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1.
Artículo en Inglés | MEDLINE | ID: mdl-38978497

RESUMEN

The black saltmarsh mosquito, Aedes taeniorhynchus, is a prominent nuisance mosquito within St. Johns County, Florida. Due to their characteristically large outbreaks, and the elevated amount of insecticide application correlated with the outbreaks, local populations of Ae. taeniorhynchus are at an increased risk of developing insecticide resistance. This study was established to form a baseline susceptibility of Ae. taeniorhynchus against two technical grade materials, permethrin, and chlorpyrifos. Centers for Disease Control and Prevention bottle bioassays were conducted with technical-grade materials during two outbreaks in the fall of 2023. Results indicated a baseline susceptibility against the materials tested, but most notably, the phenotypic expression of knockdown resistance (kdr) was observed. Results highlight the need for continued monitoring and investigation into the resistance status and resistance level of this common Florida species.

2.
Adv Healthc Mater ; : e2401371, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38994663

RESUMEN

Iontophoretic transdermal drug delivery (TDD) devices are known to enhance the transdermal transport of drugs. However, conventional transdermal iontophoretic devices require external power sources, wired connections, or mechanical parts, which reduce the comfort level for patients during extended use. In this work, a self-powered, wearable transdermal iontophoretic patch (TIP) is proposed by harvesting ambient humidity for energy generation, enabling controlled TDD. This patch primarily uses moist-electric generators (MEGs) as its power source, thus obviating the need for complex power management modules and mechanical components. A single MEG unit can produce an open-circuit voltage of 0.80 V and a short-circuit current of 11.65 µA under the condition of 80% relative humidity. Amplification of the electrical output is feasible by connecting multiple generator units in series and parallel, facilitating the powering of certain commercial electronic devices. Subsequently, the MEG array is integrated with the TDD circuit to create the wearable TIP. After 20 min of application, the depth of drug penetration through the skin is observed to increase threefold. The effective promotion effect of TIP on the transdermal delivery of ionized drugs is corroborated by simulations and experiments. This wearable TIP offers a simple, noninvasive solution for TDD.

3.
Sci Rep ; 14(1): 16314, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39009692

RESUMEN

The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.


Asunto(s)
Glucosa , Grafito , Homeostasis , Rayos Infrarrojos , Condicionamiento Físico Animal , Animales , Ratones , Glucosa/metabolismo , Grafito/farmacología , Grafito/química , Proteínas Quinasas Activadas por AMP/metabolismo , Masculino , Microbioma Gastrointestinal , Músculo Esquelético/metabolismo , Ratones Endogámicos C57BL , Hipertermia Inducida/métodos , Tolerancia al Ejercicio , Microbiota
4.
Neurosurg Rev ; 47(1): 328, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39004661

RESUMEN

STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: The purpose of this study is to investigate whether the removal of the posterior longitudinal ligament (PLL) affects the mid-term outcome of anterior cervical fusion for cervical spondylosis with sympathetic symptoms(CSSS). METHODS: From January 2012 to July 2013, 66 patients who were diagnosed with CSSS with ≥ 10-year follow-up at our institution were assessed. All patients were divided into two groups: Group A (36 cases) in which patients underwent anterior cervical fusion with PLL resection and Group B (30 cases) in which patients underwent anterior cervical fusion without PLL resection. The sympathetic symptom 20-point system was used to evaluate the sympathetic symptoms, such as tinnitus, headache and vertigo, etc. And the neurological status was assessed by the Japanese Orthopedic Association (JOA) scores. Clinical and radiologic data were evaluated preoperatively, 9 days, 3 months, 6 months, 12 months, 24 months, 60 months, and 120 months postoperatively. Data collected included all perioperative complications as morbidities that occurred during the period of follow-up. RESULTS: The postoperative JOA scores and 20-point score can be significantly improved compared with preoperative whether the PLL is removed in both groups. However, the postoperative 20-point score of patients in group A was significantly different from that in group B. No loosening and displacement of prosthesis occurred. CONCLUSION: A better clinical effect could be attained when resecting the PLL in the operation. The PLL may play an important role in CSSS. The mid-term outcomes of anterior cervical fusion with PLL resection were satisfied in treating CSSS.


Asunto(s)
Vértebras Cervicales , Ligamentos Longitudinales , Fusión Vertebral , Espondilosis , Humanos , Masculino , Femenino , Espondilosis/cirugía , Espondilosis/complicaciones , Persona de Mediana Edad , Fusión Vertebral/métodos , Estudios Retrospectivos , Vértebras Cervicales/cirugía , Resultado del Tratamiento , Anciano , Ligamentos Longitudinales/cirugía , Adulto , Estudios de Cohortes , Estudios de Seguimiento
5.
Neuromolecular Med ; 26(1): 29, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014255

RESUMEN

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.


Asunto(s)
Apoptosis , Demencia Vascular , Hipocampo , Trastornos de la Memoria , Neuronas , Fármacos Neuroprotectores , Estrés Oxidativo , Ratas Sprague-Dawley , Xantófilas , Animales , Xantófilas/uso terapéutico , Xantófilas/farmacología , Hipocampo/efectos de los fármacos , Demencia Vascular/tratamiento farmacológico , Ratas , Masculino , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/etiología , Estrés Oxidativo/efectos de los fármacos , Neuronas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Muerte Celular/efectos de los fármacos , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Prueba del Laberinto Acuático de Morris/efectos de los fármacos
6.
ACS Nano ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39028766

RESUMEN

In order to expand the applicability of materials and improve their performance, the combined use of different materials has increasingly been explored. Among these materials, inorganic-organic hybrid materials often exhibit properties superior to those of single materials. Covalent organic frameworks (COFs) are famous crystalline porous materials constructed by organic building blocks linked by covalent bonds. In recent years, the combination of COFs with other materials has shown interesting properties in diverse fields, and the composite materials of COFs and TiO2 have been investigated more and more. These two outstanding materials are combined through covalent bonding, physical mixing, and other methods and exhibit excellent performance in various fields, including photocatalysis, electrocatalysis, sensors, separation, and energy storage and conversion. In this Review, the current preparation methods and applications of COF-TiO2 hybrid materials are introduced in detail, and their future development and possible problems are discussed and prospected, which is of great significance for related research. It is believed that these interesting hybrid materials will show greater application value as research progresses.

7.
Int J Biol Macromol ; 275(Pt 1): 133303, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38917923

RESUMEN

The use of facile methods to synthesize environmentally friendly and multifunctional hydrogel dressings is still a major challenge in development. Herein, Turkish gall extract (TGE) and carboxymethyl chitosan (CMCS) were combined and sprayed using a dual syringe to form a multifunctional TGE-CMCS hydrogel (TC gel) in one step through abundant hydrogen bonding between functional groups as a green approach. TC gel showed rapid gelation at 19.0 ± 2.9 s. Apart from the advantage of being able to adapt to different wound shapes, TC gel retained the antioxidant, antibacterial, hemostatic and anti-inflammatory properties of TGE. In vitro antibacterial experiments showed that TC-gel eliminated 98.27 ± 0.79 % of Staphylococcus aureus and 98.87 ± 1.08 % of Escherichia coli. Compared with TGE or CMCS alone, TC gel accelerates skin wound healing due to its three-dimensional network structure and continuous release of active components at the wound site, enhancing re-epithelialization, improving collagen deposition, and increasing angiogenesis. The wound healing rate of full-thickness skin defect rats treated with TC gel was 93.98 ± 0.63 % on the 10th day. These results suggest that TC gel combined with a facile and scalable manufacturing method is a promising multifunctional wound dressing for clinical wound management.

8.
World Neurosurg ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38857870

RESUMEN

OBJECTIVE: The purpose of this study was to explore the impact of central obesity on spinal sagittal balance in adults aged 18 and older by examining correlations between waist circumference (WC) and abdominal circumference (AC) and spinopelvic alignment parameters. METHODS: This prospective cohort study included 350 adults aged 18 and older. Participants underwent whole-body biplanar radiography using the EOS imaging system. Spinal and pelvic parameters were measured and correlated with body mass index, WC, and AC. Statistical analyses included one-way analysis of variance, Wilcoxon rank-sum tests for data with nonhomogeneous variances, and chi-squared tests for categorical data. Intra-rater and inter-rater reliability were assessed using intraclass correlation coefficients, with subsequent analyses to explore correlations between body measurements and spinal parameters. RESULTS: The study found significant correlations between increased WC and AC and changes in spinopelvic parameters. However, obesity did not uniformly influence all sagittal alignment parameters. Significant variations in spinal measurements indicate that central obesity plays a role in altering spinal stability and alignment. CONCLUSIONS: The findings highlight the impact of central obesity on spinal alignment and emphasize the importance of considering central obesity in clinical assessments of spinal pathologies. Further research is essential to better understand the relationship between obesity, spinal sagittal balance, and related health conditions.

9.
Nat Commun ; 15(1): 5035, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866788

RESUMEN

Radio-immunotherapy exploits the immunostimulatory features of ionizing radiation (IR) to enhance antitumor effects and offers emerging opportunities for treating invasive tumor indications such as melanoma. However, insufficient dose deposition and immunosuppressive microenvironment (TME) of solid tumors limit its efficacy. Here we report a programmable sequential therapeutic strategy based on multifunctional fusogenic liposomes (Lip@AUR-ACP-aptPD-L1) to overcome the intrinsic radio-immunotherapeutic resistance of solid tumors. Specifically, fusogenic liposomes are loaded with gold-containing Auranofin (AUR) and inserted with multivariate-gated aptamer assemblies (ACP) and PD-L1 aptamers in the lipid membrane, potentiating melanoma-targeted AUR delivery while transferring ACP onto cell surface through selective membrane fusion. AUR amplifies IR-induced immunogenic death of melanoma cells to release antigens and damage-associated molecular patterns such as adenosine triphosphate (ATP) for triggering adaptive antitumor immunity. AUR-sensitized radiotherapy also upregulates matrix metalloproteinase-2 (MMP-2) expression that combined with released ATP to activate ACP through an "and" logic operation-like process (AND-gate), thus triggering the in-situ release of engineered cytosine-phosphate-guanine aptamer-based immunoadjuvants (eCpG) for stimulating dendritic cell-mediated T cell priming. Furthermore, AUR inhibits tumor-intrinsic vascular endothelial growth factor signaling to suppress infiltration of immunosuppressive cells for fostering an anti-tumorigenic TME. This study offers an approach for solid tumor treatment in the clinics.


Asunto(s)
Aptámeros de Nucleótidos , Inmunoterapia , Liposomas , Melanoma , Microambiente Tumoral , Liposomas/química , Aptámeros de Nucleótidos/química , Animales , Ratones , Línea Celular Tumoral , Inmunoterapia/métodos , Melanoma/terapia , Melanoma/inmunología , Humanos , Microambiente Tumoral/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/metabolismo , Oro/química , Ratones Endogámicos C57BL , Femenino , Antígeno B7-H1/metabolismo , Antígeno B7-H1/inmunología , Adenosina Trifosfato/metabolismo
10.
Exp Gerontol ; : 112499, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901772

RESUMEN

OBJECTIVES: Lifelong learning facilitates active ageing, and intragenerational learning-the process by which older adults learn from their peers-is an effective means of achieving this goal. The present research aims to elucidate the mechanisms and differences between intergenerational and intragenerational learning models for older adults as evidenced by brain-to-brain synchrony. METHODS: Fifty-six instructor-learner dyads completed a study comparing intergenerational and intragenerational learning models, as well as task difficulty. The study utilized a block puzzle task and functional near-infrared spectroscopy (fNIRS) for hyperscanning. RESULTS: The instructor-learner dyads showed greater interpersonal neural synchrony (INS) and learning acquisition in the intragenerational learning model in the difficult task condition (t (54) = 3.49, p < 0.01), whereas the two learning models yielded similar results in the easy condition (t (54) = 1.96, p = 0.06). In addition, INS and self-efficacy mediated the association between learning models and learning acquisition in older adults (b = 0.14, SEM = 0.04, 95 % CI [0.01 0.16]). DISCUSSION: This study is the first to provide evidence of interbrain synchrony in an investigation of the intragenerational learning model in older adults. Our findings suggest that intra-learning is as effective as traditional inter-learning and may be more effective in certain contexts, such as difficult tasks. Encouraging intra-learning in community service or educational activities can effectively mitigate the challenge of limited volunteers and enhance learning acquisition among older adults.

11.
Mol Biomed ; 5(1): 23, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38871861

RESUMEN

Sleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3' untranslated region of Ckip-1 (Ckip-1 3'UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3'UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3'UTR in treating SD-induced heart disease.


Asunto(s)
Regiones no Traducidas 3' , Proteínas Quinasas Activadas por AMP , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina , Transducción de Señal , Privación de Sueño , Animales , Masculino , Ratones , Regiones no Traducidas 3'/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/genética , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Ratones Endogámicos C57BL , Miocardio/metabolismo , Miocardio/patología , Privación de Sueño/genética , Privación de Sueño/metabolismo , Privación de Sueño/complicaciones , Troponina I/metabolismo , Troponina I/genética
12.
Bioorg Chem ; 150: 107493, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38870703

RESUMEN

2. This research investigates the impact of the EGCG-CSH/n-HA/CMC composite material on bone defect repair, emphasizing its influence on macrophage polarization and osteogenic differentiation of BMSCs. Comprehensive evaluations of the composite's physical and chemical characteristics were performed. BMSC response to the material was tested in vitro for proliferation, migration, and osteogenic potential. An SD rat model was employed for in vivo assessments of bone repair efficacy. Both transcriptional and proteomic analyses were utilized to delineate the mechanisms influencing macrophage behavior and stem cell differentiation. The material maintained excellent structural integrity and significantly promoted BMSC functions critical to bone healing. In vivo results confirmed accelerated bone repair, and molecular analysis highlighted the role of macrophage M2 polarization, particularly through changes in the SIRPA gene and protein expression. EGCG-CSH/n-HA/CMC plays a significant role in enhancing bone repair, with implications for macrophage and BMSC function. Our findings suggest that targeting SIRPA may offer new therapeutic opportunities for bone regeneration.


Asunto(s)
Catequina , Diferenciación Celular , Macrófagos , Osteogénesis , Ratas Sprague-Dawley , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/citología , Animales , Catequina/farmacología , Catequina/análogos & derivados , Catequina/química , Ratas , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Relación Estructura-Actividad , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología
13.
Food Chem ; 454: 139839, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38810444

RESUMEN

Probiotic lactic acid bacteria have been widely studied, but much less was focused on probiotic yeasts in food systems. In this study, probiotic Saccharomyces cerevisiae var. boulardii CNCM I-745 was employed to prepare ice cream added with and without inulin (1%, w/v). Metabolomics analysis on the effect of inulin showed 84 and 147 differentially expressed metabolites identified in the ice cream samples from day 1 and day 30 of storage (-18 °C), respectively. Various potential functional metabolites were found, including citric acid, ornithine, D-glucuronic acid, sennoside A, stachyose, maltotetraose, maltopentaose, maltohexaose, maltoheptaose, cis-aconitic acid, gamma-aminobutyric acid, L-threonine, L-glutamic acid, tryptophan, benzoic acid, and trehalose. Higher expression of these metabolites suggested their possible roles through relevant metabolic pathways in improving survivability of the probiotic yeast and functionality of ice cream. This study provides further understanding on the metabolic characteristics of probiotic yeast that potentially affect the functionality of ice cream.


Asunto(s)
Helados , Inulina , Metabolómica , Prebióticos , Probióticos , Saccharomyces cerevisiae , Simbióticos , Inulina/metabolismo , Probióticos/metabolismo , Simbióticos/análisis , Prebióticos/análisis , Saccharomyces cerevisiae/metabolismo , Helados/análisis , Helados/microbiología , Saccharomyces boulardii/metabolismo , Saccharomyces boulardii/química
14.
Obesity (Silver Spring) ; 32(7): 1349-1361, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38816990

RESUMEN

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an escalating health problem in pediatric populations. This study aimed to investigate the role of N-acetyltransferase 10 (NAT10) in maternal high-fat diet (HFD)-induced MASLD in offspring at early life. METHODS: We generated male hepatocyte-specific NAT10 knockout (Nat10HKO) mice and mated them with female Nat10fl/fl mice under chow or HFD feeding. Body weight, liver histopathology, and expression of lipid metabolism-associated genes (Srebp1c, Fasn, Pparα, Cd36, Fatp2, Mttp, and Apob) were assessed in male offspring at weaning. Lipid uptake assays were performed both in vivo and in vitro. The mRNA stability assessment and RNA immunoprecipitation were performed to determine NAT10-regulated target genes. RESULTS: NAT10 deletion in hepatocytes of male offspring alleviated perinatal lipid accumulation induced by maternal HFD, decreasing expression levels of Srebp1c, Fasn, Cd36, Fatp2, Mttp, and Apob while enhancing Pparα expression. Furthermore, Nat10HKO male mice exhibited reduced lipid uptake. In vitro, NAT10 promoted lipid uptake by enhancing the mRNA stability of CD36 and FATP2. RNA immunoprecipitation assays exhibited direct interactions between NAT10 and CD36/FATP2 mRNA. CONCLUSIONS: NAT10 deletion in offspring hepatocytes ameliorates maternal HFD-induced hepatic steatosis through decreasing mRNA stability of CD36 and FATP2, highlighting NAT10 as a potential therapeutic target for pediatric MASLD.


Asunto(s)
Dieta Alta en Grasa , Hígado Graso , Hepatocitos , Metabolismo de los Lípidos , Hígado , Ratones Noqueados , Animales , Dieta Alta en Grasa/efectos adversos , Masculino , Femenino , Ratones , Embarazo , Hígado/metabolismo , Hígado/patología , Hepatocitos/metabolismo , Hígado Graso/etiología , Hígado Graso/metabolismo , Acetiltransferasas/genética , Acetiltransferasas/metabolismo , Antígenos CD36/metabolismo , Antígenos CD36/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Efectos Tardíos de la Exposición Prenatal , PPAR alfa/metabolismo , PPAR alfa/genética , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología
15.
Adv Sci (Weinh) ; 11(26): e2402059, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38704728

RESUMEN

White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno-associated virus delivery of vascular endothelial growth factor-C (VEGF-C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF-C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.


Asunto(s)
Sistema Glinfático , Meninges , Sustancia Blanca , Sistema Glinfático/metabolismo , Animales , Sustancia Blanca/metabolismo , Sustancia Blanca/patología , Humanos , Masculino , Ratas , Femenino , Meninges/metabolismo , Modelos Animales de Enfermedad , Vasos Linfáticos/metabolismo , Anciano , Imagen por Resonancia Magnética/métodos , Estudios Longitudinales
16.
Eur Spine J ; 33(7): 2569-2576, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38764090

RESUMEN

BACKGROUND: Understanding spinal sagittal balance is crucial for assessing and treating spinal deformities in pediatric populations. OBJECTIVE: The aim of the present observational study is to examine the parameters of sagittal alignment of the regional spine and spinopelvic region in asymptomatic pediatric populations and the characteristics of these parameters with age and sex. METHODS: We enrolled 217 participants, consisting of 112 males (51.6%) and 105 females (48.4%), aged between 4 and 15 years, with an average age of 12.19 years. Pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, T1 slope, C7 slope, cervical sagittal vertical axis, and C2-7 Cobb angle were measured. Three spine surgeons conducted radiographic measurements utilizing the PACS software. The measurement reliability was assessed through ICCs. RESULTS: Our results show significant age-related changes in pelvic tilt and cervical sagittal vertical axis, with notable gender differences in pelvic tilt, lumbar lordosis, and thoracic kyphosis. Girls have larger PT, boys have larger cSVA. PI, PT, and cSVA also differ among different age groups. Correlation analysis shows that a series of relationships that align with adult population patterns between pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, and thoracic kyphosis. CONCLUSION: Significant variations in PT and cSVA across diverse age cohorts highlights notable disparities in the distribution of PT and cSVA values within the pediatric population. Gender-based differences in PT, LL, and TK and correlation in spinopelvic parameter could enhances our understanding of compensatory mechanisms.


Asunto(s)
Columna Vertebral , Humanos , Masculino , Femenino , Niño , Adolescente , Preescolar , Columna Vertebral/diagnóstico por imagen , Pelvis/diagnóstico por imagen , Lordosis/diagnóstico por imagen , Cifosis/diagnóstico por imagen , Cifosis/epidemiología , Huesos Pélvicos/diagnóstico por imagen , Radiografía/métodos
17.
Cell Commun Signal ; 22(1): 252, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698453

RESUMEN

BACKGROUND: Ischemic postconditioning (IPostC) has been reported as a promising method for protecting against myocardial ischemia-reperfusion (MI/R) injury. Our previous study found that the infarct-limiting effect of IPostC is abolished in the heart of diabetes whose cardiac expression of DJ-1 (also called PARK7, Parkinsonism associated deglycase) is reduced. However, the role and in particular the underlying mechanism of DJ-1 in the loss of sensitivity to IPostC-induced cardioprotection in diabetic hearts remains unclear. METHODS: Streptozotocin-induced type 1 diabetic rats were subjected to MI/R injury by occluding the left anterior descending artery (LAD) and followed by reperfusion. IPostC was induced by three cycles of 10s of reperfusion and ischemia at the onset of reperfusion. AAV9-CMV-DJ-1, AAV9-CMV-C106S-DJ-1 or AAV9-DJ-1 siRNA were injected via tail vein to either over-express or knock-down DJ-1 three weeks before inducing MI/R. RESULTS: Diabetic rats subjected to MI/R exhibited larger infarct area, more severe oxidative injury concomitant with significantly reduced cardiac DJ-1 expression and increased PTEN expression as compared to non-diabetic rats. AAV9-mediated cardiac DJ-1 overexpression, but not the cardiac overexpression of DJ-1 mutant C106S, restored IPostC-induced cardioprotection and this effect was accompanied by increased cytoplasmic DJ-1 translocation toward nuclear and mitochondrial, reduced PTEN expression, and increased Nrf-2/HO-1 transcription. Our further study showed that AAV9-mediated targeted DJ-1 gene knockdown aggravated MI/R injury in diabetic hearts, and this exacerbation of MI/R injury was partially reversed by IPostC in the presence of PTEN inhibition or Nrf-2 activation. CONCLUSIONS: These findings suggest that DJ-1 preserves the cardioprotective effect of IPostC against MI/R injury in diabetic rats through nuclear and mitochondrial DJ-1 translocation and that inhibition of cardiac PTEN and activation of Nrf-2/HO-1 may represent the major downstream mechanisms whereby DJ-1 preserves the cardioprotective effect of IPostC in diabetes.


Asunto(s)
Diabetes Mellitus Experimental , Poscondicionamiento Isquémico , Daño por Reperfusión Miocárdica , Fosfohidrolasa PTEN , Proteína Desglicasa DJ-1 , Ratas Sprague-Dawley , Animales , Proteína Desglicasa DJ-1/metabolismo , Proteína Desglicasa DJ-1/genética , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Diabetes Mellitus Experimental/metabolismo , Masculino , Ratas , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Transporte de Proteínas , Estreptozocina , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología
18.
Psychol Med ; : 1-8, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738283

RESUMEN

BACKGROUND: Microstates of an electroencephalogram (EEG) are canonical voltage topographies that remain quasi-stable for 90 ms, serving as the foundational elements of brain dynamics. Different changes in EEG microstates can be observed in psychiatric disorders like schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). However, the similarities and disparatenesses in whole-brain dynamics on a subsecond timescale among individuals diagnosed with SCZ, BD, and MDD are unclear. METHODS: This study included 1112 participants (380 individuals diagnosed with SCZ, 330 with BD, 212 with MDD, and 190 demographically matched healthy controls [HCs]). We assembled resting-state EEG data and completed a microstate analysis of all participants using a cross-sectional design. RESULTS: Our research indicates that SCZ, BD, and MDD exhibit distinct patterns of transition among the four EEG microstate states (A, B, C, and D). The analysis of transition probabilities showed a higher frequency of switching from microstates A to B and from B to A in each patient group compared to the HC group, and less frequent transitions from microstates A to C and from C to A in the SCZ and MDD groups compared to the HC group. And the probability of the microstate switching from C to D and D to C in the SCZ group significantly increased compared to those in the patient and HC groups. CONCLUSIONS: Our findings provide crucial insights into the abnormalities involved in distributing neural assets and enabling proper transitions between different microstates in patients with major psychiatric disorders.

20.
Sleep Med ; 119: 155-163, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38678759

RESUMEN

OBJECTIVES: Sleep is associated with cognitive function in older adults. In the current study, we examined this relationship from subjective and objective perspectives, and determined the robustness and dimensional specificity of the associations using a comprehensive modelling approach. METHODS: Multiple dimensions of subjective (sleep quality and daytime sleepiness) and objective sleep (sleep stages, sleep parameters, sleep spindles, and slow oscillations), as well as subjectively reported and objectively measured cognitive function were collected from 55 older adults. Specification curve analysis was used to examine the robustness of correlations for the effects of sleep on cognitive function. RESULTS: Robust associations were found between sleep and objectively measured cognitive function, but not with subjective cognitive complaints. In addition, subjective sleep showed robust and consistent associations with global cognitive function, whereas objective sleep showed a more domain-specific association with episodic memory. Specifically, subjective sleep quality and daytime sleepiness correlated with global cognitive function, and objective sleep parameters correlated with episodic memory. CONCLUSIONS: Overall, associations between sleep and cognitive function in older adults depend on how they are measured and which specific dimensions of sleep and domains of cognitive function are considered. It highlights the importance of focusing on specific associations to ameliorate the detrimental effects of sleep disturbance on cognitive function in later life.


Asunto(s)
Cognición , Calidad del Sueño , Humanos , Masculino , Femenino , Anciano , Cognición/fisiología , Sueño/fisiología , Polisomnografía , Memoria Episódica , Pruebas Neuropsicológicas/estadística & datos numéricos , Anciano de 80 o más Años , Fases del Sueño/fisiología
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