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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124934, 2025 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-39216369

RESUMEN

Two coordination polymers (CPs), [Zn5(L)2(phen)5](1) and [Cd2(HL)(2,2-bpy)(H2O)3](2), were synthesized by using 2',3,3',5,5'-Diphenyl ether pentacarboxylic acid (H5L), phenanthroline (phen), and 2,2'-bipyridine (2,2'-bpy) under hydrothermal conditions. The L5- ligand adopts the µ6-к2: к2: к1: к1: к1: к1 mode in 1 and the µ5-к2: к2: к2: к2: к1 mode in 2. Sensing experiments show that 1 and 2 are fluorescence probes with high sensitivity and rapid detection of nitro explosives, antibiotics, and pesticides. In order to verify the ability of 2 to detect FLU in actual samples, we performed a spiked recovery experiment in green pepper water. The spiked recoveries were 97.77-101.18 %. Interestingly, because H5L is not completely deprotonated in 2, there is abundant hydrogen bonding, which makes the fluorescence quenching rate higher and the detection limit lower. The possible fluorescence quenching mechanism of 1 and 2 can be explained by their UV-VIS absorption spectra and orbital energy levels.

2.
Metabolism ; : 156041, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39362518

RESUMEN

BACKGROUND: Metabolic reprogramming is a hallmark of cancer, characterized by a high dependence on glycolysis and an enhanced utilization of acetate as an alternative carbon source. ACSS2 is a critical regulator of acetate metabolism, playing a significant role in the development and progression of various malignancies. ACSS2 facilitates the conversion of acetate to acetyl-CoA, which participates in multiple metabolic pathways and functions as an epigenetic regulator of protein acetylation, thereby modulating key cellular processes such as autophagy. However, the roles and intrinsic connections of ACSS2, glycolysis, protein acetylation, and autophagy in ovarian cancer (OC) remain to be elucidated. BASIC PROCEDURES: Utilizing clinical specimens and online databases, we analysed the expression of ACSS2 in OC and its relationship with clinical prognosis. By knocking down ACSS2, we evaluated its effects on the malignant phenotype, acetate metabolism, glycolysis, and autophagy. The metabolic alterations in OC cells were comprehensively analysed using Seahorse assays, transmission electron microscopy, membrane potential measurements, and stable-isotope labeling techniques. CUT&TAG and co-immunoprecipitation techniques were employed to explore the deacetylation of autophagy-related proteins mediated by ACSS2 via SIRT1. Additionally, through molecular docking, transcriptome sequencing, and metabolomics analyses, we validated the pharmacological effects of paeonol on ACSS2 and the glycolytic process in OC cells. Finally, both in vitro and in vivo experiments were performed to investigate the impact of paeonol on autophagy and its anti-OC effects mediated through the ACSS2/SIRT1 deacetylation axis. MAIN FINDINGS: ACSS2 is significantly upregulated in OC and is associated with poor prognosis. Knockdown of ACSS2 inhibits OC cells proliferation, migration, invasion, angiogenesis, and platinum resistance, while reducing tumour burden in vivo. Mechanistically, inhibiting ACSS2 reduces acetate metabolism and suppresses glycolysis by targeting HXK2. This glycolytic reduction promotes the translocation of ACSS2 from the cytoplasm to the nucleus, leading to increased expression of the deacetylase SIRT1. SIRT1 mediates the deacetylation of autophagy-related proteins, such as ATG5 and ATG2B, thereby significantly activating autophagy in OC cells and exerting antitumor effects. Paeonol inhibits acetate metabolism and glycolysis in OC cells by targeting ACSS2. Paeonol activates autophagy through the ACSS2/SIRT1/ATG5/ATG2B deacetylation axis, demonstrating inhibition of OC in vitro and in vivo. PRINCIPAL CONCLUSIONS: Pae can serve as an effective, low-toxicity, multi-targeted drug targeting ACSS2 and glycolysis. It activates autophagy through the ACSS2/SIRT1/ATG5/ATG2B deacetylation signalling cascade, thereby exerting anti-OC effects. Our study provides new insights into the malignant mechanisms of OC and offers a novel strategy for its treatment.

3.
Pharm Biol ; 62(1): 691-701, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39363520

RESUMEN

CONTEXT: Achyranthes bidentata Blume (ABB), a plant of Amaranthaceae family, has been one of the more commonly used phytomedicine remedies for thousands of years, and recent studies have highlighted the efficacy of its extracts in the treatment of osteoporosis. Nonetheless, a thorough analysis of its benefits is currently absent. OBJECTIVE: This meta-analysis assessed the effects of ABB root extract (ABBRE) on osteoporotic rats and provides a rationale for future clinical studies. METHODS: Searches were conducted in seven different Chinese and English databases, and the search period was from their establishment to January 2024. This study was registered in PROSPERO (CRD42023418917). Selected research regarding the ABBRE treatment of osteoporotic rats, and the corresponding research has distinctly reported outcomes, and the data on the bone mineral density (BMD), bone histomorphometrics, biomechanical parameters, and bone biochemical markers of osteoporotic rats can be extracted. RESULTS: Through screening, 11 studies met the eligibility requirements for inclusion, in which 222 animals were studied. The treatment group with ABBRE exhibited increased bone mineral density (standardized mean difference [SMD] = 1.64, 95% CI = 0.52 to 2.77). Based on subgroup analysis, the greatest increase in bone mineral density was observed when the dose of ABBRE was ≤ 400 mg/kg/day and the duration of treatment was ≤ 12 weeks. CONCLUSIONS: ABBRE is a phytomedicine that can effectively promote the enhancement of bone mineral density and ease osteoporosis. It can be developed into a new alternative therapy by conducting experiments and clinical studies on larger samples.


Asunto(s)
Achyranthes , Densidad Ósea , Osteoporosis , Extractos Vegetales , Raíces de Plantas , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Ratas , Osteoporosis/tratamiento farmacológico , Densidad Ósea/efectos de los fármacos , Femenino , Modelos Animales de Enfermedad
4.
Ther Adv Neurol Disord ; 17: 17562864241273087, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39314259

RESUMEN

Background: The widespread clinical use of lacosamide (LCM) has revealed significant individual differences in clinical response, with various reported influencing factors. However, it remains unclear how genetic factors related to the disposition and clinical response of LCM, as well as drug-drug interactions (DDIs), exert their influence on pediatric patients with epilepsy. Objectives: To evaluate the impact of genetic variations and DDIs on plasma LCM concentrations and clinical response. Design: Patients with epilepsy treated with LCM from June 2021 to March 2023 in the Children's Hospital of Nanjing Medical University were included in the analysis. Methods: The demographic information and laboratory examination data were obtained from the hospital information system. For the pharmacogenetic study, the left-over blood specimens, collected for routine plasma LCM concentration monitoring, were used to perform genotyping analysis for the selected 26 single nucleotide polymorphisms from 14 genes. The trough concentration/daily dose (C 0/D) ratio and efficacy outcomes were compared. Results: Patients achieved 90.1% and 68.9% responder rates in LCM mono- and add-on therapy, respectively. The genetic variant in the CYP2C19 *2 (rs4244285) was associated with a better responsive treatment outcome (odds ratio: 1.82; 95% confidence interval: 1.05-3.15; p = 0.031). In monotherapy, 36% of patients were CYP2C19 normal metabolizers (NMs), 49% were intermediate metabolizers (IMs), and 15% were poor metabolizers (PMs) carrying CYP2C19 *2 or *3. Of note, the C 0/D ratios of IMs and PMs were 9.1% and 39.6% higher than those of NMs, respectively. Similar results were in the add-on therapy group, and we also observed a substantial decrease in the C 0/D ratio when patients were concomitant with sodium channel blockers (SCBs). Conclusion: This study was the first to confirm that CYP2C19 *2 or *3 variants impact the disposition and treatment response of LCM in children with epilepsy. Moreover, concomitant with SCBs, particularly oxcarbazepine, also decreased plasma LCM concentration.


CYP2C19 genotype and sodium channel blockers in lacosamide-treated children with epilepsy: two major determinants of plasma lacosamide concentration or treatment efficacy This study examined the impact of genetic factors and drug combinations on the effectiveness and plasma concentrations of lacosamide, an antiseizure medication, in patients under 18. Analyzing blood samples from 316 patients at the Children's Hospital of Nanjing Medical University, researchers discovered that genetic variations in the CYP2C19 (i.e. *2 and *3), along with metabolic capacity, and co-medication with sodium channel blockers, all influence plasma lacosamide concentration. Understanding these genetic influences could inform personalized dosing strategies, improving the medication's management for pediatric epilepsy patients.

5.
Eur J Pharm Biopharm ; : 114484, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39251033

RESUMEN

BACKGROUND: Several population pharmacokinetic (PopPK) models of caffeine in preterm infants have been published, but the extrapolation of these models to facilitate model-informed precision dosing (MIPD) in clinical practice is uncertain. This study aimed to comprehensively evaluate their predictive performance using an external, independent dataset. METHODS: Data used for external evaluation were based on an independent cohort of preterm infants. Currently available PopPK models for caffeine in preterm infants were identified and re-established. Prediction- and simulation-based diagnostics were used to assess model predictability. The influence of prior information was assessed using Bayesian forecasting. RESULTS: 120 plasma samples from 76 preterm infants were included in the evaluation dataset. Twelve PopPK models of caffeine in preterm infants were re-established based on our previously published study. Although two models showed superior predictive performance, none of the 12 PopPK models met all the clinical acceptance criteria of these external evaluation items. Besides, the external predictive performances of most models were unsatisfactory in prediction- and simulation-based diagnostics. Nevertheless, the application of Bayesian forecasting significantly improved the predictive performance, even with only one prior observation. CONCLUSIONS: Two models that included the most covariates had the best predictive performance across all external assessments. Inclusion of different covariates, heterogeneity of preterm infant characteristics, and different study designs influenced predictive performance. Thorough evaluation is needed before these PopPK models can be implemented in clinical practice. The implementation of MIPD for caffeine in preterm infants could benefit from the combination of PopPK models and Bayesian forecasting as a helpful tool.

6.
Neural Netw ; 180: 106705, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39255634

RESUMEN

This paper concerns complete synchronization (CS) problem of discrete-time fractional-order BAM neural networks (BAMNNs) with leakage and discrete delays. Firstly, on the basis of Caputo fractional difference theory and nabla l-Laplace transform, two equations about the nabla sum are strictly proved. Secondly, two extended Halanay inequalities that are suitable for discrete-time fractional difference inequations with arbitrary initial time and multiple types of delays are introduced. In addition, through applying Caputo fractional difference theory and combining with inequalities gained from this paper, some sufficient CS criteria of discrete-time fractional-order BAMNNs with leakage and discrete delays are established under adaptive controller. Finally, one numerical simulation is utilized to certify the effectiveness of the obtained theoretical results.

7.
Cell Death Dis ; 15(9): 661, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256367

RESUMEN

De novo purine synthesis metabolism plays a crucial role in tumor cell survival and malignant progression. However, the specific impact of this metabolic pathway on chemoresistance in ovarian cancer remains unclear. This study aims to elucidate the influence of de novo purine synthesis on chemoresistance in ovarian cancer and its underlying regulatory mechanisms. We analyzed metabolic differences between chemosensitive and chemoresistant ovarian cancer tissues using mass spectrometry-based metabolomics. Cell growth, metabolism, chemoresistance, and DNA damage repair characteristics were assessed in vitro using cell line models. Tumor growth and chemoresistance were assessed in vivo using ovarian cancer xenograft tumors. Intervention of purines and NEK6-mediated purine metabolism on chemoresistance was investigated at multiple levels. Chemoresistant ovarian cancers exhibited higher purine abundance and NEK6 expression. Inhibiting NEK6 led to decreased de novo purine synthesis, resulting in diminished chemoresistance in ovarian cancer cells. Mechanistically, NEK6 directly interacted with FOXO3, contributing to the phosphorylation of FOXO3 at S7 through its kinase activity, thereby inhibiting its nuclear translocation. Nuclear FOXO3 promoted FBXW7 transcription, leading to c-MYC ubiquitination and suppression of de novo purine synthesis. Paeonol, by inhibiting NEK6, suppressed de novo purine synthesis and enhanced chemosensitivity. The NEK6-mediated reprogramming of de novo purine synthesis emerges as a critical pathway influencing chemoresistance in ovarian cancer. Paeonol exhibits the potential to interfere with NEK6, thereby inhibiting chemoresistance.


Asunto(s)
Resistencia a Antineoplásicos , Proteína Forkhead Box O3 , Quinasas Relacionadas con NIMA , Neoplasias Ováricas , Proteínas Proto-Oncogénicas c-myc , Purinas , Femenino , Humanos , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Purinas/farmacología , Purinas/metabolismo , Línea Celular Tumoral , Animales , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Quinasas Relacionadas con NIMA/metabolismo , Quinasas Relacionadas con NIMA/genética , Ratones , Ratones Desnudos , Núcleo Celular/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
8.
BMC Health Serv Res ; 24(1): 1089, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294738

RESUMEN

BACKGROUND: Pharmacogenetics/pharmacogenomics (PGx) focuses on the genetic variation that causes the heterogeneity of pharmacokinetics and drug response among individuals and has the potential to predict individual efficacy and/or side effects. This study aims to investigate and understand the implementation of genetic testing for the personalized medication (GTPM) in children's hospitals in Mainland China. METHODS: A survey was conducted on 50 children's hospitals from 31 provinces, municipalities, and autonomous regions across Mainland China, and statistical analysis and recommendations were made. RESULTS: Questionnaire response was rate of 76.0% (38/50). Data from 15 hospitals conducting GTPM were included in this study, but only 6 hospitals had offered PGx tests for no less than five drug-related genes, and only 5 hospitals had covered more than ten drugs, which was a small scale overall. 20.0% of the laboratories did not conduct internal quality control, and 33.3% did not participate in inter-laboratory quality assessment. 46.7% of the practitioners did not receive external training. The primary goal for GTPM was to optimize drug dosage in the 15 hospitals, while the main challenge for GTPM was the implementation cost. CONCLUSION: Although GTPM in pediatrics has made major progress in Mainland China in recent years, there were still various problems in terms of software, hardware configuration, personnel allocation, business scale, quality control, and result interpretation. This requires joint efforts of health administration, medical insurance departments, researchers, and hospitals to promote and improve GTPM.


Asunto(s)
Medicina de Precisión , Humanos , China , Niño , Medicina de Precisión/métodos , Encuestas y Cuestionarios , Pruebas de Farmacogenómica , Hospitales Pediátricos , Farmacogenética , Pueblos del Este de Asia
9.
BMC Infect Dis ; 24(1): 988, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289626

RESUMEN

BACKGROUND: Corynebacterium striatum (C. striatum), a common skin and mucosal colonizer, is increasingly considered as an opportunistic pathogen causing bloodstream infections (BSIs). This study aims to investigate the clinical features and outcomes of C. striatum-BSI. METHODS: We included hospitalized cases with C. striatum-positive blood cultures from January 2014 to June 2022 and classified them into C. striatum-BSI group and contamination group; Clinical characteristics, treatments, and outcomes were compared between the C. striatum-BSI group and contamination group, Methicillin-resistant Staphylococcus aureus (MRSA)-BSI and Methicillin-resistant Staphylococcus epidermidis (MRSE)-BSI. RESULTS: Fifty-three patients with positive C. striatum blood cultures were identified. Among them, 25 patients were classified as C. striatum-BSI, with 21 as contamination cases. And 62 cases of MRSA-BSI and 44 cases of MRSE-BSI were identified. Compared to the contaminated group, the C. striatum-BSI group had a shorter time to positivity of blood cultures (27.0 h vs. 42.5 h, P = 0.011). C. striatum-BSI group had a longer time to positivity (27 h) when compared to both the MRSA (20 h) and MRSE groups (19 h) (p < 0.05). Appropriate therapy within 24 h of BSI onset was significantly lower in the C. striatum group (28%) compared to the MRSA (64.5%) and MRSE (65.9%) groups (p < 0.005). The 28-day mortality was higher in the C. striatum group (52.0%) compared to the MRSA (25.8%) and MRSE (18.2%) groups.  CONCLUSIONS: Given the distinct characteristics of C. striatum-BSI, including a longer time to positivity than other Gram-positive bacteria and higher mortality rates, we suggest prescribing early appropriate antibiotics if C. striatum-BSI is suspected.


Asunto(s)
Bacteriemia , Infecciones por Corynebacterium , Corynebacterium , Staphylococcus aureus Resistente a Meticilina , Humanos , Corynebacterium/aislamiento & purificación , Corynebacterium/clasificación , Corynebacterium/genética , Masculino , Femenino , Persona de Mediana Edad , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones por Corynebacterium/microbiología , Infecciones por Corynebacterium/tratamiento farmacológico , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Anciano , Staphylococcus epidermidis/aislamiento & purificación , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Estudios Retrospectivos , Anciano de 80 o más Años
10.
Sci Total Environ ; 952: 175877, 2024 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-39226951

RESUMEN

Infertility has gradually become a global health concern, and evidence suggests that exposure to environmental endocrine-disrupting chemicals (EDCs) represent one of the key causes of infertility. Benzo(a)pyrene (BaP) is a typical EDC that is widespread in the environment. Previous studies have detected BaP in human urine, semen, cervical mucus, oocytes and follicular fluid, resulting in reduced fertility and irreversible reproductive damage. However, the mechanisms underlying the effects of gestational BaP exposure on offspring fertility in male mice have not been fully explored. In this study, pregnant mice were administered BaP at doses of 0, 5, 10 and 20 mg/kg/day via gavage from Days 7.5 to 12.5 of gestation. The results revealed that BaP exposure during pregnancy disrupted the structural integrity of testicular tissue, causing a disorganized arrangement of spermatogenic cells, compromised sperm quality, elevated levels of histone modifications and increased apoptosis in the testicular tissue of F1 male mice. Furthermore, oxidative stress was also increased in the testicular tissue of F1 male mice. BaP activated the AhR/ERα signaling pathway, affected H3K4me3 expression and induced apoptosis in testicular tissue. AhR and Cyp1a1 were overexpressed, and the expression of key molecules in the antioxidant pathway, including Keap1 and Nrf2, was reduced. The combined effects of these molecules led to apoptosis in testicular tissues, damaging and compromising sperm quality. This impairment in testicular cells further contributed to compromised testicular tissues, ultimately impacting the reproductive health of F1 male mice.


Asunto(s)
Apoptosis , Benzo(a)pireno , Estrés Oxidativo , Animales , Benzo(a)pireno/toxicidad , Masculino , Femenino , Ratones , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Embarazo , Testículo/efectos de los fármacos , Testículo/metabolismo , Disruptores Endocrinos/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Células Germinativas/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Exposición Materna/efectos adversos , Histonas/metabolismo , Código de Histonas/efectos de los fármacos
11.
J Colloid Interface Sci ; 678(Pt B): 221-232, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39243722

RESUMEN

Constructing amorphous/crystalline heterophase structure with high porosity is a promising strategy to effectively tailor the physicochemical properties of electrode materials and further improve the electrochemical performance of supercapacitors. Here, the porous C-doped NiO (C-NiO) with amorphous/crystalline heterophase grown on NF was prepared using NF as Ni source via a self-sacrificial template method. Calcining the self-sacrificial NiC2O4 template at a suitable temperature (400 °C) was beneficial to the formation of porous heterophase structure with abundant cavities and cracks, resulting in high electrical conductivity and rich ion/electron-transport channels. The density functional theory (DFT) calculations further verified that in-situ C-doping could modulate the electronic structure and enhance the OH- adsorption capability. The unique porous amorphous/crystalline heterophase structure greatly accelerated electrons/ions transfer and Faradaic reaction kinetic, which effectively improved the charge storage. The C-NiO calcined at 400 °C (C-NiO(400)) displayed a markedly enhanced specific charge, outstanding rate property and excellent cycling stability. Furthermore, the hybrid supercapacitor assembled by C-NiO(400) and active carbon achieved a high energy density of 49.0 Wh kg-1 at 800 W kg-1 and excellent cycle stability (90.9 % retention at 5 A/g after 10 000 cycles). This work provided a new strategy for designing amorphous/crystalline heterophase electrode materials in high-performance energy storage.

12.
Diagnostics (Basel) ; 14(18)2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39335688

RESUMEN

Objectives: Optical coherence tomography (OCT) has recently been used in gynecology to detect cervical lesions in vivo and proven more effective than colposcopy in clinical trials. However, most gynecologists are unfamiliar with this new imaging technique, requiring intelligent computer-aided diagnosis approaches to help them interpret cervical OCT images efficiently. This study aims to (1) develop a clinically-usable deep learning (DL)-based classification model of 3D OCT volumes from cervical tissue and (2) validate the DL model's effectiveness in detecting high-risk cervical lesions, including high-grade squamous intraepithelial lesions and cervical cancer. Method: The proposed DL model, designed based on the convolutional neural network architecture, combines a feature pyramid network (FPN) with texture encoding and deep supervision. We extracted, represent, and fused four-scale texture features to improve classification performance on high-risk local lesions. We also designed an auxiliary classification mechanism based on deep supervision to adjust the weight of each scale in FPN adaptively, enabling low-cost training of the whole model. Results: In the binary classification task detecting positive subjects with high-risk cervical lesions, our DL model achieved an 81.55% (95% CI, 72.70-88.51%) F1-score with 82.35% (95% CI, 69.13-91.60%) sensitivity and 81.48% (95% CI, 68.57-90.75%) specificity on the Renmin dataset, outperforming five experienced medical experts. It also achieved an 84.34% (95% CI, 74.71-91.39%) F1-score with 87.50% (95% CI, 73.20-95.81%) sensitivity and 90.59% (95% CI, 82.29-95.85%) specificity on the Huaxi dataset, comparable to the overall level of the best investigator. Moreover, our DL model provides visual diagnostic evidence of histomorphological and texture features learned in OCT images to assist gynecologists in making clinical decisions quickly. Conclusions: Our DL model holds great promise to be used in cervical lesion screening with OCT efficiently and effectively.

13.
Nurs Open ; 11(9): e70045, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39325729

RESUMEN

AIM: To determine whether social support and psychological resiliency are significant mediators of the associations between risk perception and quality of working life in Chinese nurses working with infectious diseases. DESIGN: A cross-sectional study. METHODS: A cross-sectional survey of 879 nurses in infectious diseases department of specialty or general hospitals in China completed online questionnaires on the nurses' risk perception questionnaire, quality of working life, psychological resilience and the social support rating scale. RESULTS: Our study observed that risk perception directly negatively influences the quality of working life of infectious disease nurses, while psychological resilience and social support positively chain mediate this relationship. CONCLUSION: Critical elements impacting the quality of working life of infectious disease nurses are risk perception, psychological resilience and social support. Managers may think about decreasing the level of risk perception and enhancing the quality of working life of infectious disease nurses by enhancing their psychological resilience and providing support. PUBLIC CONTRIBUTION: The quality of working life of infectious disease nurses should be a priority for nursing management; it is critical to maintain their health and well-being, raise the quality of care and lower turnover. Managers should create resilience-building programmes and support tools to assist nurses properly perceive risks and adopt protective strategies to deal with them to improve the quality of working life for nurses.


Asunto(s)
Calidad de Vida , Resiliencia Psicológica , Apoyo Social , Humanos , Estudios Transversales , China , Adulto , Femenino , Encuestas y Cuestionarios , Masculino , Calidad de Vida/psicología , Enfermeras y Enfermeros/psicología , Enfermedades Transmisibles/psicología , Enfermedades Transmisibles/enfermería , Percepción , Persona de Mediana Edad , Personal de Enfermería en Hospital/psicología , Satisfacción en el Trabajo
14.
Expert Opin Drug Metab Toxicol ; 20(9): 923-938, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39167118

RESUMEN

BACKGROUND: Considerable interindividual variability for the pharmacokinetics of caffeine in preterm infants has been demonstrated, emphasizing the importance of personalized dosing. This study aimed to develop and apply a repository of currently published population pharmacokinetic (PopPK) models of caffeine in preterm infants to facilitate model-informed precision dosing (MIPD). RESEARCH DESIGN AND METHODS: Literature search was conducted using PubMed, Embase, Scopus, and Web of Science databases. Relevant publications were screened, and their quality was assessed. PopPK models were reestablished to develop the model repository. Covariate effects were evaluated and the concentration-time profiles were simulated. An online simulation and calculation tool was developed as an instance. RESULTS: Twelve PopPK models were finally included in the repository. Preterm infants' age and body size, especially the postnatal age and current weight, were identified as the most clinically critical covariates. Simulated blood concentration-time profiles across these models were comparable. Caffeine citrate-dose regimen should be adjusted according to the age and body size of preterm infants. The developed online tool can be used to facilitate clinical decision-making. CONCLUSIONS: The first developed repository of PopPK models for caffeine in preterm infants has a wide range of potential applications in the MIPD of caffeine.


Asunto(s)
Cafeína , Relación Dosis-Respuesta a Droga , Recien Nacido Prematuro , Modelos Biológicos , Humanos , Cafeína/administración & dosificación , Cafeína/farmacocinética , Recién Nacido , Estimulantes del Sistema Nervioso Central/farmacocinética , Estimulantes del Sistema Nervioso Central/administración & dosificación , Factores de Edad , Medicina de Precisión/métodos , Simulación por Computador , Citratos
15.
Nutrients ; 16(16)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39203718

RESUMEN

BACKGROUND: Puerarin is an isoflavone compound isolated from the roots of a leguminous plant, the wild kudzu. Various functional activities of this compound in multiple diseases have been reported. However, the effect and mechanism of puerarin in improving blood pressure remain non-elucidated. PURPOSE: The current study was designed to assess the preventive effects of puerarin on the onset and progression of hypertension and to verify the hypothesis that puerarin alleviates blood pressure by inhibiting the ROS/TLR4/NLRP3 inflammasome signaling pathway in the hypothalamic paraventricular nucleus (PVN) of salt-induced prehypertensive rats. METHODS: Male Dahl salt-sensitive rats were fed low NaCl salt (3% in drinking water) for the control (NS) group or 8% (HS) to induce prehypertension. Each batch was divided into two group and treated by bilateral PVN microinjection with either artificial cerebrospinal fluid or puerarin through a micro-osmotic pump for 6 weeks. The mean arterial pressure (MAP) was recorded, and samples were collected and analyzed. RESULTS: We concluded that puerarin significantly prevented the elevation of blood pressure and effectively alleviated the increase in heart rate caused by high salt. Norepinephrine (NE) in the plasma of salt-induced prehypertensive rats also decreased upon puerarin chronic infusion. Additionally, analysis of the PVN sample revealed that puerarin pretreatment decreased the positive cells and gene level of TLR4 (Toll-like receptor 4), NLRP3, Caspase-1 p10, NOX2, MyD88, NOX4, and proinflammatory cytokines in the PVN. Puerarin pretreatment also decreased NF-κBp65 activity, inhibited oxidative stress, and alleviated inflammatory responses in the PVN. CONCLUSION: We conclude that puerarin alleviated blood pressure via inhibition of the ROS/TLR4/NLRP3 inflammasome signaling pathway in the PVN, suggesting the therapeutic potential of puerarin in the prevention of hypertension.


Asunto(s)
Presión Sanguínea , Inflamasomas , Isoflavonas , Proteína con Dominio Pirina 3 de la Familia NLR , Núcleo Hipotalámico Paraventricular , Especies Reactivas de Oxígeno , Transducción de Señal , Receptor Toll-Like 4 , Animales , Masculino , Ratas , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Isoflavonas/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Prehipertensión/tratamiento farmacológico , Ratas Endogámicas Dahl , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Cloruro de Sodio Dietético , Receptor Toll-Like 4/metabolismo
16.
Mikrochim Acta ; 191(9): 519, 2024 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110252

RESUMEN

Functional materials with organic/inorganic composites as the main matrix and rare earth ion complexes as the guest have shown a very broad application prospect for antibiotic sensors. However, Eu3+-complex often relies on a single fluorescence response signal, which is susceptible to changes in the detection environment and cannot simultaneously detect and remove tetracycline (TC). Herein, green fluorescent covalent two-dimensional organic framework (COF-TD) is synthesized, followed by modification of Eu3+ to synthesize COF-TD@Eu3+. In the ratiometric sensor, Eu3+ serves as the recognition site and specific response probe for TC, while COF-TD is the fluorescence reference and carrier for Eu3+. Due to the antenna effect, TC enhances the red fluorescence of Eu3+, while the green fluorescence of COF-TD remains almost stable. Based on the change of fluorescence intensity and fluorescence color from green to red, the efficient ratiometric sensing can be finished in 1 min. The developed method shows high sensitivity with a detection limit of 0.3 µM and high selectivity to TC which makes the method applicable to detect TC in traditional Chinese medicine preparations. In addition, due to the high specific surface area of COFs and specific adsorption sites, COF-TD@Eu3+ also shows good performance for TC removal. The findings show that the maximum adsorption capacity is 137.3 mg g-1 and the adsorption equilibrium is reached in 30 min. Smartphone assisted COF-TD@Eu3+ for both ratiometric fluorescence detection and detecting the absorption of TC is proposed for the first time. The molecular cryptosteganography that transforms the selective response of COF-TD@Eu3+ to binary strings is anticipated to advance utilization of nanomaterials in logic sensing and information safety.


Asunto(s)
Europio , Colorantes Fluorescentes , Límite de Detección , Estructuras Metalorgánicas , Espectrometría de Fluorescencia , Tetraciclina , Europio/química , Estructuras Metalorgánicas/química , Tetraciclina/análisis , Tetraciclina/química , Adsorción , Espectrometría de Fluorescencia/métodos , Colorantes Fluorescentes/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Antibacterianos/análisis , Antibacterianos/química , Fluorescencia
17.
J Chem Phys ; 161(8)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39171713

RESUMEN

Transition-metal selenides have been extensively studied as promising electrode materials for supercapacitors. Engineering amorphous/crystalline heterostructures is an effective strategy to improve rich active sites for accelerating redox reaction kinetics but still lacks exploration. In this study, an amorphous/crystalline heterostructure was designed and constructed by selenizing the self-sacrificial template NiMnS to generate amorphous Mn/polycrystalline Ni0.85Se-NiSe2 heterophase via the phase transformation from metal sulfide into metal selenide. The synergy of the complementary multi-components and amorphous/polycrystalline heterophase could enrich electron/ion-transport channels and expose abundant active sites, which accelerated electron/ion transfer and Faradaic reaction kinetics during charging/discharging. As expected, the optimal NiMnSe exhibited a high specific charge (1389.1 C g-1 at 1 A g-1), a good rate capability, and an excellent lifespan (88.9% retention). Moreover, the fabricated NiMnSe//activated carbon device achieved a long cycle life and energy density of 48.0 W h kg-1 at 800 W kg-1, shedding light on the potential for use in practical applications, such as electrochemical energy-storage devices.

18.
Chin J Integr Med ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136837

RESUMEN

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.

19.
BMC Ophthalmol ; 24(1): 348, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148060

RESUMEN

BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.


Asunto(s)
Fibras Nerviosas , Atrofia Óptica Hereditaria de Leber , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Atrofia Óptica Hereditaria de Leber/fisiopatología , Atrofia Óptica Hereditaria de Leber/diagnóstico , Masculino , Femenino , Fibras Nerviosas/patología , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Estudios de Seguimiento , Adulto , Agudeza Visual/fisiología , Adulto Joven , Disco Óptico/patología , Disco Óptico/diagnóstico por imagen , Adolescente , Persona de Mediana Edad , Estudios Retrospectivos , Campos Visuales/fisiología
20.
Int J Cardiol ; 414: 132417, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39098611

RESUMEN

BACKGROUND: Immune thrombocytopenia (ITP) is a prevalent autoimmune bleeding disorder, with the primary objective of treatment being the prevention of bleeding. Clinical investigations have indicated that individuals with ITP face an elevated risk of thrombosis, and the occurrence of thromboembolic events in ITP patients can be attributed to a multitude of factors. However, establishing a definitive causal relationship between ITP and thrombosis remains challenging. METHODS: A two-sample Mendelian randomization (MR) study utilizing summary data from FinnGen consortium and UK Biobank was undertaken to investigate the causal association between ITP and thrombosis. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary analyses were conducted using the MR-Egger, weighted median, and MR-PRESSO approaches. RESULTS: Based on IVW method, there was a statistically significant but small positive correlation between ITP and thrombosis. Specifically, ITP patients exhibited a suggestive positive correlation with myocardial infarction and deep-vein thrombosis. However, our investigation did not identify any causal relationship between ITP and cerebral infarction, arterial embolism, other arterial embolisms, pulmonary embolism, thrombophlebitis, or portal vein thrombosis. Sensitivity analyses further confirmed the accuracy and robustness of these findings. CONCLUSIONS: This study presents empirical support for the causal relationship between ITP and thrombosis. It is important to note that a diminished platelet count does not serve as a preventive measure against thrombus formation. Consequently, when managing a newly diagnosed ITP patient, clinicians need to be aware that there is a slight elevation in the risk of thrombosis during treatment.


Asunto(s)
Análisis de la Aleatorización Mendeliana , Púrpura Trombocitopénica Idiopática , Trombosis , Humanos , Púrpura Trombocitopénica Idiopática/epidemiología , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/genética , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/sangre , Trombosis/epidemiología , Trombosis/etiología , Trombosis/diagnóstico , Trombosis/genética , Factores de Riesgo
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