Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.163
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Cell ; 187(6): 1387-1401.e13, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38412859

RESUMEN

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.


Asunto(s)
Proteínas del Tejido Nervioso , Degeneración Retiniana , Animales , Ratones , Traslocación Bacteriana , Proteínas del Ojo/genética , Amaurosis Congénita de Leber/genética , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Retina/metabolismo , Degeneración Retiniana/genética , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/metabolismo , Retinitis Pigmentosa/patología
2.
Cell Mol Life Sci ; 81(1): 226, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775844

RESUMEN

Vemurafenib has been used as first-line therapy for unresectable or metastatic melanoma with BRAFV600E mutation. However, overall survival is still limited due to treatment resistance after about one year. Therefore, identifying new therapeutic targets for melanoma is crucial for improving clinical outcomes. In the present study, we found that lowering intracellular cholesterol by knocking down DHCR24, the limiting synthetase, impaired tumor cell proliferation and migration and abrogated the ability to xenotransplant tumors. More importantly, administration of DHCR24 or cholesterol mediated resistance to vemurafenib and promoted the growth of melanoma spheroids. Mechanistically, we identified that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol synthesized by the enzyme cytochrome P450 27A1 (CYP27A1), reproduces the phenotypes induced by DHCR24 or cholesterol administration and activates Rap1-PI3K/AKT signaling. Accordingly, CYP27A1 is highly expressed in melanoma patients and upregulated by DHCR24 induction. Dafadine-A, a CYP27A1 inhibitor, attenuates cholesterol-induced growth of melanoma spheroids and abrogates the resistance property of vemurafenib-resistant melanoma cells. Finally, we confirmed that the effects of cholesterol on melanoma resistance require its metabolite 27HC through CYP27A1 catalysis, and that 27HC further upregulates Rap1A/Rap1B expression and increases AKT phosphorylation. Thus, our results suggest that targeting 27HC may be a useful strategy to overcome treatment resistance in metastatic melanoma.


Asunto(s)
Proliferación Celular , Colestanotriol 26-Monooxigenasa , Colesterol , Hidroxicolesteroles , Melanoma , Células Madre Neoplásicas , Vemurafenib , Vemurafenib/farmacología , Vemurafenib/uso terapéutico , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Melanoma/metabolismo , Melanoma/genética , Hidroxicolesteroles/metabolismo , Hidroxicolesteroles/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Colestanotriol 26-Monooxigenasa/metabolismo , Colestanotriol 26-Monooxigenasa/genética , Colesterol/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Línea Celular Tumoral , Ratones , Resistencia a Antineoplásicos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Proc Natl Acad Sci U S A ; 119(40): e2206990119, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36161913

RESUMEN

Rapid detection of pathogenic bacteria within a few minutes is the key to control infectious disease. However, rapid detection of pathogenic bacteria in clinical samples is quite a challenging task due to the complex matrix, as well as the low abundance of bacteria in real samples. Herein, we employ a label-free single-particle imaging approach to address this challenge. By tracking the scattering intensity variation of single particles in free solution, the morphological heterogeneity can be well identified with particle size smaller than the diffraction limit, facilitating the morphological identification of single bacteria from a complex matrix in a label-free manner. Furthermore, the manipulation of convection in free solution enables the rapid screening of low-abundance bacteria in a small field of view, which significantly improves the sensitivity of single-particle detection. As a proof of concept demonstration, we are able to differentiate the group B streptococci (GBS)-positive samples within 10 min from vaginal swabs without using any biological reagents. This is the most rapid and low-cost method to the best of our knowledge. We believe that such a single-particle imaging approach will find wider applications in clinical diagnosis and disease control due to its high sensitivity, rapidity, simplicity, and low cost.


Asunto(s)
Bacterias , Enfermedades Transmisibles , Análisis de la Célula Individual , Bacterias/aislamiento & purificación , Bacterias/patogenicidad , Enfermedades Transmisibles/diagnóstico por imagen , Femenino , Humanos , Tamaño de la Partícula , Análisis de la Célula Individual/métodos , Frotis Vaginal
4.
Apoptosis ; 29(3-4): 289-302, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38095762

RESUMEN

Metal ions play an important role in living organisms and are involved in essential physiological activities. However, the overload state of ions can cause excess free radicals, cell damage, and even cell death. Ferroptosis and cuproptosis are specific forms of cell death that are distinct from apoptosis, necroptosis, and other regulated cell death. These unique modalities of cell death, dependent on iron and copper, are regulated by multiple cellular metabolic pathways, including steady-state metal redox treatment mitochondrial activity of lipid, amino acid and glucose metabolism, and various signaling pathways associated with disease. Although the mechanisms of ferroptosis and cuproptosis are not yet fully understood, there is no doubt that ion overload plays a crucial act in these metal-dependent cell deaths. In this review, we discussed the core roles of ion overload in ferroptosis and cuproptosis, the association between metabolism imbalance and ferroptosis and cuproptosis, the extract the diseases caused by ion overload and current treatment modalities.


Asunto(s)
Ferroptosis , Enfermedades Renales , Muerte Celular Regulada , Humanos , Ferroptosis/genética , Apoptosis , Iones
5.
New Phytol ; 242(6): 2604-2619, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38563391

RESUMEN

Soil contamination with arsenic (As) can cause phytotoxicity and reduce crop yield. The mechanisms of As toxicity and tolerance are not fully understood. In this study, we used a forward genetics approach to isolate a rice mutant, ahs1, that exhibits hypersensitivity to both arsenate and arsenite. Through genomic resequencing and complementation tests, we identified OsLPD1 as the causal gene, which encodes a putative lipoamide dehydrogenase. OsLPD1 was expressed in the outer cell layer of roots, root meristem cells, and in the mesophyll and vascular tissues of leaves. Subcellular localization and immunoblot analysis demonstrated that OsLPD1 is localized in the stroma of plastids. In vitro assays showed that OsLPD1 exhibited lipoamide dehydrogenase (LPD) activity, which was strongly inhibited by arsenite, but not by arsenate. The ahs1 and OsLPD1 knockout mutants exhibited significantly reduced NADH/NAD+ and GSH/GSSG ratios, along with increased levels of reactive oxygen species and greater oxidative stress in the roots compared with wild-type (WT) plants under As treatment. Additionally, loss-of-function of OsLPD1 also resulted in decreased fatty acid concentrations in rice grain. Taken together, our finding reveals that OsLPD1 plays an important role for maintaining redox homeostasis, conferring tolerance to arsenic stress, and regulating fatty acid biosynthesis in rice.


Asunto(s)
Arsénico , Ácidos Grasos , Regulación de la Expresión Génica de las Plantas , Homeostasis , Oryza , Oxidación-Reducción , Proteínas de Plantas , Plastidios , Estrés Fisiológico , Oryza/genética , Oryza/efectos de los fármacos , Oryza/metabolismo , Homeostasis/efectos de los fármacos , Arsénico/toxicidad , Oxidación-Reducción/efectos de los fármacos , Ácidos Grasos/metabolismo , Ácidos Grasos/biosíntesis , Plastidios/metabolismo , Plastidios/efectos de los fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacos , Mutación/genética , Dihidrolipoamida Deshidrogenasa/metabolismo , Dihidrolipoamida Deshidrogenasa/genética , Especies Reactivas de Oxígeno/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Adaptación Fisiológica/efectos de los fármacos , Adaptación Fisiológica/genética , Estrés Oxidativo/efectos de los fármacos , Arsenitos/toxicidad
6.
Plant Cell Environ ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38722055

RESUMEN

Waterlogging stress (WS) hinders kernel development and directly reduces peanut yield; however, the mechanism of kernel filling in response to WS remains unknown. The waterlogging-sensitive variety Huayu 39 was subjected to WS for 3 days at 7 days after the gynophores touched the ground (DAG). We found that WS affected kernel filling at 14, 21, and 28 DAG. WS decreased the average filling rate and kernel dry weight, while transcriptome sequencing and widely targeted metabolomic analysis revealed that WS inhibited the gene expression in starch and sucrose metabolism, which reduced sucrose input and transformation ability. Additionally, genes related to ethylene and melatonin synthesis and the accumulation of tryptophan and methionine were upregulated in response to WS. WS upregulated the expression of the gene encoding tryptophan decarboxylase (AhTDC), and overexpression of AhTDC in Arabidopsis significantly reduced the seed length, width, and weight. Therefore, WS reduced the kernel-filling rate, leading to a reduction in the 100-kernel weight. This survey informs the development of measures that alleviate the negative impact of WS on peanut yield and quality and provides a basis for exploring high-yield and high-quality cultivation, molecular-assisted breeding, and waterlogging prevention in peanut farming.

7.
BMC Cancer ; 24(1): 458, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609917

RESUMEN

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.


Asunto(s)
Leucemia Mieloide Aguda , Nomogramas , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Área Bajo la Curva , Leucemia Mieloide Aguda/diagnóstico por imagen
8.
Immunity ; 42(4): 613-26, 2015 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-25862091

RESUMEN

Epigenetic regulation of lineage-specific genes is important for the differentiation and function of T cells. Ten-eleven translocation (Tet) proteins catalyze 5-methylcytosine (5 mC) conversion to 5-hydroxymethylcytosine (5 hmC) to mediate DNA demethylation. However, the roles of Tet proteins in the immune response are unknown. Here, we characterized the genome-wide distribution of 5 hmC in CD4(+) T cells and found that 5 hmC marks putative regulatory elements in signature genes associated with effector cell differentiation. Moreover, Tet2 protein was recruited to 5 hmC-containing regions, dependent on lineage-specific transcription factors. Deletion of Tet2 in T cells decreased their cytokine expression, associated with reduced p300 recruitment. In vivo, Tet2 plays a critical role in the control of cytokine gene expression in autoimmune disease. Collectively, our findings suggest that Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells.


Asunto(s)
Citocinas/biosíntesis , Proteínas de Unión al ADN/inmunología , Epigénesis Genética/inmunología , Proteínas Proto-Oncogénicas/inmunología , Células TH1/inmunología , Células Th17/inmunología , 5-Metilcitosina/análogos & derivados , Animales , Diferenciación Celular , Citocinas/inmunología , Citosina/análogos & derivados , Citosina/inmunología , Citosina/metabolismo , ADN/inmunología , ADN/metabolismo , Metilación de ADN , Proteínas de Unión al ADN/genética , Dioxigenasas , Proteína p300 Asociada a E1A/genética , Proteína p300 Asociada a E1A/inmunología , Regulación de la Expresión Génica , Genoma , Humanos , Ratones , Ratones Transgénicos , Proteínas Proto-Oncogénicas/genética , Factor de Transcripción STAT4/genética , Factor de Transcripción STAT4/inmunología , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/inmunología , Células TH1/citología , Células TH1/enzimología , Células Th17/citología , Células Th17/enzimología
9.
Pediatr Res ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38763946

RESUMEN

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is caused by perinatal hypoxia and subsequent reductions in cerebral blood flow and is one of the leading causes of severe disability or death in newborns. Despite its prevalence, we currently lack an effective drug therapy to combat HIE. Celastrol (Cel) is a pentacyclic triterpene extracted from Tripterygium Wilfordi that can protect against oxidative stress, inflammation, and cancer. However, whether Cel can alleviate neonatal hypoxic-ischemic (HI) brain damage remains unclear. METHODS: Here, we established both in vitro and in vivo models of HI brain damage using CoCl2-treated PC12 cells and neonatal rats, respectively, and explored the neuroprotective effects of Cel in these models. RESULTS: Analyses revealed that Cel administration reduced brain infarction size, microglia activation, levels of inflammation factors, and levels of oxidative stress markers by upregulating levels of p-AMPKα, Nrf2, HO-1, and by downregulating levels of TXNIP and NLRP3. Conversely, these beneficial effects of Cel on HI brain damage were largely inhibited by AMPKα inhibitor Compound C and its siRNA. CONCLUSIONS: We present compelling evidence that Cel decreases inflammation and oxidative stress through the AMPKα/Nrf2/TXNIP signaling pathway, thereby alleviating neonatal HI brain injury. Cel therefore represents a promising therapeutic agent for treating HIE. IMPACT: We firstly report that celastrol can ameliorate neonatal hypoxic-ischemic brain injury both in in vivo and in vitro, which represents a promising therapeutic agent for treating related brain injuries. Celastrol activates the AMPKα/Nrf2/TXNIP signaling pathway to relieve oxidative stress and inflammation and thereby alleviates neonatal hypoxic-ischemic brain injury.

10.
J Org Chem ; 89(4): 2656-2664, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38324782

RESUMEN

We have developed a metal-free photocatalytic selective hydroxylation of benzylic methylenes to secondary alcohols. This approach utilizes low-cost eosin Y as photocatalyst, O2 as green oxidant, and inexpensive triethylamine as inhibitor for overoxidation. The mild reaction conditions enable the production of secondary alcohols with 56-95% yields, making it a promising and environmental-friendly method for the synthesis of secondary alcohols from benzylic methylenes.

11.
Aging Male ; 27(1): 2336625, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38647199

RESUMEN

BACKGROUND: Benign prostatic hyperplasia (BPH) affects 30% of men worldwide, folate is essential for life. However, few studies have investigated the relationship between folate levels and BPH. The present study aims to explore the relationship between red blood cell (RBC) folate, a better indicator of long-term folate intake, and BPH in United States (US) men. METHODS: We used statistics from four cycles of the "National Health and Nutrition Examination Survey" (NHANES2001-2008), RBC folate data come from laboratory data and BPH date come from questionnaire data. A multivariate conditional logistic regression model and subgroup analysis were using to assess the association between RBC folate and BPH. RESULTS: 647 males from four survey cycles in the NHANES2001-2008, of which, 574 men (88.7%) had BPH. After adjusting for potential confounders, a considerable correlation was observed between RBC folate and BPH; With the first quintiles of RBC folate as the reference, multivariable-adjusted odds ratios (ORs) and confidence intervals (95% CIs) of the second, third, fourth, and the highest quintiles were 1.19 (0.58 ∼ 2.44), 1.39 (0.65 ∼ 2.97), 2.27 (0.96 ∼ 5.39), 2.26 (1.35 ∼ 3.76) and 5.37 (1.85 ∼ 15.59), respectively. CONCLUSIONS: Individuals with high levels of RBC folate were associated with an increased risk of self-reported benign prostatic hyperplasia of US men.


Asunto(s)
Eritrocitos , Ácido Fólico , Encuestas Nutricionales , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/sangre , Hiperplasia Prostática/epidemiología , Ácido Fólico/sangre , Persona de Mediana Edad , Estados Unidos/epidemiología , Eritrocitos/química , Eritrocitos/metabolismo , Anciano , Adulto , Modelos Logísticos , Factores de Riesgo
12.
Clin Exp Rheumatol ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38910565

RESUMEN

Gout is a self-limited inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints and surrounding tissues due to abnormal purine metabolism. Neutrophil extracellular traps (NETs) are formed by neutrophils in response to pathogen attack. During gout, NETs induced by MSU crystals exacerbate inflammation, and aggregated NETs (aggNETs) promote the resolution of gout-associated inflammation by encapsulating MSU crystals, degrading cytokines and chemokines, and blocking the recruitment and activation of neutrophils. With disease progression, NETs participate in the formation of tophi. Therefore, aggNETs are a possible mechanism of spontaneous gout regression. Studying the specific mechanism by which NETs affect inflammatory bursts and spontaneous regression in gout patients is important. This review summarises the role of NETs in different stages of gout and the specific pathogenesis of NETs in gout to provide new ideas for the diagnosis and treatment of gout.

13.
Inorg Chem ; 63(11): 5269-5280, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38427948

RESUMEN

Artificial photosynthesis provides a sustainable strategy for producing usable fuels and fine chemicals and attracts broad research interest. However, conventional approaches suffer from low reactivity or low selectivity. Herein, we demonstrate that photocatalytic reduction of CO2 coupled with selective oxidation of aromatic alcohol into corresponding syngas and aromatic aldehydes can be processed efficiently and fantastically over the designed S-scheme ZnIn2S4@CdS core-shell hollow nanocage under visible light. In the ZnIn2S4@CdS heterostructure, the photoexcited electrons and holes with weak redox capacities are eliminated, while the photoexcited electrons and holes with powder redox capacities are separated spatially and preserved on the desired active sites. Therefore, even if there are no cocatalysts and no vacancies, ZnIn2S4@CdS exhibits high reactivity. For instance, the CO production of ZnIn2S4@CdS is about 3.2 and 3.4 times higher than that of pure CdS and ZnIn2S4, respectively. More importantly, ZnIn2S4@CdS exhibits general applicability and high photocatalytic stability. Trapping agent experiments, 13CO2 isotopic tracing, in situ characterizations, and theoretical calculations reveal the photocatalytic mechanism. This study provides a new strategy to design efficient and selective photocatalysts for dual-function redox reactions by tailoring the active sites and regulating vector separation of photoexcited charge carriers.

14.
Phys Chem Chem Phys ; 26(17): 12957-12964, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38632968

RESUMEN

Compared to the effect of the active hydrogen atom in the cation in protic ionic liquids (ILs) on their properties and applications, there are very few reports on the role of the active hydrogen atom in the anion. In order to better understand the role of the active hydrogen atom in the anion, the physical properties, CO2 capture and conversion of three hydantoin-based anion-functionalized ILs ([P4442][Hy], [P4442]2[Hy], and [HDBU][Hy]) have been investigated via experiments, spectroscopy, and DFT calculations in this work. The results show that the active hydrogen atom in the anion can form anionic hydrogen bonding networks, which significantly increase the melting point and viscosity and decrease the basicity of the IL, thereby weakening its ability to capture and convert CO2. Interestingly, [P4442][Hy] undergoes a solid/liquid two-phase transition during CO2 absorption/desorption due to the formation of quasi-intramolecular hydrogen bonding between the active hydrogen atom and the O- atom of the absorbed CO2, suggesting that the presence of the active hydrogen atom gives [P4442][Hy] the potential to be an excellent molecular switch. As there is no active hydrogen atom in the anion of [P4442]2[Hy], it shows excellent CO2 capture and conversion performance through the double-site interaction. [HDBU][Hy] shows the weakest catalytic CO2 conversion due to the presence of active hydrogen atoms on both its anion and cation. Therefore, the active hydrogen atom in the anion may play a more important role in the properties and potential applications of ILs than the active hydrogen atom in the cation.

15.
Nature ; 564(7734): 130-135, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30487606

RESUMEN

Dysfunctional T cells in the tumour microenvironment have abnormally high expression of PD-1 and antibody inhibitors against PD-1 or its ligand (PD-L1) have become commonly used drugs to treat various types of cancer1-4. The clinical success of these inhibitors highlights the need to study the mechanisms by which PD-1 is regulated. Here we report a mechanism of PD-1 degradation and the importance of this mechanism in anti-tumour immunity in preclinical models. We show that surface PD-1 undergoes internalization, subsequent ubiquitination and proteasome degradation in activated T cells. FBXO38 is an E3 ligase of PD-1 that mediates Lys48-linked poly-ubiquitination and subsequent proteasome degradation. Conditional knockout of Fbxo38 in T cells did not affect T cell receptor and CD28 signalling, but led to faster tumour progression in mice owing to higher levels of PD-1 in tumour-infiltrating T cells. Anti-PD-1 therapy normalized the effect of FBXO38 deficiency on tumour growth in mice, which suggests that PD-1 is the primary target of FBXO38 in T cells. In human tumour tissues and a mouse cancer model, transcriptional levels of FBXO38 and Fbxo38, respectively, were downregulated in tumour-infiltrating T cells. However, IL-2 therapy rescued Fbxo38 transcription and therefore downregulated PD-1 levels in PD-1+ T cells in mice. These data indicate that FBXO38 regulates PD-1 expression and highlight an alternative method to block the PD-1 pathway.


Asunto(s)
Proteínas F-Box/genética , Neoplasias/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T/inmunología , Ubiquitinación , Animales , Proteínas F-Box/metabolismo , Femenino , Células HEK293 , Humanos , Interleucina-2/inmunología , Lisina/metabolismo , Masculino , Melanoma Experimental/inmunología , Ratones , Receptor de Muerte Celular Programada 1/química , Complejo de la Endopetidasa Proteasomal/metabolismo , Microambiente Tumoral
16.
Arch Toxicol ; 98(3): 779-790, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38224356

RESUMEN

Hair analysis is a crucial method in forensic toxicology with potential applications in revealing doping histories in sports. Despite its widespread use, knowledge about detectable substances in hair is limited. This study systematically assessed the detectability of prohibited substances in sports using a multifaceted approach. Initially, an animal model received a subset of 17 model drugs to compare dose dependencies and detection windows across different matrices. Subsequently, hair incorporation data from the animal experiment were extrapolated to all substances on the World Anti-Doping Agency's List through in-silico prediction. The detectability of substances in hair was further validated in a proof-of-concept human study involving the consumption of diuretics and masking agents. Semi-quantitative analysis of substances in specimens was performed using ultra-performance liquid chromatography-tandem mass spectrometry. Results showed plasma had optimal dose dependencies with limited detection windows, while urine, faeces, and hair exhibited a reasonable relationship with the administered dose. Notably, hair displayed the highest detection probability (14 out of 17) for compounds, including anabolic agents, hormones, and diuretics, with beta-2 agonists undetected. Diuretics such as furosemide, canrenone, and hydrochlorothiazide showed the highest hair incorporation. Authentic human hair confirmed diuretic detectability, and their use duration was determined via segmental analysis. Noteworthy is the first-time reporting of canrenone in human hair. Anabolic agents were expected in hair, whereas undetectable compounds, such as peptide hormones and beta-2 agonists, were likely due to large molecular mass or high polarity. This study enhances understanding of hair analysis in doping investigations, providing insights into substance detectability.


Asunto(s)
Anabolizantes , Doping en los Deportes , Animales , Humanos , Canrenona/análisis , Doping en los Deportes/métodos , Diuréticos/análisis , Heces/química , Cabello/química , Detección de Abuso de Sustancias/métodos
17.
BMC Public Health ; 24(1): 908, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38539176

RESUMEN

BACKGROUND: As the internet develops and 5G technology becomes increasingly prominent, the internet has become a major source of health-related information. Increasingly, people use the internet to find health-related information, and digital health literacy is now a set of essential capabilities to improve their health in the digital era. However, little is known about the factors that influencing digital health literacy. This study aimed to assess digital health literacy scores and identify its influencing factors among internet users in China. Additionally, this study explored the participant's actual skills using an additional set of performance-based items from the Digital Health Literacy Instrument (DHLI). METHODS: An online cross-sectional study was conducted in August 2022. Participants aged ≥18 years were recruited to complete the survey. Data were collected using the Chinese revised version of the DHLI, the self-reported internet use questionnaire, and the sociodemographic questionnaire. We conducted multivariate linear regression analyses to explore the relationships among the sociodemographic variables, behavior of internet use, and the digital health literacy scores. RESULTS: In total, 702 participants completed the survey. The mean DHLI score was 2.69 ± 0.61. Multivariate linear regression analyses showed that the age groups 35-49 (ß = - 0.08, P = 0.033), 50-64 (ß = - 0.161, P < 0.001), and ≥ 65 (ß = - 0.138, P < 0.001) were negatively associated with DHL scores. However, education level, including bachelor's or associate degree (ß = 0.255, P = 0.002) and master's degree and above (ß = 0.256, P < 0.001), frequency of health-related Internet usage (ß = 0.192, P < 0.001), the number of digital devices used (ß = 0.129, P = 0.001), and OHISB (ß = 0.103, P = 0.006) showed a positive relationship with DHL scores. CONCLUSIONS: The study findings demonstrate that age, educational levels, number of technological devices used, and greater use of the web for health information were independently associated with DHL scores. Healthcare providers should consider providing training programs tailored to specific sociodemographic factors to improve the ability that find and use accurate information online to meet digital health services, which contributes to enhance their self-management and reduce health disparities.


Asunto(s)
Alfabetización en Salud , Telemedicina , Humanos , Adolescente , Adulto , Salud Digital , Estudios Transversales , Encuestas y Cuestionarios , Internet , China
18.
World J Surg Oncol ; 22(1): 69, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38403630

RESUMEN

BACKGROUND: Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. MATERIALS AND METHODS: A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). RESULTS: We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. CONCLUSION: DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.


Asunto(s)
Neoplasias , Tromboembolia Venosa , Humanos , Heparina de Bajo-Peso-Molecular/efectos adversos , Anticoagulantes/efectos adversos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Neoplasias/cirugía
19.
Artículo en Inglés | MEDLINE | ID: mdl-38870506

RESUMEN

Objective: This study aims to investigate the use of proton pump inhibitors (PPIs) among inpatients in a hospital and analyze the rationality of their use. Methods: We analyzed the medication records of 1986 inpatients from January 2023 to June 2023, focusing on patients using PPIs under the "Internet + medical service" model. Additionally, we compared and analyzed the drug use patterns, including dosage form, dosage, medication frequency, average daily cost, and sales amount, between two groups: those treated before and after the implementation of the "Internet + medical service" model. The control group comprised 1962 inpatients treated with PPIs from July 2022 to December 2022. We also compared drug inventory time, account coincidence rate, error rate, and nursing satisfaction between the two periods. Results: Among the hospitalized patients using PPIs, 892 cases were male (44.91%) and 1094 cases were female (55.09%). Regarding age distribution, 456 cases were aged 18-45 (22.96%), 845 cases were aged 46-65 (42.55%), and 685 cases were over 65 years old (34.49%). The top 10 departments with the highest frequency of PPI use included gastroenterology (8.36%), oncology, hematology, trauma orthopedics (6.95% each), cardiovascular medicine, neurology (6.39% each), general surgery (6.29%), respiratory, critical care (5.84%), renal rheumatology, immunology (5.79%), and spine surgery (5.59%). Omeprazole enteric-coated capsules accounted for the highest proportion (25.08%), followed by rabeprazole enteric-coated tablets (22.96%) and pantoprazole sodium enteric-coated tablets (20.04%). After implementing the "Internet + medical service" model, there was a reduction in irrational PPI use, medication error rates, and inventory time. Moreover, the account coincidence rate and satisfaction rate increased significantly (P < .05). Conclusion: The utilization of PPIs in hospitals is notably high. Implementing the "Internet + medical service" model can effectively improve the rationality of PPI use. Clinicians should adhere to relevant indications when prescribing PPIs and conduct drug interventions to prevent overuse.

20.
Ecotoxicol Environ Saf ; 280: 116571, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38850703

RESUMEN

BACKGROUND: Nickel is a common metallic element in orthopedic implanted devices and living environment exposures. It is associated with varieties of diseases. The purpose of this investigation was to explore the correlation between nickel exposure and the prevalence of arthritis. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2018. Multivariate logistic regression was utilized to analyze the relationship between urinary nickel levels and arthritis. In addition, hierarchical modeling further explored the interactions and trends between urinary nickel levels and arthritis. Propensity score matching (PSM) method was used to reduce the effect of confounders. Additionally, restricted cubic spline curve (RCS) was used to assess the possible nonlinear association between urinary nickel and arthritis. RESULTS: The investigation was comprised of 139 arthritis patients and 547 healthy participants. After correction by PSM, there was a positive correlation between arthritis and Nickel exposure levels. The risk of developing arthritis was significantly increased when nickel exposure levels were in the Q4 interval (OR=2.25, 95 % CI=1.03-5.02). When stratified by age and sex, nickel exposure was significantly and positively associated with arthritis in the subgroup aged over 65 years. (OR=2.78,95 %CI=1.20-6.46). Also, the difference between nickel exposure and arthritis was significant in the different gender subgroups (interaction P<0.05). Restricted cubic spline (RCS) results showed a significant linear association between nickel exposure levels and arthritis. In addition, there was a non-linear association between nickel exposure and arthritis across gender and age subgroups. CONCLUSION: A significant positive association between nickel exposure levels and arthritis was showed by the experimental data. Controlling the use of nickel-containing medical prostheses and reducing exposure to nickel-containing daily necessity could help to slow the onset of arthritis.


Asunto(s)
Artritis , Exposición a Riesgos Ambientales , Níquel , Níquel/orina , Humanos , Femenino , Masculino , Estudios Transversales , Artritis/epidemiología , Artritis/inducido químicamente , Persona de Mediana Edad , Exposición a Riesgos Ambientales/estadística & datos numéricos , Anciano , Adulto , Encuestas Nutricionales , Contaminantes Ambientales/orina , Prevalencia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA