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1.
Sci Rep ; 14(1): 19054, 2024 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154111

RESUMEN

Stroke is a severe cerebrovascular disease. This study aimed to determine the association between triglyceride­glucose (TyG) index and stroke among middle-aged and elderly Chinese. Data was extracted from China Health and Retirement Longitudinal Study survey 2015 and survey 2018. Logistic regression, trend test and subgroup analysis were conducted to assess the association. Possible nonlinear relationships were explored with restricted cubic spline (RCS). Propensity score matching (PSM) was conducted to attenuate the effect of confounding factors. ORs of stroke was positively associated with TyG index. The ORs in RCS analysis also increased with the rising TyG, though p for non-linearity was bigger than 0.05. After PSM, the ORs in the full adjusted models were 1.28 (1.01, 1.62). TyG was suggested as an independent risk factor for stroke in the middle aged and elderly Chinese.


Asunto(s)
Glucemia , Accidente Cerebrovascular , Triglicéridos , Humanos , Estudios Longitudinales , Triglicéridos/sangre , China/epidemiología , Anciano , Femenino , Masculino , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/sangre , Persona de Mediana Edad , Factores de Riesgo , Glucemia/análisis , Pueblos del Este de Asia
2.
Sci Total Environ ; 949: 174990, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39094640

RESUMEN

Plants are known for their significant dust retention capacity and are widely used to alleviate atmospheric pollution. Urban green plants are exposed to periodic particulate matter pollution stress, and the time intervals between periods of pollution exposure are often inconsistent. The impact of stress memory and pollution intervals on plant dust retention capacity and physiological characteristics during periodic stress is not yet clear. In this study, the common urban landscaping species Nerium oleander L. was selected as the test plant, and stable isotope (15NH4Cl) tracing technology and aerosol generators were used to simulate periodic PM2.5 pollution. This study included two particulate pollution periods (each lasting 14 days) and one recovery period with three different durations (7, 14, and 21 days). The results indicated that periodic particulate matter pollution-induced stress decreased the dust retention capacity of N. oleander leaf surfaces, but particle adsorption to the wax layer was more stable. As the duration of the recovery period increased, leaf particle absorption, which accounted for the greatest proportion of total dust retention, increased, indicating that leaves are the primary organ for dust retention in Nerium oleander L. Root absorption also increased with increasing recovery periods. Prior pollution stress increased oleander physiological and morphological responses, and the plant's air pollution tolerance significantly improved after a recovery period of >14 days.


Asunto(s)
Contaminantes Atmosféricos , Polvo , Nerium , Material Particulado , Contaminantes Atmosféricos/análisis , Polvo/análisis , Material Particulado/análisis , Contaminación del Aire/estadística & datos numéricos , Monitoreo del Ambiente , Hojas de la Planta
3.
Artículo en Inglés | MEDLINE | ID: mdl-39093393

RESUMEN

China's new urbanization strategy serves as a key instrument for achieving sustainable development goals in urban areas. However, a consensus on how and whether new urbanization affects urban green total factor productivity (GTFP) has yet to be reached. This analysis targets 276 prefecture-level and above cities, using panel data from 2011 to 2019 to assess the impact of the new urbanization pilot policy (NUPP) on GTFP. The research findings demonstrate that implementing China's NUPP has significantly enhanced urban GTFP. Furthermore, the population-land-industry coupling coordination degree (PLICCD), as well as the industry-environment-economy coupling coordination degree (IEECCD), play crucial facilitating roles in the aforementioned enhancement effects. The results remain robust even after employing PSM-staggered difference-in-differences (DID) estimation and excluding other policy interferences. Furthermore, heterogeneity analysis, based on urban characteristics, reveals that the NUPP significantly enhances GTFP in resource-based, non-resource-based, industrial, non-intensive compactness, and non-expansionary urbanization cities. Finally, the paper offers three policy recommendations. First, new urbanization initiatives should be more actively promoted in China and other developing countries. Second, the construction of new urbanization plans should focus on the coordinated development of "population-land-industry" and "industry-environment-economy." Third, the government should implement new urbanization initiatives tailored to the specific characteristics of different cities. This study provides valuable insights for the general public, policymakers, and scholars to better understand the potential of coordinating the development of population, land, industry, the environment, and the economy to improve GTFP. Moreover, it offers a broad perspective for evaluating sustainable urban development.

4.
World Neurosurg ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38996962

RESUMEN

OBJECTIVE: Patients with moderate traumatic brain injury (TBI) are under the threat of intracranial hypertension (IHT). However, it is unclear which moderate TBI patient will develop IHT and should receive intracranial pressure (ICP)-lowering treatment or invasive ICP monitoring after admission. The purpose of the present study was to develop and validate a prediction model that estimates the risk of IHT in moderate TBI patients. METHODS: Baseline data collected on admission of 296 moderate TBI patients with Glasgow Coma Scale (GCS) score of 9-11 was collected and analyzed. Multi-variable logistic regression modeling with backward stepwise elimination was used to develop a prediction model for IHT. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated. Finally, the prediction model was validated in a separate cohort of 122 patients from 3 hospitals. RESULTS: Four independent prognostic factors for IHT were identified: GCS score, Marshall head computed tomography score, injury severity score and location of contusion. The C-statistic of the prediction model in internal validation was 84.30% (95% confidence interval [CI]: 0.794-0.892). The area under the curve for the prediction model in external validation was 82.80% (95% CI: 0.747∼0.909). CONCLUSIONS: A prediction model based on baseline parameters was found to be highly sensitive in distinguishing moderate TBI patients with GCS score of 9-11 who would suffer IHT. The high discriminative ability of the prediction model supports its use in identifying moderate TBI patients with GCS score of 9-11 who need ICP-lowering therapy or invasive ICP monitoring.

5.
Acta Pharmacol Sin ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38942954

RESUMEN

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

6.
Front Aging Neurosci ; 16: 1359320, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694258

RESUMEN

The morphology and function of the cerebellum are associated with various developmental disorders and healthy aging. Changes in cerebellar morphology during the aging process have been extensively investigated, with most studies focusing on changes in cerebellar regional volume. The volumetric method has been used to quantitatively demonstrate the decrease in the cerebellar volume with age, but it has certain limitations in visually presenting the morphological changes of cerebellar atrophy from a three-dimensional perspective. Thus, we comprehensively described cerebellar morphological changes during aging through volume measurements of subregions and shape analysis. This study included 553 healthy participants aged 20-80 years. A novel cerebellar localized segmentation algorithm based on convolutional neural networks was utilized to analyze the volume of subregions, followed by shape analysis for localized atrophy assessment based on the cerebellar thickness. The results indicated that out of the 28 subregions in the absolute volume of the cerebellum, 15 exhibited significant aging trends, and 16 exhibited significant sex differences. Regarding the analysis of relative volume, only 11 out of the 28 subregions of the cerebellum exhibited significant aging trends, and 4 exhibited significant sex differences. The results of the shape analysis revealed region-specific atrophy of the cerebellum with increasing age. Regions displaying more significant atrophy were predominantly located in the vermis, the lateral portions of bilateral cerebellar hemispheres, lobules I-III, and the medial portions of the posterior lobe. This atrophy differed between sexes. Men exhibited slightly more severe atrophy than women in most of the cerebellar regions. Our study provides a comprehensive perspective for observing cerebellar atrophy during the aging process.

7.
Crit Care Res Pract ; 2024: 3807532, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38766547

RESUMEN

Delirium is a serious and complex problem facing critically ill patients. This retrospective study aimed to explore the association between prognostic nutrition index (PNI) and delirium in critically ill patients in the intensive care unit (ICU). This study was based on the Medical Information Mart Intensive Care IV (MIMIC IV) database. Patients over 18 years of age were enrolled. Univariate and multivariate logistic regression analyses were performed to explore the association between PNI and delirium. Tendency analysis, subgroups analysis, and restricted cubic spline (RCS) were selected to further certify the association. The receiver operating characteristic curve (ROC) was adopted to assess the predictability of PNI to delirium. Propensity score matching (PSM) was used to reduce the interference of confounders. A total of 3,105 patients participated in this study. As the grade of malnutrition increases, the incidence of delirium increases in all models. The odds ratios (OR) of delirium in the fully adjusted model were 1.00 (reference), 1.04 (0.80, 1.36), 1.53 (1.17, 1.99), and 1.93 (1.44, 2.59). Strong U-shaped curves were found with RCS analysis between delirium and PNI in the subgroups of patients over 60 years of age and patients with chronic obstructive pulmonary disease (COPD). After PSM, the ORs of delirium were 1.44 (1.16, 1.79) and 1.53 (1.22, 1.93), respectively, in the univariate and multivariate logistic regression models. PNI is negatively associated with the prevalence of delirium in critically ill adults in the ICU. PNI is an independent risk factor for the incidence of delirium in adults in the ICU.

8.
Environ Res ; 256: 119237, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38810829

RESUMEN

Ionizing radiation (IR) poses a significant threat to both the natural environment and biological health. Exposure to specific doses of ionizing radiation early in an organism's development can lead to developmental toxicity, particularly neurotoxicity. Through experimentation with Xenopus laevis (X. laevis), we examined the effects of radiation on early developmental stage. Our findings revealed that radiation led to developmental abnormalities and mortality in X. laevis embryos in a dose-dependent manner, disrupting redox homeostasis and inducing cell apoptosis. Additionally, radiation caused neurotoxic effects, resulting in abnormal behavior and neuron damage in the embryos. Further investigation into the underlying mechanisms of radiation-induced neurotoxicity indicated the potential involvement of the neuroactive ligand-receptor interaction pathway, which was supported by RNA-Seq analysis. Validation of gene expression associated with this pathway and analysis of neurotransmitter levels confirmed our hypothesis. In addition, we further validated the important role of this signaling pathway in radiation-induced neurotoxicity through edaravone rescue experiments. This research establishes a valuable model for radiation damage studying and provides some insight into radiation-induced neurotoxicity mechanisms.


Asunto(s)
Embrión no Mamífero , Radiación Ionizante , Xenopus laevis , Animales , Embrión no Mamífero/efectos de la radiación , Síndromes de Neurotoxicidad/etiología , Transducción de Señal/efectos de la radiación , Apoptosis/efectos de la radiación , Ligandos
9.
Sensors (Basel) ; 24(10)2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38794106

RESUMEN

Road traffic safety facilities (TSFs) are of significant importance in the management and maintenance of traffic safety. The complexity and variety of TSFs make it challenging to detect them manually, which renders the work unsustainable. To achieve the objective of automatic TSF detection, a target detection dataset, designated TSF-CQU (TSF data collected by Chongqing University), was constructed based on images collected by a car recorder. This dataset comprises six types of TSFs and 8410 instance samples. A detection transformer with an improved denoising anchor box (DINO) was selected to construct a model that would be suitable for this scenario. For comparison purposes, Faster R-CNN (Region Convolutional Neural Network) and Yolov7 (You Only Look Once version 7) were employed. The DINO model demonstrated the highest performance on the TSF-CQU dataset, with a mean average precision (mAP) of 82.2%. All of the average precision (AP) values exceeded 0.8, except for streetlights (AP = 0.77) and rods (AP = 0.648). The DINO model exhibits minimal instances of erroneous recognition, which substantiates the efficacy of the contrastive denoising training approach. The DINO model rarely makes misjudgments, but a few missed detection.

10.
Cerebellum ; 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38581612

RESUMEN

Preterm birth is associated with increased risk for a spectrum of neurodevelopmental disabilities. The cerebellum is implicated in a wide range of cognitive functions extending beyond sensorimotor control and plays an increasingly recognized role in brain development. Morphometric studies based on volume analyses have revealed impaired cerebellar development in preterm infants. However, the structural covariance between the cerebellum and cerebral cortex has not been studied during the neonatal period, and the extent to which structural covariance is affected by preterm birth remains unknown. In this study, using the structural MR images of 52 preterm infants scanned at term-equivalent age and 312 full-term controls from the Developing Human Connectome Project, we compared volumetric growth, local cerebellum shape development and cerebello-cerebral structural covariance between the two groups. We found that although there was no significant difference in the overall volume measurements between preterm and full-term infants, the shape measurements were different. Compared with the control infants, preterm infants had significantly larger thickness in the vermis and lower thickness in the lateral portions of the bilateral cerebral hemispheres. The structural covariance between the cerebellum and frontal and parietal lobes was significantly greater in preterm infants than in full-term controls. The findings in this study suggested that cerebellar development and cerebello-cerebral structural covariance may be affected by premature birth.

11.
Mikrochim Acta ; 191(5): 263, 2024 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619658

RESUMEN

A green and sensitive ratio fluorescence strategy was proposed for the detection of formaldehyde (FA) in food based on a kind of metal-organic frameworks (MOFs), MIL-53(Fe)-NO2, and nitrogen-doped Ti3C2 MXene quantum dots (N-Ti3C2 MQDs) with a blue fluorescence at 450 nm. As a type of MOFs with oxidase-like activity, MIL-53(Fe)-NO2 can catalyze o-phenylenediamine (OPD) into yellow fluorescent product 2,3-diaminophenazine (DAP) with a fluorescent emission at 560 nm. DAP has the ability to suppress the blue light of N-Ti3C2 MQDs due to inner filter effect (IFE). Nevertheless, Schiff base reaction can occur between FA and OPD, inhibiting DAP production. This results in a weakening of the IFE which reverses the original fluorescence color and intensity of DAP and N-Ti3C2 MQDs. So, the ratio of fluorescence intensity detected at respective 450 nm and 560 nm was designed as the readout signal to detect FA in food. The linear range of FA detection was 1-200 µM, with a limit of detection of 0.49 µM. The method developed was successfully used to detect FA in food with satisfactory results. It indicates that MIL-53(Fe)-NO2, OPD, and N-Ti3C2 MQDs (MON) system constructed by integrating the mimics enzyme, enzyme substrate, and fluorescent quantum dots has potential application for FA detection in practical samples.


Asunto(s)
Estructuras Metalorgánicas , Fenilendiaminas , Puntos Cuánticos , Colorantes Fluorescentes , Dióxido de Nitrógeno , Formaldehído
12.
Foods ; 13(6)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38540810

RESUMEN

Zongzi, made from glutinous rice, is usually thought to stay in the stomach for a long time, causing many people to shy away. In our research, Zongzi was prepared from three indica glutinous rice samples, and three japonica glutinous rice samples were digested in vitro in a human gastric simulator (HGS). It was found that digestion performance in HGS (gastric emptying) was mainly related to the hardness and stickiness of texture properties, and surprisingly, the hardness and stickiness of Zongzi were positively correlated, which contradicts past perception. Through the extraction and analysis of the coated layer on the surface of glutinous rice grains in Zongzi, the main source of its stickiness was the entanglement between the long chains of leached amylopectin molecules. The hardness was also mainly due to the high proportion of long chains in its glutinous rice starch, which made it difficult to gelatinize. Studies suggested that stickiness gradually disappeared during digestion, while hardness had a longer impact on digestive performance. The indica glutinous rice Zongzi with a higher long-chain level showed a higher resistant-starch (RS) level and slow hydrolysis in the intestinal digestion stage. Therefore, the texture and digestibility of Zongzi can be adjusted by changing the molecular structure of glutinous rice starch.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38546428

RESUMEN

Objective: To investigate whether transcutaneous electrical acupoint stimulation (TEAS) at PC6 could reduce hypotension after spinal anesthesia (SA) in parturients and to compare the effect of TEAS at different frequencies. Methods: From February 20, 2023, to August 29, 2023, 90 parturients scheduled for c-section under SA were randomly assigned to receive no treatment (Control), TEAS at high frequency (TEAS-HF), or TEAS at low frequency (TEAS-LF). Treatments started immediately after SA and lasted for 30 min. The primary endpoint was incidence of hypotension by 30 min after SA. Secondary endpoints included lowest systolic blood pressure (SBP) during 30 min after SA, dose of ephedrine, dose of atropine, Apgar score at 1 min, and adverse events, including nausea, vomiting, dizziness, dyspnea, and chest congestion. Results: In the TEAS-HF group, the incidence of hypotension by 30 min after SA was lower (13.3%) than in the Control (53.3%, p = 0.001; OR 1.9, 95% confidence interval [CI]: 1.2-2.8) and TEAS-LF group (40.0%, p = 0.02, OR 1.4, 95% CI: 1.0-2.0). The lowest SBP during 30 min after SA was higher in the TEAS-HF group (100.0 ± 9.4 mm Hg) than in the Control group (91.5 ± 16.5 mm Hg) and TEAS-LF group (93.9 ± 16.6 mm Hg). Patients who received TEAS showed a lower score of nausea and vomiting (both p = 0.02). Patients in the group TEAS-HF showed a lower incidence of dizziness, dyspnea, and of chest congestion than those in the other two groups. There was no difference with respect to atropine consumption and neonatal Apgar score. Conclusions: TEAS-HF at PC6 reduced hypotension after SA in parturients, while TEAS-LF did not. Trial registration: ClinicalTrials.gov (NCT05724095).

14.
Epigenomics ; 16(7): 461-472, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38482663

RESUMEN

Aim: To elucidate the epigenetic consequences of DNA methylation in healthspan termination (HST), considering the current limited understanding. Materials & methods: Genetically predicted DNA methylation models were established (n = 2478). These models were applied to genome-wide association study data on HST. Then, a poly-methylation risk score (PMRS) was established in 241,008 individuals from the UK Biobank. Results: Of the 63,046 CpGs from the prediction models, 13 novel CpGs were associated with HST. Furthermore, people with high PMRSs showed higher HST risk (hazard ratio: 1.18; 95% CI: 1.13-1.25). Conclusion: The study indicates that DNA methylation may influence HST by regulating the expression of genes (e.g., PRMT6, CTSK). PMRSs have a promising application in discriminating subpopulations to facilitate early prevention.


Asunto(s)
Metilación de ADN , Epigénesis Genética , Humanos , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Marcadores Genéticos , Islas de CpG , Proteínas Nucleares , Proteína-Arginina N-Metiltransferasas
15.
Foods ; 13(5)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38472772

RESUMEN

Prunella vulgaris L. (PV) is a widely distributed plant species, known for its versatile applications in both traditional and contemporary medicine, as well as in functional food development. Despite its broad-spectrum antimicrobial utility, the specific mechanism of antibacterial action remains elusive. To fill this knowledge gap, the present study investigated the antibacterial properties of PV extracts against methicillin-resistant Staphylococcus aureus (MRSA) and assessed their mechanistic impact on bacterial cells and cellular functions. The aqueous extract of PV demonstrated greater anti-MRSA activity compared to the ethanolic and methanolic extracts. UPLC-ESI-MS/MS tentatively identified 28 phytochemical components in the aqueous extract of PV. Exposure to an aqueous extract at ½ MIC and MIC for 5 h resulted in a significant release of intracellular nucleic acid (up to 6-fold) and protein (up to 10-fold) into the extracellular environment. Additionally, this treatment caused a notable decline in the activity of several crucial enzymes, including a 41.51% reduction in alkaline phosphatase (AKP), a 45.71% decrease in adenosine triphosphatase (ATPase), and a 48.99% drop in superoxide dismutase (SOD). Furthermore, there was a decrease of 24.17% at ½ MIC and 27.17% at MIC in tricarboxylic acid (TCA) cycle activity and energy transfer. Collectively, these findings indicate that the anti-MRSA properties of PV may stem from its ability to disrupt membrane and cell wall integrity, interfere with enzymatic activity, and impede bacterial cell metabolism and the transmission of information and energy that is essential for bacterial growth, ultimately resulting in bacterial apoptosis. The diverse range of characteristics exhibited by PV positions it as a promising antimicrobial agent with broad applications for enhancing health and improving food safety and quality.

16.
Angew Chem Int Ed Engl ; 63(22): e202403581, 2024 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-38514603

RESUMEN

Nanozymes possess multi-enzyme activities over the natural enzymes, which produce multi-pathway synergistic effects for varies of biomedical applications. Unfortunately, their multi-enzyme activities are in fighting, significantly reducing the synergistic effects. Dynamic regulation of their multi-enzyme activities is the bottleneck for intelligent therapies. Herein, we construct a novel oxygen-nitrogen functionalized carbon quantum dots (O/N-CQDs) with peroxidase-like (Reactive oxygen species (ROS) producer) activity. Interestingly, the peroxidase-like activity can be reversibly converted to catalase-like (ROS scavenger) activity under visible light irradiation. It is found that both the peroxidase/catalase-like activity of O/N-CQDs can be precisely manipulated by the light intensity. The mechanism of switchable enzyme activities is attributed to the polarization of quinoid nitrogen in polyaniline (PANI) precursor retained on O/N-CQDs under visible light, which consumes the ROS to produce O2 and H2O. As a proof-of-concept demonstration, we are able to non-intrusively up and down regulate the ROS level in cells successfully by simply switching off and on the light respectively, potentially facilitating the precise medicine based on the development of the disease. Indeed, the photo-switchable peroxidase/catalase-like activity of O/N-CQDs opens a non-invasive strategy for better manipulations of the multi-activity of nanozymes, promising their wider and more intelligent biomedical applications.


Asunto(s)
Carbono , Catalasa , Luz , Puntos Cuánticos , Especies Reactivas de Oxígeno , Puntos Cuánticos/química , Carbono/química , Catalasa/metabolismo , Catalasa/química , Humanos , Especies Reactivas de Oxígeno/metabolismo , Peroxidasa/metabolismo , Peroxidasa/química , Procesos Fotoquímicos
17.
Nat Cell Biol ; 26(3): 450-463, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38326554

RESUMEN

Memory CD8+ T cells play a crucial role in infection and cancer and mount rapid responses to repeat antigen exposure. Although memory cell transcriptional programmes have been previously identified, the regulatory mechanisms that control the formation of CD8+ T cells have not been resolved. Here we report ECSIT as an essential mediator of memory CD8+ T cell differentiation. Ablation of ECSIT in T cells resulted in loss of fumarate synthesis and abrogated TCF-1 expression via demethylation of the TCF-1 promoter by the histone demethylase KDM5, thereby impairing memory CD8+ T cell development in a cell-intrinsic manner. In addition, ECSIT expression correlated positively with stem-like memory progenitor exhausted CD8+ T cells and the survival of patients with cancer. Our study demonstrates that ECSIT-mediated fumarate synthesis stimulates TCF-1 activity and memory CD8+ T cell development during viral infection and tumorigenesis and highlights the utility of therapeutic fumarate analogues and PD-L1 inhibition for tumour immunotherapy.


Asunto(s)
Linfocitos T CD8-positivos , Virosis , Humanos , Carcinogénesis/genética , Carcinogénesis/metabolismo , Transformación Celular Neoplásica/metabolismo , Regiones Promotoras Genéticas , Virosis/metabolismo
18.
Bioorg Chem ; 145: 107219, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38377821

RESUMEN

SET domain bifurcated methyltransferase 1 (SETDB1) serves as a histone lysine methyltransferase, catalyzing the di- and tri-methylation of histone H3K9. Mounting evidence indicates that the abnormal expression or activity of SETDB1, either through amplification or mutation, plays a crucial role in tumorigenesis and progression. This is particularly evident in the context of tumor immune evasion and resistance to immune checkpoint blockade therapy. Furthermore, there is a robust association between SETDB1 dysregulation and an unfavorable prognosis across various types of tumors. The oncogenic role of SETDB1 primarily arises from its methyltransferase function, which contributes to the establishment of a condensed and transcriptionally inactive heterochromatin state. This results in the inactivation of genes that typically hinder cancer development and silencing of retrotransposons that could potentially trigger an immune response. These findings underscore the substantial potential for SETDB1 as an anti-tumor therapeutic target. Nevertheless, despite significant strides in recent years in tumor biology research, challenges persist in SETDB1-targeted therapy. To better facilitate the development of anti-tumor therapy targeting SETDB1, we have conducted a comprehensive review of SETDB1 in this account. We present the structure and function of SETDB1, its role in various tumors and immune regulation, as well as the advancements made in SETDB1 antagonists. Furthermore, we discuss the challenges encountered and provide perspectives for the development of SETDB1-targeted anti-tumor therapy.


Asunto(s)
Histonas , Neoplasias , Humanos , Histonas/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Neoplasias/tratamiento farmacológico , Metilación
19.
Front Pharmacol ; 15: 1279584, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38420190

RESUMEN

Shenfu injection (SFI), composed of ginseng and aconite, is a Chinese patent developed from the classic traditional prescription Shenfu Decoction created more than 700 years ago. SFI has been widely used in China for over 30 years for treating cardiovascular diseases. The main components in it include ginsenosides and aconitum alkaloids. In recent years, the role of SFI in the treatment of cardiovascular diseases has attracted much attention. The pharmacological effects and therapeutic applications of SFI in cardiovascular diseases are summarized here, highlighting pharmacological features and potential mechanisms developments, confirming that SFI can play a role in multiple ways and is a promising drug for treating cardiovascular diseases.

20.
Int J Endocrinol ; 2024: 4002839, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410172

RESUMEN

Background: The association between atherogenic index of plasma (AIP) and hyperuricemia remains indistinct. This study was aimed to examine the relationship between AIP and hyperuricemia among the middle-aged and the elderly Chinese population. Methods: Datasets were retrieved from the China Health and Retirement Longitudinal Study (CHARLS) survey conducted in 2011 and 2015. 13,021 participants in the CHARLS in 2011 and 7,017 participants involved both in 2011 and 2015 were included, respectively. The measurement of AIP and hyperuricemia was based on the test of fasting blood. Association between AIP and hyperuricemia was assessed by logistic regression, and the nonlinear association was examined by restricted cubic splines (RCS). The cutoff point of AIP was calculated using receiver operator curve (ROC). 1 : 1 propensity score matching (PSM) was adopted to further explore the relationship between AIP and hyperuricemia. Results: In the section of a cross-sectional study, a positive association between AIP and hyperuricemia was found. The odds ratios (ORs) of hyperuricemia were 1.00 (reference), 1.52 (1.10-2.10), 1.80 (1.31-2.47), and 3.81 (2.84-5.11). Nonlinear association was not detected using RCS analysis. There were 664 hyperuricemia cases during the four years follow-up. The hyperuricemia prevalence was 9.5%. In the fully adjusted longitudinal analysis, the ORs for hyperuricemia across the quartiles of AIP were 1.00 (reference), 1.00 (0.74-1.37), 1.59 (1.20-2.11), and 2.55 (1.94-3.35), respectively. In the longitudinal analysis after PSM, the OR of hyperuricemia were 1.91 (1.45, 2.51) and 1.92 (1.45, 2.54) in the univariate and multivariate model, respectively. Conclusion: AIP can predict the prevalence of hyperuricemia in the Chinese middle-aged and elderly population.

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