMD.


Asunto(s)
Adrenomedulina/farmacología , Hipertensión Pulmonar/tratamiento farmacológico , Hipertrofia Ventricular Derecha/prevención & control , Neuropéptidos/farmacología , Arteria Pulmonar/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Arginina/metabolismo , Proliferación Celular/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hipertensión Pulmonar Primaria Familiar , Proteínas de Choque Térmico/metabolismo , Hipertensión Pulmonar/fisiopatología , Hipertrofia Ventricular Derecha/fisiopatología , Hipoxia/complicaciones , Masculino , Glicoproteínas de Membrana/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Óxido Nítrico/metabolismo , Arteria Pulmonar/citología , Arteria Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley
19.
Zhong Yao Cai ; 37(10): 1798-800, 2014 Oct.
Artículo en Zh | MEDLINE | ID: mdl-25895387

RESUMEN

OBJECTIVE: To investigate the chemical constituents of active fraction of Cynanchum versicolor. METHODS: The ethanol extract of Cynanchum versicolor was purified by macroporous resin, silica gel column and Sephadex LH-20 column chromatography, and structures of the isolated compounds were identified by spectroscopic analysis and comparison with those of literatures. RESULTS: Six compounds were isolated and identified as glaucogenin C (I), 24-methyl-5α-cholesta-7,22-diene-3ß,5,6ß-triol (II), syringic acid (III), 3,4-dihydroxyacetophenone (IV), 4-hydroxyacetophenone (V), and 4-hyroxy-3-methoxyacetophenone (VI). CONCLUSION: Compounds I, II and IV are isolated from this plant for the first time.


Asunto(s)
Cynanchum/química , Fitoquímicos/aislamiento & purificación , Acetofenonas/química , Acetofenonas/aislamiento & purificación , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Ácido Gálico/aislamiento & purificación , Fitoquímicos/química
20.
PLoS One ; 19(6): e0305670, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38913637

RESUMEN

PURPOSE: To compare the risk of developing subsequent primary lung cancer among cervical cancer patients and the general population. METHODS: Several databases were searched from inception to April 25, 2023. The standard incidence ratios (SIRs) with 95% confidence intervals (CIs) were combined to identify the risk for second primary lung cancer after cervical carcinoma. Subgroup analyses based on the follow-up period, age, degree of malignancy and source of SIR were conducted. All the statistical analyses were performed with STATA 15.0 software. RESULTS: A total of 22 retrospective studies involving 864,627 participants were included. The pooled results demonstrated that cervical cancer patients had a significantly greater risk for lung cancer than did the general population (SIR = 2.63, 95% CI: 2.37-2.91, P<0.001). Furthermore, subgroup analyses stratified by follow-up period (<5 years and ≥5 years), age (≤50 years and <50 years), and degree of malignancy (invasive and in situ) also revealed an increased risk of developing lung cancer among cervical carcinoma patients. CONCLUSION: Cervical cancer patients are more likely to develop subsequent primary lung cancer than the general population, regardless of age, follow-up time or degree of malignancy. However, more high-quality prospective studies are still needed to verify our findings.


Asunto(s)
Neoplasias Pulmonares , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/patología , Femenino , Neoplasias Pulmonares/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Neoplasias Primarias Secundarias/epidemiología , Incidencia , Estudios Retrospectivos , Adulto , Anciano
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