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This study examines the impact of Notoginsenoside R1 (NGR1), a compound from Panax notoginseng, on the maturation of porcine oocytes and their embryonic development, focusing on its effects on antioxidant levels and mitochondrial function. This study demonstrates that supplementing in vitro maturation (IVM) medium with NGR1 significantly enhances several biochemical parameters. These include elevated levels of glutathione (GSH), nuclear factor erythrocyte 2-related factor 2 (NRF2) and mRNA expression of catalase (CAT) and GPX. Concurrently, we observed a decrease in reactive oxygen species (ROS) levels and an increase in JC-1 immunofluorescence, mitochondrial distribution, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear NRF2 mRNA levels. Additionally, there was an increase in ATP production and lipid droplets (LDs) immunofluorescence. These biochemical improvements correlate with enhanced embryonic outcomes, including a higher blastocyst rate, increased total cell count, enhanced proliferative capacity and elevated octamer-binding transcription factor 4 (Oct4) and superoxide dismutase 2 (Sod2) gene expression. Furthermore, NGR1 supplementation resulted in decreased apoptosis, reduced caspase 3 (Cas3) and BCL2-Associated X (Bax) mRNA levels and decreased glucose-regulated protein 78 kD (GRP78) immunofluorescence in porcine oocytes undergoing in vitro maturation. These findings suggest that NGR1 plays a crucial role in promoting porcine oocyte maturation and subsequent embryonic development by providing antioxidant levels and mitochondrial protection.
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Antioxidantes , Desarrollo Embrionario , Ginsenósidos , Técnicas de Maduración In Vitro de los Oocitos , Mitocondrias , Oocitos , Animales , Antioxidantes/farmacología , Ginsenósidos/farmacología , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Mitocondrias/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Oocitos/efectos de los fármacos , Femenino , Porcinos , Especies Reactivas de Oxígeno/metabolismo , Técnicas de Cultivo de Embriones/veterinariaRESUMEN
Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality, and significant heterogeneity among patients. In this study, we aimed to explore the role and mechanism of CLK2 in CRC, a kinase that phosphorylates SR proteins involved in splicing. Based on the analysis from The Cancer Genome Atlas (TCGA) dataset and tissue microarray, we found that CLK2 was upregulated in CRC tissues and associated with a higher tumor stage and poorer overall survival. Consistent with the bioinformatics analysis, the functional experiments validated that CLK2 acted as a tumor-promoting factor in CRC progression. CLK2 knockdown suppressed aggressive cell proliferation, migration, and invasion in vitro, as well as restrained tumor growth in vivo. In terms of mechanism, we found that the Wnt/ß-catenin signaling pathway was responsible for the CLK2-induced CRC progression, based on the results of pathway enrichment analysis and subsequent experimental validation. Thus, our study, for the first time, identified the role of CLK2 in CRC development and provided a compelling biomarker for targeted therapy in CRC treatment.
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Neoplasias Colorrectales , Proteínas Serina-Treonina Quinasas , Proteínas Tirosina Quinasas , Vía de Señalización Wnt , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Centers for Disease Control and Prevention, U.S. , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Tirosina Quinasas/genética , Estados Unidos , Vía de Señalización Wnt/genética , beta Catenina/metabolismoRESUMEN
To examine the regulatory effect of histone acetylation on memory related molecules, 34 healthy male SD rats were randomly divided into control and basolateral amygdala (BLA) intracranial positioning operation groups. In the process of conditioned place preference (CPP) training, Trichostafin A (TSA) was administrated by the route of BLA and morphine was injected into enterocoelia with dimethyl sulfoxide or saline as control. Expression levels of H3K14 acetylation and brain-derived neurotrophic factor (BDNF) in BLA were evaluated by Western blotting.The results showed that CPP could be established by intraperitoneal injection of morphine. Compared with control groups, a stronger place preference was established and expression of H3K14 acetylation and BDNF was significantly increased in the group treated with TSA and morphine. In addition, there was a synergistic effect between morphine and TSA. Our results suggested that the level of histone acetylation in BLA is associated with the formation of morphine memory in rats. Inhibition of the activity of histone deacetylases in BLA can promote the formation of cue-associated memory induced by morphine and the involvement of BDNF in BLA maybe was regulated by histone acetylation.
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Complejo Nuclear Basolateral/metabolismo , Histonas/metabolismo , Dependencia de Morfina/metabolismo , Morfina/metabolismo , Acetilación , Secuencias de Aminoácidos , Animales , Histonas/química , Humanos , Masculino , Memoria , Dependencia de Morfina/genética , Dependencia de Morfina/psicología , Ratas , Ratas Sprague-DawleyRESUMEN
To determine the optimum process conditions for dry granulating technique of Qibai Pingfei granule, granule excipient type, rolling wheel speed and pressure and feeding speed were studied. Taking shaping rate at a time, moisture absorption and dissolubility as index, the type and amount of granule excipient were determined. In addition, taking shaping rate at a time as index, parameters of rolling wheel speed and pressure and feeding speed were researched through single factor test and response surface methodology. The optimum parameters were as follows: lactose as excipient, dry extract powder to excipient at 1:2, rolling wheel speed and pressure at 10.9 Hz and 6.4 MPa and feeding speed at 7.2 Hz. After validation of three batches pilot-scale production, the optimum processing parameters for dry granulating technique of Qibai Pingfei granule is reasonable and feasible, which can provide reliable basis for production.
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Medicamentos Herbarios Chinos , Tecnología Farmacéutica/métodos , PolvosRESUMEN
BACKGROUND: Gastric cancer (GC) is one of the most common cancers worldwide. Morbidity and mortality have increased in recent years, making it an urgent issue to address. Laparoscopic radical surgery (LRS) is a crucial method for treating patients with GC; However, its influence on tumor markers is still under investigation. AIM: To determine the effects of LRS on patients with GC and their serum tumor markers. METHODS: The data of 194 patients treated at Chongqing University Cancer Hospital between January 2018 and January 2019 were retrospectively analyzed. Patients who underwent traditional open surgery and LRS were assigned to the control (n = 90) and observation groups (n = 104), respectively. Independent sample t-tests and χ2 tests were used to compare the two groups based on clinical efficacy, changes in tumor marker levels after treatment, clinical data, and the incidence of postoperative complications. To investigate the association between tumor marker levels and clinical efficacy in patients with GC, three-year recurrence rates in the two groups were compared. RESULTS: Patients in the observation group had a shorter duration of operation, less intraoperative blood loss, an earlier postoperative eating time, and a shorter hospital stay than those in the control group (P < 0.05). No significant difference was observed between the two groups regarding the number of lymph node dissections (P > 0.05). After treatment, the overall response rate in the control group was significantly lower than that in the observation group (P = 0.001). Furthermore, after treatment, the levels of carbohydrate antigen 19-9, cancer antigen 72-4, carcinoembryonic antigen, and cancer antigen 125 decreased significantly. The observation group also exhibited a significantly lower incidence rate of postoperative complications compared to the control group (P < 0.001). Additionally, the two groups did not significantly differ in terms of three-year survival and recurrence rates (P > 0.05). CONCLUSION: LRS effectively treats early gastric cancer by reducing intraoperative bleeding, length of hospital stays, and postoperative complications. It also significantly lowers tumor marker levels, thus improving the short-term prognosis of the disease.
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We employ the fluctuation-exchange approximation to study the relation of superconducting pairing symmetries and density-wave fluctuations based on the extended triangular Hubbard model upon electron doping and interactions, with an possible application to the layered metal dichalcogenide SnSe2. For the case where the interactions between electrons contain only the on-site Hubbard term, the superconducting pairings are mainly mediated by spin fluctuations, and the spin-singlet pairing with thed-wave symmetry robustly dominates in the low and moderate doping levels, and ad-wave to extendeds-wave transition is observed as the electron doping reachesn = 1. When the near-neighbor site Coulomb interactions are also included, the charge fluctuations are enhanced, and the spin-triplet pairings with thep-wave andf-wave symmetries can be realized in the high and low doping levels, respectively.
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Objective: This study evaluated the effect of maximal oxygen pulse (O 2P max) on patients with chronic obstructive pulmonary disease (COPD) and confirmed the predictive effect on acute exacerbations of COPD (AECOPD). Methods: This retrospective study included 91 participants who underwent cardiopulmonary exercise testing (CPET), lung function testing, a dyspnea scale assessment, and a 3-year follow-up. The participants were divided into two groups according to the O 2P max value. Exercise capacity, ventilatory conditions, gas exchange efficiency, and dyspnea symptoms were compared, and the correlations between O 2P max and these indices were evaluated. The ability of O 2P max to predict AECOPD was examined. Results: Exercise capacity, ventilatory conditions, and gas exchange efficiency were lower, and dyspnea symptom scores were higher in the impaired O 2P max group ( P < 0.05). O 2P max was positively correlated with forced vital capacity (FVC)%, forced expiratory volume in 1 sec (FEV 1)%, FEV 1/FVC%, anaerobic threshold (AT), work rate (WR)%, aximal oxygen uptake (VÌO 2max)%, VÌO 2/kg max, VÌO 2/kg max%, WR AT, WR max, VÌO 2AT, VÌO 2max, and VÌ Emax, and was negatively correlated with EqCO 2AT, and EqCO 2max ( P < 0.05). Most importantly, O 2P max could be used to predict AECOPD, and the best cut-off value was 89.5% (area under the curve, 0.739; 95% CI, 0.609-0.869). Conclusion: O 2P max reflected exercise capacity, ventilation capacity, gas exchange capacity, and dyspnea symptoms in patients with COPD and may be an independent predictor of AECOPD.
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Tolerancia al Ejercicio , Enfermedad Pulmonar Obstructiva Crónica , Disnea/etiología , Humanos , Oxígeno , Consumo de Oxígeno , Estudios RetrospectivosRESUMEN
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by progressive memory loss and cognitive dysfunction. Long non-coding RNAs (lncRNAs) have been shown to be among the most promising biomarkers and therapeutic targets of AD. Here, we aimed to investigate whether lncRNA BACE1-AS plays a role in the potential mechanisms of AD. The expression of BACE1-AS, miR-214-3p and ATG5 mRNA was detected using qRT-PCR. The expression of the LC3, P62, ATG5, Bcl-2, p-Tau and cleaved-caspase 3 proteins was examined using western blot analysis. Cell apoptosis, cytotoxicity and ROS levels were estimated using flow cytometry, an LDH kit and a DCFH-DA assay, respectively. The interaction between BACE1-AS or ATG5 and miR-214-3p was validated using a dual-luciferase reporter assay. HE staining and a TUNEL assay were employed to evaluate hippocampal neuronal injury. The BACE1-AS level was found to be upregulated in serum samples of AD patients, brain tissues of AD transgenic (Tg) mice and Aß1-42-treated SH-SY5Y cells. Autophagy activity was increased in both Tg mice and Aß1-42-treated cells. BACE1-AS knockdown alleviated Aß1-42-induced cell injury. Rapamycin abolished the protective effects of sh BACE1-AS against Aß1-42 induced cell injury. BACE1-AS indirectly regulated ATG5 expression by binding miR-214-3p. The miR-214-3p inhibitor reversed the protective effects of sh BACE1-AS and sh ATG5 against Aß1-42-induced cell injury. Knockdown of BACE1-AS alleviated neuronal injury by repressing autophagy in vivo. Our findings demonstrate that silencing of BACE1-AS alleviated neuronal injury by regulating autophagy through the miR-214-3p/ATG5 signalling axis in AD.
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Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , MicroARNs , Enfermedades Neurodegenerativas , ARN Largo no Codificante , Enfermedad de Alzheimer/genética , Animales , Ácido Aspártico Endopeptidasas/genética , Autofagia , Proteína 5 Relacionada con la Autofagia/genética , Humanos , Ratones , MicroARNs/genética , ARN Largo no Codificante/genéticaRESUMEN
Various biogeochemical processes complicate carbon dioxide (CO2) behaviour in coastal oceans. Through eight summer surveys, detailed variations in CO2 mechanisms in the urbanized Jiaozhou Bay, China, were analysed. During the rainless period, respiration and dissolved inorganic carbon input from treated wastewater made the northeastern region a strong CO2 source, while the western region with cleaner seawater was a weak source because calcium carbonate (CaCO3) precipitation exceeded primary production. Rainfall events with different intensities and locations caused significantly different effects. When rainfall occurred over the sea, enhanced primary production caused a CO2 sink; when rainfall induced little terrestrial pollutant input, CaCO3 precipitation exceeded net primary production, leading to a CO2 source. When heavy rain caused bulk runoff, the northeastern region was a strong CO2 source because rivers flowing through downtown regions inputted considerable organic matter, while in the western region, runoff through suburbs and wetlands led to a strong sink.
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Dióxido de Carbono/análisis , Agua de Mar/análisis , Bahías , Carbonato de Calcio , Carbono/análisis , Secuestro de Carbono , China , Clorofila , Monitoreo del Ambiente , Concentración de Iones de Hidrógeno , Océanos y Mares , Lluvia , Ríos , Salinidad , Estaciones del Año , Temperatura , Urbanización , Aguas Residuales/análisis , HumedalesRESUMEN
With rapid development of global wastewater treatment plants (WWTPs), acidification and enhanced CO2 release in receiving waters caused by high-CO2 treated wastewater input have raised concerns. Insights into the variations in dissolved inorganic carbon (DIC) species in treated wastewater contribute to understanding the mechanisms of the acidification process. Here, we investigated three large-scale municipal WWTPs that discharged into the coast of Qingdao, China, for variations in effluent DIC species and their control mechanisms. The results showed that the effluent DIC concentrations, with a range of 2554-5718 µmol/L, significantly exceeded the concentration in seawater and mainly increased from winter to spring and decreased from summer to autumn. The effluent DIC and its δ13CDIC showed a good negative correlation. The ratios of effluent DIC to total alkalinity (DIC/TAlk) ranged from 1.00 to 1.24, and the proportions of CO2 in DIC ranged from 0.9 to 19.7%; both sets of values significantly exceeded those in seawater. The proportions of CO32- in DIC were only ~ 0.4%. These features determined that the CO2 concentrations in effluents fluctuated from 3 to 80 times the concentration in seawater, whereas the CO32- concentrations were less than 1/15 of those in seawater. Organic matter degradation and nitrogen removal processes made important contributions to the high effluent CO2 concentrations. The increase in solubility induced by decreased temperature may be the main cause for the higher effluent CO2 concentrations during winter as well as spring months with low effluent temperatures. Correspondingly, the effluent pH values were significantly lower than the seawater pH values and showed a good negative logarithmic correlation with the DIC/TAlk values, reflecting the control of DIC species on the pH values in treated wastewater. Variations in DIC species in treated wastewater can cause changes in the affected region and the degree of the induced acidification in receiving waters.
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Carbono/análisis , Carbono/química , Agua de Mar/química , Eliminación de Residuos Líquidos/métodos , Dióxido de Carbono/análisis , Dióxido de Carbono/química , Carbonatos/análisis , Carbonatos/química , China , Concentración de Iones de Hidrógeno , Nitrógeno/química , Estaciones del Año , Agua de Mar/análisis , Temperatura , Aguas Residuales/análisis , Aguas Residuales/químicaRESUMEN
In a previous study, the suppressor of IKBKE 1 expression level was confirmed to be higher in vincristine (VCR)-resistant HCT-8 (HCT-8/V) colon cancer cells than in non-VCR-resistant HCT-8 cells. In the current study, IKBKE 1 expression in VCR-resistant colon cancer cells was investigated further. HCT-8 and HCT-8/V human colon cancer cells were used, and polymerase chain reaction (PCR) primers were designed to amplify the IKBKE 1 gene. Fluorescence reverse transcription-quantitative PCR (RT-qPCR) was performed to detect differences in IKBKE 1 expression between sensitive and drug-resistant colon cancer cell lines. Western blotting was performed to further observe IKBKE 1 expression. Based on the RT-qPCR and western blot results, IKBKE 1 expression was observed to be markedly higher in the HCT-8/V cells, and this difference was significant (P<0.05). Thus, IKBKE 1 expression was identified to be associated with the resistance of colon cancer cells to VCR.
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The functions of T helper 17 (Th17) and regulatory T (Treg) cells are tightly orchestrated through independent differentiation pathways that are involved in the secretion of pro- and anti-inflammatory cytokines induced by high-salt dietary. However, the role of imbalanced Th17/Treg ratio implicated in inflammation and target organ damage remains elusive. Here, by flow cytometry analysis, we demonstrated that switching to a high-salt diet resulted in decreased Th17 cells and reciprocally increased Treg cells, leading to a decreased Th17/Treg ratio. Meanwhile, Th17-related pathway was down-regulated after one day of high salt loading, with the increase in high salt loading as shown by microarray and RT-PCR. Subsequently, blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) observed hypoxia in the renal medulla (increased R2(*) signal) during high-salt loading, which was regressed to its baseline level in a step-down fashion during low-salt feeding. The flow-mediated vasodilatation (FMD) of the branchial artery was significantly higher on the first day of high salt loading. Collectively, these observations indicate that a short-term increase in dietary salt intake could induce reciprocal switches in Th17/Treg ratio and related cytokines, which might be the underlying cellular mechanism of high-salt dietary induced end organ inflammation and potential atherosclerotic risk.
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Inflamación/etiología , Cloruro de Sodio Dietético/efectos adversos , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Inmunidad Adaptativa , Aterosclerosis/etiología , Aterosclerosis/inmunología , Subgrupos de Linfocitos B/efectos de los fármacos , Subgrupos de Linfocitos B/inmunología , Presión Sanguínea/efectos de los fármacos , Arteria Braquial/efectos de los fármacos , Arteria Braquial/fisiología , Hipoxia de la Célula/efectos de los fármacos , Citocinas/metabolismo , Diuresis/efectos de los fármacos , Ontología de Genes , Humanos , Inflamación/genética , Inflamación/inmunología , Médula Renal/irrigación sanguínea , Médula Renal/inmunología , Médula Renal/patología , Imagen por Resonancia Magnética , Masculino , Especificidad de Órganos , Cloruro de Sodio Dietético/farmacología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Transcriptoma , Vasodilatación/efectos de los fármacosRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of short hairpin RNA (shRNA) and XAV939, a specific inhibitor for β-catenin, on growth and apoptosis of mantle cell lymphoma(MCL) Jeko-1 cell line.</p><p><b>METHODS</b>β-catenin shRNA eukaryotic expression vector was transfected into Jeko-1 cells, the antiproliferative effect of shRNA on Jeko-1 cells was detected by RT-PCR and Western blot. The proliferation inhibitory rate of Jeko-1 cells treated by different doses of XAV939 was assayed by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow cytometry; the expression levels of apoptosis-related protein BCL-2, BAX, CyclinD1, C-MYC and Caspase-3 in Jeko-1 cells were determined by Western blot.</p><p><b>RESULTS</b>The expression of β-catenin mRNA and growth of Jeko-1 cell line were inhibited by shRNA; after Jeko-1 cells treated with 0,2 and 8 µmol/L XAV939 for 48 hours, the cell proliferation rate decreased, while the cell apoptosis rate increased, the expressions of apoptosis-related protein BCL-2, CyclinD1 and C-MYC were down-regulated, on the contrary, the expression of BAX and caspase-3 were up-regulated.</p><p><b>CONCLUSION</b>The specific inhibition of β-catenin can inhibit Jeko-1 cell proliferation and promote the cell apoptosis.</p>
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Humanos , Apoptosis , Caspasa 3 , Línea Celular Tumoral , Proliferación Celular , Compuestos Heterocíclicos con 3 Anillos , Linfoma de Células del Manto , ARN Mensajero , ARN Interferente Pequeño , Transfección , beta CateninaRESUMEN
<p><b>OBJECTIVE</b>This study was purposed to detect the expressions of β-catenin and P-GSK-3 β in Wnt signaling pathway of patients with mantle cell lymphoma(MCL), and investigate its relationship with the pathogenesis of MCL.</p><p><b>METHODS</b>The expression levels of β -catenin protein and P-GSK-3 protein in mantle cell lymphoma and hyperplastic lymphadenitis were detected by using anti-β-catenin, P-GSK-3β polyclonal antibody and S-P staining technique.</p><p><b>RESULTS</b>The abnormal expression of β-catenin protein(73.33%) in mantle cell lymphoma group was significantly higher than that (6.7%) in reactive lymph node hyperplasia group (P<0.05); and the positive rate of P-GSK-3 β(66.67%) in mantle cell lymphoma group was significantly higher than that (16.67%) in reactive hyperplasia of lymph node group (P<0.05). Spearman correlation analysis showed that there was obvious positive correlation (R=0.852, P<0.01).</p><p><b>CONCLUSION</b>The abnormal high expressions of β-catenin and P-GSK-3 β protein have been confirmed to appeare in mantle cell lymphoma.</p>
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Humanos , Glucógeno Sintasa Quinasa 3 , Glucógeno Sintasa Quinasa 3 beta , Linfoma de Células del Manto , Transducción de Señal , Vía de Señalización Wnt , beta CateninaRESUMEN
<p><b>OBJECTIVE</b>To study the aberration in histone H3K4 and H3K9 methylation and H3 and H4 acetylation in human acute leukemia (AL) cells.</p><p><b>METHODS</b>The histone H3K4 and H3K9 methylation and H3 and H4 acetylation were detected by Western blot in 34 AL patients and 13 controls (9 non leukemia patients, 4 healthy volunteers).</p><p><b>RESULTS</b>The level of H3K4 methylation was significantly lower in 19 AL patients than in non leukemia (0.220 ± 0.096 vs 0.447 ± 0.186, P < 0.01), while the level of H3K9 methylation was significantly higher (0.409 ± 0.106 vs 0.168 ± 0.015, P < 0.01); Both level of histone H3 and H4 acetylation in 15 AL patients were significantly lower (H3: 0.128 ± 0.013 vs 0.386 ± 0.104, H4: 0.096 ± 0.008 vs 0.341 ± 0.096, respectively, both P < 0.01).</p><p><b>CONCLUSION</b>Aberration of histone methylation and deficient histone acetylation in AL may represent the markers for an aberrant post-translational modification of histones and chromatin structure. It might be a potential epigenetic target for anti-leukemia agent.</p>