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Oxidized low-density lipoprotein (ox-LDL) is well known to disrupt normal functionality of endothelium, which plays a prominent role in endothelial dysfunction in many cardiovascular diseases. CO-releasing molecule 2 (CORM-2) is a promising candidate for treatment of cardiovascular diseases. However, it has not been defined whether CORM-2 might improve endothelial injury induced by ox-LDL. The present study was undertaken to determine the regulatory role of CORM-2 in cell injury of ox-LDL-treated human umbilical vein endothelial cells (HUVECs). Our results showed that ox-LDL inhibited the cell proliferation, but promoted apoptosis and release of cytochrome c (cytc) from mitochondrion into cytoplasm, stimulated the cleavage of caspase-3 and mitochondrial permeability transition pore (MPTP) opening. In addition, ox-LDL-incubated HUVECs exhibited excessive reactive oxygen species (ROS), increased protein levels of NADPH oxidase subunits p22phox, p47phox, NOX-2 and activation of Wnt/ß-catenin signaling pathway. However, pretreatment with CORM-2 significantly reduced cell apoptosis, release of cytc from mitochondrion into cytoplasm, MPTP opening and cleavage of caspase-3, suppressed the superoxide anion generation and Wnt/ß-catenin pathway activation in HUVECs response to ox-LDL. Collectively, we provide the evidence that CORM-2 attenuated ox-LDL-mediated endothelial apoptosis and oxidative stress by recovering the mitochondrial function and blocking Wnt/ß-catenin pathway.
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Células Endoteliais/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Compostos Organometálicos/farmacologia , Substâncias Protetoras/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Citocromos c/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Background: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) might worsen the clinical outcomes, and a reliable predictive system is needed to identify the risk of hemorrhagic transformation after IVT. Methods: Retrospective collection of patients with acute cerebral infarction treated with intravenous thrombolysis in our hospital from 2018 to 2022. 197 patients were included in the research study. Multivariate logistic regression analysis was used to screen the factors in the predictive nomogram. The performance of nomogram was assessed on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots and decision curve analysis (DCA). Results: A total of 197 patients were recruited, of whom 24 (12.1%) developed HT. In multivariate logistic regression model National Institute of Health Stroke Scale (NIHSS) (OR, 1.362; 95% CI, 1.161-1.652; p = 0.001), N-terminal pro-brain natriuretic peptide (NT-pro BNP) (OR, 1.012; 95% CI, 1.004-1.020; p = 0.003), neutrophil to lymphocyte ratio (NLR) (OR, 3.430; 95% CI, 2.082-6.262; p < 0.001), systolic blood pressure (SBP) (OR, 1.039; 95% CI, 1.009-1.075; p = 0.016) were the independent predictors of HT which were used to generate nomogram. The nomogram showed good discrimination due to AUC-ROC values. Calibration plot showed good calibration. DCA showed that nomogram is clinically useful. Conclusion: Nomogram consisting of NIHSS, NT-pro BNP, NLR, SBP scores predict the risk of HT in AIS patients treated with IVT.
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The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.
Assuntos
Neoplasias Colorretais , Linfócitos T Citotóxicos , Humanos , Animais , Camundongos , Interferon gama/farmacologia , Linfócitos T CD8-Positivos , Microambiente Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologiaRESUMO
Background: The zebrafish xenograft model has become a reliable in vivo model for human cancer research. Compared to a mouse model, the zebrafish xenograft has many advantages, including optical transparency, intuitive in vivo observation, and speed. Long noncoding RNAs (lncRNAs) have been identified as crucial regulatory factors in the progression of colorectal cancer (CRC). The biological function of lncRNA small nucleolar RNA host gene 4 (SNHG4) in CRC is still unclear. Methods: We analyzed the expression of SNHG4 in CRC patient samples by the Gene Expression Profiling Interactive Analysis (GEPIA) software. The quantitative real time-polymerase chain reaction (qRT-PCR) was used to verify in CRC cell lines. The colony formation assay was used to study the cell proliferation, and we used the transwell assay to detect the migration ability. Then the zebrafish xenograft models were used to confirm these roles of SNHG4 in vivo. Moreover, we detected epithelial mesenchymal transition (EMT) related genes by qRT-PCR. Results: We found the expression of SNHG4 was upregulated in CRC patient samples by analyzing GEPIA software, which was also verified in CRC cell lines. We also found that silencing SNHG4 inhibited the proliferation and migration of CRC cells, and its roles were verified in zebrafish xenografts in vivo. Further, we found that the expression of E-cadherin was significantly upregulated and N-cadherin was downregulated when knocking-down SNHG4 in CRC cells. Conclusions: Our findings demonstrated that SNHG4 played oncogenic roles in CRC, which could be a potential target for treatment of CRC patients, and the results strongly revealed that zebrafish xenograft could be used for functional research of lncRNAs in human cancer.
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OBJECTIVE: To analyze the chemical constituents of Polygonum multiflorum extract which may cause human liver cell damage and to explore the mechanism. METHODS: Raw and processed Polygonum multiflorum were extracted by 70% ethanol, then raw and processed Polygonum multiflorum water-eluted material (RW and PW), 50% ethanol-eluted material (R50 and P50) and 95% ethanol-eluted material (R95 and P95) were obtained by absorbing through AB-8 macroporous resin, followed by water, 50% ethanol and 95% ethanol elution in order. The water extracts of raw and processed Polygonum multiflorum (RWE or PWE) were obtained by boiling them in water as usual. Normal human liver L02 cells were treated by different concentrations of eluted Polygonum multiflorum materials for different time, and the cell growth inhibition of each group was determined by methylthiazolyldiphenyl-tetrazolium bromide method. The chemical constituents which had a significant cytotoxicity to L02 cells were analyzed by high-performance liquid chromatography (HPLC). Morphological changes of L02 cells were observed by Giemsa staining and cell cycle distribution was observed by flow cytometry. RESULTS: It was found that 95% ethanol-eluted extracts of raw and processed Polygonum multiflorum showed significant growth inhibition on normal human liver L02 cells, while the other components showed no significant inhibition on cell growth. HPLC analysis showed that the main component in 95% ethanol-eluted extract of raw and processed Polygonum multiflorum was emodin at content of (18.53+/-2.96)% and (10.28+/-1.34)% respectively. Cell cycle analysis showed that 95% ethanol-eluted material of Polygonum multiflorum and emodin had a similar significant effect of S phase arrest and all could induce L02 cell apoptosis. CONCLUSION: The main part of Polygonum multiflorum causing liver cell damage is the 95% ethanol-eluted extract, and emodin is one of the important chemical constituents leading to liver cell damage.
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Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polygonum/química , Pontos de Checagem do Ciclo Celular , Linhagem Celular , Hepatócitos/citologia , HumanosRESUMO
Anaerobic digested residue (DR) is the main by-product from biogas plants, and it is predominantly used as organic fertilizer after composting. To resolve the problems of long duration and nitrogen loss in conventional composting, bulking agents are always added during the composting process. In this study, oyster shell (OS) was used as a bulking agent for DR composting. Four treatments were conducted by mixing DR and OS at different concentrations (0%, 10%, 20% and 30%, based on wet weight) and then composting the mixtures for 40 days. The results showed that the organic matter (OM) degradation efficiency was enhanced by 5.62%, 12.15% and 16.98% with increasing amounts of OS addition. The increased content of microbial biomass carbon in the compost indicated a suitable living environment for aerobic microbes with added OS, which could explain the increased OM degradation efficiency. Compared with the control, the NH3 emissions in the treatments with 10%, 20% and 30% OS were decreased by 13.81%, 33.33% and 53.76%, respectively. The increase in total nitrogen content in the compost is probably due to the absorption of NH3 by OS. Results indicated that OS is a suitable bulking agent for DR composting and that the addition of 20-30% OS can significantly enhance composting performance.
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Compostagem , Ostreidae , Anaerobiose , Animais , Fertilizantes , Esterco , Nitrogênio/análise , SoloRESUMO
Methane is a greenhouse gas with significant global warming potential. The methane-oxidizing bacteria (MOB) immobilized on biocarrier could perform effectively and environmentally in methane elimination. To further improve the efficiencies of MOB immobilization and methane elimination, the surface biocompatibility of biocarrier needs to be improved. In this work, the oil shale semicoke (SC) was chemically modified by sodium p-styrenesulfonate hydrate (SS) and 2-(methacryloyloxy)ethyltrimethylammonium chloride (DMC) to promote surface hydrophilicity and positive charge, respectively. Results revealed that, under methane concentrations of ~10% (v/v) and ~0.5% (v/v), the MOB immobilized on semicoke modified with 1.0â¯molâ¯L-1 of SS permitted improved methane elimination capacities (ECs), which were 15.02% and 11.11% higher than that on SC, respectively. Additionally, under methane concentrations of ~10% (v/v) and ~0.5% (v/v), the MOB immobilized on semicoke modified with 0.4â¯molâ¯L-1 of DMC held superior ECs, which were 17.88% and 11.29% higher than that on SC, respectively. The qPCR analysis indicated that the MOB abundance on modified semicoke were higher than that on SC. In consequence, the surface biocompatibility of semicoke could be promoted by SS and DMC modifications, which potentially provided methods for other biocarriers to improve surface biocompatibility.
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Poluentes Atmosféricos/metabolismo , Coque/análise , Metano/metabolismo , Methylococcaceae/metabolismo , Metacrilatos , Oxirredução , Poliestirenos/químicaRESUMO
Phenotypic switch of vascular smooth muscle cells (VSMCs) is characterized by increased expressions of VSMC synthetic markers and decreased levels of VSMC contractile markers, which is an important step for VSMC proliferation and migration during the development and progression of cardiovascular diseases including atherosclerosis. Chicoric acid (CA) is identified to exert powerful cardiovascular protective effects. However, little is known about the effects of CA on VSMC biology. Herein, in cultured VSMCs, we showed that pretreatment with CA dose-dependently suppressed platelet-derived growth factor type BB (PDGF-BB)-induced VSMC phenotypic alteration, proliferation and migration. Mechanistically, PDGF-BB-treated VSMCs exhibited higher mammalian target of rapamycin (mTOR) and P70S6K phosphorylation, which was attenuated by CA pretreatment, diphenyleneiodonium chloride (DPI), reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) and nuclear factor-κB (NFκB) inhibitor Bay117082. PDGF-BB-triggered ROS production and p65-NFκB activation were inhibited by CA. In addition, both NAC and DPI abolished PDGF-BB-evoked p65-NFκB nuclear translocation, phosphorylation and degradation of Inhibitor κBα (IκBα). Of note, blockade of ROS/NFκB/mTOR/P70S6K signaling cascade prevented PDGF-BB-evoked VSMC phenotypic transformation, proliferation and migration. CA treatment prevented intimal hyperplasia and vascular remodeling in rat models of carotid artery ligation in vivo. These results suggest that CA impedes PDGF-BB-induced VSMC phenotypic switching, proliferation, migration and neointima formation via inhibition of ROS/NFκB/mTOR/P70S6K signaling cascade.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Desdiferenciação Celular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-sis/metabolismo , Transdução de Sinais/efeitos dos fármacos , Succinatos/farmacologia , Animais , Becaplermina , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Objective: To explore risk factors affecting treatment for deep neck space infections (DNSIs) so as to provide guidance for appropriate early managements. Methods: A retrospective cohort study was conducted on inpatients with DNSIs admitted to the Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Qingdao University from March 2013 to February 2021. Patients were divided into surgical and non-surgical groups based on whether they had surgery or not. Information collected included demographic data, disease-related signs and symptoms, treatment history, systemic comorbidities, imaging data and laboratory indicators. Hypothesis testing, univariate Logistic regression and multivariate Logistic regression were used for data processing. Resuts A total of 61 patients were included, including 37 males and 24 females, aged 6-96 years. There were 35 cases (57.4%) in the surgical group and 26 cases (42.6%) in the non-surgical group. Multivariate analysis showed that risk factors for surgery as followings: neck dyskinesia (OR=0.03, 95%CI: 0.00-0.24), dysphagia (OR=0.10, 95%CI: 0.02-0.72), serum white blood cell count≥16.74×109/L (OR=1.18, 95%CI: 1.01-1.39) and interspace gas (OR=0.03, 95%CI: 0.00-0.30). Conclusion: Clinicians should be alert to these risk factors for surgery in the course of treatment and timely surgical treatment for patients who meet the conditions.
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Masculino , Feminino , Humanos , Estudos Retrospectivos , Pescoço/cirurgia , Fatores de Risco , Transtornos de DeglutiçãoRESUMO
Colon cancer is one of the major causes of cancer-related death in the world. Understanding the molecular mechanism underlying this malignancy will facilitate the diagnosis and treatment. Serine-arginine protein kinase 2 (SRPK2) has been reported to be upregulated in several cancer types. However, its expression and functions in colon cancer remains unknown. In this study, it was found that the expression of SRPK2 was up-regulated in the clinical colon cancer samples. Overexpression of SRPK2 promoted the growth and migration of colon cancer cells, while knocking down the expression of SRPK2 inhibited the growth, migration and tumorigenecity of colon cancer cells. Molecular mechanism studies revealed that SRPK2 activated ERK signaling in colon cancer cells. Taken together, our study demonstrated the tumor promoting roles of SRPK2 in colon cancer cells and SRPK2 might be a promising therapeutic target for colon cancer.
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Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Colo/patologia , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos NusRESUMO
APP/PS1/tau triple transgenic (3xTg) mouse is a classical animal model of Alzheimer's disease (AD), which has abnormalities in recognition and electrophysiological properties at early 6-month-old age. However, few studies were performed by using simultaneously recording cognitive behavior and brain electrical activity in the conscious 3xTg mice. By using a new wireless recording system, we recorded hippocampal Theta oscillations in 3xTg mice during the process of fear conditioning test. The results showed that: (1) in training session, no significant difference in the fear behavior and hippocampal Theta activity was found between 3xTg mice and WT mice; (2) in test session, 3xTg mice showed a significant decrease in freezing ratio compared with WT mice when they were exposed to conditioning stimulus (CS); (3) the 3xTg mice showed lower peak power in Theta oscillation in both Pre-CS and CS duration compared with WT mice; (4) CS effectively induced an increase in the peak frequency of Theta oscillation in WT mice, but not in 3xTg mice. These results indicated that the impairment of cognition behavior in 3xTg mice was accompanied with the decreased peak power and peak frequency of Theta oscillation in the hippocampus, suggesting that a decline in Theta oscillation might be involved in the impairments of the fear conditioning, and the enhanced hippocampal Theta oscillation may be beneficial for improving AD cognitive function.