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1.
Clin Exp Pharmacol Physiol ; 49(8): 797-804, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35576104

RESUMEN

Lung cancer is one of the fastest growing malignancies in morbidity and mortality, and current therapies are in general not sufficiently effective for this deadly disease. This study characterizes the anticancer effects of glaucocalyxin A (GLA) and explores the underlying mechanisms using human non-small cell lung carcinoma (NSCLC) cells. First, our data showed that GLA suppressed the viability of cancer cells, whereas no effect was observed in the normal bronchial epithelial cell BEAS-2B cells. Second, GLA inhibited colony formation, induced apoptosis of cancer cells. Third, GLA downregulated the expression of B-cell lymphoma-2 (Bcl-2) protein; upregulated the expression of Bcl2-associated X protein (Bax), and strengthened cleavage of caspase 3 and polyadenyl diphosphate ribose polymerase (PARP). Fourth, GLA also diminished mitochondrial membrane potential and inhibited phosphatidylinositol 3-kinase (PI3K)/Akt/ glycogen synthase kinase-3ß (GSK3ß) pathway. In addition, injection of GLA (20 mg/kg) every 2 days significantly inhibited A549 xenograft tumour growth, accompanied by increased apoptosis and decreased proliferation. Together, our study provides evidence that the anticancer effect of GLA in NSCLC is mediated by inducing apoptosis through inhibiting PI3K/Akt/GSK3ß pathway and suggests that GLA may be used as a promising natural medicine for NSCLC therapy.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Diterpenos de Tipo Kaurano , Neoplasias Pulmonares , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/uso terapéutico , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal
2.
Neural Regen Res ; 12(2): 235-241, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28400805

RESUMEN

3'-Daidzein sulfonate sodium is a new synthetic water-soluble compound derived from daidzein (an active ingredient of the kudzu vine root). It has been shown to have a protective effect on cerebral ischemia/reperfusion injury in rats. We plan to study the mechanism of its protective effect. 3'-Daidzein sulfonate sodium was injected in rats after cerebral ischemia/reperfusion injury. Results showed that 3'-daidzein sulfonate sodium significantly reduced mitochondrial swelling, significantly elevated the mitochondrial membrane potential, increased mitochondrial superoxide dismutase and glutathione peroxidase activities, and decreased mitochondrial malondialdehyde levels. 3'-Daidzein sulfonate sodium improved the structural integrity of the blood-brain barrier and reduced blood-brain barrier permeability. These findings confirmed that 3'-daidzein sulfonate sodium has a protective effect on mitochondrial functions after cerebral ischemia/reperfusion injury, improves brain energy metabolism, and provides protection against blood-brain barrier damage.

3.
Soft Matter ; 10(8): 1142-50, 2014 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-24651451

RESUMEN

Here we report on the preparation and mechanical characterization of a 2-D self-assembled membrane formed by ionically crosslinking the polyelectrolyte parts of a gradient amphiphilic copolymer at oil and water interfaces. To fabricate these membranes, chloroform solutions of styrene-acrylic acid copolymers were suspended as pendant drops in an aqueous embedding phase. Due to the amphiphilic nature of these molecules, the copolymer chains migrate to the oil-water interface creating an interfacial layer. Upon the addition of zinc acetate to the embedding phase, crosslinks between copolymer molecules are formed via zinc-carboxylate complexes. While ionically crosslinked block copolymer membranes were critically damaged after one expansion cycle, ionically crosslinked gradient copolymers formed durable membranes that maintained their physical integrity through multiple expansion-compression-expansion cycles. This difference in mechanical behavior is attributed to the fact that gradient copolymers are more effective interfacial modifiers and have a significantly different molecular alignment at the oil-water interface. Additionally by changing the incubation time from 20 to 30 minutes, the low-strain dilatational modulus of these membranes was significantly increased due to higher interfacial coverage and crosslinking density. Longer incubation times also led to a distinct yield point and plastic deformation behavior at larger strains. Further mechanical characterization of the membranes showed that they can be quite robust and that by replacing the internal oil phase with an aqueous solution, future testing of membrane filtration and permeation may be possible.

4.
J Am Chem Soc ; 132(23): 8180-6, 2010 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-20527938

RESUMEN

Graphite oxide sheet, now called graphene oxide (GO), is the product of chemical exfoliation of graphite and has been known for more than a century. GO has been largely viewed as hydrophilic, presumably due to its excellent colloidal stability in water. Here we report that GO is an amphiphile with hydrophilic edges and a more hydrophobic basal plane. GO can act like a surfactant, as measured by its ability to adsorb on interfaces and lower the surface or interfacial tension. Since the degree of ionization of the edge -COOH groups is affected by pH, GO's amphiphilicity can be tuned by pH. In addition, size-dependent amphiphilicity of GO sheets is observed. Since each GO sheet is a single molecule as well as a colloidal particle, the molecule-colloid duality makes it behave like both a molecular and a colloidal surfactant. For example, GO is capable of creating highly stable Pickering emulsions of organic solvents like solid particles. It can also act as a molecular dispersing agent to process insoluble materials such as graphite and carbon nanotubes in water. The ease of its conversion to chemically modified graphene could enable new opportunities in solution processing of functional materials.

5.
Langmuir ; 26(5): 3261-7, 2010 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-19968259

RESUMEN

The behavior of styrene/acrylic acid gradient and diblock copolymers at liquid/liquid interfaces was investigated by using drop shape analysis to measure the interfacial tension. Copolymers were dissolved in chloroform, and pendant drops of these solutions were created in water. Molecular conformations at the interface were inferred by measuring changes in the interfacial tension as the interface was contracted and expanded through control of the drop volume. In this way, we were able to independently determine the interfacial pressure and area modulus of the adsorbed layer. Gradient copolymers showed the largest interfacial pressure, a result that is attributed to kinetic factors associated with the nature of the micellar aggregates that form in the chloroform phase. The area modulus of the adsorbed layer depended on the processing history and was not directly related to the interfacial pressure. This result is attributed to a local segmental desorption process where portions of the molecules reversibly desorb while the number of copolymer molecules at the interface remains fixed.

6.
Asian J Androl ; 7(3): 277-88, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16110356

RESUMEN

AIM: To identify a novel alternative transcript of the novel retinal pigment epithelial cell gene (NORPEG) expressed in the human testis. METHODS: A human testis cDNA microarray was established and hybridized with cDNA probes from human fetal testes, adult testes and human spermatozoa. Differentially expressed clones were sequenced and analyzed. One of these clones was a short transcript of NORPEG which we proceeded to analyze by RT-PCR. RESULTS: The novel short alternative transcript of NORPEG was isolated and named sNORPEG. It was 3486 bp in length and contained a 2952-bp open reading frame, encoding a 110.4-kDa protein of 983 amino acids. Amino acid sequence analysis showed that the sNORPEG protein contains six ankyrin repeats and two coiled-coil domains. It shares a high homology with the NORPEG and ankycorbin proteins in both its sequence and motifs. Blasting the human genome database localized sNORPEG to human chromosome 5p13.2-13.3. Expression profiles showed that sNORPEG was expressed in human fetal testes, adult testes and spermatozoa. Moreover, sNORPEG was found to be ubiquitously expressed in human tissues. CONCLUSION: sNORPEG is expressed in different developmental stages of the testis and encodes a protein that may have roles in human testis development and spermatogenesis.


Asunto(s)
Empalme Alternativo , Proteínas del Citoesqueleto/genética , ARN Mensajero/genética , Testículo/metabolismo , Factores de Transcripción/genética , Secuencia de Aminoácidos , Secuencia de Bases , ADN Complementario , Perfilación de la Expresión Génica , Humanos , Masculino , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido
7.
Int J Mol Med ; 15(2): 315-21, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15647849

RESUMEN

In this study, a human adult testis cDNA microarray was constructed and hybridized with (33)P-labeled human adult testis, embryo testis and sperm cDNA probes, respectively. A novel alternative splice variant of BRDT gene, named BRDT-NY, presumably involved in testicular function was cloned. It was expressed 3.96-fold more in human adult than embryo testis and also expressed in human spermatozoa. Similarly, RT-PCR revealed a differential expression pattern of this gene in human adult testes and fetal testes. The full length of BRDT-NY was 3438 bp and contained a 2883 bp open reading frame, encoding a 960-amino-acid protein. Sequence analysis showed that it has two bromodomains in N-terminal of the protein. Multiple tissue RT-PCR results showed that BRDT-NY was exclusively expressed in testis. mRNA expression of BRDT-NY gene was deleted in some azoospermic patients' testes. These experiments suggested that BRDT-NY gene may have an important role in the process of spermatogenesis and may be correlated with male infertility.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica , Proteínas Nucleares/genética , Proteínas Nucleares/fisiología , Empalme Alternativo , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , ADN Complementario/metabolismo , Humanos , Infertilidad Masculina , Masculino , Modelos Genéticos , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Análisis de Secuencia por Matrices de Oligonucleótidos , Estructura Terciaria de Proteína , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Testículo/embriología , Testículo/metabolismo , Distribución Tisular
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