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1.
World J Urol ; 42(1): 206, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561548

RESUMEN

OBJECTIVE: Identification of superficial inguinal lymph nodes during low-risk penile cancer surgery using near-infrared (NIR) fluorescence to improve the accuracy of lymph-node dissection and reduce the incidence of missed micrometastases and complications. METHODS: Thirty-two cases were selected, which were under the criteria of < T1, and no lymph-node metastasis was found with magnetic resonance imaging (MRI) detection. Two groups were randomly divided based on the fluorescence technique, the indocyanine green (ICG) group and the non-ICG group. In the ICG group, the ICG preparation was subcutaneously injected into the edge of the penile tumor 10 min before surgery, and the near-infrared fluorescence imager was used for observation. After the lymph nodes were visualized, the superficial inguinal lymph nodes were removed first, and then, the penis surgery was performed. The non-ICG group underwent superficial inguinal lymph-node dissection and penile surgery. RESULTS: Among the 16 patients in the ICG group, we obtained 11 lymph-node specimens using grayscale values of images (4.13 ± 0.72 vs. 3.00 ± 0.82 P = 0.003) along with shorter postoperative healing time (7.31 ± 1.08 vs. 8.88 ± 2.43 P = 0.025), and less lymphatic leakage (0 vs. 5 P = 0.04) than the 16 patients in the non-ICG group. Out of 11, 3 lymph nodes that are excised were further grouped into fluorescent and non-fluorescent regions (G1/G2) and found to be metastasized. CONCLUSION: Near-infrared fluorescence-assisted superficial inguinal lymph-node dissection in penile carcinoma is accurate and effective, and could reduce surgical complications.


Asunto(s)
Neoplasias del Pene , Humanos , Masculino , Colorantes , Verde de Indocianina , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Neoplasias del Pene/diagnóstico por imagen , Neoplasias del Pene/cirugía , Neoplasias del Pene/patología , Biopsia del Ganglio Linfático Centinela/métodos
2.
Biochem Biophys Res Commun ; 650: 9-16, 2023 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-36764210

RESUMEN

CTBP1 has been demonstrated as a co-repressor in the transcriptional regulation of downstream genes and is involved in various cell process. However, the mechanism of CTBP1 in the progression of prostate cancer is still unclear. Here, we aim to investigate how CTBP1 exerts its role in prostate cancer progression, especially how CTBP1 was regulated by the upstream genes. We found that CTBP1 was highly expressed in prostate cancer and promoted the cell viability, migration, invasion and glycolysis of prostate cancer cells. CDH1 was verified to be the target of CTBP1. We determined that CTBP1 could directly bind with SP1 to inhibit the transcription of CDH1. Moreover, succinylation of CTBP1 was found to be up-regulated in prostate cancer cell. Further studies demonstrated that KAT2A promotes the succinylation of CTBP1 and mediates the transcription suppressing activity of it. In addition, the K46 and K280 was confirmed to be the two sites that regulated by KAT2A. In vivo studies further indicated that CTBP1 could promote the growth of prostate cancer, and this effect of CTBP1 could be partially reversed by KAT2A knockdown. Taken together, we found that succinylation of CTBP1 mediated by KAT2A suppresses the inhibitory activity of CTBP1 on the transcription of CDH1, thus act as an oncogene.


Asunto(s)
Proteínas de Unión al ADN , Neoplasias de la Próstata , Humanos , Masculino , Oxidorreductasas de Alcohol/metabolismo , Antígenos CD , Cadherinas/metabolismo , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica , Histona Acetiltransferasas/metabolismo , Neoplasias de la Próstata/genética , Factores de Transcripción/metabolismo
3.
Molecules ; 28(19)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37836594

RESUMEN

Periploca forrestii Schltr. (P. forrestii) is a classical medicinal plant and is commonly used in traditional medicine for the treatment of rheumatoid arthritis, soft tissue injuries, and traumatic injuries. The aim of this study was to evaluate the anti-arthritic effects of three fractions of P. forrestii alcoholic extracts (PAE), P. forrestii water extracts (PWE), and total flavonoids from P. forrestii (PTF) on Freund's complete adjuvant (FCA)-induced arthritis in rats, and to use a non-targeted lipidomic method to investigate the mechanism of action of the three fractions of P. forrestii in the treatment of rheumatoid arthritis. To assess the effectiveness of anti-rheumatoid arthritis, various indicators were measured, including joint swelling, histopathological changes in the joints, serum cytokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6)), and the joint inflammatory substance prostaglandin E2 (PGE2). Finally, ultra-performance liquid chromatography-quadrupole-orbitrap-high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) was used to determine the non-targeted lipid histology of the collected rat serum and urine samples to investigate the possible mechanism of action. PWE, PAE, and PTF were all effective in treating FCA-induced rheumatoid arthritis. The administered groups all reduced joint swelling and lowered serum inflammatory factor levels in rats. In the screening of lipid metabolite differences between serum and urine of the rat model group and the normal group, a total of 52 different metabolites were screened, and the levels of lipid metabolites in PWE, PAE, and PTF were significantly higher than those in the normal group after administration. In addition, PWE, PAE, and PTF may have significant therapeutic effects on FCA-induced arthritis by modulating nicotinic acid, nicotinamide, and histidine metabolic pathways.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Periploca , Ratas , Animales , Periploca/química , Extractos Vegetales/análisis , Ratas Sprague-Dawley , Lipidómica , Artritis Reumatoide/tratamiento farmacológico , Colágeno/uso terapéutico , Interleucina-6 , Adyuvantes Inmunológicos/uso terapéutico , Adyuvante de Freund , Adyuvantes Farmacéuticos , Lípidos/uso terapéutico , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología
4.
Molecules ; 27(11)2022 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-35684454

RESUMEN

The clinical pharmacodynamics of tacrolimus in renal transplant patients has significant interindividual variability. T lymphocytes were selected to study the pharmacodynamic response of tacrolimus, which was significantly correlated with renal function and the outcome of renal transplant patients. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectroscopy (UPLC/Q-TOF-MS) was performed to obtain the metabolic profiles of 109 renal transplant patients. A partial least squares (PLS) model was constructed to screen potential biomarkers that could predict the efficacy of tacrolimus. Multinomial logistic regression analysis established a bridge that could quantify the relationship between the efficacy of tacrolimus and biomarkers. The results showed a good correlation between endogenous molecules and the efficacy of tacrolimus. Metabolites such as serum creatinine, mesobilirubinogen, L-isoleucine, 5-methoxyindoleacetate, eicosapentaenoic acid, N2-succinoylarginine, tryptophyl-arginine, and butyric acid were indicated as candidate biomarkers. In addition, the key biomarkers could correctly predict the efficacy of tacrolimus with an accuracy of 82.5%. Finally, we explored the mechanism of individual variation by pathway analysis, which showed that amino acid metabolism was significantly related to the efficacy of tacrolimus. Moreover, orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there was no difference in key metabolites among different pharmacodynamic groups at 1 month and 3 months after dose adjustment, suggesting that pharmacometabonomics is a useful tool to predict individual differences in pharmacodynamics and thus to facilitate individualized drug therapy.


Asunto(s)
Trasplante de Riñón , Metabolómica , Biomarcadores , Cromatografía Líquida de Alta Presión , Humanos , Espectrometría de Masas/métodos , Metabolómica/métodos , Tacrolimus
5.
J Sep Sci ; 44(9): 1833-1842, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33586849

RESUMEN

Heterocyclic aromatic amines, as a group of mutagenic and carcinogenic compounds, have gained worldwide concern. In this study, an accurate, rapid, and sensitive confirmation and quantification method of four major heterocyclic aromatic amines in roasted pork was developed based on Q-Orbitrap along with Quick, Easy, Cheap, Effective, Rugged, and Safe extraction. The limit of detections and limit of quantitations were found to be 0.2-1.2 µg/kg and 0.6-3.5 µg/kg, respectively, revealing the high sensitivity of this method. Obtained results showed recoveries ranging from 78.1 to 97.4%, depending on the different heterocyclic aromatic amines and spiked levels. Precision was in the range of 2.6-4.5% for four heterocyclic aromatic amines at different levels. In addition, the developed method had been applied to investigate the inhibitory effects of astaxanthin on the above-mentioned heterocyclic aromatic amines in roasted pork. The amount of astaxanthin with the best inhibitory effects was 7.5 mg (0.0375%), which led to significant reduction in heterocyclic aromatic amines levels over 50%.


Asunto(s)
Aminas/análisis , Análisis de los Alimentos , Compuestos Heterocíclicos/análisis , Carne de Cerdo/análisis , Aminas/antagonistas & inhibidores , Animales , Compuestos Heterocíclicos/antagonistas & inhibidores , Porcinos , Xantófilas/química , Xantófilas/farmacología
6.
Ecotoxicol Environ Saf ; 222: 112506, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34265531

RESUMEN

While numerous studies have shown that fluoride or arsenic exposure may damage the reproductive system, there are few reports of co-exposure to fluoride and arsenic. In addition, the literature on autophagy and intestinal flora composition in reproductive toxicity studies of co-exposure to fluoride and arsenic is insufficient. In this study, we developed a rat model of fluoride and arsenic exposure via drinking water from pre-pregnancy to 90 days postnatal. Sprague-Dawley rats were randomly divided into sterile water control group, fluoride group (100 mg/L NaF), arsenic group (50 mg/L NaAsO2) and combined exposure group (100 mg/L NaF+50 mg/L NaAsO2). Our results showed that fluoride and arsenic exposure caused a reduction in testicular weight and significant pathological damage to tissue. We found that the levels of follicle-stimulating hormone, luteinizing hormone, and testosterone were reduced to varying degrees. Meanwhile experiments showed that fluoride and arsenic exposure can modulate autophagic flux, causing increased levels of Beclin1 and LC3 expression and decreased p62 expression. Analogously, by performing 16S sequencing of rat feces, we found 24 enterobacterial genera that differed significantly among the groups. Furthermore, the flora associated with testicular injury were identified by correlation analysis of hormonal indices and autophagy alterations with intestinal flora composition at the genus level, respectively. In summary, our study shows that fluoride and arsenic co-exposure alters autophagic flux in the testis, causes testicular injury, and reveals an association between altered intestinal flora composition and testicular injury.


Asunto(s)
Arsénico , Microbioma Gastrointestinal , Animales , Arsénico/toxicidad , Autofagia , Femenino , Fluoruros/toxicidad , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Testículo
7.
BMC Womens Health ; 20(1): 146, 2020 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-32677935

RESUMEN

BACKGROUND: Recent study found that vitamin D before conception was considered as a potential additional determinant for achieving pregnancy and live births. The study aimed to evaluate the serum 25 hydroxyvitamin D (25(OH)D) levels and its affecting factors among preconception fertile women. METHODS: This cross-sectional study enrolled 410 women aged 22-44 years who attended a preconception genetic counseling clinic from January 2018 to May 2019. Sociodemographic characteristics and reproductive history of women were collected, and height and weight were measured. Serum 25(OH)D concentration was assayed with chemiluminescence immunoassay. Descriptive statistics were used to examine serum 25(OH)D concentration, and socio-demographic characteristics and reproductive history among preconception women. Determinants of vitamin D deficiency and its affecting factors were assessed using χ2 test and logistic regression. RESULTS: Findings showed 84.4% of women had serum 25(OH)D concentration below 20 ng/mL. Women working indoors as well as without a history of childbirth had significantly lower 25(OH)D levels compared with those non-working individuals and having delivered a previous child (both P < 0.05). The 25(OH)D levels were the lowest in winter among that in spring, summer, and autumn (all P < 0.001). Women in winter have significantly elevated OR of 5.00 (95%CI 1.75-14.25) to develop vitamin D deficiency. Seasonal variation in serum 25(OH)D levels was not present in non-working individuals and women aged 31-44 years. CONCLUSIONS: Vitamin D deficiency is common among preconception women especially nulliparous women and working women, which propose to screen serum 25(OH)D on preconception evaluation and emphasize need vitamin D supplements and get sunshine exposure.


Asunto(s)
Atención Preconceptiva , Vitamina D/análogos & derivados , Adulto , Índice de Masa Corporal , Niño , China/epidemiología , Estudios Transversales , Empleo , Femenino , Humanos , Embarazo , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Adulto Joven
8.
Ecotoxicol Environ Saf ; 197: 110605, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32311614

RESUMEN

Fluorosis is a worldwide public health problem, and its adverse effects on the heart have been confirmed by many studies. Abnormal myocardial contractions are often associated with impairment of cardiac function as a cause or consequence. We designed two-part experiments to search for biomarkers and clarify the underlying molecular mechanism of fluoride on myocardial contraction. First, we used Pressure-volume Loop analysis to evaluate changes in myocardial function indexes with multiple fluoride exposure levels in mice (0, 30, 70, and 150 mg/L) exposed for 4 weeks. The results showed that fluoride exposure affects the heart pump function and reduces cardiac contractility. Then, we established a rat model of fluoride exposure (0, 30, 60, and 90 mg/L) for 6 months to carry out proteomic analysis of fluoride-induced myocardial contractile injury. Hematoxylin-eosin (H&E) staining was used to determine the severity of myocardial injury, and myocardial tissue samples were submitted for isobaric tags for relative and absolute quantitation (ITRAQ) analysis. A total of 1607 proteins were successfully identified with 294 differentially expressed proteins (DEPs) in fluoride treated groups. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, 12 DEPs were confirmed to be involved in pathways related to myocardial contraction. Furthermore, we constructed a protein-protein interaction (PPI) network for these 12 core DEPs to illustrate the role and location of each DEP in the myocardial contraction pathway. The results of this study are helpful for identify a potential mechanism and biomarkers of fluoride-induced myocardial contraction function damage, moreover, which can provide a new insight into the heart toxicity of fluoride in animals at the proteomics level.


Asunto(s)
Cardiomiopatías/inducido químicamente , Fluoruros/toxicidad , Contracción Miocárdica/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Ontología de Genes , Masculino , Ratones , Mapeo de Interacción de Proteínas , Proteínas/metabolismo , Proteómica/métodos , Ratas
9.
Chem Biodivers ; 17(12): e2000763, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33085165

RESUMEN

Many phytopathogenic fungi cause severe damage to crop yields. In continuation of our research aimed at the discovery and development of natural products-based fungicides, a series of thirty-one sarisan attached 3-phenylisoxazolines were synthesized and evaluated for their antifungal activities against five phytopathogenic fungi (B. cinerea, C. lagenarium, A. solani, F. solani, and F. graminearum). Among all title sarisan derivatives, compounds IV2, IV14 and IV23 showed potent antifungal activity against some phytopathogenic fungi. In particular, compound IV2 exhibited a broad-spectrum and more potent antifungal activity against A. solani, F. solani, and F. graminearum than the commercial fungicide Hymexazol. In addition, compounds IV2, IV14 and IV23 also displayed relative low toxicity on normal NRK-52E cells. This work will give some insights into the development of sarisan derivatives as new fungicide candidates in plant protection.


Asunto(s)
Productos Biológicos/síntesis química , Productos Biológicos/farmacología , Dioxolanos/química , Fungicidas Industriales/síntesis química , Fungicidas Industriales/farmacología , Oxazoles/química , Enfermedades de las Plantas/prevención & control , Productos Biológicos/química , Hongos/efectos de los fármacos , Fungicidas Industriales/química , Pruebas de Sensibilidad Microbiana , Enfermedades de las Plantas/microbiología , Relación Estructura-Actividad
10.
Molecules ; 24(17)2019 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-31480657

RESUMEN

Alnustone, a nonphenolic diarylheptanoid, first isolated from Alnus pendula (Betulaceae), has recently received a great deal of attention due to its various beneficial pharmacological effects. However, its pharmacokinetic profile in vivo remains unclear. The purpose of this study is to establish a fast and sensitive quantification method of alnustone using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate the pharmacokinetic and tissue distribution profiles of alnustone in rats. The sample was precipitated with acetonitrile with 0.5% formic acid and separated on BEH C18 Column. The mobile phase was composed of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL/min. Alnustone and the internal standard (caffeine) were quantitatively monitored with precursor-to-product ion transitions of m/z 262.9→105.2 and m/z 195.2→138.0, respectively. The calibration curve for alnustone was linear from 1 to 2000 ng/mL. The intra- and inter-day assay precision (RSD) ranged from 1.1-9.0 % to 3.3-8.6%, respectively and the intra- and inter-day assay accuracy (RE) was between -8.2-9.7% and -10.3-9.9%, respectively. The validated method was successfully applied to the pharmacokinetic studies of alnustone in rats. After single-dose intravenous administration of alnustone (5 mg/kg), the mean peak plasma concentration (Cmax) value was 7066.36 ± 820.62 ng/mL, and the mean area under the concentration-time curve (AUC0-t) value was 6009.79 ± 567.30 ng/mL∙h. Our results demonstrated that the residence time of alnustone in vivo was not long and it eliminated quickly from the rat plasma. Meanwhile, the drug is mainly distributed in tissues with large blood flow, and the lung and liver might be the target organs for alnustone efficacy. The study will provide information for further application of alnustone.


Asunto(s)
Cromatografía Liquida/métodos , Diarilheptanoides/administración & dosificación , Diarilheptanoides/farmacocinética , Espectrometría de Masas en Tándem/métodos , Administración Intravenosa , Animales , Cafeína/química , Calibración , Diarilheptanoides/sangre , Diarilheptanoides/química , Límite de Detección , Masculino , Ratas Sprague-Dawley , Estándares de Referencia , Reproducibilidad de los Resultados , Distribución Tisular
11.
Mar Drugs ; 15(5)2017 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-28452963

RESUMEN

Carboxymethyl chitosan (CMCS) microparticles are a potential candidate for hemostatic wound dressing. However, its low swelling property limits its hemostatic performance. Poly(γ-glutamic acid) (PGA) is a natural polymer with excellent hydrophilicity. In the current study, a novel CMCS/PGA composite microparticles with a dual-network structure was prepared by the emulsification/internal gelation method. The structure and thermal stability of the composite were determined by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The effects of preparation conditions on the swelling behavior of the composite were investigated. The results indicate that the swelling property of CMCS/PGA composite microparticles is pH sensitive. Levofloxacin (LFX) was immobilized in the composite microparticles as a model drug to evaluate the drug delivery performance of the composite. The release kinetics of LFX from the composite microparticles with different structures was determined. The results suggest that the CMCS/PGA composite microparticles are an excellent candidate carrier for drug delivery.


Asunto(s)
Quitosano/análogos & derivados , Ácido Poliglutámico/análogos & derivados , Quitosano/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Cinética , Espectroscopía de Fotoelectrones/métodos , Ácido Poliglutámico/química , Polímeros/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Termogravimetría/métodos , Difracción de Rayos X/métodos
12.
Arch Biochem Biophys ; 606: 128-33, 2016 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-27477959

RESUMEN

The multiple functions of vitamin D3 have stimulated interest in the role that this vitamin may play during pregnancy. The present study investigated the expression of the vitamin D receptor (VDR) in women during the first trimester of pregnancy in order to determine whether VDR is associated with recurrent pregnancy loss (RPL). Forty women at 7-10 weeks gestation with RPL and 40 women of similar gestational age with a healthy pregnancy were recruited. VDR mRNA and protein in chorionic villi and decidua were evaluated by immunohistochemistry, confocal laser scanning microscopy (CLSM), western blot, and quantitative real-time polymerase chain reaction. The serum levels of VDR were measured by an enzyme-linked immunosorbent assay. Women with RPL had a significantly weaker expression of VDR mRNA in villi and decidual tissues compared with the control women (both p < 0.0001). Western blot analysis showed an approximately 46% decrease in VDR expression in villi and a 52% decrease in decidua in the RPL vs. the controls. Serum VDR levels were also significantly lower in the RPL group than in the control group (p = 0.003). Compared with the controls, immunohistochemical and CLSM analysis revealed significantly lower VDR expression in villous cytotrophoblasts and stromal cells, as well as in decidual glandular epithelial and stromal cells (all p < 0.05). In conclusion, these observations show that women with RPL have lower levels of VDR expression in chorionic villi, decidua and serum compared with normal pregnant women, suggesting that decreased VDR expression in the first trimester pregnancy may be associated with RPL.


Asunto(s)
Aborto Habitual/metabolismo , Vellosidades Coriónicas/metabolismo , Decidua/metabolismo , Receptores de Calcitriol/metabolismo , Células del Estroma/metabolismo , Trofoblastos/metabolismo , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Microscopía Confocal , Embarazo , Primer Trimestre del Embarazo , ARN Mensajero/metabolismo , Ultrasonografía Prenatal
13.
Nurse Educ Pract ; 79: 104087, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39142120

RESUMEN

OBJECTIVES: To address the nursing crisis, it is imperative to comprehend the factors that influence nursing competencies, which are crucial for the delivery of quality patient care. BACKGROUND: Facing demographic shifts and increasingly complex healthcare demands, China's nursing sector struggles with workforce shortages and the need to enhance core competencies. This research explores the interplay of social support, psychological resilience, mindfulness and nursing competencies in various hospital environments in China. METHODS: Through a cross-sectional survey, 941 nurses across tertiary, secondary and private healthcare settings completed self-assessment questionnaires. The analysis included multiple linear regression and comparative methods to assess how psychological resilience, mindfulness and social support have an impact on nursing competencies. RESULTS: Findings revealed a strong relationship between psychological resilience and nursing competencies, with resilience being a key predictor. Mindfulness and social support also significantly contributed to competency levels. Nurses in tertiary hospitals showed greater competencies than those in secondary or private facilities. CONCLUSION: Enhancing nursing competencies requires targeted interventions focusing on professional development and supportive workplace cultures. Incorporating psychological resilience, social support and mindfulness into nurse training is crucial for improving practice and policy.


Asunto(s)
Competencia Clínica , Atención Plena , Resiliencia Psicológica , Apoyo Social , Humanos , China , Estudios Transversales , Encuestas y Cuestionarios , Femenino , Adulto , Masculino , Persona de Mediana Edad , Lugar de Trabajo/psicología
14.
Anal Methods ; 16(7): 1050-1057, 2024 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-38269419

RESUMEN

Selinexor is a nuclear exportin-1 (XPO1) inhibitor that has been approved for the treatment of multiple myeloma patients. However, sustained use of selinexor may result in some undesirable consequences. Furthermore, selinexor has moderate inter-patient variability. Herein, we developed an ultrahigh-performance liquid chromatography tandem mass spectrometry method for measuring selinexor levels in human plasma ranging from 1 to 1000 ng mL-1. Furthermore, the developed approach was validated in accordance with FDA criteria. The established approach demonstrated inter-day and intra-day precision, expressed as the relative standard deviation, of less than 8%, with accuracies of less than 6%, expressed as relative error. The results showed that the protein depletion was quite complete for selinexor extraction, with recoveries ranging from 85.89 to 108.38%. The validated method facilitates the quantitation of selinexor in multiple myeloma patients. The selinexor plasma concentration exhibits obvious inter-patient' variability after administration. Thus, it is necessary to make a personalized prescription through therapeutic drug monitoring. Furthermore, the change in platelet counts before and after selinexor treatment was shown to be related to the plasma concentration at 3 h after administration, which provides the basis for therapeutic drug monitoring sampling time points and a method for predicting the occurrence of thrombocytopenia. In conclusion, the developed method can be used for the quantification of the plasma concentration of selinexor, and it is of great significance to conduct therapeutic drug monitoring for patients taking selinexor in order to enhance therapeutic effects and prevent the occurrence of adverse reactions.


Asunto(s)
Hidrazinas , Mieloma Múltiple , Triazoles , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/metabolismo , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , China
15.
Front Psychol ; 15: 1309901, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38323158

RESUMEN

Objective: To explore the chain-mediated role of sense of career benefit and sense of career mission in the mechanism of psychological flexibility's effect on nurses' work engagement. Methods: Adopting the convenience sampling method, 1032 nurses in 10 general hospitals in Sichuan Province were surveyed by questionnaires using the General Information Questionnaire, Sense of Occupational Benefit Scale, Sense of Occupational Mission Scale, Psychological Flexibility Scale, and work engagement Scale in August-October 2022, and the model of the chained-mediated effect was constructed and validated. Results: The total psychological resilience score of nurses in 10 general hospitals in Sichuan Province was (91.29 ± 17.38), the total score of sense of occupational benefit was (137.85 ± 21.02), the total score of sense of occupational mission was (40.27 ± 7.37), and the total score of work engagement was (34.99 ± 9.80). The total score of nurses' work engagement was positively correlated with the total scores of psychological elasticity, sense of professional benefit, and sense of professional mission (all P < 0.05). The direct effect of psychological elasticity on nurses' work engagement was significant, with an effect value of 0.321; the chain mediation effects of occupational benefit and occupational mission as separate mediators and the chain mediation effects of the two were 0.039, 0.032, and 0.062, respectively. Conclusion: Nurses' work engagement in 10 general hospitals in Sichuan province is at a medium level, and occupational benefit and occupational mission play a significant role in the mechanism of the psychological elasticity's effects on nurses' work commitment, and the chain mediation effect of occupational mission in the mechanism of psychological elasticity is established. The chain mediation effect in the mechanism was established. Managers should pay attention to nurses with low psychological elasticity, improve their sense of occupational benefit, and enhance their sense of occupational mission in order to further promote the enhancement of work engagement.

16.
Sci Total Environ ; 948: 174392, 2024 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-38955277

RESUMEN

Neonicotinoid pollution has increased rapidly and globally in recent years, posing significant risks to agricultural areas. Quantifying use and emission, transport and fate of these contaminants, and risks is critical for proper management of neonicotinoids in river basin. This study elucidates use and emissions of neonicotinoid pesticides in a typical large-scale agriculture basin of China, the Pearl River Basin, as well as the resulting agricultural non-point source pollution and related ecological risks using market surveys, data analysis, and the Soil and Water Assessment Tool. Neonicotinoid use in the basin was estimated at 1361 t in 2019, of which 83.1 % was used in agriculture. After application, approximately 99.1 t neonicotinoids were transported to the Pearl River, accounting for 7.2 % of the total applied. Estimated aquatic concentrations of neonicotinoids showed three seasonal peaks. Several distinct groups of neonicotinoid chemicals can be observed in the Pearl River, as estimated by the model. An estimated 3.9 % of the neonicotinoids used were transported to the South China Sea. Based on the present risk assessment result, several neonicotinoids posed risks to aquatic organism. Therefore, the use of alternative products and/or reduced use is deemed necessary. This study provides novel insights into the fate and ecological risks of neonicotinoid insecticides in large-scale watersheds, and underscores the need for greater efficiency of use and extensive environmental monitoring.


Asunto(s)
Agricultura , Monitoreo del Ambiente , Insecticidas , Neonicotinoides , Ríos , Contaminantes Químicos del Agua , China , Insecticidas/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis , Neonicotinoides/análisis , Medición de Riesgo
17.
J Med Chem ; 67(11): 9302-9317, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38491982

RESUMEN

The escalation of multidrug-resistant bacterial infections, especially infections caused by methicillin-resistant Staphylococcus aureus (MRSA), underscores the urgent need for novel antimicrobial drugs. Here, we synthesized a series of amphiphilic 2-phenyl-1H-phenanthro[9,10-d]imidazole-antimicrobial peptide (AMP) mimic conjugates (III1-30). Among them, compound III13 exhibited excellent antibacterial activity against G+ bacteria and clinical MRSA isolates (MIC = 0.5-2 µg/mL), high membrane selectivity, and low toxicity. Additionally, compared with traditional clinical antibiotics, III13 demonstrated rapid bactericidal efficacy and was less susceptible to causing bacterial resistance. Mechanistic studies revealed that III13 targets phosphatidylglycerol (PG) on bacterial membranes to disrupt membrane integrity, leading to an increase in intracellular ROS and leakage of proteins and DNA, ultimately causing bacterial cell death. Furthermore, III13 possessed good fluorescence properties with potential for further dynamic monitoring of the antimicrobial process. Notably, III13 showed better in vivo efficacy against MRSA compared to vancomycin, suggesting its potential as a promising candidate for anti-MRSA medication.


Asunto(s)
Antibacterianos , Péptidos Antimicrobianos , Imidazoles , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Imidazoles/química , Imidazoles/farmacología , Imidazoles/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Animales , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/síntesis química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/farmacología , Relación Estructura-Actividad , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Ratones , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología
18.
Evol Lett ; 8(4): 494-504, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39100238

RESUMEN

Reindeer have long been served as vital subsistence resources for inhabitants of Arctic and subarctic regions owing to their domestication. However, the evolutionary relationships and divergence times among different reindeer populations, genetic traits that distinguish domesticated reindeer, and factors that contribute to their relative docility compared with that of other Cervidae specie, remain unclear. In this study, we sequenced the genomes of 32 individuals from wild and domestic reindeer populations that inhabit Arctic and subarctic regions. We found that reindeer experienced 2 or more independent domestication events characterized by weak artificial selection pressure and limited significant differences in genomic parameters between wild and domestic populations. Alterations in conserved noncoding elements in the reindeer genomes, particularly those associated with nervous system development, may have contributed to their domestication by rendering the nervous system less responsive. Together, our results suggest that inherent species-specific traits, rather than intense artificial selection, may have played a significant role in the relatively docile behavior of reindeer and offer valuable insights into the domestication process of these animals.

19.
Open Life Sci ; 18(1): 20220679, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37589003

RESUMEN

The aim of this study was to investigate the effects of adiponectin (APN) on the proliferation and phenotypic transformation of human skin fibroblasts (HSFs) induced by TGF-ß1. Primary fibroblast cultures were collected from prepuce surgery, and the cell viability and proliferative activity of HSFs were detected by Cell Counting Kit-8 and EdU assays. In addition, cell migration was detected by Transwell assay. The protein levels of related genes in HSF were detected by Western blotting. The results showed that the proliferation and migration abilities of HSF in the TGF-ß1 group were significantly improved, and the relative protein expression levels of PCNA, α-SMA, and Collagen I in the TGF-ß1 group were greatly increased. Furthermore, TGF-ß1 stimulated the phosphorylation of p38 in HSF, while APN pretreatment significantly inhibited the TGF-ß1-induced phosphorylation of p38. Additionally, blocking the p38 MAPK signaling pathway relieved the injury in the HSF induced by TGF-ß1 and enhanced the therapeutic effect of APN in the TGF-ß1-treated HSF. In conclusion, APN inhibits TGF-ß1-induced HSF proliferation and myofibroblast phenotypic transformation by activating the p38 MAPK signaling pathway. APN is expected to become a potential target for preventing and treating skin fibrosis and pathological scars.

20.
PLoS One ; 18(8): e0289105, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37561799

RESUMEN

BACKGROUND: The development of core competency is crucial for the success of new nurses, enabling them to deliver high-quality care. Psychological capital (PsyCap), encompassing self-efficacy, optimism, hope, and resilience, significantly influences individuals' abilities and achievements across various professions. However, limited research has specifically examined the impact of PsyCap on the core competency of new nurses. This study aims to bridge this gap by investigating the relationship between PsyCap and core competency development in new nurses, providing valuable strategic insights for improving PsyCap and promoting core competence acquisition. METHODS: 142 new nurses were chosen for the investigation using a convenient cluster sampling method. The questionnaire included components on socio-demographic characteristics, the Competency Inventory for Registered Nurses (CIRN), and the PsyCap Questionnaire-24 (PCQ-24). The t-test, One-Way ANOVA, Pearson correlation analysis and hierarchical multiple regression were used for statistical analysis. RESULT: The number of valid questionnaires was 138, and the effective return rate was 97.2%. The overall mean score for core competencies was 171.01 (SD 25.34), and the PsyCap score was 104.76(SD 13.71). The PsyCap of new nurses was highly correlated with core competency, with a correlation coefficient of r = 0.7, p < 0.01. Self-efficacy of PsyCap is a significant independent predictor of core competency (adjust R2 = 0.49). CONCLUSION: Self-efficacy in PsyCap is an important predictor of new nurses' core competency. Nursing managers should pay sufficient attention to the cultivation and development of new nurses' PsyCap, with particular emphasis on enhancing self-efficacy to improve their core competency.


Asunto(s)
Enfermeras y Enfermeros , Optimismo , Humanos , Estudios Transversales , Encuestas y Cuestionarios , Autoeficacia
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