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1.
Nat Nanotechnol ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740934

RESUMEN

Nutrient avidity is one of the most distinctive features of tumours. However, nutrient deprivation has yielded limited clinical benefits. In Gaucher disease, an inherited metabolic disorder, cells produce cholesteryl-glucoside which accumulates in lysosomes and causes cell damage. Here we develop a nanoparticle (AbCholB) to emulate natural-lipoprotein-carried cholesterol and initiate Gaucher disease-like damage in cancer cells. AbCholB is composed of a phenylboronic-acid-modified cholesterol (CholB) and albumin. Cancer cells uptake the nanoparticles into lysosomes, where CholB reacts with glucose and generates a cholesteryl-glucoside-like structure that resists degradation and aggregates into microscale crystals, causing Gaucher disease-like damage in a glucose-dependent manner. In addition, the nutrient-sensing function of mTOR is suppressed. It is observed that normal cells escape severe damage due to their inferior ability to compete for nutrients compared with cancer cells. This work provides a bioinspired strategy to selectively impede the metabolic action of cancer cells by taking advantage of their nutrient avidity.

2.
Ophthalmic Physiol Opt ; 44(3): 576-583, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38351864

RESUMEN

PURPOSE: To investigate the post-operative refractive stabilisation time and provide evidence for the optimal timing of a spectacle prescription in myopic post-cataract surgery patients. METHODS: A total of 116 consecutive myopic cataract patients were recruited from the Zhongshan Ophthalmic Center in this prospective study. Post-operative subjective refraction was assessed after 1 week and 1 month (4-6 weeks), with the interval for the new spectacle acquisition being recorded. Visual Function Index-14 (VF-14) questionnaires were used to assess the vision-related quality of life. RESULTS: There was no significant difference in spherical (p = 0.33), cylindrical (p = 0.65) or spherical equivalent refractions (p = 0.45) obtained 1 week and 1 month post-operatively, indicating that subjects achieved refractive stability within 1 week. In subgroups having differing age and axial lengths, there were also no significant differences between the 1 week and 1 month findings. The spherical equivalent refractive shift between 1 week and 1 month was significantly correlated with the post-operative prediction error (R = 0.35; p < 0.001). Only five (4.3%) out of 116 patients obtained new spectacles 1 week post-surgery. The VF-14 values improved from 85.77 ± 7.24 to 90.45 ± 5.39 after acquiring new spectacles (p < 0.01). CONCLUSIONS: The stabilisation of subjective refraction occurred within 1 week in myopic cataract patients. Shortening the interval before prescribing a new spectacle prescription is recommended for myopic patients following cataract surgery to improve their vision-related quality of life.


Asunto(s)
Extracción de Catarata , Catarata , Miopía , Humanos , Recién Nacido , Estudios Prospectivos , Anteojos , Calidad de Vida , Refracción Ocular , Miopía/cirugía
3.
Sci Total Environ ; 921: 171150, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38395166

RESUMEN

Rapid global urbanization has resulted in increased biodiversity problems, particularly the loss of ground-dwelling fauna in urban areas. Urban riparian corridors are an important green infrastructure for biodiversity conservation, in which urban vegetation plays an essential role. The influence of urban vegetation on ground-dwelling faunal diversity is poorly understood. In this study, we used camera traps to collect the species, functional and phylogenetic diversity of ground-dwelling fauna in the Wenyu River-North Canal riparian corridor in Beijing, and analyzed the effects of the vegetation structure and plant community composition on the diversity and community composition of ground-dwelling animals. A plant-ground dwelling animal interaction network was also built to investigate the food supply of plants for ground-nesting animals. We found that at the vegetation structure level, the high connectivity within a radius of 2000 m and the homogeneous distribution within a radius of 1000 m of vegetation patches had generally positive effects on ground-dwelling animals, and shrublands exhibited a supportive role for mammals in riparian corridors. At the plant community level, tall herbs were instrumental in increasing the willingness of ground-dwelling animals to stay in and pass through the area. Native plants were the main plant food resource for ground-dwelling animals. Given the significant effects of vegetation on ground-dwelling fauna, we advocate that habitat conservation and food supply for ground-dwelling animals be supported through appropriate plant landscape planning and design strategies in ecological corridors in urban areas in the future.


Asunto(s)
Biodiversidad , Ecosistema , Animales , Beijing , Filogenia , Mamíferos , Plantas , Animales Domésticos
5.
Invest Ophthalmol Vis Sci ; 64(11): 23, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37589983

RESUMEN

Purpose: To assess age-related biometric changes of the eye in nonhuman primates (NHPs), to and decipher the growth and aging rates and their comparability with humans. Methods: Ocular anatomic measurements were performed on 341 macaca fascicularis aged 0.5 to 23 years via multimodal approaches including IOLMaster 700. Linear or polynomial regression models were simulated to determine the best fitted age-related function. The metrics were compared with human equivalents in published reports. Results: Macaques exhibited a postnatal eye growth pattern similar to humans, characterized by continuous eye extension coordinated with dramatic reshaping of the lens but not the cornea. The age-related growth of lens thickness (LT), anterior chamber depth (ACD), and axis length (AL) exhibited nonlinear and bipolar patterns. The inflection points were 10 to 12 years old for LT and ACD and 13 to 15 years old for AL in macaques, which were comparable in chronological age at a ratio of ∼1: ratio with that in humans. In contrast, the speed of aging, including the increase in lens density and the decrease in retinal nerve fiber layer thickness, was comparable in relative age at a ratio of ∼1:3 according to the differences in lifespan between macaques and humans. Lens density was a robust indicator for the aging process. Conclusions: Macaque eyes recapitulated the age-related process of human eyes to varying extents with different growth and aging rates. Chronological age or relative age should be considered in different scenarios when macaques are included in preclinical studies.


Asunto(s)
Envejecimiento , Cristalino , Animales , Humanos , Niño , Córnea , Retina , Macaca fascicularis
6.
Biomaterials ; 301: 122291, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37619263

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent hepatic disease characterized as lipid accumulation, yet without any approved drug. And development of therapeutic molecules is obstructed by low efficiency and organ toxicity. Herein, we develop a long-term, low-toxic and liver-selected nano candidate, nabCK, to alleviate NAFLD. NabCK is simply composed by natural compound ginsenoside compound K (CK) and albumin. As a major metabolite of ginseng, ginsenoside CK has excellently modulating functions for lipid metabolism, but accompanied by an extremely poor bioavailability <1%. Albumin is a key lipid carrier secreted and metabolized by livers. Thereby, it can improve solubility and liver-localization of CK. In adipocytes and hepatocytes, nabCK prevents lipid deposition and eliminates lipid droplets. Transcriptomic analysis reveals that nabCK rectifies various pathways that involved in steatosis development, including lipid absorption, lipid export, fatty acid biosynthesis, lipid storage and inflammation. All these pathways are modulated by mTOR, the pivotal feedback sensor that is hyperactive in NAFLD. NabCK suppresses mTOR activation to restores lipid homeostasis. In high-fat diet (HFD) induced NAFLD mice, nabCK retards development of steatosis and fibrosis, coupling a protective effect on cardiac tissues from lipotoxicity. Together, nabCK is a safe and potent candidate to offer benefits for NAFLD treatment.


Asunto(s)
Ginsenósidos , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Albúminas , Homeostasis , Lípidos
7.
Am J Ophthalmol ; 254: 203-209, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37327960

RESUMEN

PURPOSE: To objectively quantify the lens opacity of posterior subcapsular cataracts (PSCs) using the swept-source optical coherence tomography (SS-OCT)-based devices including IOL Master 700 and CASIA-2. DESIGN: Prospective cross-sectional study. METHODS: A total of 101 eyes of 101 patients with PSCs were enrolled in Zhongshan Ophthalmic Center from 2021 to 2022. The IOL Master 700 and CASIA-2 were used to obtain lens images. The average posterior subcapsular density (APSD) and the maximum posterior subcapsular density (MPSD) within the pupil area (radius: 3 or 5 mm) were measured by Image J. Spearman and Pearson correlation analysis were performed to assess the associations. RESULTS: APSD-3mm, APSD-5mm, MPSD-3mm, and MPSD-5mm had positive correlations with best corrected visual acuity (BCVA; r = 0.658, 0.641, 0.583, and 0.572, P < .001, respectively), all of which were higher than the correlation between LOCS-III P score and BCVA (r = 0.548, P < .001). Particularly, the APSD-3mm showed the highest correlation with BCVA. APSD could distinguish severe PSCs (LOCS-III P score ≥ 5) with an area under the receiver operating characteristic curve (AUC) of 0.836 (95% CI 0.743-0.930) for APSD-3mm and with AUC 0.758 (95% CI 0.643-0.873) for APSD-5mm, highlighting the better performance of APSD-3mm. The APSD-3mm of IOL Master 700 correlated strongly with that of CASIA-2 (r = 0.789, P < .001). CONCLUSIONS: This study presented an objective method for quantifying PSCs using IOL Master 700 and CASIA-2. APSD-3mm can be used as a new accurate and objective index for the quantitative assessment of PSCs.


Asunto(s)
Catarata , Cristalino , Humanos , Agudeza Visual , Estudios Transversales , Estudios Prospectivos , Catarata/diagnóstico , Cristalino/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos
8.
Phys Chem Chem Phys ; 25(17): 12450-12457, 2023 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-37096403

RESUMEN

Lead-free perovskites (A3B2X9) have drawn much attention in recent years. However, a thorough understanding of these materials is still in its early stages. This is because A3B2X9 perovskites have large-scale component tunability, in which the A+, B3+, and X- ions can be replaced or partially substituted with other elements. Here, based on density functional theory and machine learning techniques we propose a data-driven method to find suitable configurations for photocatalytic water splitting. By replacing atoms in A3B2X9, 3.4 million configurations are constructed and studied. Our results show that the substitutional position plays an important role in determining the photocatalytic performance. Specifically, the co-existence of Br and I elements is favorable for X-sites, while for B-site atoms, it is better to choose atoms from groups IIIB and IIIA with a period greater than 3. Considering their rarity and toxicity, we believe that In is a good choice for B-sites and propose CsRb2BiInBr5I4 as a promising candidate. These results may provide guidance for the discovery of novel lead-free perovskites for photocatalytic applications.

9.
Artículo en Inglés | MEDLINE | ID: mdl-37056065

RESUMEN

INTRODUCTION: NPC2 is well known as a player for cholesterol transport. However, the biological role of NPC2 in cancer development and therapy is far from clear. METHODS: Here, we explore the potential role of NPC2 in prognosis and immunotherapy across multiple cancer types by integrating RNA-seq data from TCGA and GTEx, protein data from CPTAC, and multiple web analysis databases. RESULTS: Expression depiction between tumour and normal tissues indicated that NPC2 is overexpressed in the majority of the most common cancer types, including glioblastoma and pancreatic cancer, two cancers mostly difficult to diagnose and treat. CONCLUSION: Cancer stemness in glioblastoma is negatively associated with NPC2 level. NPC2 expression is positively correlated with immune cell infiltration and the expression of several immune checkpoints. IDH1 mutation in GBM is negatively correlated with NPC2 level, while a positive correlation has been found between TP53 mutation and NPC2 expression in pancreatic cancer. NPC2 is also correlated with levels of serum biomarkers used for diagnosis of pancreatic cancer.


Asunto(s)
Glioblastoma , Neoplasias Pancreáticas , Humanos , RNA-Seq , Inmunoterapia , Biomarcadores , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Pronóstico , Proteínas de Transporte Vesicular , Neoplasias Pancreáticas
10.
Ophthalmol Ther ; 11(5): 1869-1881, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35917084

RESUMEN

INTRODUCTION: To evaluate and compare the effectiveness for reducing the prediction error (PE) of the second eye using formula-specific factors, artificial intelligence (AI) formulas (PEARL-DGS and Kane), and the Cooke-modified axial length (CMAL) methods in bilateral cataract patients with long axial length (AL). METHODS: A total of 98 patients with long AL who underwent sequential bilateral cataract surgeries were retrospectively enrolled. The second-eye IOL power was calculated by the formula-specific factors, AI formulas, and CMAL methods when the first eye suffered from refraction surprise. The correction factors of eight formulas were calculated by regression analysis. RESULTS: There was a significant correlation between bilateral preoperative biometric parameters (P < 0.05) as well as bilateral PE (P < 0.05). The Kane formula displayed the lowest median absolute error (MedAE) and highest proportion of PE within ± 0.50 and ± 1.00 D compared with other formulas for the first eye. For the second-eye refinement, all three methods could reduce the second-eye MedAE. The formula-specific correction factors were 0.250, 0.331, 0.343, 0.394, 0.409, 0.452, 0.503, and 0.520 for Kane, Barrett Universal II (BUII), PEARL-DGS, Holladay 2, Holladay 1, Haigis, Hoffer Q, and SRK/T, respectively. The new AI-based Kane and PEARL-DGS with or without the CMAL methods could improve the refractive outcomes of the second eye in sequential bilateral cataract patients with long AL. The Kane, BUII, and PEARL-DGS with specific correction factors displayed higher accuracy compared with the other two methods (P < 0.05). CONCLUSIONS: The new AI-based Kane and PEARL-DGS with or without the CMAL methods could improve the refractive outcomes of the second eye in sequential bilateral cataract patients with long AL. Notably, the Kane, PEARL-DGS, and BUII with specific correction factors displayed higher accuracy.

11.
Sci Total Environ ; 826: 154001, 2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35192821

RESUMEN

Heterogeneous land cover affects near-surface heat and humidity distribution in urban areas. Effective land cover arrangements can create a more sustainable local thermal environment. However, spatial differentiation in neighborhood climates and their spatial response range to the surrounding land cover composition (LCC) in high-density urban environments remains unclear. In this study, field monitoring of the air temperature (Ta) and relative humidity (Rh) was conducted in summer (August 2016) and winter (December 2016 and January 2017) in a neighborhood in Beijing, China. A multi-radius approach was developed to quantify the effective response range of Ta and Rh at unshaded measuring points to the surrounding LCC. Our results demonstrated that the: (1) spatial distribution of Ta and Rh in a typical neighborhood varies significantly in both summer and winter and is dependent on the local land cover; (2) Ta at measurement points generally increases with growing surrounding vegetation coverage and decreases with less impervious pavement and building coverage, whereas the opposite applies to Rh; (3) response of Ta and Rh to land cover composition is spatially dependent; and (4) Ta and Rh have an effective response range of up to 200-m to surrounding vegetation coverage in both seasons, whereas their response range to pavement coverage is 150- and 100-m in summer and winter, respectively. Overall, LCC within a radius of 100-150-m has a significant impact on the Ta and Rh of the measuring points in a high-density urban neighborhood. These findings elucidate the spatial response of a neighborhood climate to surrounding land cover and demonstrate that landscape infrastructure intervention is an effective means of improving urban thermal environments.


Asunto(s)
Clima , Beijing , China , Estaciones del Año , Temperatura
12.
Front Cell Dev Biol ; 9: 680947, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34434927

RESUMEN

Diabetic retinopathy, as one of the common complications of diabetes mellitus, is the leading cause of blindness in the working-age population worldwide. The disease is characterized by damage to retinal vasculature, which is associated with the activation of retina microglial and induces chronic neurodegeneration. Previous studies have identified the effects of activated microglial on the retinal neurons, but the cellular and molecular mechanisms underlying microglial activation is largely unknown. Here, we performed scRNA-seq on the retina of non-human primates with diabetes mellitus, and identified cell-type-specific molecular changes of the six major cell types. By identifying the ligand-receptor expression patterns among different cells, we established the interactome of the whole retina. The data showed that TNF-α signal mediated the activation of microglia through an autocrine manner. And we found TGFß2, which was upregulated in cone dramatically by hyperglycemia, inhibited microglia activation at the early stage of diabetic retinopathy. In summary, our study is the first to profile cell-specific molecular changes and the cell-cell interactome of retina under diabetes mellitus, paving a way to dissect the cellular and molecular mechanisms underlying early-stage diabetic retinopathy.

13.
Invest Ophthalmol Vis Sci ; 62(3): 30, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33749721

RESUMEN

Purpose: This study aims to reveal retinal abnormities in a spontaneous diabetic nonhuman primate model and explore the mechanism of featured injuries. Methods: Twenty-eight cynomolgus monkeys were identified to suffer from spontaneous type 2 diabetes from a colony of more than eight-hundred aged monkeys, and twenty-six age-matched ones were chosen as controls. Their blood biochemistry profiles were determined and retinal changes were examined by multimodal imaging, hematoxylin and eosin staining, and immunofluorescence. Retinal pigment epithelium (RPE) cells were further investigated by RNA sequencing and computational analyses. Results: These diabetic monkeys were characterized by early retinal vascular and neural damage and dyslipidemia. The typical acellular capillaries and pericyte ghost were found in the diabetic retina, which also exhibited reduced retinal nerve fiber layer thickness compared to controls (all P < 0.05). Of note, distinct sub-RPE drusenoid lesions were extensively observed in these diabetic monkeys (46.43% vs. 7.69%), and complements including C3 and C5b-9 were deposited in these lesions. RNA-seq analysis revealed complement activation, AGE/RAGE activation and inflammatory response in diabetic RPE cells. Consistently, the plasma C3 and C4 were particularly increased in the diabetic monkeys with drusenoid lesions (P = 0.028 and 0.029). Conclusions: The spontaneous type 2 diabetic monkeys featured with early-stage retinopathy including not only typical vascular and neural damage but also a distinct sub-RPE deposition. The complement activation of RPE cells in response to hyperglycemia might contribute to the deposition, revealing an unrecognized role of RPE cells in the early-stage pathological process of diabetic retinopathy.


Asunto(s)
Complemento C3/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Retinopatía Diabética/metabolismo , Modelos Animales de Enfermedad , Epitelio Pigmentado de la Retina/metabolismo , Animales , Activación de Complemento , Diabetes Mellitus Tipo 2 , Retinopatía Diabética/diagnóstico , Dislipidemias/diagnóstico , Hiperglucemia/diagnóstico , Macaca fascicularis , Imagen Multimodal , Drusas Retinianas/diagnóstico , Epitelio Pigmentado de la Retina/patología , Vasos Retinianos/patología
14.
Nat Commun ; 11(1): 5148, 2020 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-33051455

RESUMEN

The differences in transcription start sites (TSS) and transcription end sites (TES) among gene isoforms can affect the stability, localization, and translation efficiency of mRNA. Gene isoforms allow a single gene diverse functions across different cell types, and isoform dynamics allow different functions over time. However, methods to efficiently identify and quantify RNA isoforms genome-wide in single cells are still lacking. Here, we introduce single cell RNA Cap And Tail sequencing (scRCAT-seq), a method to demarcate the boundaries of isoforms based on short-read sequencing, with higher efficiency and lower cost than existing long-read sequencing methods. In conjunction with machine learning algorithms, scRCAT-seq demarcates RNA transcripts with unprecedented accuracy. We identified hundreds of previously uncharacterized transcripts and thousands of alternative transcripts for known genes, revealed cell-type specific isoforms for various cell types across different species, and generated a cell atlas of isoform dynamics during the development of retinal cones.


Asunto(s)
Caperuzas de ARN/genética , Isoformas de ARN/genética , Análisis de Secuencia de ARN/métodos , Transcripción Genética , Humanos , Análisis de Secuencia de ARN/economía , Análisis de la Célula Individual , Especificidad de la Especie , Sitio de Iniciación de la Transcripción
15.
J Cell Mol Med ; 24(21): 12789-12798, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32985079

RESUMEN

In this study, a new water and alkaline-soluble polysaccharide (ALP), with an average molecular weight of 6.63 × 104  Da, was successfully purified from the rhizomes of Atractylodes lancea. GC analysis demonstrated that ALP was a kind of glucan. The effect of the ALP on the interaction between E-selectin and sialyl Lewis X (sLex ) was examined in human osteosarcoma U-2 OS cells. It was obvious that the expression of sLex antigen on the surface of U-2 OS cells was visible under fluorescence microscopy. The addition of ALP (0.5, 1 and 2 mg/mL) resulted in a marked inhibition on the adhesion, migration and invasion of U-2 OS cells to human umbilical vein endothelial cells (HUVECs), which was achieved by the decreased sLex expression on U-2 OS cells. Additionally, the induction of apoptosis can be observed in U-2 OS cells following ALP treatment using TUNEL staining and Annexin V-FITC/PI double-staining analysis on flow cytometry. In conclusion, these results indicated that ALP exerted anti-metastatic activity towards osteosarcoma cells via inhibition of sLex /E-selectin binding, which suggested that ALP could be a potent agent for human osteosarcoma intervention.


Asunto(s)
Atractylodes/química , Selectina E/metabolismo , Osteosarcoma/patología , Polisacáridos/farmacología , Antígeno Sialil Lewis X/metabolismo , Apoptosis/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Movimiento Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Monosacáridos/análisis , Metástasis de la Neoplasia , Polisacáridos/aislamiento & purificación , Unión Proteica/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología
16.
Proteomics ; 20(13): e1900271, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32223079

RESUMEN

In recent years, the emergence of single-cell omics technologies, which can profile genomics, transcriptomics, epigenomics, and proteomics, has provided unprecedented insights into characteristics of cancer, enabling higher resolution and accuracy to decipher the cellular and molecular mechanisms relating to tumorigenesis, evolution, metastasis, and immune responses. Single-cell multi-omics technologies, which are developed based on the combination of multiple single-cell mono-omics technologies, can simultaneously analyze RNA expression, single nucleotide polymorphism, epigenetic modification, or protein abundance, enabling the in-depth understanding of gene expression regulatory mechanisms. In this review, the state-of-the-art single-cell multi-omics technologies are summarized and the prospects of their application in cancer biology are discussed.


Asunto(s)
Metabolómica , Neoplasias , Epigenómica , Genómica , Humanos , Estudios Prospectivos , Proteómica
17.
Methods Mol Biol ; 1979: 363-377, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31028648

RESUMEN

Single-cell transcriptome and single-cell methylome analysis have successfully revealed the heterogeneity in transcriptome and DNA methylome between single cells, and have become powerful tools to understand the dynamics of transcriptome and DNA methylome during the complicated biological processes, such as differentiation and carcinogenesis.Inspired by the success of using these single-cell -omics methods to understand the regulation of a particular "-ome," more interests have been put on elucidating the regulatory relationship among multiple-omics at single-cell resolution. The simultaneous profiling of multiple-omics from the same single cell would provide us the ultimate power to understand the relationship among different "-omes," but this idea is not materialized for decades due to difficulties to assay extremely tiny amount of DNA or RNA in a single cell.To address this technical challenge, we have recently developed a novel method named scMT-seq that can simultaneously profile both DNA methylome and RNA transcriptome from the same cell. This method enabled us to measure, from a single cell, the DNA methylation status of the most informative 0.5-1 million CpG sites and mRNA level of 10,000 genes, of which 3200 genes can be further analyzed with both promoter DNA methylation and RNA transcription. Using the scMT-seq data, we have successfully shown the regulatory relationship between DNA methylation and transcriptional level in a single dorsal root ganglion neuron (Hu et al., Genome Biol 17:88, 2016). We believe the scMT-seq would be a powerful technique to uncover the regulatory mechanism between transcription and DNA methylation, and would be of wide interest beyond the epigenetics community.


Asunto(s)
Metilación de ADN , Epigenómica/métodos , Perfilación de la Expresión Génica/métodos , ARN Mensajero/genética , Análisis de la Célula Individual/métodos , Animales , Islas de CpG , ADN/genética , Epigénesis Genética , Humanos , Reacción en Cadena de la Polimerasa/métodos , Análisis de Secuencia de ARN/métodos , Programas Informáticos , Transcriptoma
18.
Life Sci ; 228: 258-265, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-30953645

RESUMEN

Diabetes is an independent risk factor for knee osteoarthritis (OA), and hyperglycaemia-induced inflammation is considered to play an important role in their connection. The Toll-like receptor 4 (TLR4) regulates inflammatory responses in several pathological conditions including diabetes and OA. However, its role in diabetes-associated OA is poorly understood. In this study, we found that TLR4 expression was higher in OA cartilage from patients with type 2 diabetes mellitus (T2DM) than that from non-T2DM patients. Similarly, its expression was induced in primary mouse chondrocytes treated with high glucose, which suggests that TLR4 upregulation in T2DM-associated OA cartilage may originate from hyperglycaemia stimulation. We further discovered that TLR4 promoted high glucose-induced catabolic and inflammatory responses in chondrocytes, and mechanistically, these effects could be explained by the exacerbated activation of the transcription factor nuclear factor kappa B (NF-κB) pathway, since its inhibition by Bay 11-7082 abrogated TLR4 effects on high glucose-treated chondrocytes. Taken together, these findings may reveal a promotive role of TLR4 in regulating hyperglycaemia-induced catabolism and inflammation in T2DM-associated OA, and also implicate that TLR4 inhibition might be of therapeutic significance in treating T2DM-associated OA.


Asunto(s)
Condrocitos/inmunología , Diabetes Mellitus Tipo 2/inmunología , Glucosa/inmunología , FN-kappa B/inmunología , Osteoartritis/inmunología , Receptor Toll-Like 4/inmunología , Animales , Células Cultivadas , Condrocitos/patología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Humanos , Inflamación/complicaciones , Inflamación/inmunología , Inflamación/patología , Masculino , Ratones Endogámicos C57BL , Osteoartritis/complicaciones , Osteoartritis/patología
19.
Graefes Arch Clin Exp Ophthalmol ; 257(3): 455-463, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30684011

RESUMEN

PURPOSE: The aim of this study was to identify the morphological features of the retina and choroid in Macaca fascicularis of different ages using multimodal imaging. METHODS: A total of 27 Macaca fascicularis with no ocular diseases were studied (mean age, 104.2 months; range, 1.2-223.6 months). Multimodal imaging was obtained from each subject. The morphological features were compared within four subgroups according to age. RESULTS: On spectrum-domain optical coherence tomography (SD-OCT), four hyper-reflective bands could be observed in the outer retina in non-infant macaques (21/21, 100%), while the interdigitation zone could not be observed in the six infant macaques. A narrow hypo-reflective band just posterior to the retinal pigment epithelium (RPE) was noted in most eyes (25/27, 92.6%). The choroidal-scleral junction (CSJ) was visible in 83.3% of infants but only in 12.5% of adults and 14.3% of the geriatric population, and it could not be seen in juveniles. There was a significant difference in CSJ visibility between the infant group and the other three groups (P < 0.001). Tessellated fundus, in which the choroidal vessels are visible through the retina, could be observed clearly with near-infrared reflectance imaging (NIR). Some granular spots were noted in juveniles, and they accumulated dramatically with age, but were absent in infants. CONCLUSION: Notable morphological features can be observed in the Macaca fascicularis subjects using multimodal imaging, and these features vary distinctly according to their age. It is important to note that infant macaques had no interdigitation zone, while the other macaques had no visible CSJ but did have well-defined choroidal capillaries. Age and the features should be considered seriously in future animal studies.


Asunto(s)
Envejecimiento , Coroides/diagnóstico por imagen , Imagen Multimodal , Retina/diagnóstico por imagen , Animales , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Macaca fascicularis , Modelos Animales , Valores de Referencia , Reproducibilidad de los Resultados , Tomografía de Coherencia Óptica/métodos , Pruebas del Campo Visual
20.
Environ Sci Pollut Res Int ; 26(3): 2314-2327, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30465245

RESUMEN

The microscale environment is a very important human-scale outdoor spatial unit. Aimed at investigating the effects of microscale land-cover type and pattern on levels of PM10 and PM2.5, we monitored PM10 and PM2.5 concentrations among different land-cover type and pattern sites through field measurements, during four seasons (December 2015 to November 2016) in Beijing, China. Differences of daily PM10 and PM2.5 concentrations among seven typical land-cover types, and correlations between daily two-sized PM levels and various microscale land-cover patterns as explained by landscape metrics were analyzed. Results show that concentrations of the two-sized particles had stable daytime and seasonal trends. During the four seasons, there were various differences in daily PM10 and PM2.5 levels among the seven land-cover types. Overall, bare soil always had the highest daily PM10 level, whereas high canopy density vegetation and water bodies had low levels. Maximum PM2.5 levels were always found in high canopy density vegetation. Moderate canopy density vegetation and water bodies had lower concentrations. Correlations between different landscape metrics and daily levels of two-sized PM varied by season. Metrics reflecting the dominance and distribution of land-cover classifications had closer relationships with particle concentrations in the microscale environment. The patterns of pavement along with low and moderate canopy density vegetation had a greater impact on PM10 level. The responses of PM2.5 level to patterns of building and low and moderate canopy density vegetation were sensitive. Reasonable design of land-cover structure would be conducive to ameliorate air particle concentrations in the microscale environment. Graphical abstract ᅟ.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Material Particulado/análisis , Beijing , Tamaño de la Partícula , Estaciones del Año
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