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BACKGROUND: Decision fatigue is a new concept in the field of psychology and refers to a state of fatigue alongside impaired cognitive processing and emotional regulation ability. Previous studies have confirmed that nurses are prone to decision fatigue, and nurses who experience decision fatigue may implement nursing measures that are inconsistent with clinical evidence, thus affecting patients' benefits. COVID-19, as a large-scale global public health emergency, increased the workload and burden of nurses and aggravated decision fatigue. However, the factors leading to decision fatigue among nurses have not yet been identified. METHODS: This study is guided by interpretative phenomenology. During the epidemic period of COVID-19: From November 2022 to February 2023, a one-to-one, semi-structured in-depth interview was conducted among nurses with decision fatigue experience who were participating in front-line work in Jilin Province using homogenous sampling. The interview recordings and related data were transcribed into text within 24 h, and data analysis was assisted by NVivo 12.0 software. RESULTS: After a total of 14 front-line nurses were analyzed in this study, The thematic level reaches saturation, the findings present a persuasive and coherent narrative, and the study is terminated, and finally extracted and formed three core themes: "Cognition, influence and attitude of decision fatigue", "Approaching factors of decision fatigue" and "Avoidant factors of decision fatigue". CONCLUSION: This study confirmed that decision fatigue was widespread in the work of front-line nurses, affecting the physical and psychological health of nurses, the quality of nursing work, the degree of benefit of patients and the clinical outcome. However, nursing staff do not know enough about decision fatigue, so the popularization and research of decision fatigue should be strengthened. Improve the attention of medical institutions, nursing managers and nursing staff.Some suggestions are put forward for the intervention of decision fatigue through personnel, task, tool and technology, organization and environment.
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BACKGROUND: Pancreaticoduodenectomy is the first choice surgical intervention for the radical treatment of pancreatic tumors. However, an anastomotic fistula is a common complication after pancreaticoduodenectomy with a high mortality rate. With the development of minimally invasive surgery, open pancreaticoduodenectomy (OPD), laparoscopic pancreaticoduodenectomy (LPD), and robotic pancreaticoduodenectomy (RPD) are gaining interest. But the impact of these surgical methods on the risk of anastomosis has not been confirmed. Therefore, we aimed to integrate relevant clinical studies and explore the effects of these three surgical methods on the occurrence of anastomotic fistula after pancreaticoduodenectomy. METHODS: A systematic literature search was conducted for studies reporting the RPD, LPD, and OPD. Network meta-analysis of postoperative anastomotic fistula (Pancreatic fistula, biliary leakage, gastrointestinal fistula) was performed. RESULTS: Sixty-five studies including 10,026 patients were included in the network meta-analysis. The rank of risk probability of pancreatic fistula for RPD (0.00) was better than LPD (0.37) and OPD (0.62). Thus, the analysis suggests the rank of risk of the postoperative pancreatic fistula for RPD, LPD, and OPD. The rank of risk probability for biliary leakage was similar for RPD (0.15) and LPD (0.15), and both were better than OPD (0.68). CONCLUSIONS: This network meta-analysis provided ranking for three different types of pancreaticoduodenectomy. The RPD and LPD can effectively improve the quality of surgery and are safe as well as feasible for OPD.
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Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Fístula Pancreática/etiologia , Fístula Pancreática/complicações , Metanálise em Rede , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/patologia , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Laparoscopia/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Tempo de InternaçãoRESUMO
Oleanolic acid (OA), one of the major pentacyclic triterpenes abundantly present in nature, is a promising compound with various biological activities, including anti-inflammatory, anti-ulcer, hepatoprotective, antidiabetic, fungicidal and antiparasitic properties. Therefore, a series of derivatives of 1α,2α-epoxy-3ß-hydroxyl oleanolic acid derivatives were designed and synthesized, and their antibacterial activities were investigated in vitro. Based on these results, the compounds with antibacterial activity were screened by RT-PCR to determine whether they can regulate the expression of genes related to metabolism, haemolysis, and ß-lactamase in vitro, and the structure-microbicidal activity relationship of each compound was analyzed. Our study shows that some of the modifications in the synthetic compounds, such as the introduction of an ortho-cyano-substituted benzyl group and a short chain alkyl ester at the 28-carboxyl, as well as the introduction of an acetyl group at the 3-hydroxyl group of ring A, could enhance antibacterial activity. This provides basic evidence for the optimization of 1α,2α-epoxy-3ß-hydroxyl oleanolic acid derivatives. The antibacterial mechanism of the active OA derivatives appears to involve the regulation of expression of metabolism-associated genes in Escherichia coli, haemolysis-associated genes in Bacillus subtilis, metabolism-related genes in Klebsiella pneumonia and ß-lactamase-associated genes in Acinetobacter baumannii. Some OA derivatives were bactericidal to three of the strains and appeared to regulate gene expression associated with metabolism, haemolysis, and ß-lactamase in vitro. These newly designed OA derivatives possess unique antibacterial activities and may be potentially useful for prophylactic or therapeutic intervention of bacterial infections.
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Antibacterianos/química , Ácido Oleanólico/análogos & derivados , beta-Lactamases/metabolismo , Acinetobacter/efeitos dos fármacos , Acinetobacter/genética , Acinetobacter/metabolismo , Antibacterianos/síntese química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana , Ácido Oleanólico/síntese química , Ácido Oleanólico/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Relação Estrutura-Atividade , Triterpenos/química , beta-Lactamases/genéticaRESUMO
BACKGROUND: XinJiErKang (XJEK), a Chinese herbal formula, is identified as an effective preparation to treat coronary heart disease and myocarditis. The aim of the study is to investigate the anti-hypertensive effects of XJEK by oral administration and also to find out whether the drug has any role in oxidative stress and vascular endothelial function. METHODS: Clipping of the renal artery resulted in gradual elevation of the systolic blood pressure (SBP) which reached a plateau after 4 weeks of surgery. Treatment of hypertensive rats (20 mmHg higher than basic systolic blood pressure) with XJEK (6, 12, 24 g/kg/day) and fosinopril (15 mg/kg/day) respectively by intragastric administration started 4 weeks after surgery and continued for 4 weeks. The sham-operated (Sh-Op) controls received drinking water. BP was monitored weekly using tail-cuff apparatus. At the end of 8 wk, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate of rise of left ventricular pressure (±dp/dtmax) were examined (PowerLab 8/30, AD Instruments, Australia). The myocardial hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes were investigated by hematoxylin and eosin (HE) and Van Gieson (VG) stain. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) content in serum, contents of hydroxyproline (Hyp) in the ventricular tissue were assayed by xanthin oxidase method, thiobarbituric acid (TBA) method, Griess method and alkaline hydrolysis method, respectively. Angiotensin II (Ang II) content in serum was detected by radioimmunoasssay method. RESULTS: XJEK therapy potently improved cardiac function, inhibited myocardial hypertrophy, improved cardiac pathology change, decreased the myocardial cross-section area (CSA), collagen volume fraction (CVF) and perivascular circumferential collagen area (PVCA), reduced the content of Hyp in the left ventricular tissue, inhibited the decrease of SOD activity and increase of MDA, Ang II content in serum. Moreover, treatment with XJEK improved endothelial dysfunction (ED) manifested by promoting endothelial-dependent vasodilation of thoracic aortic rings and enhancing the NO activity in serum. CONCLUSIONS: These findings suggest that administration of XJEK possess protective effects against 2K1C induced hypertension and cardiac remodeling in rats, preserve NO activity and endothelial function.
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Medicamentos de Ervas Chinesas/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Coração/efeitos dos fármacos , Hipertensão/patologia , Miocárdio , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Angiotensina II/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aorta Torácica , Austrália , Pressão Sanguínea , Medicamentos de Ervas Chinesas/farmacologia , Hipertensão/sangue , Hipertensão/metabolismo , Magnoliopsida , Masculino , Malondialdeído/sangue , Medicina Tradicional Chinesa , Miocárdio/metabolismo , Miocárdio/patologia , Óxido Nítrico/sangue , Ratos , Superóxido Dismutase/metabolismo , Vasodilatação/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
Growing experimental and clinical data highlights the important roles of increased reactive oxygen species production in cardiovascular remodeling (CR). Oligomeric grape seed proanthocyanidins (GSPs) have been shown to be potent antioxidants and free radical scavengers. Mice were treated with DOCA-salt to induce CR and were given distilled water or oligomeric GSPs for 4 weeks. The heart weight (HW) index and kidney weight (KW) index were expressed as heart weight/body weight (HW/BW) and kidney weight/body weight (KW/BW); the histological changes were investigated by hematoxylin and eosin and Van Gieson staining.The endothelial-dependent vasodilation function induced by acetylcholine was investigated in isolated thoracic aorta ring. Colorimetric analysis was used to assay superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and nitric oxide (NO) content in serum and hydroxyproline content in cardiac tissue. Administration of GSPs markedly alleviated the elevation of HW/BW ratio, KW/BW ratio and cross-sectional area of cardiomyocytes, decreased collagen deposition in heart and attenuated histopathology injury, and improves endothelial-dependent aorta ring relaxation in vitro accompany by increasing of NO content in serum. Meanwhile, treatment with GSPs significantly ameliorated oxidative stress via increasing SOD activities and decreasing MDA formation. These findings suggest that administration of GSPs has the potential to attenuate DOCA-salt induced CR and KH and preserve NO activity and endothelial function, which mechanism may contribute to its antioxidant characteristic, at least in part.
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Aorta/efeitos dos fármacos , Extrato de Sementes de Uva/farmacologia , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Estresse Oxidativo , Proantocianidinas/farmacologia , Animais , Peso Corporal , Desoxicorticosterona , Rim/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Miocárdio/patologia , Óxido Nítrico/sangue , Tamanho do Órgão , Superóxido Dismutase/metabolismo , Remodelação Ventricular , Vitis/químicaRESUMO
Neurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages, such as its short biological half-life, its contribution to pain response, and its inability to cross the blood-brain barrier. Considering that let-7 (human miRNA) targets and regulates nerve growth factor, and that let-7 is a core regulator in peripheral nerve regeneration, we evaluated the possibilities of let-7 application in nerve repair. In this study, anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship, and functional screening. Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve, including Schwann cells, fibroblasts and macrophages. Use of hydrogel effectively achieved controlled, localized, and sustained delivery of let-7a antagomir. Finally, let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft, which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection. Our study provides an experimental basis for potential in vivo application of let-7a.
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INTRODUCTION: Vascular neointimal hyperplasia, a pathological process observed in cardiovascular diseases such as atherosclerosis and pulmonary hypertension, involves the abundant presence of vascular smooth muscle cells (VSMCs). The proliferation, migration, and autophagy of VSMCs are associated with the development of neointimal lesions. Circular RNAs (circRNAs) play critical roles in regulating VSMC proliferation and migration, thereby participating in neointimal hyperplasia. However, the regulatory roles of circRNAs in VSMC autophagy remain unclear. OBJECTIVES: We aimed to identify circRNAs that are involved in VSMC autophagy-mediated neointimal hyperplasia, as well as elucidate the underlying mechanisms. METHODS: Dual-luciferase reporter gene assay was performed to validate two competing endogenous RNA axes, hsa_circ_0001402/miR-183-5p/FKBP prolyl isomerase like (FKBPL) and hsa_circ_0001402/miR-183-5p/beclin 1 (BECN1). Cell proliferation and migration analyses were employed to investigate the effects of hsa_circ_0001402, miR-183-5p, or FKBPL on VSMC proliferation and migration. Cell autophagy analysis was conducted to reveal the role of hsa_circ_0001402 or miR-183-5p on VSMC autophagy. The role of hsa_circ_0001402 or miR-183-5p on neointimal hyperplasia was evaluated using a mouse model of common carotid artery ligation. RESULTS: Hsa_circ_0001402 acted as a sponge for miR-183-5p, leading to the suppression of miR-183-5p expression. Through direct interaction with the coding sequence (CDS) of FKBPL, miR-183-5p promoted VSMC proliferation and migration by decreasing FKBPL levels. Besides, miR-183-5p reduced BECN1 levels by targeting the 3'-untranslated region (UTR) of BECN1, thus inhibiting VSMC autophagy. By acting as a miR-183-5p sponge, overexpression of hsa_circ_0001402 increased FKBPL levels to inhibit VSMC proliferation and migration, while simultaneously elevating BECN1 levels to activate VSMC autophagy, thereby alleviating neointimal hyperplasia. CONCLUSION: Hsa_circ_0001402, acting as a miR-183-5p sponge, increases FKBPL levels to inhibit VSMC proliferation and migration, while enhancing BECN1 levels to activate VSMC autophagy, thus alleviating neointimal hyperplasia. The hsa_circ_0001402/miR-183-5p/FKBPL axis and hsa_circ_0001402/miR-183-5p/BECN1 axis may offer potential therapeutic targets for neointimal hyperplasia.
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Many studies have shown that the relationship between alcohol consumption and most cardiovascular diseases is U-shaped, with nondrinkers and heavier drinkers having higher risks than moderate drinkers. However, the association between cardiac arrhythmias and acute alcohol consumption is not well understood. We set up several experimental arrhythmia animal models to examine the effects of acute administration of ethanol on arrhythmia. The results showed 0.4, 0.8 and 1.6 g/kg ethanol consumption obviously delayed the onset time of atrial fibrillation (AF) (P < 0.05 or P < 0.01) and increased the survival rates on acetylcholine-CaCl2-induced AF in mice. Ethanol (0.4, 0.8 and 1.6 g/kg) consumption significantly delayed the onset time of ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA) (P < 0.01), and 0.4 and 0.8 g/kg ethanol consumption increased the survival rates on CaCl2-induced arrhythmia in rats. Ethanol (0.4 g/kg) essentially increased the cumulative dosage of aconitine required to CA (P < 0.05), and 0.8 g/kg, 1.6 g/kg ethanol reduced the cumulative aconitine dosage to induce VT, VF and CA (P < 0.05 or P < 0.01) on aconitine-induced arrhythmia in rats. Ethanol (0.4, 0.8 and 1.6 g/kg) consumption remarkably increased the cumulative dosage of deslanoside to induce ventricualr premature contraction (P < 0.01) on deslanoside-induced arrhythmia in guinea pigs. Collectively, our results indicate that low concentrations of ethanol had anti-arrhythmic effect on experimental arrhythmia, and high concentrations of ethanol may aggravated the occurrence of experimental arrhythmia.
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Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Acetilcolina/toxicidade , Aconitina/toxicidade , Animais , Arritmias Cardíacas/mortalidade , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Cloreto de Cálcio/toxicidade , Cardiotônicos/toxicidade , Depressores do Sistema Nervoso Central/sangue , Agonistas Colinérgicos/toxicidade , Deslanosídeo/toxicidade , Modelos Animais de Doenças , Interações Medicamentosas , Etanol/sangue , Cobaias , Parada Cardíaca/induzido quimicamente , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-Dawley , Fatores de Risco , Taquicardia Ventricular/induzido quimicamente , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/mortalidade , Fibrilação Ventricular/induzido quimicamente , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/mortalidade , Agonistas do Canal de Sódio Disparado por Voltagem/toxicidadeRESUMO
OBJECTIVE: To investigate the effects of Xinjierkang on two kidney one clip -induced hypertension and target organ injury in rats. METHODS: Two kidney one clip-induced hypertension rats model was established. Rats were divided into control group, model group, Xinjierkang group, and fosinopril group. At the end of 8th w, the hemodynamics indexes were recorded. The cardiac hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes of heart, aorta and kidney were investigated by HE and/or Van Gieson stain. RESULTS: Compared with control group, the heart systolic and diastolic function were impaired, the heart weight index, cardiomyocytes cross section area (CSA), cardiac collagen deposition, vascular remodeling index and glomerulus area were increased markedly in model group rats. Administration of Xinjierkang and fosinopril markedly ameliorated hemodynamic indexes, inhibited the elevation of HW/BW ratio, CSA of cardiomyocytes, vascular remodeling index and glomerulus hypertrophy, decreased collagen deposition in heart. CONCLUSION: Xinjierkang has protective effects against two kidney one clip-induced hemodynamic impairment, cardiovascular remodeling and glomerulus hypertrophy in rats.
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Anti-Hipertensivos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Hipertensão Renal/tratamento farmacológico , Glomérulos Renais/patologia , Miocárdio/patologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Fosinopril/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão Renal/complicações , Hipertensão Renal/patologia , Glomérulos Renais/efeitos dos fármacos , Masculino , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Artéria Renal/cirurgia , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the effects of Xinji' erkang (XJEK), a compound Chinese herbal medicine, on isoproterenol-induced ventricular remodeling in mice. METHODS: Isoproterenol was given subcutaneously (1 mg/kg, twice per day for 7 d) to induce ventricular remodeling in mice. Mice were divided into normal control group, model group, XJEK low-, medium- and high- dose groups, XJEK water layer group, XJEK n-butanol layer group and metoprolol group. All drugs were given by intragastric administration. At the end of the 7th day, the hearts of the rats were weighted, and myocardial hypertrophy index was expressed as heart weight/body weight (HW/BW). The histological changes were observed by hemotoxylin-eosin and Van Gieson staining. Colorimetric method was used to determine the content of hydroxyproline in heart, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum. RESULTS: Compared with the isoproterenol injection only, XJEK potently inhibited cardiomyocyte hypertrophy and the increase of hydroxyproline content in heart (P<0.01), improved cardiac pathology change, inhibited the decrease of SOD activity and the increase of MDA content in serum (P<0.01). XJEK water layer also inhibited the increase of cardiomyocyte hypertrophy (P<0.01) while XJEK n-butanol layer inhibited cardiomyocyte hypertrophy and fibrosis (P<0.01). CONCLUSION: XJEK possesses protective effects against isoproterenol-induced ventricular remodeling in mice, which may be related to its actions in reducing the oxidative stress and improving the antioxidant activity of the body. XJEK water layer and XJEK n-butanol layer attenuated ventricular remodeling without significant oxidative stress state changing, which indicates that a non-antioxidative stress mechanism may exist.
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Medicamentos de Ervas Chinesas/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Isoproterenol/efeitos adversos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: We aim to assess the efficacy and safety profiles of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer using a meta-analysis. METHODS: We extracted and examined data from phase I, II and III clinical trials from PubMed, Embase, Web of Science, and Cochrane Library, which included patients with metastatic castration-resistant prostate cancer who were treated with immune checkpoint inhibitors. We performed a meta-analysis to investigate several indexes of efficacy and safety, including the objective response rate, 1-year overall survival (OS) rate, prostate-specific antigen response rate, and adverse event rate of immune checkpoint inhibitors. The material data were calculated and pooled using The R Project for Statistical Computing and STATA 12.0 software. RESULTS: We identified 12 clinical trials in our study. We assessed the pooled frequencies of all-grade AEs and grade ≥ 3 AEs first and showed 0.82 (95% CI: 0.74-0.91, I2 = 94%, P < .01) and 0.42 (95% CI: 0.33-0.54, I2 = 96%, P < .01), respectively. The objective response rate was 0.10 (95% CI: 0.04-0.19, I2 = 70%, P < .01), and the 1-year OS and prostate-specific antigen response rate were 0.55 (95% CI: 0.45-0.67, I2 = 93%, P < .01) and 0.18 (95% CI: 0.16-0.20, I2 = 43%, P = .03), respectively. CONCLUSION: The immune checkpoint inhibitors therapy was well tolerated and showed potential to improve tumor responses in patients with metastatic castration-resistant prostate cancer.
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Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , MasculinoRESUMO
UNLABELLED: The up-regulation and nuclear relocation of epithelial-mesenchymal transition (EMT) regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). The term vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. However, the relationship between Twist1 and VM formation is not clear. In this study, we explored HCC as a VM and EMT model in order to investigate the role of Twist1 in VM formation. We first examined the expression of Twist1 in human HCC samples and cell lines and found that Twist1 was frequently overexpressed in the nuclear relocation occurring in VM-positive HCCs (13/18 [72%]). Twist1 nuclear expression was likewise significantly associated with VM formation. Clinicopathological analysis revealed that both VM and Twist1 nuclear expressions present shorter survival durations than those without expression. We consistently demonstrated that an overexpression of Twist1 significantly enhanced cell motility, invasiveness, and VM formation in an HepG2 cell. Conversely, a knockdown of Twist1 by the short hairpin RNA approach remarkably reduced Bel7402 cell migration, invasion, and VM formation. Using chromatin immunoprecipitation, we also showed that Twist1 binds to the vascular endothelial (VE)-cadherin promoter and enhances its activity in a transactivation assay. CONCLUSION: The results of this study indicate that Twist1 induces HCC cell plasticity in VM cells more through the suppression of E-cadherin expression and the induction of VE-cadherin up-regulation than through the VM pattern in vivo and in a three-dimensional in vitro system. Our findings also demonstrate a novel cogitation in cancer stem-like cell differentiation and that related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis.
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Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/metabolismo , Neovascularização Patológica , Proteínas Nucleares/fisiologia , Proteína 1 Relacionada a Twist/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/biossíntese , Células Tumorais Cultivadas , Proteína 1 Relacionada a Twist/biossínteseRESUMO
The effects of oligomerized grape seed proanthocyanidins (GSP) on haemodynamics, cardiac hypertrophy and fibrosis as well as apoptosis signal-regulating kinase 1 (ASK1) and nuclear factor-κB (NF-κB) cascades in isoproterenol (Iso)-induced cardiac remodelling (CR) rat model were investigated, in addition, the serum SOD activities and MDA content were assayed. Rats were treated with Iso to induce CR and were given distilled water or GSP for 1 week. Control rats received vehicle instead of Iso. Administration of GSP markedly alleviated the elevation of the left ventricle weight (LVW)/body weight (BW), heart weight (HW)/body weight (BW) ratio and cross-sectional area of cardiomyocytes, decreased collagen deposition in the heart, and improved the haemodynamic index. Meanwhile, treatment with GSP significantly ameliorated oxidative stress by improving SOD activities and decreasing MDA formation. Moreover, GSP apparently inhibited the expression ASK1, NF-κB and its targeted gene - COX-2. These findings suggest that administration of GSP has the potential to attenuate Iso-induced CR by repressing oxidative stress and inhibiting the activation of the cellular signaling cascades involving the ASK1 and NF-κB pathways, at least in part, providing a molecular mechanism for the cardioprotective effect of GSP.
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Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Extrato de Sementes de Uva/farmacologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Proantocianidinas/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Cardiotônicos/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Extrato de Sementes de Uva/uso terapêutico , Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/induzido quimicamente , Isoproterenol/farmacologia , MAP Quinase Quinase Quinase 5/metabolismo , Masculino , Malondialdeído/sangue , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Proantocianidinas/uso terapêutico , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Superóxido Dismutase/efeitos dos fármacos , Vitis/químicaRESUMO
OBJECTIVE: To study the correlation between the expression of matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF) and vasculogenic mimicry (VM) in gastrointestinal stromal tumors (GIST). METHODS: The immunohistochemical staining indices (SI) of MMP-2, MMP-9, VEGF were assessed on specimens of 84 human cases with GIST (21 VM-positive cases). Gelatin zymography analysis of the activity of MMP-2 and MMP-9 activities were performed on another 42 human cases of GIST with fresh tissue (22 VM-positive cases). RESULTS: The staining indices (SI) of MMP-2 and MMP-9 were higher in the VM-positive group (4.10 +/- 2.05 and 3.43 +/- 1.89 respectively) than in the VM-negative group (2.98 +/- 1.97 and 2.38 +/- 1.84 respectively, both P < 0.05); there was no statistic difference in the SI of VEGF between VM-positive and VM-negative group. Gelatin zymography analysis showed that the activity of MMP-2 and MMP-9 were significantly higher in the VM-positive group (3.62 +/- 3.95 and 4.77 +/- 5.29 respectively) than in the VM-negative group (1.26 +/- 1.21 and 2.11 +/- 1.54 respectively, both P < 0.05). CONCLUSION: The expression of MMP-2 and MMP-9 correlates with VM formation in GIST.
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Tumores do Estroma Gastrointestinal/irrigação sanguínea , Tumores do Estroma Gastrointestinal/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
OBJECTIVE: Bone-marrow derived mesenchymal stem cells (BMSC) have the potential to differentiate into endothelial cells. The aim of the study was to investigate the induction process of BMSC by B16 melanoma cells in vitro and to analyze the role of VEGF-a in the process. METHODS: A co-culture system containing BMSC and B16 melanoma cells based on transwell indirect model was established, and the induction process of BMSC by B16 melanoma cells was studied in vitro. RESULTS: BMSC were isolated from the bone marrow of C57 mice. BMSC expressed CD105, CD90, CD73, CD44 and CD166, and acquired expressin of endothelial phenotype markers including VEGFR-1, VEGFR-2 and Factor VIII after co-culture with B16 melanoma cells for 48 hours. The expression level of VEGFR-2 would be double and Factor VIII threefold more by extending the co-culture time to 72 hours. In the co-culture system, B16 melanoma cells also up-regulated the expression of VEGF-a. CONCLUSIONS: VEGF-a plays a significant role in the differentiation of BMSC into cells of endothelial phenotype, therefore, is important to tumor angiogenesis.
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Células da Medula Óssea/citologia , Células Endoteliais/citologia , Melanoma Experimental/patologia , Células-Tronco Mesenquimais/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Células Endoteliais/metabolismo , Fator VIII/metabolismo , Masculino , Melanoma Experimental/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Projetos Piloto , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To explore the existence of vasculogenic mimicry (VM) in ovarian carcinoma and its correlationship with the clinicopathologic features and prognosis of the tumor. METHODS: A total of 84 ovarian carcinoma cases were collected with complete clinical and prognostic data. CD31 immunohistochemistry and PAS special stain were used to investigate VM in the tumor tissue. Immunohistochemical staining of VEGF, MMP-2, MMP-9, E-cadherin, beta-catenin, and Vimentin were used to explore the pathogenesis of VM. RESULTS: Totally 36 of 84 cases exhibited evidence of VM. FIGO classification, pathologic grades and histological types were significantly different between the VM and non-VM groups. Expression of VEGF, MMP-2, MMP-9, E-cadherin and beta-catenin were higher in the VM group than in the non-VM group. Kaplan-Meier survival curve analysis showed that cases of the VM group had a lower survival rate than that of the non-VM group (P = 0.04). CONCLUSIONS: Vasculogenic mimicry exists in ovarian carcinoma. Ovarian carcinomas with a high grade malignancy have a high incidence of VM formation, a higher incidence of metastases and a lower survival rate. High expression of MMP-2 and MMP-9 may contribute to the formation of VM in the ovarian cancer.
Assuntos
Cistadenocarcinoma Seroso/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/patologia , Neoplasias Ovarianas/patologia , Caderinas/metabolismo , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patologia , Cistadenocarcinoma Mucinoso/metabolismo , Cistadenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Seroso/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neovascularização Patológica/metabolismo , Neoplasias Ovarianas/metabolismo , Taxa de Sobrevida , Fator A de Crescimento do Endotélio Vascular/metabolismo , beta Catenina/metabolismoRESUMO
MicroRNAs (miRNAs) can regulate the modulation of the phenotype of Schwann cells. Numerous novel miRNAs have been discovered and identified in rat sciatic nerve segments, including miR-3099. In the current study, miR-3099 expression levels following peripheral nerve injury were measured in the proximal stumps of rat sciatic nerves after surgical crush. Real-time reverse transcription-polymerase chain reaction was used to determine miR-3099 expression in the crushed nerve segment at 0, 1, 4, 7, and 14 days post sciatic nerve injury, which was consistent with Solexa sequencing outcomes. Expression of miR-3099 was up-regulated following peripheral nerve injury. EdU and transwell chamber assays were used to observe the effect of miR-3099 on Schwann cell proliferation and migration. The results showed that increased miR-3099 expression promoted the proliferation and migration of Schwann cells. However, reduced miR-3099 expression suppressed the proliferation and migration of Schwann cells. The potential target genes of miR-3099 were also investigated by bioinformatic tools and high-throughput outcomes. miR-3099 targets genes Aqp4, St8sia2, Tnfsf15, and Zbtb16 and affects the proliferation and migration of Schwann cells. This study examined the levels of miR-3099 at different time points following peripheral nerve injury. Our results confirmed that increased miR-3099 level induced by peripheral nerve injury can promote the proliferation and migration of Schwann cells.
RESUMO
Aflatoxin B1 (AFB1) is very harmful for broiler production and public health. The water-soluble castoff in gluten production, i.e., the water-soluble substances of wheat (WSW) that contains 14% pentosan has positive effect on animal nutrient absorption, immunity, and antioxidation. Our study aims to investigate the preventive effects of WSW against AFB1-induced broiler liver injury. One day-old Arbor Acres broilers were randomly separated to 4 groups and were, respectively, fed with control diet, diet with 5 mg/kg AFB1 standard, diet with 5 mg/kg AFB1 standard and 214 ml/kg WSW, and diet with 214 ml/kg WSW continuously for 28 d. The histopathological, ultra-structural, and serological changes were tested to evaluate liver damage. The hallmarks of hepatocellular autophagy, apoptosis, and inflammation were measured by Western Blot and real-time polymerase chain reaction. The content of AFB1 in chicken liver was detected with an ultra-high performance liquid chromatography linked with the fluorescence detection method. The results showed that (i) WSW restored AFB1-induced changes in serum biochemical parameters, and ameliorated histomorphological changes in hepatocytes, (ii) WSW reduced the content of AFB1 in chicken liver, (iii) WSW alleviated AFB1-induced autophagy inhibition by up-regulating hepatic LC3, beclin-1, and down-regulating hepatic mTOR and cytoplasmic P53 expressions, (iv) WSW alleviated AFB1-induced hepatocellular apoptosis via inhibiting pro-apoptotic gene expression (nuclear P53, Caspase3, Bax), and promoting anti-apoptotic gene expression (bcl-2), (v) WSW feeding ameliorated AFB1-induced liver inflammation via impeding TLR4/NF-${{\bf \kappa }}$B and IL-1/NF-${{\bf \kappa }}$B signaling pathways, down-regulating pro-inflammatory cytokines (IL-1${{\bf \beta }}$, IL-6, and IL-8), and markedly up-regulating anti-inflammatory genes (IL-10 and HO-1). Conclusively, WSW is a potential preventer of AFB1-induced broiler liver damage by reducing the AFB1 content in liver, accelerating hepatocellular autophagy and inhibiting hepatocytes apoptosis and liver inflammation.
Assuntos
Aflatoxina B1/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Poliéster Sulfúrico de Pentosana/farmacologia , Substâncias Protetoras/farmacologia , Triticum/química , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Galinhas , Hepatócitos/efeitos dos fármacos , Inflamação/genética , Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologiaRESUMO
MicroRNAs refer to a class of endogenous, short non-coding RNAs that mediate numerous biological functions. MicroRNAs regulate various physiological and pathological activities of peripheral nerves, including peripheral nerve repair and regeneration. Previously, using a rat sciatic nerve injury model, we identified many functionally annotated novel microRNAs, including miR-sc14. Here, we used real-time reverse transcription-polymerase chain reaction to examine miR-sc14 expression in rat sciatic nerve stumps. Our results show that miR-sc14 is noticeably altered following sciatic nerve injury, being up-regulated at 1 day and diminished at 7 days. EdU and transwell chamber assay results showed that miR-sc14 mimic promoted proliferation and migration of Schwann cells, while miR-sc14 inhibitor suppressed their proliferation and migration. Additionally, bioinformatic analysis examined potential target genes of miR-sc14, and found that fibroblast growth factor receptor 2 might be a potential target gene. Specifically, our results show changes of miR-sc14 expression in the sciatic nerve of rats at different time points after nerve injury. Appropriately, up-regulation of miR-sc14 promoted proliferation and migration of Schwann cells. Consequently, miR-sc14 may be an intervention target to promote repair of peripheral nerve injury. The study was approved by the Jiangsu Provincial Laboratory Animal Management Committee, China on March 4, 2015 (approval No. 20150304-004).
RESUMO
Bone-marrow derived mesenchymal stem cells (BMSCs) have the potential to differentiate into osteocytes, chondrocytes, adipocytes and endothelial cells. The interaction between BMSCs and epithelial tumor cell was enhanced on proliferation. Our previous study had shown that BMSCs maybe participate in angiogenesis in melanoma in vivo. The aim of this study was to investigate the interaction between B16 melanoma cells and BMSCs in vitro, the mechanism of BMSCs participating in melanoma angiogenesis in vivo is unclear, so a co-culture system containing BMSCs and B16 melanoma cells, based on transwell indirect model, was established, and the interaction between BMSCs and B16 melanoma cells was studied in vitro. In our study, BMSCs were generated out of bone marrow from C57 mouse, isolated BMSCs were positive for the markers CD105, CD90, CD73, CD44 and CD166 and negative for endothelial markers, which acquired endothelial phenotype (including the expression of VEGFR-1, VEGFR-2, Factor VIII) after co-culture with B16 melanoma cells; at the same time, B16 melanoma cells also up-regulated the expression of VEGF-a, VEGFR-1, VEGFR-2 and Factor VIII. The proliferation rate of B16 melanoma cells and BMSCs were also found to be increased. We could show the differentiation of BMSCs into cells with phenotypic features of endothelial cells. BMSCs promoted proliferation of tumor cells and improved the microenvironment in tumor. Our study suggests that the BMSCs may play an important role in tumor angiogenesis.