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1.
Cell ; 151(5): 1029-41, 2012 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-23178122

RESUMEN

Defects in primary cilia lead to devastating disease because of their roles in sensation and developmental signaling but much is unknown about ciliary structure and mechanisms of their formation and maintenance. We used cryo-electron tomography to obtain 3D maps of the connecting cilium and adjacent cellular structures of a modified primary cilium, the rod outer segment, from wild-type and genetically defective mice. The results reveal the molecular architecture of the cilium and provide insights into protein functions. They suggest that the ciliary rootlet is involved in cellular transport and stabilizes the axoneme. A defect in the BBSome membrane coat caused defects in vesicle targeting near the base of the cilium. Loss of the proteins encoded by the Cngb1 gene disrupted links between the disk and plasma membranes. The structures of the outer segment membranes support a model for disk morphogenesis in which basal disks are enveloped by the plasma membrane.


Asunto(s)
Cilios/ultraestructura , Enfermedades de la Retina/patología , Segmento Externo de la Célula en Bastón/ultraestructura , Animales , Membrana Celular/metabolismo , Cilios/química , Canales Catiónicos Regulados por Nucleótidos Cíclicos/metabolismo , Proteínas del Citoesqueleto/metabolismo , Modelos Animales de Enfermedad , Proteínas del Ojo/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Retina/química , Retina/metabolismo , Segmento Externo de la Célula en Bastón/química , Segmento Externo de la Célula en Bastón/metabolismo , Vesículas Transportadoras/metabolismo
2.
Neoplasma ; 70(2): 229-239, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36964720

RESUMEN

Wilms' tumor 1-associated protein (WTAP), a component of the m6A methyltransferase complex, recruits the m6A methyltransferases METTL3 and METTL14 to the corresponding mRNA targets to participate in the formation of N6-methyladenosine. However, the molecular mechanism of WTAP in the tumorigenesis and progression of nasopharyngeal carcinoma (NPC) remains unclear. This study aimed to explore the prognostic value and biological function of WTAP in NPC. We assessed WTAP expression and its prognostic significance using microarray datasets from the Gene Expression Omnibus (GSE12452) database and 100 NPC tissues via bioinformatics analysis and immunohistochemistry (IHC), respectively. Moreover, gene ontology (GO) and gene set enrichment analysis (GSEA) were performed. In addition, the correlation of WTAP expression with the expression of immune cell biomarkers was analyzed. The results showed that WTAP expression was significantly overexpressed in NPC tissues in GSE12452. The overexpression of WTAP was validated by the external datasets including NPC tissues (GSE150430) and NPC cell lines (GSE39826). GO analysis suggested enrichment in the nucleoplasm (cellular component) and cell cycle (biological process). The GSEA revealed that differentially expressed genes were enriched in E2F-targets, Myc_targets_v1, G2M checkpoint, Myc_targets_v2, and Interferon-alpha-response. In IHC analysis, WTAP was upregulated in NPC tissues, and high levels of WTAP expression were significantly correlated with the advanced T stage (p=0.047) and advanced N stage (p=0.018). Cox regression demonstrated that WTAP overexpression was an independent biomarker of poor prognosis for overall survival (hazard ratio [HR], 4.747; 95% confidence interval [CI], 1.671-13.482; p=0.003). In IHC analysis, the expression of WTAP was positively correlated with CD206 (biomarker for M2 macrophages) (p=0.018) but negatively correlated with CD8a (biomarker for cytotoxic T cells) (p=0.001). In conclusion, WTAP is a promising prognostic biomarker and may participate in the regulation of immune cell infiltration in NPC.


Asunto(s)
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Línea Celular Tumoral , Pronóstico , Ciclo Celular/genética , Neoplasias Nasofaríngeas/genética , Metiltransferasas/genética , Metiltransferasas/metabolismo , Factores de Empalme de ARN , Proteínas de Ciclo Celular/metabolismo
3.
Ecotoxicol Environ Saf ; 256: 114901, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37054475

RESUMEN

Deoxynivalenol (DON) can affect health and growth performance of pigs, resulting in significant economic losses in swine production. The aim of this study was to investigate the effect of glycyrrhizic acid combined with compound probiotics, i.e. Enterococcus faecalis plus Saccharomyces cerevisiae (GAP) on improving growth performance, intestinal health and its fecal microbiota composition change of piglets challenged with DON. A total of 160 42-day-old weaned piglets (Landrace × Large White) were used and the experimental period was 28 d. The results showed that supplementing GAP in the diet significantly improved the growth performance of piglets challenged with DON and alleviate DON-induced intestinal damage by reducing ALT, AST and LDH concentrations in serum, increasing the morphological parameters of jejunum, and decreasing DON residues in serum, liver and feces. Moreover, GAP could significantly decrease the expressions of inflammation and apoptosis genes and proteins (IL-8, IL-10, TNF-α, COX-2, Bax, Bcl-2 and Caspase 3), and increase the expressions of tight-junction proteins and nutrient transport factor genes and proteins (ZO-1, Occludin, Claudin-1, ASCT2 and PePT1). In addition, it was also found that GAP supplementation could significantly increase the diversity of gut microbiota, maintain microbial flora balance and promote piglet growth by significantly increasing the abundance of beneficial bacterium such as Lactobacillus and reducing the abundance of harmful bacterium such as Clostridium_sensu_stricto_1. In conclusion, GAP addition to piglet diets contaminated with DON could significantly promote the health and growth performance of piglets though alleviating DON-induced hazards. This study provided a theoretical basis for the application of GAP to alleviate DON toxicity for animals.


Asunto(s)
Probióticos , Tricotecenos , Porcinos , Animales , Ácido Glicirrínico/farmacología , Intestinos
4.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-34204592

RESUMEN

NADH dehydrogenase (ubiquinone) Fe-S protein 8 (NDUFS8) is a nuclear-encoded core subunit of human mitochondrial complex I. Defects in NDUFS8 are associated with Leigh syndrome and encephalomyopathy. Cell-penetrating peptide derived from the HIV-1 transactivator of transcription protein (TAT) has been successfully applied as a carrier to bring fusion proteins into cells without compromising the biological function of the cargoes. In this study, we developed a TAT-mediated protein transduction system to rescue complex I deficiency caused by NDUFS8 defects. Two fusion proteins (TAT-NDUFS8 and NDUFS8-TAT) were exogenously expressed and purified from Escherichia coli for transduction of human cells. In addition, similar constructs were generated and used in transfection studies for comparison. The results showed that both exogenous TAT-NDUFS8 and NDUFS8-TAT were delivered into mitochondria and correctly processed. Interestingly, the mitochondrial import of TAT-containing NDUFS8 was independent of mitochondrial membrane potential. Treatment with TAT-NDUFS8 not only significantly improved the assembly of complex I in an NDUFS8-deficient cell line, but also partially rescued complex I functions both in the in-gel activity assay and the oxygen consumption assay. Our current findings suggest the considerable potential of applying the TAT-mediated protein transduction system for treatment of complex I deficiency.


Asunto(s)
Complejo I de Transporte de Electrón/deficiencia , Potencial de la Membrana Mitocondrial , Mitocondrias/genética , Mitocondrias/metabolismo , NADH Deshidrogenasa/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo , Secuencia de Aminoácidos , Línea Celular , Supervivencia Celular , Células Cultivadas , Proteínas del Complejo de Cadena de Transporte de Electrón/genética , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , NADH Deshidrogenasa/genética , Transporte de Proteínas , Interferencia de ARN , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética
5.
J Appl Toxicol ; 40(10): 1362-1372, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32324309

RESUMEN

Deoxynivalenol (DON) is a common mycotoxin, which often induces oxidative stress and cytotoxicity in humans and animals. Astilbin (AST), as a natural antioxidant, exhibits multiple pharmacological functions. The aim of this study was to investigate the effects of AST on alleviating DON-induced cytotoxicity in intestinal porcine epithelial cells (IPEC-J2). The results demonstrated that 0.5 µg/mL DON stimulation for 6 hours induced oxidative stress, inflammation and apoptosis in IPEC-J2 cells. AST enhanced the cell viability in a dose- and time-dependent manner. The addition of 20 µg/mL AST significantly increased cell viability, superoxide dismutase and catalase activities, Bcl-2 gene expression and the Bcl-2/Bax ratio (P < .05), and decreased lactate dehydrogenase release, malondialdehyde content and the relative expressions of genes associated with inflammation and apoptosis such as interleukin-6 and -8, tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor-kappaB, Bax and caspase-3 (P < .05). Simultaneously, zonula occludens-1, claudin-1 and PepT1 gene expressions were upregulated and occludin, ASCT2 and GLUT2 gene expressions were downregulated by the addition of AST, compared with the DON group (P < .05). These results indicated that 20 µg/mL AST could ameliorate oxidative stress, inflammation and apoptosis by enhancing antioxidant enzyme activities and intestinal barrier function, and reducing the expressions of inflammation and apoptosis genes, as well as improve the barrier function and nutrient transport and absorption in DON-induced IPEC-J2 cells.


Asunto(s)
Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Flavonoles/metabolismo , Intestinos/efectos de los fármacos , Micotoxinas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Tricotecenos/toxicidad , Animales , Células Cultivadas/efectos de los fármacos , Humanos , Modelos Animales , Porcinos
6.
Ecotoxicol Environ Saf ; 194: 110420, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32151861

RESUMEN

In order to alleviate toxic effects of aflatoxins B1 (AFB1) and zearalenone (ZEA) on broiler production performance and gut microbiota, three kinds of compound probiotics (CP) were selected. The optimal ratios of Bacillus subtilis, Lactobacillus casei and Candida utilis in broiler diets were 7, 5 and 6 log CFU/g for ZEA biodegradation (CP1); 6, 7 and 7 log CFU/g for AFB1 biodegradation (CP2); 7, 6 and 7 log CFU/g for ZEA + AFB1 biodegradation (CP3). A total of 350 1-day-old Ross broilers were randomly divided into 7 groups. Group A was the basal diet, group B-G contained ZEA, AFB1, ZEA + AFB1, ZEA + CP1, AFB1+CP2, ZEA + AFB1+CP3, respectively. The experiment showed that AFB1 or AFB1+ZEA significantly decreased broiler production performance, damaged liver and jejunum, increased mycotoxin residues in broiler body; however, three kinds of compound probiotics additions could alleviate mycotoxin negative effects on the above parameters (p < 0.05). The gut microbiota analysis indicated that AFB1+ZEA increased jejunal microbial richness, but which were decreased to almost the same level as the control group by CP3 addition. CP3 addition significantly increased jejunal Firmicutes and Lactobacillus aviarius abundances. The correlative analysis showed that gut Lactobacillus aviarius abundance was positively correlated with average daily gain (ADG) of broilers (p < 0.05), while AFB1+ZEA addition decreased its relative abundance, indicating that CP3 addition increased broiler growth by increasing Lactobacillus aviarius abundance. AFB1 and ZEA residues in broiler body were negatively correlated with the gut beneficial bacterial abundances (p < 0.01), but positively correlated with the potentially harmful bacterial abundances (p < 0.05), which inferred that CP3 addition could decrease mycotoxin residues through positively regulating gut relative bacterial abundances. In conclusion, compound probiotics could keep gut microbiota stable, degrade mycotoxins, alleviate histological lesions, increase production performance and reduce mycotoxin toxicity for broilers.


Asunto(s)
Aflatoxina B1/toxicidad , Pollos/crecimiento & desarrollo , Microbioma Gastrointestinal/efectos de los fármacos , Probióticos/farmacología , Zearalenona/toxicidad , Alimentación Animal/análisis , Alimentación Animal/microbiología , Animales , Bacillus subtilis/aislamiento & purificación , Pollos/metabolismo , Dieta , Suplementos Dietéticos , Firmicutes/aislamiento & purificación , Distribución Aleatoria
7.
Ecotoxicol Environ Saf ; 205: 111376, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32961488

RESUMEN

Deoxynivalenol (DON) is extensively detected in many kinds of foods and feeds to harm human and animal health. This research aims to investigate the effect of chlorogenic acid (CGA) on alleviating inflammation and apoptosis of swine jejunal epithelial cells (IPEC-J2) triggered by DON. The results demonstrated that cell viability was decreased when DON concentrations increased or incubation time expanded. The pretreatment with CGA (40 µg/mL) for 1 h increased cell viability, decreased lactate dehydrogenase (LDH) release and apoptosis in cells triggered by DON at 0.5 µg/mL for 6 h, compared with the DON alone-treated cells. Moreover, the mRNA abundances of IL-8, IL-6, TNF-α, COX-2, caspase-3, Bax and ASCT2 genes, and protein expressions of COX-2, Bax and ASCT2 were significantly down-regulated; while the mRNA abundances of ZO-1, claudin-1, occludin, PePT1 and GLUT2 genes, and protein expressions of ZO-1, claudin-1 and PePT1 were significantly up-regulated in the CGA + DON group, compared with the DON alone group. This study indicated that CGA pretreatment alleviated cytotoxicity, inflammation and apoptosis in DON-triggered IPEC-J2 cells, and protected intestinal cell integrity from DON damages.


Asunto(s)
Ácido Clorogénico/farmacología , Sustancias Protectoras/farmacología , Tricotecenos/toxicidad , Animales , Apoptosis/efectos de los fármacos , Caspasa 3 , Recuento de Células , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ácido Clorogénico/metabolismo , Células Epiteliales/efectos de los fármacos , Inflamación/metabolismo , Intestinos/efectos de los fármacos , Ocludina/genética , Porcinos
8.
J Cell Biochem ; 120(5): 7167-7173, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30552707

RESUMEN

OBJECTIVE: To evaluate the predictive efficacy and prognostic value of rs7435335 located in the UGT2B7 gene as a genetic marker in breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: A total of 190 patients with breast cancer treated with NAC were enrolled to detect the rs7435335 SNP by sequenom. Miller-Payne grades were used to evaluate the treatment efficacy. The association between rs7435335 and chemotherapy efficacy and prognosis was analyzed. RESULTS: Altogether, 42 cases (22.1%) achieved pathologic complete response (pCR). The results of the univariate analysis showed that rs7435335 had no statistically significant difference with pCR and Miller-Payne grades (P > 0.05). When grouping was done in accordance with the ER status, the pCR and Miller-Payne grades significantly associated with rs7435335 ( P < 0.05) only in the ER-negative group. Multivariate logistic regression analysis suggested that rs7435335 in the ER-negative group was an independent predictor of pCR ( P < 0.05). Survival analysis showed that the disease-free survival (DFS) time in patients with GA genotype was longer than that of GG genotype, and rs7435335 predicted the DFS in the ER-negative group. CONCLUSION: The UGT2B7 rs7435335 is associated with the NAC efficacy and prognosis. Patients with GA genotype have better efficacy and prognosis. Rs7435335 was found to be a possible gene marker for pCR and prognosis in ER-negative patients who received NAC.

9.
Radiology ; 291(3): 677-686, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30912722

RESUMEN

Background Nasopharyngeal carcinoma (NPC) may be cured with radiation therapy. Tumor proximity to critical structures demands accuracy in tumor delineation to avoid toxicities from radiation therapy; however, tumor target contouring for head and neck radiation therapy is labor intensive and highly variable among radiation oncologists. Purpose To construct and validate an artificial intelligence (AI) contouring tool to automate primary gross tumor volume (GTV) contouring in patients with NPC. Materials and Methods In this retrospective study, MRI data sets covering the nasopharynx from 1021 patients (median age, 47 years; 751 male, 270 female) with NPC between September 2016 and September 2017 were collected and divided into training, validation, and testing cohorts of 715, 103, and 203 patients, respectively. GTV contours were delineated for 1021 patients and were defined by consensus of two experts. A three-dimensional convolutional neural network was applied to 818 training and validation MRI data sets to construct the AI tool, which was tested in 203 independent MRI data sets. Next, the AI tool was compared against eight qualified radiation oncologists in a multicenter evaluation by using a random sample of 20 test MRI examinations. The Wilcoxon matched-pairs signed rank test was used to compare the difference of Dice similarity coefficient (DSC) of pre- versus post-AI assistance. Results The AI-generated contours demonstrated a high level of accuracy when compared with ground truth contours at testing in 203 patients (DSC, 0.79; 2.0-mm difference in average surface distance). In multicenter evaluation, AI assistance improved contouring accuracy (five of eight oncologists had a higher median DSC after AI assistance; average median DSC, 0.74 vs 0.78; P < .001), reduced intra- and interobserver variation (by 36.4% and 54.5%, respectively), and reduced contouring time (by 39.4%). Conclusion The AI contouring tool improved primary gross tumor contouring accuracy of nasopharyngeal carcinoma, which could have a positive impact on tumor control and patient survival. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Chang in this issue.


Asunto(s)
Aprendizaje Profundo , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Adolescente , Adulto , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nasofaringe/diagnóstico por imagen , Estudios Retrospectivos , Adulto Joven
10.
Sensors (Basel) ; 19(11)2019 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-31167389

RESUMEN

Underwater sensor networks ( UWSNs ) based barrier coverage is increasingly important for intrusion detection due to the scarcity of underwater sensor resource. To improve UWSNs' detection performance and prolong their lifetime, an efficient barrier coverage strategy is very important. In this paper, a novel concept: hierarchy graph is proposed. Hierarchy graph can make the network's topology more clarity. In accordance with the hierarchy graph, 1-barrier coverage algorithm and k-barrier coverage algorithm are presented to construct the barrier with less sensors for higher energy efficiency. Both analytical and simulation studies demonstrate that the proposed algorithms can provide high detection probability and long lifetime for UWSNs.

11.
Arch Anim Nutr ; 71(2): 120-133, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28201936

RESUMEN

This study was carried out to investigate the effects of orally administrated Lactobacillus casei and Enterococcus faecalis on performance, immune function and gut microbiota of suckling piglets. Neonatal piglets (n = 120) were randomly assigned to 4 groups, with 30 suckling piglets in each group. The piglets were from 15 litters, one male and one female piglet were selected for each group in each litter. The Control group was administrated with normal saline, the other groups with L. casei or E. faecalis or a combination of L. casei and E. faecalis at a ratio of 3:1. Each piglet was orally administrated with 1, 2, 3 and 4 ml probiotics or normal saline at the age of 1, 7, 14 and 21 d, respectively. The piglets were weaned at the age of 21 d. The results showed that compared with the Control group, the average daily gain of piglets administrated with probiotics was significantly increased, and the diarrhoea rate and mortality were significantly decreased (p < 0.05). After supplementation of the combined probiotics, the protease activity in stomach, duodenum and colon was increased and in all supplemented groups, the immunoglobulin A concentration in plasma was significantly higher (p < 0.05). The combined probiotics significantly increased villus length and the expression level of transforming growth factor-ß in the jejunum (p < 0.05) but decreased the expression level of the jejunal tumour necrosis factor-α (p < 0.05). In addition, probiotics could regulate gut microbiota and increase microbial similarity coefficients for keeping piglet gut microbiota stable.


Asunto(s)
Enterococcus faecalis/inmunología , Microbioma Gastrointestinal , Lacticaseibacillus casei/inmunología , Probióticos , Sus scrofa/crecimiento & desarrollo , Sus scrofa/microbiología , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Distribución Aleatoria
12.
J Asian Nat Prod Res ; 18(11): 1079-90, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27314303

RESUMEN

5,6-Dihydroxy-3,7,4'-trimethoxyflavonol (AH5), 5,6,3'-trihydroxy-3,7,4'-trimethoxyflavonol (AH22), artemetin, and oroxylin A are four flavonoids with the same 2-phenyl-chromone skeleton isolated from the Chinese herb Aster himalaicus. The aim of this study was to evaluate the structure-activity relationship of these four analogs and the mediation of AH5 cytotoxicity via G2/M arrest and apoptosis in human hepatocellular carcinoma (HCC) cells. 3-(4,5-Dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated AH5 showed the better potency to inhibit proliferation in human HCC cells, which suggested hydroxyl binding to C6 is necessary to anticancer properties, whereas binding to C3' attenuated the activities and increased toxicity in tested cells. Flow cytometry analysis revealed that AH5-induced G2/M arrest and significantly apoptosis in these cell lines. HepG-2 cells were used to further evaluate the antitumor effects and mechanisms of AH5. AH5-induced apoptosis was further confirmed by 4',6-diamidino-2-phenylindole (DAPI) staining and the increased ratio of Bax/Bcl-2. Moreover, AH5 induced the release of cytochrome C and the activation of caspase-9 and caspase-3, thus suggesting mitochondria activation might be involved. Western blot showed that AH5 induced the phosphorylation of Cdc2 and decreased the level of Cyclin B1. These results demonstrated that AH5 could be a proapoptotic leading compound for developing novel anticancer drugs.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Flavonoles/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Ciclina B1/metabolismo , Citocromos c/metabolismo , Diseño de Fármacos , Flavonoides/química , Flavonoles/química , Células Hep G2/efectos de los fármacos , Humanos , Indoles/química , Neoplasias Hepáticas/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Estructura Molecular , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Relación Estructura-Actividad
13.
Int J Gynecol Cancer ; 25(8): 1353-63, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26332389

RESUMEN

OBJECTIVE: The aim of this study is to investigate the clinicopathologic significance and potential role of metastasis-associated in colon cancer-1 (MACC1) in the progression of cervical cancer. METHODS: MACC1 expression was examined in cervical cancer cell lines, 6 matched cervical cancer tissues, and adjacent noncancerous tissues using Western blotting and real-time reverse transcriptase polymerase chain reaction. MACC1 protein expression and localization were determined in 181 paraffin-embedded archived cervical cancer samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. The effects of MACC1 on cell migration, invasion, and angiogenesis were examined using migration assay, wound healing assay, 3-dimensional morphogenesis assay, and chicken chorioallantoic membrane assay. Western blotting was performed to examine the impact of MACC1 on the Akt and nuclear factor κB signaling pathways. RESULTS: Both protein and messenger RNA levels of MACC1 was up-regulated in cervical cancer cell lines and cervical cancer tissues, as compared with normal tissues. High MACC1 expression was detected in 96 (53%) of 181 of the cervical cancer tissues. In addition, high MACC1 expression correlated significantly with aggressiveness of cervical cancer, including International Federation of Gynecology and Obstetric stage (P = 0.001), pelvic lymph node metastasis (P = 0.004), recurrence (P = 0.037), and poor survival (P = 0.001). Moreover, enforced expression of MACC1 in cervical cancer cell lines significantly enhanced cell migration, invasion, and angiogenesis. Conversely, knockdown of MACC1 caused an inhibition of cell migration, invasion, and angiogenesis. Up-regulation of MACC1 increased, but knockdown of MACC1 decreased the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9. Furthermore, enforced expression of MACC1 could enhance, but knockdown of MACC1 could reduce AKT and nuclear factor κB pathway activity. CONCLUSIONS: Our findings suggest that MACC1 protein, as a valuable marker of cervical cancer prognosis, plays an important role in the progression of human cervical cancer cells.


Asunto(s)
Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Regulación Neoplásica de la Expresión Génica , Neovascularización Patológica , Factores de Transcripción/fisiología , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/genética , Biomarcadores de Tumor/fisiología , Western Blotting , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/genética , Movimiento Celular , Proliferación Celular , Membrana Corioalantoides/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Tasa de Supervivencia , Transactivadores , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/irrigación sanguínea , Neoplasias del Cuello Uterino/genética
14.
Ecotoxicol Environ Saf ; 114: 312-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25037070

RESUMEN

The aim of this study was to evaluate antioxidative responses in roots, stem and leaves of four alfalfa cultivars to different concentrations of zinc (Zn) (0, 300, 600 and 900 µM) for 23 days. Among the four cultivars, Aohan displayed the highest Zn concentrations in tissues and the largest Zn amount in aerial parts. Zn stress induced the production of H2O2 and increased the content of free proline and activities of antioxidative enzymes in roots, stem and leaves of Aohan. Based on the above results, we concluded that Aohan is superior to other three cultivars for Zn phyto-remediation, which indicated that Aohan is a novel Zn accumulator and able to tolerate Zn-induced toxicity by activating the antioxidative defense system.


Asunto(s)
Antioxidantes/metabolismo , Medicago sativa/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Zinc/toxicidad , Peróxido de Hidrógeno/metabolismo , Medicago sativa/enzimología , Medicago sativa/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Prolina/metabolismo
15.
J Hepatol ; 60(6): 1127-34, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24583247

RESUMEN

BACKGROUND & AIMS: We compared the mortality and treatment response between lamivudine (LAM) and entecavir (ETV) in chronic hepatitis B (CHB) patients with severe acute exacerbation and hepatic decompensation. METHODS: From 2003 to 2010 (the LAM group) and 2008 to 2010 (the ETV group), 215 and 107 consecutive CHB naïve patients with severe acute exacerbation and hepatic decompensation treated with LAM and ETV respectively, were recruited. RESULTS: At baseline, the LAM group had higher AST levels and end-stage liver disease (MELD) scores, and lower albumin levels than the ETV group. Univariate analysis showed that the LAM group had a higher rate of overall (p=0.02) and liver-related mortality (p=0.052) at week 24 than the ETV group, including in patients with acute-on-chronic liver failure. Multivariate analysis showed that MELD scores, ascites, and hepatic encephalopathy were independent factors for overall and liver-related mortality at week 24. ETV or LAM treatment was not an independent factor for mortality in all patients or patients with acute-on-chronic liver failure. The best cut-off value of MELD scores were 24 for 24-week liver-related mortality. The ETV group achieved better virological response (HBV DNA <300 copies/ml) than the LAM group at week 24 (p=0.043) and 48 (p=0.007). The T1753C/A mutation was also an independent predictor associated with overall and liver-related mortality at week 24. CONCLUSIONS: The choice between ETV and LAM was not an independent factor for mortality in CHB patients with acute exacerbation and hepatic decompensation. Patients with ascites, hepatic encephalopathy, and MELD scores ⩾24 were associated with poor outcome and should be considered for liver transplantation.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Enfermedad Hepática en Estado Terminal/tratamiento farmacológico , Guanina/análogos & derivados , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/administración & dosificación , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adulto , Antivirales/administración & dosificación , Farmacorresistencia Viral/genética , Enfermedad Hepática en Estado Terminal/mortalidad , Femenino , Estudios de Seguimiento , Genotipo , Guanina/administración & dosificación , Hepatitis B Crónica/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo de Longitud del Fragmento de Restricción , Valor Predictivo de las Pruebas , Pronóstico , Índice de Severidad de la Enfermedad
16.
Acta Pharmacol Sin ; 35(10): 1311-22, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25176399

RESUMEN

AIM: Telekin, isolated from the Chinese herb Carpesium divaricatum, has shown anti-proliferation effects against various cancer cells, including hepatocellular carcinoma cells. In this study, we investigated the anti-proliferation mechanisms of telekin in human hepatocellular carcinoma HepG2 cells in vitro. METHODS: HepG2 cells were treated with telekin. Cell viability was evaluated using MTT assay. Flow cytometry was used to measure cell cycle profiles, ROS level and apoptosis. The protein expression levels were analyzed with Western blotting. RESULTS: Telekin (3.75-30 µmol/L) dose-dependently inhibited the viability of HepG2 cells and induced l apoptosis. Furthermore, the treatment induced cell cycle arrest at G2/M phase, accompanied by significantly increased the phosphorylation of Cdc25A and Cdc2, and decreased Cyclin B1 level. Moreover, the treatment significantly stimulated ROS production, and increased the phosphorylation of p38 and MAPKAPK-2 in the cells. Pretreatment with the antioxidant NAC (2.5, 5, and 10 mmol/L), or the p38 MAPK inhibitor SB203580 (2.5 and 5 µmol/L) dose-dependently attenuated these telekin-induced effects in the cells. CONCLUSION: Telekin suppresses hepatocellular carcinoma cells in vitro by inducing G2/M phase arrest via activating the p38 MAPK pathway.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Sesquiterpenos de Eudesmano/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Apoptosis/efectos de los fármacos , Proteína Quinasa CDC2 , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciclina B1/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Células Hep G2 , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fosfatasas cdc25/metabolismo
17.
Prep Biochem Biotechnol ; 44(8): 795-804, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24279837

RESUMEN

In order to express swine hepcidin gene in Pichia pastoris, a DNA fragment coding hepcidin gene was synthesized with adaptation to yeast codon usage of highly expressed genes. A Kex2 signal cleavage site was fused in the 5' end of the DNA fragment for getting a peptide with the same N-end as native hepcidin. The 96-bp DNA fragment was ligated into the expression plasmid of pGAPZaA to construct pGAPZaA-hepcidin vector, which was transferred into P. pastoris (X33) to express hepcidin gene for extracellular secretion of protein at 86 µg/mL. A band of 2.76 kD molecular mass was detected by Tricine sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) analysis. Through antibacterial assay, the expressed hepcidin displayed obvious antibacterial activity. The minimal inhibitory concentration (MIC) was 5.38 and 2.69 µg/mL for Staphylococcus aureus and Bacillus subtilis prolification inhibitions, respectively.


Asunto(s)
Clonación Molecular/métodos , ADN/síntesis química , ADN/genética , Hepcidinas/genética , Pichia/genética , Porcinos/genética , Animales , Antibacterianos/metabolismo , Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Secuencia de Bases , Codón/genética , Vectores Genéticos/genética , Hepcidinas/farmacología , Humanos , Plásmidos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos
18.
Front Nutr ; 11: 1370975, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606017

RESUMEN

With the development of animal husbandry, the shortage of animal feedstuffs has become serious. Dietary fiber plays a crucial role in regulating animal health and production performance. The aim of this study was to investigate the effects of three kinds of corn straw-saccharification fibers (CSSF) such as high-fiber and low-saccharification (HFLS), medium-fiber and medium-saccharification (MFMS), low-fiber and high-saccharification (LFHS) CSSF on the reproductive performance of sows. Thirty-two primiparous Yorkshire sows were randomly assigned to 4 groups, 8 sows for each group. Group A was the basal diet as the control group; groups B - D were added with 6% HFLSCSSF, 6% MFMSCSSF and 6% LFHSCSSF to replace some parts of corn meal and wheat bran in the basal diet, respectively. The experimental period was from day 85 of gestation to the end of lactation (day 25 post-farrowing). The results showed that 6% LFHSCSSF addition significantly increased number of total born (alive) piglets, litter weight at birth (p < 0.05), whereas three kinds of CSSF significantly decreased backfat thickness of sows during gestation (p < 0.001), compared with the control group. Furthermore, CSSF improved the digestibility of crude protein, ether extract and fiber for sows. In addition, the levels of total cholesterol, total triglycerides, and high-density lipoprotein cholesterol in serum of sows were decreased by different kinds of CSSF. Further analysis revealed that CSSF regulated lipid metabolism through adjusting the serum metabolites such as 4-pyridoxic acid, phosphatidyl cholines and L-tyrosine. In summary, CSSF addition to the diets of sows during late gestation and lactation regulated lipid metabolism and improved reproductive performance of sows. This study provided a theoretical basis for the application of corn straw in sow diets.

19.
Bioorg Med Chem Lett ; 23(4): 1008-12, 2013 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-23312473

RESUMEN

A series of novel berberine triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All target compounds and their precursors were screened for antimicrobial activities in vitro against four Gram-positive bacteria, four Gram-negative bacteria and two fungal strains. Bioactive assay indicated that most of the prepared compounds exhibited good antibacterial and antifungal activities with low MIC values ranging from 2 to 64 µg/mL, which were comparable to or even better than the reference drugs Berberine, Chloromycin, Norfloxacin and Fluconazole. The competitive interactions between compound 5a and metal ions to Human Serum Albumin (HSA) revealed that the participation of Mg(2+) and Fe(3+) ions in compound 5a-HSA association could result in the concentration increase of free compound 5a, shorten the storage time and half-life of compound 5a in the blood, thus improving its antimicrobial efficacy.


Asunto(s)
Antibacterianos/síntesis química , Antifúngicos/síntesis química , Berberina/síntesis química , Metales/química , Albúmina Sérica/metabolismo , Triazoles/síntesis química , Triazoles/farmacología , Antibacterianos/sangre , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/sangre , Antifúngicos/química , Antifúngicos/farmacología , Berberina/sangre , Berberina/química , Unión Competitiva , Cationes/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Triazoles/sangre , Triazoles/química
20.
Bioorg Med Chem ; 21(14): 4158-69, 2013 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-23743440

RESUMEN

A series of novel hybrids of metronidazole and berberine as new type of antimicrobial agents were synthesized and characterized by (1)H NMR, (13)C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that most of the prepared compounds exhibited effective antibacterial and antifungal activities and some showed comparable or superior potency against Methicillin-resistant Staphylococcus aureus to reference drugs Norfloxacin, Chloromycin and Berberine. The transportation behavior of human serum albumin (HSA) to the highly active compound 5g was evaluated and revealed that the association of imidazole derivative 5g with HSA was spontaneous and the electrostatic interactions played important roles in the transportation of HSA to 5g. The calculated parameters indicated that compound 5g could be effectively stored and carried by HSA.


Asunto(s)
Antiinfecciosos/síntesis química , Bacterias/efectos de los fármacos , Berberina/síntesis química , Berberina/farmacología , Hongos/efectos de los fármacos , Metronidazol/síntesis química , Metronidazol/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Berberina/química , Sitios de Unión , Transporte Biológico , Humanos , Espectroscopía de Resonancia Magnética , Metronidazol/química , Estructura Molecular , Albúmina Sérica/farmacocinética , Termodinámica
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