RESUMEN
BACKGROUND: Breast cancer is a common tumor in China and has become a public health problem in modern society. Stress plays an important role in the occurrence and progression of cancer. At present, the current situation of stress on breast cancer survivors (BCSs) in China has not been fully understood. This study aims to explore the stress and coping strategies of Chinese BCSs, which provide suggestions to help BCSs reduce stress. METHODS: Sixty-three BCSs from the Shanghai Cancer Rehabilitation Club in China were included in this study and were divided into eight focus groups. These were transcribed verbatim, coded using thematic analysis and analyzed using NVivo 11. RESULTS: Three themes were extracted from the data to address our research objectives: stress, coping strategies and expectations. The stress of BCSs included psychological stress, stress caused by physical pain, economic stress, stress caused by the change of life status, and stress caused by information overload; the coping strategies included self-strategies and help from others; from the perspective of the survivors, they put forward their expectations for both the society and themselves. CONCLUSIONS: This study shows that BCSs face a variety of stress. In the face of stress, BCSs need comprehensive support, including social and family support to cope with stressors. The findings from this study provide evidence for improving the quality of life among BCSs.
Asunto(s)
Adaptación Psicológica , Neoplasias de la Mama/psicología , Supervivientes de Cáncer/psicología , Calidad de Vida/psicología , Estrés Psicológico/psicología , Adulto , Anciano , Neoplasias de la Mama/etnología , China/epidemiología , Femenino , Grupos Focales , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Motivación , Investigación CualitativaRESUMEN
Endothelial-mesenchymal transition (EnMT) plays a pivotal role in various diseases, including pulmonary hypertension (PH), and transcription factors like Snail are key regulators of EnMT. In this study we investigated how these factors were regulated by PH risk factors (e.g. inflammation and hypoxia) in human umbilical vein endothelial cells (HUVECs). We showed that treatment with interleukin 1ß (IL-1ß) induced EnMT of HUVECs via activation of NF-κB/Snail pathway, which was further exacerbated by knockdown of protein tyrosine phosphatase L1 (PTPL1). We demonstrated that PTPL1 inhibited NF-κB/Snail through dephosphorylating and stabilizing IκBα. IL-1ß or hypoxia could downregulate PTPL1 expression in HUVECs. The deregulation of PTPL1/NF-κB signaling was validated in a monocrotaline-induced rat PH (MCT-PH) model and clinical PH specimens. Our findings provide novel insights into the regulatory mechanisms of EnMT, and have implications for identifying new therapeutic targets for clinical PH.
Asunto(s)
Transdiferenciación Celular/efectos de los fármacos , Interleucina-1beta/farmacología , Subunidad p50 de NF-kappa B/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 13/fisiología , Transducción de Señal/fisiología , Factores de Transcripción de la Familia Snail/metabolismo , Animales , Transdiferenciación Celular/fisiología , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/fisiopatología , Interleucina-1beta/metabolismo , Masculino , Monocrotalina , Inhibidor NF-kappaB alfa/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 13/genética , Ratas Sprague-DawleyRESUMEN
Abnormal wound healing by pulmonary artery smooth muscle cells (PASMCs) promotes vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Increasing evidence shows that both the mammalian target of rapamycin complex 1 (mTORC1) and nuclear factor-kappa B (NF-κB) are involved in the development of HPH. In this study, we explored the crosstalk between mTORC1 and NF-κB in PASMCs cultured under hypoxic condition and in a rat model of hypoxia-induced pulmonary hypertension (HPH). We showed that hypoxia promoted wound healing of PASMCs, which was dose-dependently blocked by the mTORC1 inhibitor rapamycin (5-20 nM). In PASMCs, hypoxia activated mTORC1, which in turn promoted the phosphorylation of NF-κB. Molecular docking revealed that mTOR interacted with IκB kinases (IKKs) and that was validated by immunoprecipitation. In vitro kinase assays and mass spectrometry demonstrated that mTOR phosphorylated IKKα and IKKß separately. Inhibition of mTORC1 decreased the level of phosphorylated IKKα/ß, thus reducing the phosphorylation and transcriptional activity of NF-κB. Bioinformatics study revealed that dipeptidyl peptidase-4 (DPP4) was a target gene of NF-κB; DPP4 inhibitor, sitagliptin (10-500 µM) effectively inhibited the abnormal wound healing of PASMCs under hypoxic condition. In the rat model of HPH, we showed that NF-κB activation (at 3 weeks) was preceded by mTOR signaling activation (after 1 or 2 weeks) in lungs, and administration of sitagliptin (1-5 mg/kg every day, ig) produced preventive effects against the development of HPH. In conclusion, hypoxia activates the crosstalk between mTORC1 and NF-κB, and increased DPP4 expression in PASMCs that leads to vascular remodeling. Sitagliptin, a DPP4 inhibitor, exerts preventive effect against HPH.
Asunto(s)
Miocitos del Músculo Liso/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Arteria Pulmonar/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Administración Oral , Animales , Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Biología Computacional , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Modelos Animales de Enfermedad , Células HEK293 , Humanos , Masculino , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/patología , FN-kappa B/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Fosfato de Sitagliptina/administración & dosificación , Fosfato de Sitagliptina/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Patients with coronary heart disease (CHD) frequently have cardiovascular complications after undergoing PCI. Angiopoietin-2 (Ang-2) is an important proangiogenic factor that also plays an important role in atherosclerosis. This study aimed to evaluate the value of Ang-2 in predicting cardiovascular events after elective PCI.This prospective study enrolled 97 patients with CHD who underwent elective PCI from 2013 to 2014. Blood samples were collected in the first morning after admission and within 24 to 48âh after PCI. The primary endpoint was cardiovascular events, defined as a composite of cardiac death, nonfatal myocardial infarction/repeat revascularization, readmission for severe deterioration of angina and readmission for new onset heart failure. Based on the median level of pre-PCI or post-PCI Ang-2, the patients were divided into a low level group and a high level group.During the whole follow-up period (mean, 53â±â13âmonths), Kaplan-Meier curves of cardiovascular events showed that there was no significant difference between the two pre-PCI groups (χâ=â2.22, Pâ=â.137, and log-rank test) or the two post-PCI groups (χâ=â2.83, Pâ=â.093, and log-rank test). However, in a multivariable Cox regression model, landmark analysis showed that the patients in high level group of post-PCI, not pre-PCI, were associated with remarkable higher risks of cardiovascular events compared to the low level group during the first 1.5âyears of follow-up (adjusted HRâ=â9.99, 95%CIâ=â1.99-50.13, Pâ=â.005). However, that was of no significance from 1.5âyears to maximum follow-up years (adjusted HRâ=â0.82, 95%CIâ=â0.26-2.59, Pâ=â.733).High Ang-2 levels of post-PCI can predict the occurrence of cardiovascular events in the short to medium term.
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Angiopoyetina 2/sangre , Enfermedad Coronaria/sangre , Enfermedad Coronaria/cirugía , Intervención Coronaria Percutánea/métodos , Anciano , Angiopoyetina 2/biosíntesis , Enfermedad Coronaria/complicaciones , Femenino , Cardiopatías/etiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Pronóstico , Reoperación/estadística & datos numéricos , Factores de RiesgoRESUMEN
Patients with coronary artery disease (CAD) frequently have comorbidity of chronic kidney disease (CKD). Their renal function may deteriorate because of the use of contrast agent after percutaneous coronary intervention (PCI). Angiopoietin-2 (Ang-2), which is highly expressed in the site of angiogenesis, plays an important role in both CAD and CKD. This study aimed to investigate the relation of serum Ang-2 concentrations with the renal function after PCI.This study enrolled 57 patients with CAD undergoing PCI. Blood samples for Ang-2 were collected in the first morning after admission and within 24 to 48âh after PCI. The parameters of renal function (serum creatinine, cystatin C and eGFR) were tested on the first day after admission and within 72âh after PCI.Overall, serum Ang-2 levels of post-PCI were significantly lower than those of pre-PCI [median, 1733 (IQR, 1100-2568) vs median, 2523 (IQR, 1702-3640) pg/mL; Pâ<â.001]. However, in patients with CKD (eGFRâ<â60âmL/min/1.73âm), there was no significant difference between serum Ang-2 levels of post-PCI and those of pre-PCI [median, 2851 (IQR, 1720-4286) vs. median, 2492 (IQR, 1434-4994) pg/mL; Pâ=â.925]. In addition, serum Ang-2 levels of post-PCI, but not pre-PCI, were significantly correlated with the post-PCI parameters of renal function.Serum Ang-2 concentrations of post-PCI are closely related to renal function in patients with CAD. It may have potential to be the early biomarker of contrast-induced nephropathy in the future.
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Angiopoyetina 2/sangre , Medios de Contraste/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , Intervención Coronaria Percutánea/métodos , Insuficiencia Renal Crónica/inducido químicamente , Anciano , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/sangre , Creatinina/sangre , Cistatina C/metabolismo , Receptores ErbB/metabolismo , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Pruebas de Función Renal/métodos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatologíaRESUMEN
BACKGROUND: Angiopoietin-2 (Ang-2) plays a crucial role in hypoxia-induced angiogenesis and is expressed only in sites of vascular remodeling. Ang-2 expression can be regulated by hypoxia inducible factors and other regulators with exposure to hypoxia. The objective of this study was to investigate the influence of percutaneous coronary intervention (PCI) on serum Ang-2 concentrations, and analyze the correlation between serum Ang-2 and the severity of coronary artery stenosis in patients with coronary heart disease (CHD). METHODS: Sixty-four patients with CHD were selected as the study group, each undergone PCI. Thirty-two healthy subjects were selected as the control group. Pre-PCI and post-PCI serum Ang-2 were measured by enzyme-linked immunosorbent assay. The severity of coronary artery stenosis was evaluated using angiographic Gensini scores, and the coronary collateral vessels were scored according to Rentrop's classification. RESULTS: Concentrations of pre-PCI serum Ang-2 in the study group were significantly higher than those in the control group (4625.06 ± 1838.06 vs. 1945.74 ± 1588.17 pg/ml, P < 0.01); however, concentrations of post-PCI serum Ang-2 were significantly lower than those of pre-PCI (3042.63 ± 1845.33 pg/ml vs. 4625.06 ± 1838.06 pg/ml, P < 0.01). Concentrations of pre-PCI serum Ang-2 were significantly correlated with Gensini scores (r = 0.488, P < 0.01); however, the decrease in serum Ang-2 after PCI was not correlated with Gensini scores, coronary collateral vessel grading, or left ventricular ejection fraction. CONCLUSIONS: Serum Ang-2 concentrations significantly increased in patients with CHD, and PCI treatment significantly decreased these concentrations. Serum Ang-2 concentrations, but not the decrease in serum Ang-2 concentrations, were significantly correlated with the severity of coronary artery stenosis. These results suggested that Ang-2 may be a biomarker of myocardial ischemia and vessel remodeling.
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Angiopoyetina 2/sangre , Enfermedad de la Arteria Coronaria/terapia , Intervención Coronaria Percutánea , Adulto , Enfermedad de la Arteria Coronaria/sangre , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The purpose of this study was to study the role of neurofilament (NF) mRNA and calpain in NF reduction of acrylamide (ACR) neuropathy. Male Wistar adult rats were injected i.p. every other day with ACR (20 mg/kg·bW or 40 mg/kg·bW) for 8 weeks. NF mRNA expression was detected using RT-PCR and the calpain concentration was determined using western blot analysis. The NF mRNA expression significantly decreased while the level of m-calpain and µ-calpain significantly increased in two ACR-treated rats groups regardless of the ACR dose. The light NF (NF-L) protein expression was significantly correlated with NF-L mRNA expression. Combined with previous data, the concentrations of three NF subunits were negatively correlated with the calpain levels. These findings suggest that NF-L mRNA and calpain mediated the reduction in NF of ACR neuropathy.
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Acrilamida/toxicidad , Calpaína/metabolismo , Filamentos Intermedios/genética , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/metabolismo , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Enfermedades del Sistema Nervioso Periférico/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , RatasRESUMEN
A Gram-positive, spore-forming, rod-shaped and motile bacterium, designated strain 1-25(T), was isolated from the rhizosphere of Quercus aliena var. acuteserrata in Taibai Mountain, Shaanxi Province, China. 16S rRNA gene sequence analysis showed that strain 1-25(T) belongs to the genus Paenibacillus. Strain 1-25(T) was found to be closely related to Paenibacillus harenae and Paenibacillus castaneae with 96.0 and 95.9 % 16S rRNA gene sequence similarities, respectively. The strain was observed to grow optimally at 28 °C and pH 7.5. The major isoprenoid quinone was found to be menaquinone-7. The dominant cellular fatty acids were identified as anteiso-C15:0 and iso-C15:0. The diagnostic diamino acid in the cell-wall peptidoglycan was found to be meso-diaminopimelic acid. The DNA G+C content was determined to be 41.6 mol%. On the basis of phenotypic characteristics and molecular properties, strain 1-25(T) is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus quercus sp. nov. is proposed. The type strain is 1-25(T) (=CCTCC AB2013265(T) = KCTC 33194(T)).
Asunto(s)
Paenibacillus/clasificación , Paenibacillus/aislamiento & purificación , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Composición de Base , Pared Celular/química , China , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Ácido Diaminopimélico/análisis , Ácidos Grasos/análisis , Concentración de Iones de Hidrógeno , Locomoción , Microscopía Electrónica de Rastreo , Datos de Secuencia Molecular , Paenibacillus/genética , Paenibacillus/fisiología , Peptidoglicano/química , Filogenia , Quercus/crecimiento & desarrollo , Quinonas/análisis , ARN Ribosómico 16S/genética , Rizosfera , Análisis de Secuencia de ADN , TemperaturaRESUMEN
OBJECTIVE: To investigate the incidence of malignant tumors among fluoride-exposed workers in aluminum industry. METHODS: Sampling points were set in the working positions at different radii around an workshop for treating the waste gas from aluminum electrolysis, and the concentrations of fluoride ions, aluminum, and benzo[a]pyrene (B[a]P) in air were measured by electrode method, atomic absorption spectrophotometry, and high performance liquid chromatography, respectively. The incidence of tumors among the workers in the aluminum plant from 1995 to 2009 was investigated by questionnaires and medical records and then statistically analyzed. RESULTS: There was a negative correlation between the concentrations of fluoride and aluminum and the radius around the fluoride source at each sampling point. B[a]P was not detected at each sampling point. The crude incidence rate of tumors among factory workers was 117.95/100 000 (standardized rate = 58.81/100 000); the standardized incidence rate of tumors was higher in female workers than in male workers (male-to-female ratio = 1:2.64). The peak age of onset of tumors was 40 â¼ 49 years. The most and second most common tumors were liver cancer and lung cancer in male workers and breast cancer and lung cancer in female workers. Compared with the unexposed population in the city where the aluminum plant was located, the female fluoride-exposed workers had an increased tumor incidence, 2.14 times that of the city's average level, and the fluoride-exposed workers had a younger age of onset of tumors and approximately the same types of tumors. CONCLUSION: Fluoride exposure may lead to an increasing trend in tumor incidence among female workers in aluminum industry.
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Fluoruros , Neoplasias/epidemiología , Exposición Profesional , Adulto , Aluminio , Femenino , Humanos , Masculino , Metalurgia , Persona de Mediana EdadRESUMEN
Two major endoglucanase genes (cel7B and cel5A) were cloned from Penicillium decumbens 114-2 using the method of modified thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR). The result of Southern blotting suggested that P. decumbens has a single copy of the cel5A gene and a single copy of cel7B gene in its chromosomal DNA. The expression level of cel5A and cel7B were determined by means of real-time quantitative PCR, suggesting that two genes were coordinately expressed and repressed by glucose and induced by cellulose. Both endoglucanase genes were expressed in Saccharomyces cerevisiae and the recombinant proteins were purified. The recombinant Cel7B and Cel5A were both optimal active at 60 C and pH 4.0. The recombinant Cel7B showed more than 8-fold, 30-fold, 5-fold higher enzyme activity towards carboxymethyl cellulose, barely beta-glucan and PASC respectively in comparison with that of Cel5A. However, their activities toward pNPC and Avicel were minor difference. The result suggested that Cel7B is a strict endoglucanase, while Cel5A show processivity because of its relative higher ability to hydrolyze the crystal cellulose.