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1.
Magn Reson Imaging ; 114: 110234, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39288886

RESUMEN

PURPOSE: This study aimed to assess changes in white matter microstructure among patients undergoing obstructive sleep apnea hypopnea syndrome (OSAHS) complicated by cognitive impairment through neurite orientation dispersion and density imaging (NODDI), and evaluate the relationship to cognitive impairment as well as the diagnostic performance in early intervention. METHODS: Totally 23 OSAHS patients, 43 OSAHS patients complicated by cognitive impairment, and 15 healthy controls were enrolled in OSA, OSACI and HC groups of this work. NODDI toolbox and FMRIB's Software Library (FSL) were used to calculate neurite density index (NDI), Fractional anisotropy (FA), volume fraction of isotropic water molecules (Viso), and orientation dispersion index (ODI). Tract-based spatial statistics (TBSS) were carried out to examine the above metrics with one-way ANOVA. This study explored the correlations of the above metrics with mini-mental state examination (MMSE), and montreal cognitive assessment (MoCA) scores. Furthermore, receiver operating characteristic (ROC) curves were plotted. Meanwhile, area under curve (AUC) values were calculated to evaluate the diagnostic performance of the above metrics. RESULTS: NDI, ODI, Viso, and FA were significantly different among different brain white matter regions, among which, difference in NDI showed the greatest statistical significance. In comparison with HC group, OSA group had reduced NDI and ODI, whereas elevated Viso levels. Conversely, compared to the OSA group, the OSACI group displayed a slight increase in NDI and ODI values, which remained lower than HC group, viso values continued to rise. Post-hoc analysis highlighted significant differences in these metrics, except for FA, which showed no notable changes or correlations with neuropsychological tests. ROC analysis confirmed the diagnostic efficacy of NDI, ODI, and Viso with AUCs of 0.6908, 0.6626, and 0.6363, respectively, whereas FA's AUC of 0.5042, indicating insufficient diagnostic efficacy. CONCLUSIONS: This study confirmed that NODDI effectively reveals microstructural changes in white matter of OSAHS patients with cognitive impairment, providing neuroimaging evidence for early clinical diagnosis and intervention.

2.
Adv Sci (Weinh) ; : e2405628, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39297417

RESUMEN

Retinitis pigmentosa (RP) is a complex spectrum of inherited retinal diseases marked by the gradual loss of photoreceptor cells, ultimately leading to blindness. Among these, mutations in PDE6A, responsible for encoding a cGMP-specific phosphodiesterase, stand out as pivotal in autosomal recessive RP (RP43). Unfortunately, no effective therapy currently exists for this specific form of RP. However, recent advancements in genome editing, such as base editing (BE) and prime editing (PE), offer a promising avenue for precise and efficient gene therapy. Here, it is illustrated that the engineered BE and PE systems, particularly PE, exhibit high efficiency in rescuing a target point mutation with minimal bystander effects in an RP mouse model carrying the Pde6a (c.2009A > G, p.D670G) mutation. The optimized BE and PE systems are first screened in N2a cells and subsequently assessed in electroporated mouse retinas. Notably, the optimal PE system, delivered via dual adeno-associated virus (AAV), precisely corrects the pathogenic mutation with average 9.4% efficiency, with no detectable bystander editing. This correction restores PDE6A protein expression, preserved photoreceptors, and rescued retinal function in Pde6a mice. Therefore, this study offers a proof-of-concept demonstration for the treatment of Pde6a-related retinal degeneration using BE and PE systems.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39283531

RESUMEN

The widespread use of Internet has substantially influenced adolescents' lifestyles. This paper systematically explored the impact of Internet use on adolescent obesity and unveiled the underlying mechanism in China. We discussed the relationship among Internet use, dietary habits and obesity, and estimated the impact using panel data collected by the China Health and Nutrition Survey. Results indicated that increased Internet use significantly raised the risk of obesity among adolescents by changing their dietary habits. With a longer time of Internet use, adolescents would increase more proportion of snacks, and choose food with higher fat and protein. This paper offers a new empirical evidence for understanding the mechanism of Internet use on adolescent obesity, and provides a reference for developing countries to guide adolescents toward moderate Internet use and lower the risk of obesity.

4.
Front Plant Sci ; 15: 1434097, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39188547

RESUMEN

Soil quality is defined as the ability of soil to maintain the soil environment and the biosphere. Due to the limitation of salt and alkali stress, soil quality can be reduced, which in turn affects agricultural production. Biochar is widely used in saline-alkali land improvement because of its special pore structure and strong ion exchange ability, while Piriformospora indica is widely used in saline-alkali land improvement because it can symbiose with plants and improve plant stress resistance. However, the synergistic effect of combined biochar application and inoculation of P. indica on the quality of saline-alkali soil and plant development is uncertain. Hence, we investigated the combined influences of biochar and P. indica on the soil physicochemical characteristics, as well as the growth and chlorophyll florescence of sorghum-sudangrass hybrids (Sorghum bicolor × Sorghum sudane) in our study. The results indicated that after applying biochar and P. indica together, there was a considerable drop in soil pH, conductivity, Na+, and Cl- concentrations. Meanwhile, the soil organic matter (SOM), available phosphorus (AP), and alkaline hydrolyzable nitrogen (AN) increased by 151.81%, 50.84%, and 103.50%, respectively, when the Bamboo biochar was combined with 120 ml/pot of P. indica. Eventually, sorghum-sudangrass hybrid biomass, transpiration rate, and chlorophyll content increased by 111.69%, 204.98%, and 118.54%, respectively. According to our findings, using P. indica and biochar together can enhance soil quality and plant growth. The results also provide insights to enhance the quality of saline-alkali soils and the role of microorganisms in nutrient cycling.

5.
J Clin Invest ; 134(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949024

RESUMEN

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.


Asunto(s)
Cilios , Enfermedades Renales Quísticas , Enfermedad de Leigh , Mitocondrias , Pez Cebra , Humanos , Pez Cebra/metabolismo , Pez Cebra/genética , Enfermedad de Leigh/genética , Enfermedad de Leigh/metabolismo , Enfermedad de Leigh/patología , Cilios/metabolismo , Cilios/patología , Cilios/genética , Animales , Mitocondrias/metabolismo , Mitocondrias/patología , Mitocondrias/genética , Enfermedades Renales Quísticas/genética , Enfermedades Renales Quísticas/metabolismo , Enfermedades Renales Quísticas/patología , Complejo I de Transporte de Electrón/metabolismo , Complejo I de Transporte de Electrón/genética , Proteínas del Dominio Armadillo/metabolismo , Proteínas del Dominio Armadillo/genética , Retina/metabolismo , Retina/patología , Retina/anomalías , Anomalías del Ojo/genética , Anomalías del Ojo/patología , Anomalías del Ojo/metabolismo , Ratones , Anomalías Múltiples/genética , Anomalías Múltiples/metabolismo , Anomalías Múltiples/patología , Cerebelo/metabolismo , Cerebelo/patología , Cerebelo/anomalías , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Masculino
6.
J Exp Anal Behav ; 122(1): 3-10, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38853291

RESUMEN

The vast majority of studies on discounting have focused on simple delayed outcomes, but most everyday decisions are more complicated. The present experiment focused on one such scenario, an iconic self-control situation in which immediate gains are followed by delayed losses. The same participants were studied in all conditions to permit examination of individual differences in choice behavior using intercorrelations and factor analysis. Consistent with previous research, the hyperboloid model accurately described the form of the discounting function and discounting was not affected by the amount of the delayed loss when it was presented alone. However, replicating other studies, smaller delayed losses were discounted more steeply than larger ones when presented in combination with immediate gains. Exploratory factor analysis revealed two factors, one loading primarily on loss-only conditions and the other loading primarily on conditions involving outcomes that combined gains and losses. These results imply that there are individual differences in how one combines gains and losses and that this characteristic of individual decision making might be an important predictor of decisions in the many everyday choice situations that involve complex outcomes.


Asunto(s)
Descuento por Demora , Individualidad , Humanos , Masculino , Femenino , Adulto Joven , Recompensa , Modelos Psicológicos , Conducta de Elección , Análisis Factorial , Adulto , Autocontrol/psicología
7.
Life Sci ; 352: 122811, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38862062

RESUMEN

Macrophages play key roles in atherosclerosis progression, and an imbalance in M1/M2 macrophages leads to unstable plaques; therefore, M1/M2 macrophage polarization-targeted treatments may serve as a new approach in the treatment of atherosclerosis. At present, there is little research on M1/M2 macrophage polarization-targeted nanotechnology. Proteolysis-targeting chimera (PROTAC) technology, a targeted protein degradation technology, mediates the degradation of target proteins and has been widely promoted in preclinical and clinical applications as a novel therapeutic modality. This review summarizes the recent studies on M1/M2 macrophage polarization-targeted nanotechnology, focusing on the mechanism and advantages of PROTACs in M1/M2 macrophage polarization as a new approach for the treatment of atherosclerosis.


Asunto(s)
Aterosclerosis , Macrófagos , Nanotecnología , Proteolisis , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/inmunología , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Animales , Nanotecnología/métodos , Proteolisis/efectos de los fármacos
8.
Lancet Healthy Longev ; 5(5): e356-e369, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38705153

RESUMEN

BACKGROUND: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. METHODS: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). FINDINGS: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001-0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000-0·002]) and in delayed recall (PIE 0·001 [0·000-0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000-0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. INTERPRETATION: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. FUNDING: EU Joint Programme-Neurodegenerative Disease Research (JPND) and Alzheimer's Society. TRANSLATION: For the Swedish translation of the abstract see Supplementary Materials section.


Asunto(s)
Biomarcadores , Cognición , Depresión , Humanos , Femenino , Estudios Longitudinales , Masculino , Depresión/epidemiología , Depresión/sangre , Persona de Mediana Edad , Anciano , Cognición/fisiología , Biomarcadores/sangre , Inflamación/sangre , Inflamación/epidemiología , Inglaterra/epidemiología , Envejecimiento/psicología , Envejecimiento/inmunología , Anciano de 80 o más Años , Suecia/epidemiología , Apoyo Social
9.
Scand J Med Sci Sports ; 34(5): e14651, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38760918

RESUMEN

There is some, albeit inconsistent, evidence supporting sex differences in preschoolers' motor competence (MC), with these observations not uniform when analyzed by age, and cultural groups. Thus, this study examined sex differences across ages in 3- to 5-year-old children's MC. A cross-country pooled sample of 6241 children aged 3-5 years (49.6% girls) was assessed for MC using the Test of Gross Motor Development-2nd/3rd edition, and children were categorized into groups of age in months. Multiple linear regression models and predictive margins were calculated to explore how sex and age in months affect scores of MC (i.e., locomotor and ball skills), with adjustments for country and BMI. The Chow's Test was used to test for the presence of a structural break in the data. Significant differences in favor of girls were seen at 57-59 and 66-68 months of age for locomotor skills; boys performed better in ball skills in all age periods, except for 42-44 and 45-47 months of age. The higher marginal effects were observed for the period between 45-47 and 48-50 months for locomotor skills (F = 30.21; and F = 25.90 for girls and boys, respectively), and ball skills (F = 19.01; and F = 42.11 for girls and boys, respectively). A significantly positive break point was seen at 45-47 months, highlighting the age interval where children's MC drastically improved. The identification of this breakpoint provides an evidence-based metric for when we might expect MC to rapidly increase, and an indicator of early delay when change does not occur at that age.


Asunto(s)
Destreza Motora , Humanos , Destreza Motora/fisiología , Femenino , Masculino , Preescolar , Estudios Transversales , Factores Sexuales , Factores de Edad , Desarrollo Infantil/fisiología , Modelos Lineales
10.
Hum Mol Genet ; 33(13): 1142-1151, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38557732

RESUMEN

Lowe syndrome, a rare X-linked multisystem disorder presenting with major abnormalities in the eyes, kidneys, and central nervous system, is caused by mutations in OCRL gene (NG_008638.1). Encoding an inositol polyphosphate 5-phosphatase, OCRL catalyzes the hydrolysis of PI(4,5)P2 into PI4P. There are no effective targeted treatments for Lowe syndrome. Here, we demonstrate a novel gene therapy for Lowe syndrome in patient fibroblasts using an adenine base editor (ABE) that can efficiently correct pathogenic point mutations. We show that ABE8e-NG-based correction of a disease-causing mutation in a Lowe patient-derived fibroblast line containing R844X mutation in OCRL gene, restores OCRL expression at mRNA and protein levels. It also restores cellular abnormalities that are hallmarks of OCRL dysfunction, including defects in ciliogenesis, microtubule anchoring, α-actinin distribution, and F-actin network. The study indicates that ABE-mediated gene therapy is a feasible treatment for Lowe syndrome, laying the foundation for therapeutic application of ABE in the currently incurable disease.


Asunto(s)
Fibroblastos , Edición Génica , Terapia Genética , Síndrome Oculocerebrorrenal , Monoéster Fosfórico Hidrolasas , Síndrome Oculocerebrorrenal/genética , Síndrome Oculocerebrorrenal/metabolismo , Humanos , Fibroblastos/metabolismo , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Terapia Genética/métodos , Edición Génica/métodos , Mutación , Adenina/metabolismo
11.
Lancet Reg Health Southeast Asia ; 26: 100396, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38617087

RESUMEN

Background: The UN warns that Myanmar faces the 'triple crises' of mass conflict, uncontrolled COVID-19, and economic collapse. Therefore, we aimed to assess the population mental health burden, healthcare needs, and the associated risk factors in Myanmar. Methods: We established a nationwide random sample and recruited 1038 adults via random digit dialling from July 3-Aug 9, 2021, during the ongoing conflict since Feb 1, 2021, and surge in SARS-CoV-2 infections. Probable post-traumatic stress disorder (PTSD) was assessed using the PTSD Checklist-Civilian Version. Probable depression and anxiety were assessed using the Patient Health Questionnaire-2 and the Generalized Anxiety Disorder-2. We calculated population attributable fractions for probable mental disorders using multivariable logistic regression models. Based on the mental health burden and healthcare-seeking patterns, we projected the need for mental health services. Findings: During the 'triple crises', a third of adults in Myanmar (34.9%, 95% CI 32.0-37.7) reported a probable mental disorder. Prevalence of probable PTSD, depression, and anxiety were 8.1% (6.6-9.7), 14.3% (12.0-16.6), and 22.2% (19.7-24.7), respectively. We estimated that up to 79.9% (43.8-97.9) of probable PTSD was attributable to political stress. This corresponds to 2.1 million (1.1-3.2 million) fewer adults with probable PTSD if political stress was removed from the population. The mental health burden could translate into roughly 5.9 million adults seeking mental health services. Interpretation: The mental health burden in Myanmar is substantial, and population mental health might only be restored when the three crises have ended. An accelerated peace process is critical to protecting Myanmar's population mental health. Funding: This research was supported the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU 17606122) and the Michele Tansella Award.

12.
Hum Immunol ; 85(3): 110795, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38582657

RESUMEN

The coronavirus disease 2019 (COVID-19) has merged as a global health threat since its outbreak in December 2019. Despite widespread recognition, there has been a paucity of studies focusing on the T cell receptor (TCR) bias in adaptive immunity induced by SARS-CoV-2. This research conducted a comparative analysis of the TCR immune repertoire to identify notable αß TCR bias sequences associated with the SARS-CoV-2 virus antigen. The present study encompassed 73 symptomatic COVID-19 patients, categorized as moderate/mild or severe/critical, along with 9 healthy controls. Our findings revealed specific TCR chains prominently utilized by moderate and severe patients, identified as TRAV30-J34-TRBV3-1-J2-7 and TRAV12-3-J6-TRBV28-J1-1, respectively. Additionally, our research explored critical TCR preferences in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients at various disease stages. Indeed, monitoring the dynamics of immune repertoire changes in COVID-19 patients could serve as a crucial biomarker for predicting disease progression and recovery. Furthermore, the study explored TCR bias in both peripheral blood mononuclear cells (PBMCs) and BALF. The most common αß VJ pair observed in BALF was TRAV12-3-J18-TRBV7-6-J2-7. In addition, a comparative analysis with the VDJdb database indicated that the HLA-A*02:01 allele exhibited the widest distribution and highest frequency in COVID-19 patients across different periods. This comprehensive examination provided a global characterization of the TCR immune repertoire in COVID-19 patients, contributing significantly to our understanding of TCR bias induced by SARS-CoV-2.


Asunto(s)
COVID-19 , Receptores de Antígenos de Linfocitos T alfa-beta , SARS-CoV-2 , Humanos , COVID-19/inmunología , SARS-CoV-2/inmunología , Masculino , Femenino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Adulto , Líquido del Lavado Bronquioalveolar/inmunología , Anciano , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Inmunidad Adaptativa/inmunología , Índice de Severidad de la Enfermedad
13.
J Cell Mol Med ; 28(8): e18278, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38546623

RESUMEN

Krüppel-like factors (KLFs) are crucial in the development of bone disease. They are a family of zinc finger transcription factors that are unusual in containing three highly conserved zinc finger structural domains interacting with DNA. It has been discovered that it engages in various cell functions, including proliferation, apoptosis, autophagy, stemness, invasion and migration, and is crucial for the development of human tissues. In recent years, the role of KLFs in bone physiology and pathology has received adequate attention. In addition to regulating the normal growth and development of the musculoskeletal system, KLFs participate in the pathological process of the bones and joints and are intimately linked to several skeletal illnesses, such as osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP) and osteosarcoma (OS). Consequently, targeting KLFs has emerged as a promising therapeutic approach for an array of bone disorders. In this review, we summarize the current literature on the importance of KLFs in the emergence and regulation of bone illnesses, with a particular emphasis on the pertinent mechanisms by which KLFs regulate skeletal diseases. We also discuss the need for KLFs-based medication-targeted treatment. These endeavours offer new perspectives on the use of KLFs in bone disorders and provide prognostic biomarkers, therapeutic targets and possible drug candidates for bone diseases.


Asunto(s)
Neoplasias Óseas , Enfermedades Musculoesqueléticas , Osteoporosis , Humanos , Factores de Transcripción , Factores de Transcripción de Tipo Kruppel/genética
14.
Sci Rep ; 14(1): 5078, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429394

RESUMEN

Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process of osteoarthritis (OA). Herein, we investigated the protective effect of moderate mechanical stress on chondrocyte ferroptosis and further revealed the internal molecular mechanism. Intra-articular injection of sodium iodoacetate (MIA) was conducted to induce the rat model of OA in vivo, meanwhile, interleukin-1 beta (IL-1ß) was treated to chondrocytes to induce the OA cell model in vitro. The OA phenotype was analyzed by histology and microcomputed tomography, the ferroptosis was analyzed by transmission electron microscope and immunofluorescence. The expression of ferroptosis and cartilage metabolism-related factors was analyzed by immunohistochemical and Western blot. Animal experiments revealed that moderate-intensity treadmill exercise could effectively reduce chondrocyte ferroptosis and cartilage matrix degradation in MIA-induced OA rats. Cell experiments showed that 4-h cyclic tensile strain intervention could activate Nrf2 and inhibit the NF-κB signaling pathway, increase the expression of Col2a1, GPX4, and SLC7A11, decrease the expression of MMP13 and P53, thereby restraining IL-1ß-induced chondrocyte ferroptosis and degeneration. Inhibition of NF-κB signaling pathway relieved the chondrocyte ferroptosis and degeneration. Meanwhile, overexpression of NF-κB by recombinant lentivirus reversed the positive effect of CTS on chondrocytes. Moderate mechanical stress could activate the Nrf2 antioxidant system, inhibit the NF-κB p65 signaling pathway, and inhibit chondrocyte ferroptosis and cartilage matrix degradation by regulating P53, SLC7A11, and GPX4.


Asunto(s)
Ferroptosis , Osteoartritis , Estrés Mecánico , Animales , Ratas , Condrocitos/metabolismo , Interleucina-1beta/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , FN-kappa B/fisiología , Osteoartritis/metabolismo , Osteoartritis/patología , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Microtomografía por Rayos X , Factor de Transcripción ReIA/metabolismo , Factor de Transcripción ReIA/fisiología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/fisiología
15.
Nat Prod Res ; : 1-8, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38389428

RESUMEN

Quality markers (Q-markers) are of great significance for quality evaluation of herbal medicines. Zhenyuan Capsule (ZYC) is a kind of Chinese patent medicine used to treat cardiovascular diseases. However, reliable and effective Q-markers for ZYC are still lacking. Herein, a UHPLC-Q/Orbitrap-MS/MS was performed to characterise the preliminary chemical profile of ZYC. A total of 86 components were characterised among which 20 constituents were unambiguously identified by reference compounds. Based on network pharmacology, seven major ginsenosides with great importance in the network were identified as Q-markers among which ginsenoside Re with the highest betweenness was screened to inhibit the development of coronary heart disease (CHD) by binding with vascular endothelial growth factor A (VEGFA). Docking and molecular dynamics simulation studies suggested that ginsenoside Re stably bound to VEGFA. Quantitative determination and chemical fingerprinting analysis were performed using HPLC-DAD. The results showed that ginsenosides screened might function as potential Q-markers for ZYC.

16.
Biotechnol J ; 19(2): e2300427, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38403449

RESUMEN

Three-dimensional (3D) cell cultures have garnered significant attention in biomedical research due to their ability to mimic the in vivo cellular environment more accurately. The formation of 3D cell spheroids using hanging drops has emerged as a cost-effective and crucial method for generating uniformly-sized spheroids. This study aimed to validate the potential of a tip-refill wafer (TrW), a disposable laboratory item used to hold pipette tips, in facilitating 3D cell culture. The TrW allows for easy generation of hanging drops by pipetting the solution into the holes of the wafer. The mechanical stability of the hanging drops is ensured by the surface wettability and thickness of the TrW. Hanging drops containing 60-µL of solution remained securely attached to the TrW even when subjected to orbital shaking at 210 rpm. The exceptional resistance to mechanical shaking enabled the use of inertial focusing to facilitate spheroid formation. This was demonstrated through live/dead cell staining, quantitative polymerase chain reaction (qPCR) analysis, and cytoskeleton staining, which revealed that horizontal orbiting at 60 rpm for 15 min promoted cell aggregation and ultimately led to the formation of 3D spheroids. The spheroid harvest rate is 96.1% ± 3.5% across three TrWs, each containing 60 hanging drops. In addition to generating mono-culture 3D spheroids, the TrW-based hanging drop platform also enables the formation of multicellular spheroids, and on-demand pairing and fusion of spheroids. The TrW is a disposable item that does not require any fabrication or surface modification procedures, further enhancing its application potential in conventional biological laboratories.


Asunto(s)
Técnicas de Cultivo de Célula , Esferoides Celulares , Técnicas de Cultivo de Célula/métodos
17.
Mar Environ Res ; 194: 106314, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38185000

RESUMEN

Pollutants in the ecological environment of fishery seawater are harmful to the survival and reproduction of aquatic organisms. Hexabromocyclododecanes (HBCDs) were 42.9% detected within ND-48.89 ng/L in 177 seawater samples and 30.7% within ND-1.07 ng/g dw in 88 sediment samples of the fisheries in the Yellow Sea and East China Sea, respectively. γ-HBCD accounted for 65% of seawater and 89% of sediment samples. HBCDs in seawater in winter (ND-48.89 ng/L) were significantly higher than in summer (ND-4.99 ng/L), possibly because the re-suspension caused by winds and waves could re-migrate HBCDs from the sediment to the seawater in winter. However, seasonal differences of HBCDs in sediment were not significant. The fugacities indicated HBCDs' migrating trend from seawater to sediment due to their hydrophobic nature. There is almost no terrestrial input of HBCDs from the Yangtze and Yellow Rivers, and currently used fishery materials in marine may compose long-lasting sources of HBCDs.


Asunto(s)
Monitoreo del Ambiente , Hidrocarburos Bromados , Contaminantes Químicos del Agua , Estaciones del Año , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/análisis , Caza , Agua de Mar , China
18.
Anal Chem ; 96(3): 1112-1120, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-38181398

RESUMEN

Oblique-incidence reflectivity difference (OIRD) is a novel real-time, label-free, and nondestructive optical detection method and exhibits encouraging application in the detection of antibody/DNA microarrays. In this study, for the first time, an OIRD label-free immunoassay was achieved by using adherent live cells as the probe. The cells were cultured on glass cells, and the affinity binding of antibodies targeted on the HLA class I antigen of the cell surface was detected with an OIRD. The results show that an OIRD is able to detect the binding process of anti-human HLA-A, B, and C antibodies on MDA-MB-231 cells and HUVEC cells. Control experiments and complementary fluorescence analysis confirmed the high detection specificity and good quantitative virtue of the OIRD label-free immunoassay. Label-free OIRD imaging analysis of cell microarrays was further demonstrated successfully, and the underlying optical mechanism was revealed by combining the theoretical modeling. This work explores the use of live cells as probes for an OIRD immunoassay, thus expanding the potential applications of the OIRD in the field of pathological analysis, disease diagnosis, and drug screening, among others.


Asunto(s)
Anticuerpos , Vidrio , Análisis de Secuencia por Matrices de Oligonucleótidos , Inmunoensayo
19.
In Vitro Cell Dev Biol Anim ; 60(1): 89-97, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38253954

RESUMEN

Cardiovascular disease is the deadliest disease in the world. Previous studies have shown that Dihydrotanshinone I (DHT) can improve cardiac function after myocardial injury. This study aimed to observe the protective effect and mechanism of DHT on H9c2 cells by establishing an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model. By constructing OGD/R injury simulation of H9c2 cells in a myocardial injury model, the proliferation of H9c2 cells treated with DHT concentrations of 0.1 µmol/L were not affected at 24, 48, and 72 h. DHT can significantly reduce the apoptosis of H9c2 cells caused by OGD/R. Compared with the OGD/R group, DHT treatment significantly reduced the level of MDA and increased the level of SOD in cells. DHT treatment of cells can significantly reduce the levels of ROS and Superoxide in mitochondria in H9c2 cells caused by OGD/R and H2O2. DHT significantly reduced the phosphorylation levels of P38MAPK and ERK in H9c2 cells induced by OGD/R, and significantly increased the phosphorylation levels of AKT in H9c2 cells. DHT can significantly reduce the oxidative stress damage of H9c2 cells caused by H2O2 and OGD/R, thereby reducing the apoptosis of H9c2 cells. And this may be related to regulating the phosphorylation levels of AKT, ERK, and P38MAPK.


Asunto(s)
Furanos , Peróxido de Hidrógeno , Fenantrenos , Proteínas Proto-Oncogénicas c-akt , Quinonas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular , Peróxido de Hidrógeno/metabolismo , Transducción de Señal , Oxígeno/farmacología , Oxígeno/metabolismo , Apoptosis , Glucosa/metabolismo , Miocitos Cardíacos/metabolismo
20.
J Neurosci Res ; 102(1): e25273, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38284846

RESUMEN

Primary cilia are microtubule-based sensory organelles that project from the apical surface of most mammalian cells, including oligodendrocytes, which are myelinating cells of the central nervous system (CNS) that support critical axonal function. Dysfunction of CNS glia is associated with aging-related white matter diseases and neurodegeneration, and ciliopathies are known to affect CNS white matter. To investigate age-related changes in ciliary profile, we examined ciliary length and frequency in the retinogeniculate pathway, a white matter tract commonly affected by diseases of aging but in which expression of cilia has not been characterized. We found expression of Arl13b, a marker of primary cilia, in a small group of Olig2-positive oligodendrocytes in the optic nerve, optic chiasm, and optic tract in young and aged C57BL/6 wild-type mice. While the ciliary length and ciliated oligodendrocyte cells were constant in young mice in the retinogeniculate pathway, there was a significant increase in ciliary length in the anterior optic nerve as compared to the aged animals. Morphometric analysis confirmed a specific increase in the ciliation rate of CC1+ /Olig2+ oligodendrocytes in aged mice compared with young mice. Thus, the prevalence of primary cilia in oligodendrocytes in the visual pathway and the age-related changes in ciliation suggest that they may play important roles in white matter and age-associated optic neuropathies.


Asunto(s)
Nervio Óptico , Sustancia Blanca , Animales , Ratones , Ratones Endogámicos C57BL , Oligodendroglía , Neuroglía , Mamíferos
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