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1.
Aging (Albany NY) ; 162024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38950328

RESUMEN

The current study aims to develop a new technique for the precise identification of Escherichia coli strains, utilizing matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with a long short-term memory (LSTM) neural network. A total of 48 Escherichia coli strains were isolated and cultured on tryptic soy agar medium for 24 hours for the generation of MALDI-TOF MS spectra. Eight hundred MALDI-TOF MS spectra were obtained per strain, resulting in a database of 38,400 spectra. Fifty percent of the data was utilized for LSTM neural network training, with fine-tuned parameters for strain-level identification. The other half served as the test set to assess model performance. Traditional PCA dimension reduction of MALDI-TOF MS spectra indicated 47 out of 48 strains to be unclassifiable. In contrast, the LSTM neural network demonstrated remarkable efficacy. After 20 training epochs, the model achieved a loss value of 0.0524, an accuracy of 0.999, a precision of 0.985, and a recall of 0.982. When tested on the unseen data, the model attained an overall accuracy of 92.24%. The integration of MALDI-TOF MS and LSTM neural network markedly enhances the identification of Escherichia coli strains. This innovative approach offers an effective and accurate tool for MALDI-TOF MS-based strain-level identification, thus expanding the analytical capabilities of microbial diagnostics.

2.
Front Neurol ; 15: 1396673, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952466

RESUMEN

Introduction: The online study investigated the sleep, psychological conditions, and risk factors during the wave of transmission of COVID-19 since December 7, 2022. Methods: We distributed questionnaires through networking mediums to residents to gather information about COVID-19 infection, sleep, and mental status. Results: During the extraordinary period in China, 91.9% of 1094 participants claimed to be infected with COVID-19, 36.8% reported poor sleep quality, 75.9% reported anxiety, and 65.5% reported depression. In retrospect, people have experienced lower sleep quality, longer sleep latency, enhanced rising time, and decreased sleep efficiency after the infection wave. After adjusting confounding factors, the elderly, women, urban residents, people with comorbidity, anxiety, depression, stress state, and COVID-19 infection have high risks for sleep disorders during the period. Discussion: The survey indicates that sleep disturbance caused by COVID-19 involves multiple dimensions, such as physiology, psychology, and society. The COVID-19 infection-related sleep problem should be taken seriously. Apart from conventional treatment, psychological issues of insomnia can not be ignored.

3.
J Biol Chem ; : 107516, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960036

RESUMEN

Focal segmental glomerulosclerosis (FSGS), a common cause of primary glomerulonephritis, has a poor prognosis and is pathologically featured by tubulointerstitial injury. Thrombospondin-1 (TSP-1) is an extracellular matrix protein that acts in combination with different receptors in the kidney. Here, we analyzed the tubular expression of TSP-1 and its receptor integrin ß3 (ITGB3) in FSGS. Previously the renal interstitial chip analysis of FSGS patients with tubular interstitial injury showed that the expressions of TSP-1 and ITGB3 were up-regulated. We found that the level of TSP-1 and ITGB3 increased in the tubular cells of FSGS patients. The serum level of TSP-1 increased and was correlated to the degree of tubulointerstitial lesions in FSGS patients. THBS1/ITGB3 signaling induced renal tubular injury in HK-2 cells exposure to BSA and the ADR-induced nephropathy model. THBS1 knockout ameliorated tubular injury and renal fibrosis in ADR-treated mice. THBS1 knockdown decreased the expression of KIM-1 and caspase 3 in the HK-2 cells treated with BSA, while THBS1 overexpression could induce tubular injury. In vivo, we identified cyclo-RGDfK as an agent to block the binding of TSP-1 to ITGB3. Cyclo-RGDfK treatment could alleviate ADR-induced renal tubular injury and interstitial fibrosis in mice. Moreover, TSP-1 and ITGB3 were colocalized in tubular cells of FSGS patients and ADR-treated mice. Taken together, our data showed that TSP-1/ITGB3 signaling contributed to the development of renal tubulointerstitial injury in FSGS, potentially identifying a new therapeutic target for FSGS.

4.
Allergol Immunopathol (Madr) ; 52(4): 38-45, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38970263

RESUMEN

PURPOSE: Sepsis often triggers a systemic inflammatory response leading to multi-organ dysfunction, with complex and not fully understood pathogenesis. This study investigates the therapeutic effects of cimifugin on BV-2 cells under sepsis-induced stress conditions. METHODS: We utilized a BV-2 microglial cell model treated with lipopolysaccharide (LPS) to mimic sepsis. Assessments included cellular vitality, inflammatory cytokine quantification (6 interleukin [6IL]-1ß, interleukin 6 [IL-6], and tumor necrosis factor-α [TNF-α]) via enzyme-linked-immunosorbent serologic assay, and analysis of mRNA expression using real-time polymerase chain reaction. Oxidative stress and mitochondrial function were also evaluated to understand the cellular effects of cimifugin. RESULTS: Cimifugin significantly attenuated LPS-induced inflammatory responses, oxidative stress, and mitochondrial dysfunction. It enhanced cell viability and modulated the secretion and gene expression of inflammatory cytokines IL-1ß, IL-6, and TNF-α. Notably, cimifugin activated the deacetylase sirtuin 1-nuclear factor erythroid 2-related factor 2 pathway, contributing to its protective effects against mitochondrial damage. CONCLUSION: Cimifugin demonstrates the potential of being an effective treatment for sepsis--induced neuroinflammation, warranting further investigation.


Asunto(s)
Citocinas , Lipopolisacáridos , Microglía , Estrés Oxidativo , Animales , Lipopolisacáridos/inmunología , Lipopolisacáridos/farmacología , Ratones , Estrés Oxidativo/efectos de los fármacos , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/inmunología , Citocinas/metabolismo , Supervivencia Celular/efectos de los fármacos , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Línea Celular , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Antiinflamatorios/farmacología , Transducción de Señal/efectos de los fármacos , Cromonas , Sirtuina 1
5.
Cell Mol Biol Lett ; 29(1): 99, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978023

RESUMEN

Skeletal muscular atrophy is a complex disease involving a large number of gene expression regulatory networks and various biological processes. Despite extensive research on this topic, its underlying mechanisms remain elusive, and effective therapeutic approaches are yet to be established. Recent studies have shown that epigenetics play an important role in regulating skeletal muscle atrophy, influencing the expression of numerous genes associated with this condition through the addition or removal of certain chemical modifications at the molecular level. This review article comprehensively summarizes the different types of modifications to DNA, histones, RNA, and their known regulators. We also discuss how epigenetic modifications change during the process of skeletal muscle atrophy, the molecular mechanisms by which epigenetic regulatory proteins control skeletal muscle atrophy, and assess their translational potential. The role of epigenetics on muscle stem cells is also highlighted. In addition, we propose that alternative splicing interacts with epigenetic mechanisms to regulate skeletal muscle mass, offering a novel perspective that enhances our understanding of epigenetic inheritance's role and the regulatory network governing skeletal muscle atrophy. Collectively, advancements in the understanding of epigenetic mechanisms provide invaluable insights into the study of skeletal muscle atrophy. Moreover, this knowledge paves the way for identifying new avenues for the development of more effective therapeutic strategies and pharmaceutical interventions.


Asunto(s)
Epigénesis Genética , Músculo Esquelético , Atrofia Muscular , Humanos , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Animales , Histonas/metabolismo , Histonas/genética , Metilación de ADN/genética , Empalme Alternativo/genética
6.
Sci Total Environ ; : 174642, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38992380

RESUMEN

Cognitive efficiency, characterized by the rapid and accurate processing of information, significantly enhances work and learning outcomes. This efficiency manifests in improved time management, decision-making, learning capabilities, and creativity. While the influence of thermal, acoustic, and lighting conditions on cognitive performance has been extensively studied, the role of olfactory stimuli remains underexplored. Olfactory perception, distinguished by its intensity, speed of perception, and the breadth of stimuli, plays a pivotal role in cognitive efficiency. This review investigates the mechanisms through which odor environments influence cognitive performance. We analyze how odor environments can affect cognitive efficiency through two different scenarios (work and sleep) and pathways (direct and indirect effects). Current research, which mainly focuses on the interplay between odors, emotional responses, and cognitive efficiency through both subjective and objective measures, is thoroughly analyzed. We highlight existing research gaps and suggest future directions for investigating the influence of odor environments on cognitive efficiency. This review aims to establish a theoretical basis for managing and leveraging odor environments in workplace settings.

7.
Chemosphere ; : 142841, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39004148

RESUMEN

Herein, two poly(3-aminocarbazole) derivatives containing imidazole N-type acceptor were synthesized and reported, which are named PCPI and PCBI respectively. The fluorescence spectrum shows that PCPI (Em=498 nm) and PCBI (Em=398 nm) both have a strong fluorescence emission. It is worth noting that PCPI has a larger stokes shift of 153 nm, which is beneficial for improving the sensitivity of the sensor and enhancing its anti-interference ability. As expected, our experimental results indicate that both PCPI and PCBI can cause a specific response of "fluorescence OFF" to Hg2+ compared with other ions. And PCPI and PCBI both have excellent detection capabilities for Hg2+, with detection limits of 69.8 nM and 11.4 nM respectively. Moreover, PCBI exhibits excellent absorption of Hg2+ with a maximum absorption capacity of 477.8 mg/g at 20°C. It indicates that PCBI can be used as a functional material for the detection and removal of Hg2+ in water.

8.
Life Sci ; : 122931, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39038510

RESUMEN

Cancer EMT is a pivotal process that drives carcinogenesis, metastasis, and cancer recurrence, with its initiation and regulation intricately governed by biochemical pathways in a precise spatiotemporal manner. Recently, the membrane-less biomolecular condensates formed via liquid-liquid phase separation (LLPS) have emerged as a universal mechanism underlying the spatiotemporal collaboration of biological activities in cancer EMT. In this review, we first elucidate the current understanding of LLPS formation and its cellular functions, followed by an overview of valuable tools for investigating LLPS. Secondly, we examine in detail the LLPS-mediated biological processes crucial for the initiation and regulation of cancer EMT. Lastly, we address current challenges in advancing LLPS research and explore the potential modulation of LLPS using therapeutic agents.

9.
Nano Lett ; 24(29): 8872-8879, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38989682

RESUMEN

Parlous structure integrity of the cathode and erratic interfacial microdynamics under high potential take responsibility for the degradation of solid-state lithium metal batteries (LMBs). Here, high-voltage LMBs have been operated by modulating the polymer electrolyte intrinsic structure through an intermediate dielectric constant solvent and further inducing the gradient solid-state electrolyte interphase. Benefiting from the chemical adsorption between trimethyl phosphate (TMP) and the cathode, the gradient interphase rich in LiPFxOy and LiF is induced, thereby ensuring the structural integrity and interface compatibility of the commercial LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode even at the 4.9 V cutoff voltage. Eventually, the specific capacity of NCM811|Li full cell based on TMP-modulated polymer electrolyte increased by 27.7% from 4.5 to 4.9 V. Such a universal screening method of electrolyte solvents and its derived electrode interfacial manipulation strategy opens fresh avenues for quasi-solid-state LMBs with high specific energy.

10.
BMC Cancer ; 24(1): 864, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026195

RESUMEN

BACKGROUND: Because the proportion of elderly individuals and the incidence of cancer worldwide are continually increasing, medical costs for elderly inpatients with cancer are being significantly increasing, which puts tremendous financial pressure on their families and society. The current study described the actual direct medical costs of elderly inpatients with cancer and analyzed the influencing factors for the costs to provide advice on the prevention and control of the high medical costs of elderly patients with cancer. METHOD: A retrospective descriptive analysis was performed on the hospitalization expense data of 11,399 elderly inpatients with cancer at a tier-3 hospital in Dalian between June 2016 and June 2020. The differences between different groups were analyzed using univariate analysis, and the influencing factors of hospitalization expenses were explored by multiple linear regression analysis. RESULTS: The hospitalization cost of elderly cancer patients showed a decreasing trend from 2016 to 2020. Specifically, the top 3 hospitalization costs were material costs, drug costs and surgery costs, which accounted for greater than 10% of all cancers according to the classification: colorectal (23.96%), lung (21.74%), breast (12.34%) and stomach cancer (12.07%). Multiple linear regression analysis indicated that cancer type, surgery, year and length of stay (LOS) had a common impact on the four types of hospitalization costs (P < 0.05). CONCLUSION: There were significant differences in the four types of hospitalization costs for elderly cancer patients according to the LOS, surgery, year and type of cancer. The study results suggest that the health administration department should enhance the supervision of hospital costs and elderly cancer patient treatment. Measures should be taken by relying on the hospital information system to strengthen the cost management of cancer diseases and departments, optimize the internal management system, shorten elderly cancer patients LOS, and reasonably control the costs of disease diagnosis, treatment and department operation to effectively reduce the economic burden of elderly cancer patients.


Asunto(s)
Hospitalización , Neoplasias , Centros de Atención Terciaria , Humanos , Estudios Retrospectivos , Anciano , Femenino , Masculino , Neoplasias/economía , Neoplasias/terapia , Neoplasias/epidemiología , Hospitalización/economía , China/epidemiología , Centros de Atención Terciaria/economía , Anciano de 80 o más Años , Costos de Hospital/estadística & datos numéricos , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos
11.
Small Methods ; : e2400640, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041431

RESUMEN

La3-xTe4 is a very promising high-temperature candidate applied in next-generation Radioisotope Thermoelectric Generators (RTGs). Conventional synthesis of such materials is based on the mechanochemical method, which makes the sample difficult to purify due to the high-energy ball milling. In this report, a novel synthetic method is developed, which utilizes Te-vapor transport and solid-phase diffusion to efficiently produce the RE3-xTe4 phases (RE = La, Ce, Pr, Nd). Notably, this method obviates the requirement for high-energy ball-milling instruments, conventionally indispensable in the mechanochemical syntheses. For as-synthesized La2.74Te4 material, a high figure of merit of 1.5 is achieved at 1073 K, owning to the reduced electronic thermal conductivity with metal impurities well eliminated.

12.
Immunol Res ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39042204

RESUMEN

Age-related thymic involution is characterized by the loss of T cell development and the supporting epithelial network, which are replaced by adipose tissue. We previously showed that aging functionally impairs lymphohematopoietic progenitor cells, including thymic early T cell progenitors (ETPs), contributing to thymic involution. Considering that the thymic microenvironment is essential for thymocyte incubation, we aimed to investigate its role in age-related thymic involution and the mechanisms underlying these changes. The challenge in studying these processes led us to transplant T cell-depleted fetal thymus tissue into the kidney capsule of aged mice. This model allowed us to identify the mechanisms driving age-related changes in the thymic microenvironment and to assess whether these changes could be reversed. Flow cytometry was used to detect naïve T cells (CD62L+CD44-), including CD4 CD8 double-negative, double-positive, and single-positive T cells. Real-time PCR was used to detect and quantify signal-joint T cell receptor excision circles. We rearranged δRec-ΨJα in murine peripheral blood leukocytes to evaluate the thymic output of newly developed naïve T cells in the mice and gene expression in the thymus. Age-related thymic involution decreased naïve T cells and increased memory T cells, while fetal thymus transplantation improved thymic output and T cell production and reversed the impairment of thymopoiesis due to thymic involution in aged mice. Furthermore, the expression of key cytokines was restored and ETPs in the aged mice showed normal thymic T cell development. Our study suggests that degenerative changes in the thymic microenvironment are the primary cause of thymic dysfunction, leading to immunosenescence associated with age-related thymic involution.

13.
Ren Fail ; 46(2): 2374448, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38973428

RESUMEN

BACKGROUND: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN. METHODS: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed. RESULTS: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value. CONCLUSION: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.


Asunto(s)
Autoanticuerpos , Glomerulonefritis Membranosa , Receptores de Fosfolipasa A2 , Trombofilia , Humanos , Receptores de Fosfolipasa A2/inmunología , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Trombofilia/etiología , Trombofilia/inmunología , Trombofilia/sangre , Autoanticuerpos/sangre
14.
Nat Commun ; 15(1): 5729, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977723

RESUMEN

Risk prediction for subsequent cardiovascular events remains an unmet clinical issue in patients with coronary artery disease. We aimed to investigate prognostic metabolic biomarkers by considering both shared and distinct metabolic disturbance associated with the composite and individual cardiovascular events. Here, we conducted an untargeted metabolomics analysis for 333 incident cardiovascular events and 333 matched controls. The cardiovascular events were designated as cardiovascular death, myocardial infarction/stroke and heart failure. A total of 23 shared differential metabolites were associated with the composite of cardiovascular events. The majority were middle and long chain acylcarnitines. Distinct metabolic patterns for individual events were revealed, and glycerophospholipids alteration was specific to heart failure. Notably, the addition of metabolites to clinical markers significantly improved heart failure risk prediction. This study highlights the potential significance of plasma metabolites on tailed risk assessment of cardiovascular events, and strengthens the understanding of the heterogenic mechanisms across different events.


Asunto(s)
Biomarcadores , Enfermedad de la Arteria Coronaria , Metabolómica , Humanos , Enfermedad de la Arteria Coronaria/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Infarto del Miocardio/sangre , Carnitina/sangre , Carnitina/análogos & derivados , Carnitina/metabolismo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/metabolismo , Pronóstico , Medición de Riesgo , Estudios de Casos y Controles , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/metabolismo , Metaboloma , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/metabolismo , Factores de Riesgo
15.
Sci Rep ; 14(1): 15695, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977824

RESUMEN

Hydrogels are extensively explored as biomaterials for tissue scaffolds, and their controlled fabrication has been the subject of wide investigation. However, the tedious mechanical property adjusting process through formula control hindered their application for diverse tissue scaffolds. To overcome this limitation, we proposed a two-step process to realize simple adjustment of mechanical modulus over a broad range, by combining digital light processing (DLP) and post-processing steps. UV-curable hydrogels (polyacrylamide-alginate) are 3D printed via DLP, with the ability to create complex 3D patterns. Subsequent post-processing with Fe3+ ions bath induces secondary crosslinking of hydrogel scaffolds, tuning the modulus as required through soaking in solutions with different Fe3+ concentrations. This innovative two-step process offers high-precision (10 µm) and broad modulus adjusting capability (15.8-345 kPa), covering a broad range of tissues in the human body. As a practical demonstration, hydrogel scaffolds with tissue-mimicking patterns were printed for cultivating cardiac tissue and vascular scaffolds, which can effectively support tissue growth and induce tissue morphologies.


Asunto(s)
Hidrogeles , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido , Andamios del Tejido/química , Hidrogeles/química , Ingeniería de Tejidos/métodos , Humanos , Alginatos/química , Materiales Biocompatibles/química , Resinas Acrílicas/química , Módulo de Elasticidad , Luz
16.
Acta Neurochir (Wien) ; 166(1): 291, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985355

RESUMEN

BACKGROUND: The most deadly type of spontaneous intracerebral hemorrhage is spontaneous cerebellar hemorrhage (SCH). The purpose of this meta-analysis was to investigate risk factors for prognosis in SCH patients to provide a basis for taking preventive and therapeutic measures. METHODS: Seven electronic databases were searched from inception to May 2023 for randomized controlled trial, cohort study, case control study and cross-sectional study on prognosis of spontaneous cerebellar hemorrhage. The quality of the selected studies were assessed by the American Agency for Healthcare Research and Quality (AHRQ). To assess the impact of the included risk factors on the prognosis of spontaneous cerebellar hemorrhage, combined odds ratios (ORs) with matching 95% confidence intervals (CIs) were combined. RESULTS: Eight studies were included, including 539 participants. And a total of 31 potentially associated risk factors were identified. Ultimately, 6 risk factors were included in the meta-analysis after assessing. The factors supported by moderate evidence include the hydrocephalus (OR = 4.3, 95% CI: 2.33 to 7.91) and drug-induced coagulopathy (OR = 2.74, 95% CI: 1.23 to 6.09). The factors supported by limited evidence include the intraventricular bleeding(OR = 1.86, 95% CI: 1.13 to 3.07) and hematoma size>3 cm(OR = 3.18, 95% CI: 1.87 to 5.39). Meta-analysis revealed no association between hypertension, diabetes mellitus and SCH prognosis. CONCLUSION: The current meta-analysis revealed obvious risk factors for prognosis in spontaneous cerebellar hemorrhage patients, including hydrocephalus, drug-induced coagulopathy, intraventricular bleeding and hematoma size>3 cm.


Asunto(s)
Hemorragia Cerebral , Humanos , Factores de Riesgo , Pronóstico , Hidrocefalia/etiología , Enfermedades Cerebelosas
17.
CNS Neurosci Ther ; 30(7): e14862, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39009505

RESUMEN

BACKGROUND: The emergence of cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) represented a major breakthrough in the treatment of breast cancer over the past decade. In both clinical trials and real-world settings, it was observed that patients using CDK4/6i might experience psychiatric adverse events (PAEs). Herein, we conducted a pharmacovigilance study to comprehensively assess the correlation between CDK4/6i and PAEs. METHOD: We obtained individual case safety reports submitted to the FDA Adverse Events Reporting System (FAERS) during the period from January 2015 to December 2023. In disproportionality analysis, the reporting odds ratio (ROR) and information component (IC) values were calculated for each adverse event-drug combination. Univariate logistic regression analysis was utilized to explore factors associated with PAEs following CDK4/6i treatment. RESULTS: A total of 95,591 reports related to CDK4/6i were identified, with 6.72% reporting PAEs, and this proportion exhibited an annual upward trend. Based on the ROR and IC values, 17 categories of PAEs were defined as CDK4/6i-related PAEs. Among these PAEs, insomnia, stress, eating disorder, depressed mood, and sleep disorder were very common, each accounting for over 10% of CDK4/6i reports. Ribociclib showed the highest risk signal of CDK4/6i-related PAEs (ROR = 1.89[1.75-2.04], IC025 = 0.79), followed by palbociclib (ROR = 1.47[1.41-1.53], IC025 = 0.49), while abemaciclib did not exhibit a significant signal (ROR = 0.52[0.44-0.62], IC025 = -1.13). Female sex, younger age and weight exceeding 80 kg were significant risk factors for the incidence of CDK4/6i-related PAEs. CONCLUSIONS: Using data from a real-world, large-scale spontaneous reporting system for adverse drug reactions, our study delineated the spectrum of PAEs to CDK4/6i. This potentially offered valuable insights for healthcare professionals to manage the risk of PAEs in patients receiving CDK4/6i treatment, particularly those with psychiatric disorders.


Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Trastornos Mentales , Farmacovigilancia , Inhibidores de Proteínas Quinasas , United States Food and Drug Administration , Humanos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Femenino , Masculino , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Estados Unidos/epidemiología , Persona de Mediana Edad , Anciano , Trastornos Mentales/inducido químicamente , Trastornos Mentales/epidemiología , Adulto , United States Food and Drug Administration/tendencias , Inhibidores de Proteínas Quinasas/efectos adversos , Adulto Joven , Adolescente , Anciano de 80 o más Años
18.
J Pharm Biomed Anal ; 248: 116288, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38981330

RESUMEN

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.


Asunto(s)
Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Sesquiterpenos de Germacrano , Animales , Sesquiterpenos de Germacrano/metabolismo , Ratas , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Cromatografía Líquida de Alta Presión/métodos , Distribución Tisular , Administración Oral , Heces/química
19.
Polymers (Basel) ; 16(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-39000640

RESUMEN

Triboelectric nanogenerators (TENGs) show promising potential in energy harvesting and sensing for various electronic devices in multiple fields. However, the majority of materials currently utilized in TENGs are unrenewable, undegradable, and necessitate complex preparation processes, resulting in restricted performance and durability for practical applications. Here, we propose a strategy that combines straightforward chemical modification and electrospinning techniques to construct all-cellulose nanofiber-based TENGs with substantial power output. By using cellulose acetate (CA) as the raw material, the prepared cellulose membranes (CMs) and fluorinated cellulose membranes (FCMs) with different functional groups and hydrophobic properties are applied as the tribopositive and tribonegative friction layers of FCM/CM-based triboelectric nanogenerators (FC-TENGs), respectively. This approach modulates the microstructure and triboelectric polarity of the friction materials in FC-TENGs, thus enhancing their triboelectric charge densities and contact areas. As a result, the assembled FC-TENGs demonstrate enhanced output performance (94 V, 8.5 µA, and 0.15 W/m2) and exceptional durability in 15,000 cycles. The prepared FC-TENGs with efficient energy harvesting capabilities can be implemented in practical applications to power various electronic devices. Our work strengthens the viability of cellulose-based TENGs for sustainable development and provides novel perspectives on the cost-effective and valuable utilization of cellulose in the future.

20.
Microsyst Nanoeng ; 10: 96, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006908

RESUMEN

Heart-on-a-chip (HoC) has emerged as a highly efficient, cost-effective device for the development of engineered cardiac tissue, facilitating high-throughput testing in drug development and clinical treatment. HoC is primarily used to create a biomimetic microphysiological environment conducive to fostering the maturation of cardiac tissue and to gather information regarding the real-time condition of cardiac tissue. The development of architectural design and advanced manufacturing for these "3S" components, scaffolds, stimulation, and sensors is essential for improving the maturity of cardiac tissue cultivated on-chip, as well as the precision and accuracy of tissue states. In this review, the typical structures and manufacturing technologies of the "3S" components are summarized. The design and manufacturing suggestions for each component are proposed. Furthermore, key challenges and future perspectives of HoC platforms with integrated "3S" components are discussed. Architecture design concepts of scaffolds, stimulation and sensors in chips.

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