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1.
Neural Regen Res ; 20(1): 159-173, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38767484

RESUMEN

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

2.
BMC Geriatr ; 24(1): 743, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39244553

RESUMEN

PURPOSE: This study aimed to develop a Quality of Life (QOL) assessment scale for older patients with Neuro-co-Cardiological Diseases (NCCD) and to evaluate the reliability and validity of the scale. METHOD: The study participants were derived from the Elderly Individuals with NCCD Registered Cohort Study (EINCCDRCS), a multicenter registry of patients with NCCD. The preliminary testing of the questionnaire was conducted among 10 older individuals aged 65 years and older who had NCCD and were recruited from the registry. Other patients who met the inclusion criteria participated in the field testing. After verifying the unidimensionality, local independence, and monotonicity assumptions of the scale, we employed the Rasch model within Item Response Theory framework to assess the quality of the scale through methods including internal consistency, criterion validity, Wright map, and item functioning differential. Subsequently, we assessed the construct validity of the scale by combining exploratory factor analysis with confirmatory factor analysis. RESULTS: Based on well-validated scales such as the short-form WHOQOL-OLD, HeartQOL, IQCODE, and SF-36, an original Neuro-co-Cardiological Diseases Quality of Life scale (NCCDQOL) was developed. 196 individuals from the EINCCDRCS were included in the study, with 10 participating in the preliminary testing and 186 in the field testing. Based on the results of the preliminary testing, the original questionnaire was refined through item deletion and adjustment, resulting in an 11-item NCCDQOL questionnaire. The Rasch analysis of the field testing data led to the removal of 21 misfitting individuals. The NCCDQOL demonstrated a four-category structure, achieved by combining two response categories. This structure aligned with the assumptions of unidimensionality, local independence, and monotonicity. The NCCDQOL also exhibited good validity and reliability. CONCLUSION: The revised NCCDQOL questionnaire demonstrated good reliability and validity in the Rasch model, indicating promising potential for clinical application.


Asunto(s)
Calidad de Vida , Humanos , Calidad de Vida/psicología , Anciano , Masculino , Femenino , Encuestas y Cuestionarios/normas , Estudios de Cohortes , Anciano de 80 o más Años , Enfermedades del Sistema Nervioso/psicología , Enfermedades del Sistema Nervioso/diagnóstico , Cardiopatías/psicología , Cardiopatías/diagnóstico , Reproducibilidad de los Resultados , Sistema de Registros , Comorbilidad
3.
APL Bioeng ; 8(3): 036110, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39165611

RESUMEN

Cartilage damage, a common cause of osteoarthritis, requires medical imaging for accurate diagnosis of pathological changes. However, current instruments can acquire limited imaging information due to sensitivity and resolution issues. Therefore, multimodal imaging is considered an alternative strategy to provide valuable images and analyzes from different perspectives. Among all biomaterials, gold nanomaterials not only exhibit outstanding benefits as drug carriers, in vitro diagnostics, and radiosensitizers, but are also widely used as contrast agents, particularly for tumors. However, their potential for imaging cartilage damage is rarely discussed. In this study, we developed a versatile iodinated gadolinium-gold nanomaterial, AuNC@BSA-Gd-I, and its radiolabeled derivative, AuNC@BSA-Gd-131I, for cartilage detection. With its small size, negative charge, and multimodal capacities, the probe can penetrate damaged cartilage and be detected or visualized by computed tomography, MRI, IVIS, and gamma counter. Additionally, the multimodal imaging potential of AuNC@BSA-Gd-I was compared to current multifunctional gold nanomaterials containing similar components, including anionic AuNC@BSA, AuNC@BSA-I, and AuNC@BSA-Gd as well as cationic AuNC@CBSA. Due to their high atomic numbers and fluorescent emission, AuNC@BSA nanomaterials could provide fundamental multifunctionality for imaging. By further modifying AuNC@BSA with additional imaging materials, their application could be extended to various types of medical imaging instruments. Nonetheless, our findings showed that each of the current nanomaterials exhibited excellent abilities for imaging cartilage with their predominant imaging modalities, but their versatility was not comparable to that of AuNC@BSA-Gd-I. Thus, AuNC@BSA-Gd-I could be served as a valuable tool in multimodal imaging strategies for cartilage assessment.

4.
Chin J Integr Med ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39167283

RESUMEN

OBJECTIVE: To investigate potential mechanisms of anti-atherosclerosis by berberine (BBR) using ApoE-/- mice. METHODS: Eight 8-week-old C57BL/6J mice were used as a blank control group (normal), and 56 8-week-old AopE-/- mice were fed a high-fat diet for 12 weeks, according to a completely random method, and were divided into the model group, BBR low-dose group (50 mg/kg, BBRL), BBR medium-dose group (100 mg/kg, BBRM), BBR high-dose group (150 mg/kg, BBRH), BBR+nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor group (100 mg/kg BBR+30 mg/kg ML385, BBRM+ML385), NRF2 inhibitor group (30 mg/kg, ML385), and positive control group (2.5 mg/kg, atorvastatin), 8 in each group. After 4 weeks of intragastric administration, samples were collected and serum, aorta, heart and liver tissues were isolated. Biochemical kits were used to detect serum lipid content and the expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in all experimental groups. The pathological changes of atherosclerosis (AS) were observed by aorta gross Oil Red O, aortic sinus hematoxylin-eosin (HE) and Masson staining. Liver lipopathy was observed in mice by HE staining. The morphology of mitochondria in aorta cells was observed under transmission electron microscope. Flow cytometry was used to detect reactive oxygen species (ROS) expression in aorta of mice in each group. The content of ferrous ion Fe2+ in serum of mice was detected by biochemical kit. The mRNA and protein relative expression levels of NRF2, glutathione peroxidase 4 (GPX4) and recombinant solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real time polymerase chain reaction (RT-qPCR) and Western blot, respectively. RESULTS: BBRM and BBRH groups delayed the progression of AS and reduced the plaque area (P<0.01). The characteristic morphological changes of ferroptosis were rarely observed in BBR-treated AS mice, and the content of Fe2+ in BBR group was significantly lower than that in the model group (P<0.01). BBR decreased ROS and MDA levels in mouse aorta, increased SOD activity (P<0.01), significantly up-regulated NRF2/SLC7A11/GPX4 protein and mRNA expression levels (P<0.01), and inhibited lipid peroxidation. Compared with the model group, the body weight, blood lipid level and aortic plaque area of ML385 group increased (P<0.01); the morphology of mitochondria showed significant ferroptosis characteristics; the serum Fe2+, MDA and ROS levels increased (P<0.05 or P<0.01), and the activity of SOD decreased (P<0.01). Compared with BBRM group, the iron inhibition effect of BBRM+ML385 group was significantly weakened, and the plaque area significantly increased (P<0.01). CONCLUSION: Through NRF2/SLC7A11/GPX4 pathway, BBR can resist oxidative stress, inhibit ferroptosis, reduce plaque area, stabilize plaque, and exert anti-AS effects.

5.
Sci Total Environ ; 952: 175692, 2024 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-39179038

RESUMEN

Nitrogen (N) is one of the most important pollutants on urban road surfaces. Understanding the N deposition forms, load characteristics, and influential factors can help to provide management and control strategies for road stormwater runoff pollution. This study focuses on a highly urbanized area in Guangzhou, China, and presents the characteristics of both dissolved and particulate N deposition forms as well as their correlations with land-use types and traffic factors. In addition, an artificial neural network (ANN) based classification model is utilized to estimate N pollution hotspot area and total nitrogen (TN) flux from road to receiving water bodies. The results showed that N on urban road surfaces mainly existed in the form of particulate organic nitrogen. Land use types dominated by residential area (RA) and urban village (UV) have higher TN build-up loads. Geodetector analysis indicated that land use has a greater impact on nitrogen build-up loads than traffic factors. Through classification and estimation using the ANN model, RA, and UV were classified as hotspot areas, and the TN flux from roads in the study area was calculated to be 3.35 × 105 g. Furthermore, it was estimated that the annual TN flux from roads in Guangzhou accounts for 19 % of the city's total urban domestic discharge. These findings are expected to contribute to the pollution control of stormwater runoff from urban road surfaces and provide valuable guidance for enhancing the ecological health of urban water environments.

6.
Pharmaceutics ; 16(7)2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39065625

RESUMEN

The clinical management of malignant tumours is challenging, often leading to severe adverse effects and death. Drug resistance (DR) antagonises the effectiveness of treatments, and increasing drug dosage can worsen the therapeutic index (TI). Current efforts to overcome DR predominantly involve the use of drug combinations, including applying multiple anti-cancerous drugs, employing drug sensitisers, which are chemical agents that enhance pharmacokinetics (PK), including the targeting of cellular pathways and regulating pertinent membrane transporters. While combining multiple compounds may lead to drug-drug interactions (DDI) or polypharmacy effect, the use of drug sensitisers permits rapid attainment of effective treatment dosages at the disease site to prevent early DR and minimise side effects and will reduce the chance of DDI as lower drug doses are required. This review highlights the essential use of TI in evaluating drug dosage for cancer treatment and discusses the lack of a unified standard for TI within the field. Commonly used benefit-risk assessment criteria are summarised, and the critical exploration of the current use of TI in the pharmaceutical industrial sector is included. Specifically, this review leads to the discussion of drug sensitisers to facilitate improved ratios of effective dose to toxic dose directly in humans. The combination of drug and sensitiser molecules might see additional benefits to rekindle those drugs that failed late-stage clinical trials by the removal of detrimental off-target activities through the use of lower drug doses. Drug combinations and employing drug sensitisers are potential means to combat DR. The evolution of drug combinations and polypharmacy on TI are reviewed. Notably, the novel binary weapon approach is introduced as a new opportunity to improve TI. This review emphasises the urgent need for a criterion to systematically evaluate drug safety and efficiency for practical implementation in the field.

7.
Vet Microbiol ; 295: 110160, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38964034

RESUMEN

Infection with Glaesserella parasuis, the primary pathogen behind Glässer's disease, is often associated with diverse clinical symptoms, including serofibrinous polyserositis, arthritis, and meningitis. Autophagy plays a dual role in bacterial infections, exerting either antagonistic or synergistic effects depending on the nature of the pathogen. Our previous studies have demonstrated that autophagy serves as a defense mechanism, combating inflammation and invasion caused by infection of highly virulent G. parasuis. However, the precise mechanisms remain to be elucidated. Pathogens exhibit distinct interactions with inflammasomes and autophagy processes. Herein, we explored the effect of autophagy on inflammasomes during G. parasuis infection. We found that G. parasuis infection triggers NLRP3-dependent pro-CASP-1-IL-18/IL-1ß processing and maturation pathway, resulting in increased release of IL-1ß and IL-18. Inhibition of autophagy enhances NLRP3 inflammasome activity, whereas stimulation of autophagy restricts it during G. parasuis infection. Furthermore, assembled NLRP3 inflammasomes undergo ubiquitination and recruit the autophagic adaptor, p62, facilitating their sequestration into autophagosomes during G. parasuis infection. These results suggest that the induction of autophagy mitigates inflammation by eliminating overactive NLRP3 inflammasomes during G. parasuis infection. Our research uncovers a mechanism whereby G. parasuis infection initiates inflammatory responses by promoting the assembly of the NLRP3 inflammasomes and activating NLRP3-CASP-1, both of which processes are downregulated by autophagy. This suggests that pharmacological manipulation of autophagy could be a promising approach to modulate G. parasuis-induced inflammatory responses.


Asunto(s)
Autofagia , Caspasa 1 , Infecciones por Haemophilus , Haemophilus parasuis , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Inflamasomas/inmunología , Inflamasomas/metabolismo , Haemophilus parasuis/inmunología , Haemophilus parasuis/patogenicidad , Haemophilus parasuis/genética , Caspasa 1/metabolismo , Caspasa 1/genética , Infecciones por Haemophilus/veterinaria , Infecciones por Haemophilus/inmunología , Infecciones por Haemophilus/microbiología , Porcinos , Interleucina-18/metabolismo , Interleucina-18/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/inmunología , Ratones
8.
Fa Yi Xue Za Zhi ; 40(2): 128-134, 2024 Apr 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38847026

RESUMEN

OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.


Asunto(s)
Determinación de la Edad por el Esqueleto , Pueblo Asiatico , Suturas Craneales , Aprendizaje Automático , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Determinación de la Edad por el Esqueleto/métodos , Teorema de Bayes , China/etnología , Suturas Craneales/diagnóstico por imagen , Pueblos del Este de Asia , Etnicidad , Antropología Forense/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional , Modelos Lineales , Estudios Retrospectivos , Cráneo/diagnóstico por imagen
9.
Environ Int ; 190: 108829, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38908277

RESUMEN

Exposure to environmental carcinogens is a significant contributor to cancer development, with genetic and epigenetic alterations playing pivotal roles in the carcinogenic process. However, the interplay between epigenetic regulation and genetic changes in carcinogenesis has yet to receive comprehensive attention. This study investigates the impact of continuous exposure to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on bronchial epithelial cells, leading to malignant transformation. Our findings reveal the down-regulation of the tumor suppressor-like circular RNA circNIPBL during oncogenic processes concomitant with the accumulation of the TP53-H179R, a single nucleotide variant. Diminished circNIPBL expression enhances the proliferative, distant metastatic, and tumor-forming capabilities of NNK-induced cancerous cells and lung cancer cell lines (A549, H1299), while also promoting the accumulation of TP53-H179R during NNK-induced carcinogenesis. Mechanistic investigations demonstrate that circNIPBL interacts with HSP90α to regulate the translocation of AHR into the nucleus, which may be a potential regulatory mechanism for NNK-induced carcinogenesis and TP53-H179R accumulation. This study introduces a novel perspective on the interplay between genetic alterations and epigenetic regulation in chemical carcinogenesis, which provides novel insight into the etiology of cancer.


Asunto(s)
Bronquios , Carcinogénesis , Nitrosaminas , ARN Circular , Proteína p53 Supresora de Tumor , ARN Circular/genética , Nitrosaminas/toxicidad , Humanos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Carcinogénesis/genética , Carcinogénesis/inducido químicamente , Bronquios/patología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Mutación , Carcinógenos/toxicidad , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Línea Celular Tumoral , Animales
10.
Plant Cell Rep ; 43(6): 148, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775862

RESUMEN

KEY MESSAGE: Identification of selenium stress-responsive expression and molecular docking of serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) in Cardamine hupingshanensis. A complex coupled with serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) is the key enzyme that catalyzes selenocysteine (Sec) synthesis in plants. The functions of SAT and OASTL genes were identified in some plants, but it is still unclear whether SAT and OASTL are involved in the selenium metabolic pathway in Cardamine hupingshanensis. In this study, genome-wide identification and comparative analysis of ChSATs and ChOASTLs were performed. The eight ChSAT genes were divided into three branches, and the thirteen ChOASTL genes were divided into four branches by phylogenetic analysis and sequence alignment, indicating the evolutionary conservation of the gene structure and its association with other plant species. qRT-PCR analysis showed that the ChSAT and ChOASTL genes were differentially expressed in different tissues under various selenium levels, suggesting their important roles in Sec synthesis. The ChSAT1;2 and ChOASTLA1;2 were silenced by the VIGS system to investigate their involvement in selenium metabolites in C. hupingshanensis. The findings contribute to understanding the gene functions of ChSATs and ChOASTLs in the selenium stress and provide a reference for further exploration of the selenium metabolic pathway in plants.


Asunto(s)
Cardamine , Regulación de la Expresión Génica de las Plantas , Simulación del Acoplamiento Molecular , Filogenia , Proteínas de Plantas , Selenio , Selenio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cardamine/genética , Cardamine/metabolismo , Redes y Vías Metabólicas/genética , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Liasas/metabolismo , Liasas/genética
11.
Antioxidants (Basel) ; 13(4)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38671918

RESUMEN

Imbalanced osteogenic cell-mediated bone gain and osteoclastic remodeling accelerates the development of osteoporosis, which is the leading risk factor of disability in the elderly. Harmonizing the metabolic actions of bone-making cells and bone resorbing cells to the mineralized matrix network is required to maintain bone mass homeostasis. The tricarboxylic acid (TCA) cycle in mitochondria is a crucial process for cellular energy production and redox homeostasis. The canonical actions of TCA cycle enzymes and intermediates are indispensable in oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis for osteogenic differentiation and osteoclast formation. Knockout mouse models identify these enzymes' roles in bone mass and microarchitecture. In the noncanonical processes, the metabolites as a co-factor or a substrate involve epigenetic modification, including histone acetyltransferases, DNA demethylases, RNA m6A demethylases, and histone demethylases, which affect genomic stability or chromatin accessibility for cell metabolism and bone formation and resorption. The genetic manipulation of these epigenetic regulators or TCA cycle intermediate supplementation compromises age, estrogen deficiency, or inflammation-induced bone mass loss and microstructure deterioration. This review sheds light on the metabolic functions of the TCA cycle in terms of bone integrity and highlights the crosstalk of the TCA cycle and redox and epigenetic pathways in skeletal tissue metabolism and the intermediates as treatment options for delaying osteoporosis.

12.
Small Methods ; : e2301739, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38438783

RESUMEN

Solution processing has emerged as a promising technique for the fabrication of oxide thin-film transistors (TFTs), offering advantages such as low cost, high throughput, and exceptional compositional control. However, achieving reasonable electrical properties typically demands high annealing temperatures in the fabrication process. In addressing this challenge, a novel combination strategy is proposed that involves integrating the H2 O2 inducement technique with infrared (IR) irradiation annealing. The study investigates the effects of precursors and IR irradiation annealing temperatures on the electrical properties of In2 O3 TFTs. It is found that H2 O2 can help accelerate the decomposition of organic residues, while IR irradiation annealing could enhance the film densification. By employing the proposed strategy, metal oxide TFTs consisting of a Zr-Al-O dielectric fabricated at 230 °C and an In2 O3 channel layer fabricated at 185 °C demonstrated high performance with field-effect mobility = 31.7 cm2  V-1 ·s-1 , threshold voltage = 1.3 V, subthreshold swing = 0.13 V per decade, and on-to-off current ratio = 1.1 × 105 . This work demonstrates the proposed combinational strategy is a general method to fabricate not only metal oxide semiconductors but also dielectrics.

13.
J Am Chem Soc ; 146(12): 8131-8141, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38471139

RESUMEN

The ability of molecules to move and rearrange in the solid state accounts for the polymorphic transition and stimuli-responsive properties of molecular crystals. However, how the crystal structure determines the molecular motion ability remains poorly understood. Here, we report that a three-dimensional (3D) supramolecular gear network in the green-emissive polymorph 1G of a dialkylamino-substituted anthracene-pentiptycene π-system (1) enables an unusual bifurcated polymorphic transition into a yellow-emissive polymorph (1Y) and a new green-emissive polymorph (1G*) via 3D correlated supramolecular rotation. The 90° forward correlated rotation causes the molecular conformation between the octyl and the anthracene units to change from syn to anti, the ladder-like supramolecular columns to constrict, and the gear network to disengage. This cooperative molecular motion is marked by the gradual formation of an intermediate state (1I) across the entire crystal from 170 to 230 °C, which then undergoes bifurcated (forward or backward rotation) and irreversible transitions to form polymorphs 1Y and 1G* at 230-235 °C. Notably, 1G* is similar to 1G but lacks gear engagement, preventing its transformation into 1Y. Nevertheless, 1G can be restored by grinding 1Y or 1G* or fuming with dichloromethane (DCM) vapor. This work illustrates the correlation between the crystal structure and solid-state molecular motion behavior and demonstrates how a 3D molecular gear system efficiently transmits thermal energy to drive the polymorphic transition and induce fluorochromism through significant conformational and packing changes.

14.
J Alzheimers Dis ; 98(3): 941-955, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38489185

RESUMEN

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Disfunción Cognitiva , Demencia , Masculino , Femenino , Humanos , Anciano , Estudios de Cohortes , Estudios de Casos y Controles , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Disfunción Cognitiva/epidemiología , China/epidemiología , Material Particulado/efectos adversos , Material Particulado/análisis
15.
Artículo en Inglés | MEDLINE | ID: mdl-38299406

RESUMEN

BACKGROUND: CFTR, which belongs to the ATP-binding cassette transporter family and whose members are always involved in cancer progression, is implicated in lung adenocarcinoma (LUAD) progression, but the underlying mechanism remains undefined. Therefore, this study intended to investigate how CFTR works exactly on LUAD progression. METHODS: Bioinformatics methods were utilized to analyze GATA6 and CFTR expression in LUAD and targeting relationship, followed by a pathway enrichment analysis of CFTR. GATA6 and CFTR expression levels were assessed by qRT-PCR. Cell viability and proliferation were detected through MTT and colony formation assays. An arachidonic acid (AA) assay kit was utilized to measure AA content. mRNA and protein expression levels of genes (cPLA2, COX-2, and CYP1A1) related to the AA metabolism pathway were detected by qRT-PCR and western blot, respectively. Moreover, the Dual-luciferase reporter gene assay and ChIP were used to verify the binding of GATA6 and CFTR promoters. RESULTS: GATA6 and CFTR were lowly expressed in LUAD, and CFTR was enriched in the AA metabolism pathway. GATA6 activated CFTR transcription. Cellular and rescue experiments revealed that low or high CFTR expression could foster or hamper LUAD cell viability and proliferation, and concomitant treatment of indomethacin, an AA metabolism pathway inhibitor, mitigated stimulation on LUAD progression by low CFTR expression. Silencing of GATA6 reversed the suppressive impact of CFTR overexpression on LUAD progression via modulation of the AA metabolism pathway. CONCLUSION: The activation of CFTR by GATA6 hampered LUAD progression by modulating the AA metabolism pathway, suggesting that GATA6/CFTR axis might be a therapeutic target for LUAD patients.

16.
Sci Total Environ ; 921: 170624, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38325458

RESUMEN

Phosphorus (P) is a primary pollutant that builds-up on urban road surfaces. Understanding the fraction and load characteristics of P, as well as their relationship with urban factors, is helpful for assessing the ecological risk of urban receiving water bodies. This study presents the characteristics of build-up loads of P fractions in road-deposited sediments (RDS) in Guangzhou, China, analyzes their correlation with three urban factors (road, traffic, and land-use area), and then estimates the exceedance probability of P in stormwater runoff over the past 10 years. The results showed that detrital apatite phosphorus (De-P) performed the highest build-up load on urban road surfaces, followed by apatite phosphorus (Ca-P), iron-bound phosphorus (Fe-P), exchangeable phosphorus (Ex-P), aluminum-bound phosphorus (Al-P), organophosphorus (POP), dissolved inorganic phosphorus (DIP), occluded phosphorus (Oc-P), and dissolved organic phosphorus (DOP). Depression depth, road materials, and land-use fractions affected the P fractions. The P in the RDS may have originated from three distinct sources: road background, domestic waste, and untreated wastewater discharge. In the most recent 10 years, the event mean concentrations of total P in the RDS have had a 30 % probability of exceeding 0.4 mg L-1, which indicates a serious threat of P to receiving water bodies. The outcomes of this study are expected to provide valuable guidance for elucidating the principal categories of urban non-point source P pollution and enhancing the ecological health of urban water environments.

17.
Fluids Barriers CNS ; 21(1): 8, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38243347

RESUMEN

BACKGROUND: Blood brain barrier (BBB) breakdown is one of the key mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Astrocytes interact with endothelial and regulate BBB integrity via paracrine signaling factors. More and more studies reveal astrocyte-derived extracellular vesicles (ADEVs) as an important way of intercellular communication. However, the role of ADEV in BBB integrity after ICH remains unclear. METHODS: ADEVs were obtained from astrocytes with or without oxygen and glucose deprivation (OGD) pre-stimulation and the role of ADEVs in ICH was investigated using ICH mice model and ICH cell model. The potential regulatory effect of ADEVs on endothelial barrier integrity was identified by TEER, western blot and immunofluorescence in vitro. In vivo, functional evaluation, Evans-blue leakage and tight junction proteins (TJPs) expression were analyzed. MiRNA sequencing revealed that microRNA-27a-3p (miR-27a-3p) was differentially expressed miRNA in the EVs from OGD-pretreated astrocytes compared with normal control. The regulatory mechanism of miR-27a-3p was assessed using Luciferase assay, RT-PCR, western blot and immunofluorescence. RESULTS: OGD-activated astrocytes reduced hemin-induced endothelial hyper-permeability through secreting EVs. OGD-activated ADEVs alleviated BBB dysfunction after ICH in vivo and in vitro. MicroRNA microarray analysis indicated that miR-27a-3p is a major component that was highly expressed miRNA in OGD pretreated-ADEVs. OGD-ADEVs mitigated BBB injury through transferring miR-27a-3p into bEnd.3 cells and regulating ARHGAP25/Wnt/ß-catenin pathway. CONCLUSION: Taken together, these findings firstly revealed that miR-27a-3p, as one of the main components of OGD-pretreated ADEVs, attenuated BBB destruction and improved neurological deficits following ICH by regulating endothelial ARHGAP25/Wnt/ß-catenin axis. OGD-ADEVs might be a novel strategy for the treatment of ICH. this study implicates that EVs from OGD pre-stimulated astrocytes.


Asunto(s)
Exosomas , MicroARNs , Animales , Ratones , Barrera Hematoencefálica/metabolismo , Astrocitos/metabolismo , beta Catenina/metabolismo , Células Endoteliales/metabolismo , Exosomas/metabolismo , Oxígeno/metabolismo , Glucosa , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/farmacología , Hemorragia Cerebral/metabolismo
18.
Spine (Phila Pa 1976) ; 49(12): 840-846, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38158748

RESUMEN

STUDY DESIGN: A retrospective observational study. OBJECTIVE: To assess whether the six-minute walk test (6MWT) can predict cardiopulmonary function in children with idiopathic scoliosis (IS) as an alternative to the cardiopulmonary exercise test (CPET). SUMMARY OF BACKGROUND DATA: Cardiopulmonary functional impairment in the setting of IS is a common health problem. A simple and convenient assessment method is needed. MATERIALS AND METHODS: We recruited 65 children (eight male, 57 female) aged 10.70 to 14.84 years old with IS. Radiographic characteristics of the cohort were measured, including Risser's sign and Cobb angle. We measured cardiopulmonary exercise tolerance using both the 6MWT and CPET and their corresponding indicators, including six-minute walking distance (6MWD) and peak oxygen uptake (peak VO 2 ), respectively. Pearson correlation analysis was used to determine the relationship between 6MWT indicators and IS parameters. Linear regression models were used to explore the relationship between 6MWT and CPET response indicators. RESULTS: Over a third of the cohort (35.4%) had a Risser's sign grade of 0, with 21.5% in grade 2 and 3, respectively. The cohort's mean Cobb angle was 26.02°. 6MWD was significantly positively correlated with Risser's sign ( R =0.258; P =0.038) and change in respiratory rate positively correlated with vertebral rotation ( R =0.264; P =0.034). 6MWD positively correlated with peak VO 2 , peak VO 2 /heart rate (HR), and metabolic equivalents, and negatively correlated with the ventilation equivalent of the carbon dioxide slope (VE/VCO 2 slope) ( P <0.05). These four CPET indicators were found to be predicted from 6MWD in the linear regression model ( P <0.05). CONCLUSIONS: CPET response indicators, especially peak VO 2 , can be predicted using 6MWD, among other factors. The 6MWT can therefore be used to rapidly and efficiently predict the cardiorespiratory tolerance of children with IS. LEVEL OF EVIDENCE: 3.


Asunto(s)
Tolerancia al Ejercicio , Escoliosis , Prueba de Paso , Humanos , Escoliosis/fisiopatología , Escoliosis/diagnóstico por imagen , Femenino , Masculino , Niño , Adolescente , Estudios Retrospectivos , Prueba de Paso/métodos , Tolerancia al Ejercicio/fisiología , Consumo de Oxígeno/fisiología , Prueba de Esfuerzo/métodos , Caminata/fisiología
20.
BMC Cardiovasc Disord ; 23(1): 590, 2023 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-38037012

RESUMEN

AIM: To investigate the efficacy and postoperative clinical adverse events of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for chronic kidney disease (CKD) study participants combined with coronary artery disease (CAD). METHODS: All randomized controlled trials (RCTs) that focus on the therapeutic effect evaluation of CABG and PCI and their effect on postoperative clinical adverse events as well as main adverse cardiovascular and cerebrovascular events (MACCEs) in CKD study participants with CAD were screened from the following databases, including CNKI, CBM, Wan Fang, VIP, Embase, PubMed, as well as Cochrane library clinical controlled trials. The study was conducted under the PRISMA 2020 criteria. Data were extracted, and quality control was evaluated from the modified Jadad rating scale. Meta-analysis was then undertaken through STATA 16.0 software. RESULTS: A total of 5 RCTs were obtained, including 1198 patients. Study participants were subdivided into two groups, including the PCI group (n = 604) and the CABG group (n = 594). Meta-analysis of clinical adverse events results showed that the long-term survival results of CAD patients with CKD who underwent PCI were worsened compared to CABG, such as long-term MACCEs (RR = 1.59, 95%CI: 1.04-2.43) and the long-term repeated revascularization (RR = 2.48, 95%CI: 1.76-3.49). Also, cardiac death (RR = 1.68, 95%CI:1.04-2.71), as well as cerebrovascular accident (RR = 1.74, 95%CI:1.04-2.90) in CABG group was significantly lower than that in PCI group. CONCLUSION: This meta-analysis showed that CABG provided a better therapeutic effect than PCI in CKD patients with CAD when considering long-term prognosis. However, more prospective RCTs are needed to define the proper revascularization strategy for CAD patients with CKD.


Asunto(s)
Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Resultado del Tratamiento , Puente de Arteria Coronaria/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico
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