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1.
Food Res Int ; 186: 114350, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729698

RESUMEN

In this study, three types of ß-sitosterol-based oleogels (ß-sitosterol + Î³-oryzanol oleogels, ß-sitosterol + lecithin, oleogels and ß-sitosterol + monostearate oleogels), loaded with astaxanthin, were employed as the oil phase to create oleogel-based emulsions (SO, SL, and SM) using high-pressure homogenization. The microstructure revealed that fine-scale crystals were dispersed within the oil phase of the droplets in the ß-sitosterol oleogel-based emulsion. The bioaccessibility of astaxanthin was found to be 58.13 %, 51.24 %, 36.57 %, and 45.72 % for SM, SL, SO, and the control group, respectively. Interestingly, the release of fatty acids was positively correlated with the availability of astaxanthin (P = 0.981). Further analysis of FFAs release and kinetics indicated that the structural strength of the oil-phase in the emulsions influenced the degree and rate of lipolysis. Additionally, the micellar fraction analysis suggested that the nature and composition of the oleogelators in SM and SL also impacted lipolysis and the bioaccessibility of astaxanthin. Furthermore, interfacial binding of lipase and isothermal titration calorimetry (ITC) measurements revealed that the oleogel network within the oil phase of the emulsion acted as a physical barrier, hindering the interaction between lipase and lipid. Overall, ß-sitosterol oleogel-based emulsions offer a versatile platform for delivering hydrophobic molecules, enhancing the bioavailability of active compounds, and achieving sustained release.


Asunto(s)
Emulsiones , Compuestos Orgánicos , Sitoesteroles , Xantófilas , Sitoesteroles/química , Xantófilas/química , Compuestos Orgánicos/química , Disponibilidad Biológica , Lipólisis , Lecitinas/química , Ácidos Grasos/química , Fenilpropionatos
2.
BMC Pediatr ; 24(1): 332, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745118

RESUMEN

BACKGROUND: Recent studies have found that total immunoglobulin E (IgE) and allergen-specific IgE were associated with some metabolic diseases. However, the role of IgE in metabolism among adolescents is still unclear. Herein, this study aims to investigate the associations of serum total IgE and allergen-specific IgE with insulin resistance (IR) in adolescents, in order to provide some reference for the prevention and treatment of metabolic diseases in a young age. METHODS: Data of 870 adolescents were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005-2006 in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses were utilized to screen covariates and explore the relationships of serum total IgE and allergen-specific IgE with IR. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). In addition, these relationships were also assessed in subgroups of allergy history, asthma history, and number of allergens. RESULTS: Among eligible adolescents, 168 had IR. No significant association between serum total IgE level and IR was found. However, adolescents with higher level of allergen-specific IgE to rye grass [OR = 0.47, 95%CI: (0.25-0.91)], white oak [OR = 0.57, 95%CI: (0.37-0.88)], or peanut [OR = 0.38, 95%CI: (0.15-0.97)] seemed to have lower odds of IR, whereas those had higher level of shrimp-specific IgE [OR = 2.65, 95%CI: (1.21-5.84)] have increased odds of IR. In addition, these associations between allergen-specific IgE and IR were also discovered in adolescents who had allergy history or asthma history, or had different numbers of allergens. CONCLUSION: Paying attention to different allergens in adolescents may be important in the early identification of IR among this high-risk population. The study results relatively provided some reference for further exploration on IR prevention.


Asunto(s)
Alérgenos , Inmunoglobulina E , Resistencia a la Insulina , Encuestas Nutricionales , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Adolescente , Masculino , Femenino , Estudios Transversales , Alérgenos/inmunología , Modelos Logísticos , Niño , Asma/inmunología , Asma/sangre
3.
Expert Opin Drug Metab Toxicol ; : 1-21, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38706437

RESUMEN

INTRODUCTION: Carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are among the most abundant hydrolases in humans, catalyzing the metabolism of numerous clinically important medications, such as methylphenidate and clopidogrel. The large interindividual variability in the expression and activity of CES1 and CES2 affects the pharmacokinetics (PK) and pharmacodynamics (PD) of substrate drugs. AREAS COVERED: This review provides an up-to-date overview of CES expression and activity regulations and examines their impact on the PK and PD of CES substrate drugs. The literature search was conducted on PubMed from inception to January 2024. EXPERT OPINION: Current research revealed modest associations of CES genetic polymorphisms with drug exposure and response. Beyond genomic polymorphisms, transcriptional and posttranslational regulations can also significantly affect CES expression and activity and consequently alter PK and PD. Recent advances in plasma biomarkers of drug-metabolizing enzymes encourage the research of plasma protein and metabolite biomarkers for CES1 and CES2, which could lead to the establishment of precision pharmacotherapy regimens for drugs metabolized by CESs. Moreover, our understanding of tissue-specific expression and substrate selectivity of CES1 and CES2 has shed light on improving the design of CES1- and CES2-activated prodrugs.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38676558

RESUMEN

AIM: Knowledge of how circadian rhythm influences brain health remains limited. We aimed to investigate the associations of accelerometer-measured circadian rest-activity rhythm (CRAR) with incident dementia, cognitive dysfunction, and structural brain abnormalities in the general population and underlying biological mechanisms. METHODS: Fifty-seven thousand five hundred and two participants aged over 60 years with accelerometer data were included to investigate the association of CRAR with incidental dementia. Non-parametric CRAR parameters were utilized, including activity level during active periods of the day (M10), activity level during rest periods of the day (L5), and the relative difference between the M10 and L5 (relative amplitude, RA). Associations of CRAR with cognitive dysfunction and brain structure were studied in a subset of participants. Neuroimaging-transcriptomics analysis was utilized to identify the underlying molecular mechanisms. RESULTS: Over 6.86 (4.94-8.78) years of follow-up, 494 participants developed dementia. The risk of incident dementia was associated with decreasing M10 (hazard ratio [HR] 1.45; 95% conference interval [CI], 1.28-1.64) and RA (HR 1.37; 95% CI, 1.28-1.64), increasing L5 (HR 1.14, 95% CI 1.07-1.21) and advanced L5 onset time (HR 1.12; 95% CI, 1.02-1.23). The detrimental associations were exacerbated by APOE ε4 status and age (>65 years). Decreased RA was associated with lower processing speed (Beta -0.04; SE 0.011), predominantly mediated by abnormalities in subcortical regions and white matter microstructure. The genes underlying CRAR-related brain regional structure variation were enriched for synaptic function. CONCLUSIONS: Our study underscores the potential of intervention targeting at maintaining a healthy CRAR pattern to prevent dementia risk.

6.
Sheng Wu Gong Cheng Xue Bao ; 40(4): 1237-1250, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38658160

RESUMEN

The CRISPR/Cas9 gene editing technology has proven to be valuable in crop breeding applications. Understanding and mastering this technology will provide a strong foundation for students majoring in biology, agronomy, and related fields to engage in scientific research and work. To incorporate CRISPR/Cas9 technology into experimental teaching courses at colleges, an innovative teaching experiment entitled "Enhancing the resistance of rice plants to bacterial blight disease using CRISPR/Cas9 technology" was designed. The experiment allows students to deepen their understanding of the basic principles of CRISPR/Cas technology, acquire proficiency in its protocol, and learn to apply the technology for targeted molecular breeding of rice. It not only expands students' knowledge and skills, but also promotes the reform and innovation of experimental teaching methods.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Oryza , Fitomejoramiento , Oryza/genética , Edición Génica/métodos , Enseñanza , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Plantas Modificadas Genéticamente/genética
7.
Sci Rep ; 14(1): 9662, 2024 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671173

RESUMEN

Calendula officinalis L.is a versatile medicinal plant with numerous applications in various fields. However, its chloroplast genome structure, features, phylogeny, and patterns of evolution and mutation remain largely unexplored. This study examines the chloroplast genome, phylogeny, codon usage bias, and divergence time of C. officinalis, enhancing our understanding of its evolution and adaptation. The chloroplast genome of C. officinalis is a 150,465 bp circular molecule with a G + C content of 37.75% and comprises 131 genes. Phylogenetic analysis revealed a close relationship between C. officinalis, C. arvensis, and Osteospermum ecklonis. A key finding is the similarity in codon usage bias among these species, which, coupled with the divergence time analysis, supports their close phylogenetic proximity. This similarity in codon preference and divergence times underscores a parallel evolutionary adaptation journey for these species, highlighting the intricate interplay between genetic evolution and environmental adaptation in the Asteraceae family. Moreover unique evolutionary features in C. officinalis, possibly associated with certain genes were identified, laying a foundation for future research into the genetic diversity and medicinal value of C. officinalis.


Asunto(s)
Calendula , Evolución Molecular , Genoma del Cloroplasto , Filogenia , Plantas Medicinales , Plantas Medicinales/genética , Calendula/genética , Uso de Codones , Composición de Base , Cloroplastos/genética
8.
Molecules ; 29(6)2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38543018

RESUMEN

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1ß and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.


Asunto(s)
Antioxidantes , Arbutina/análogos & derivados , Ácidos Cafeicos , Galactosa , Humanos , Ratones , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Galactosa/efectos adversos , Factor 2 Relacionado con NF-E2/metabolismo , Sirtuina 1/metabolismo , Ácido Clorogénico/farmacología , Simulación del Acoplamiento Molecular , Ácido Quínico/farmacología , Estrés Oxidativo , Transducción de Señal ,
9.
Pancreas ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38530976

RESUMEN

OBJECTIVES: Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on caerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood. METHODS: A caerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of caerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules. RESULTS: We found that exosomes derived from caerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in caerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells. CONCLUSIONS: Exosomes derived from caerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.

10.
Transl Psychiatry ; 14(1): 150, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38499546

RESUMEN

There is an emerging potential for digital assessment of depression. In this study, Chinese patients with major depressive disorder (MDD) and controls underwent a week of multimodal measurement including actigraphy and app-based measures (D-MOMO) to record rest-activity, facial expression, voice, and mood states. Seven machine-learning models (Random Forest [RF], Logistic regression [LR], Support vector machine [SVM], K-Nearest Neighbors [KNN], Decision tree [DT], Naive Bayes [NB], and Artificial Neural Networks [ANN]) with leave-one-out cross-validation were applied to detect lifetime diagnosis of MDD and non-remission status. Eighty MDD subjects and 76 age- and sex-matched controls completed the actigraphy, while 61 MDD subjects and 47 controls completed the app-based assessment. MDD subjects had lower mobile time (P = 0.006), later sleep midpoint (P = 0.047) and Acrophase (P = 0.024) than controls. For app measurement, MDD subjects had more frequent brow lowering (P = 0.023), less lip corner pulling (P = 0.007), higher pause variability (P = 0.046), more frequent self-reference (P = 0.024) and negative emotion words (P = 0.002), lower articulation rate (P < 0.001) and happiness level (P < 0.001) than controls. With the fusion of all digital modalities, the predictive performance (F1-score) of ANN for a lifetime diagnosis of MDD was 0.81 and 0.70 for non-remission status when combined with the HADS-D item score, respectively. Multimodal digital measurement is a feasible diagnostic tool for depression in Chinese. A combination of multimodal measurement and machine-learning approach has enhanced the performance of digital markers in phenotyping and diagnosis of MDD.


Asunto(s)
Trastorno Depresivo Mayor , Aplicaciones Móviles , Humanos , Trastorno Depresivo Mayor/diagnóstico , Teorema de Bayes , Actigrafía , Depresión/diagnóstico , Hong Kong
11.
Plant Foods Hum Nutr ; 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38441843

RESUMEN

The flowers of Edgeworthia gardneri are used as herbal tea and medicine to treat various metabolic diseases including hyperglycemia, hypertension, and hyperlipidemia. This paper investigate the chemical constituents and biological activities of ethanolic extract and its different fractions from E. gardneri flowers. Firstly, the E. gardneri flowers was extracted by ethanol-aqueous solution to obtain crude extract (CE), which was subsequently fractionated by different polar organic solution to yield precipitated crystal (PC), dichloromethane (DCF), ethyl acetate (EAF), n-butanol (n-BuF), and residue water (RWF) fractions. UHPLC-ESI-HRMS/MS analysis resulted in the identification of 25 compounds, and the main compounds were flavonoids and coumarins. The precipitated crystal fraction showed the highest phenolic and flavonoid contents with 344.4 ± 3.38 mg GAE/g extract and 305.86 ± 0.87 mg RE/g extract. The EAF had the strongest antioxidant capacity and inhibitory effect on α-glucosidase and pancreatic lipase with IC50 values of 126.459 ± 7.82 and 23.16 ± 0.79 µg/mL. Besides, both PC and EAF significantly regulated the glucose and lipid metabolism disorders by increasing glucose consumption and reducing TG levels in HepG2 cells. Molecular docking results suggested that kaempferol-3-O-glucoside and tiliroside had good binding ability with enzymes, indicating that they may be potential α-glucosidase and pancreatic lipase inhibitors. Therefore, the E. gardneri flowers could be served as a bioactive agent for the regulation of metabolic disorders.

12.
Bioorg Med Chem ; 103: 117685, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38503009

RESUMEN

Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along with three known compounds (3-5), were obtained by LC-MS guided isolation. The new compounds were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations, and the biosynthetic pathway was proposed on the bias of bioinformatic analysis and 13C isotope labeling evidence. This is the first report to access cryptic fungi secondary metabolites by inactivating global regulator LaeA and may provide a new approach to discovering new secondary metabolites by such genetic manipulation.


Asunto(s)
Aspergillus , Hongos , Aspergillus/genética , Aspergillus/metabolismo , Piperazinas/farmacología , Piperazinas/metabolismo
13.
Opt Express ; 32(5): 7044-7052, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38439395

RESUMEN

The carrier transport performances play key roles in the photoelectric conversion efficiency for photovoltaic effect. Hence, the low carrier mobility and high photogenerated carrier recombination in ferroelectric materials depress the separation of carriers. This work designs a ferroelectric polarization-interface-free PN junction composed with P-type semiconductor BiFeO3 (BFO) derived from the variable valence of Fe and N-type semiconductor BiFe0.98Ti0.02O3 (BFTO) through Ti donor doping. The integration of the ferroelectricity decides the PN junction without polarization coupling like the traditional heterojunctions but only existing carrier distribution differential at the interface. The carrier recombination in PN junction is significantly reduced due to the driving force of the built-in electric field and the existence of depletion layer, thereby enhancing the switching current 3 times higher than that of the single ferroelectric films. Meanwhile, the carrier separation at the interface is significantly engineered by the polarization, with open circuit voltage and short circuit current of photovoltaic effect increased obviously. This work provides an alternative strategy to regulate bulk ferroelectric photovoltaic effects by carrier transport engineering in the polarization-interface-free ferroelectric PN junction.

14.
Diabetes Metab ; 50(3): 101526, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38458351

RESUMEN

AIM: This study aimed to investigate the association of social isolation, loneliness, and their trajectory with the risk of developing type 2 diabetes mellitus (T2DM) across genetic risk. METHODS: We included 439,337 participants (mean age 56.3 ± 8.1 years) enrolled in the UK Biobank study who were followed up until May 31, 2021. Social isolation and loneliness were self-reported and were further categorized into never, transient, incident, and persistent patterns. RESULTS: During a median follow-up of 12.7 years, 15,258 incident T2DM cases were documented. Social isolation (versus no social isolation: hazard ratio (HR) 95 % confidence interval (CI) 1.04 [1.00;1.09]) and loneliness (versus no loneliness: 1.26 [1.19;1.34]) were associated with an increased T2DM risk, independent of the genetic risk for T2DM. The interactions existed between social isolation and loneliness (Pinteraction < 0.05); the increased T2DM risk associated with social isolation was only significant among participants without loneliness. In the longitudinal analysis, only persistent social isolation (versus never social isolation: 1.22 [1.02;1.45]) was associated with an increased T2DM risk, whereas incident loneliness (versus never loneliness: 1.95 [1.40;2.71]) and persistent loneliness (2.00 [1.31;3.04]) were associated with higher T2DM risks. CONCLUSION: Social isolation and loneliness, especially their persistent pattern, were independently associated with an increased incident T2DM risk, irrespective of an individual's genetic risk. Loneliness modified the association between social isolation and incident T2DM.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38444566

RESUMEN

Myasthenia gravis (MG) is an autoimmune disease which can impact pregnancy. We describe a transient neonatal myasthenia gravis (TNMG) born to an asymptomatic mother aged 26. The newborn presented cyanosis and generalized muscular weakness quickly after birth. Nasal continuous positive airway pressure (nCPAP) ventilation was performed immediately. On day 3, detailed family history showed that the neonate's 50-year-old maternal grandmother was diagnosed as ocular MG at the age of 40. Ryanodine receptor calcium release channel antibody (RyR-Ab) and acetylcholine receptor antibody (AChR-Ab) tested on day 5 were positive. However, neostigmine tests were negative for the neonate. Intravenous immunoglobulin (IVIG) and oral pyridostigmine were administered. The infant was weaned from the ventilator on day 7. On day 10, the neonate's asymptomatic mother was confirmed to have positive AChR-Ab either. The neonate regained the capability of bottle feeding on day 17 and discharged on day 26. Asymptomatic pregnant women with MG family history can also deliver infants who develop TNMG. Testing AChR antibodies in pregnant women with a family history of MG should be necessary as TNMG was a life-threatening disease. With timely diagnosis and accurate treatment, TNMG can be effectively relieved.

16.
Nat Commun ; 15(1): 2790, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555308

RESUMEN

Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data.


Asunto(s)
Ácidos Nucleicos Libres de Células , Metilación de ADN , Metilación de ADN/genética , Secuenciación Completa del Genoma/métodos , Sulfitos , Ácidos Nucleicos Libres de Células/genética , Análisis de Secuencia de ADN/métodos , Secuenciación de Nucleótidos de Alto Rendimiento
18.
Heliyon ; 10(3): e25166, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38327444

RESUMEN

Background: Assessment and validation of endothelial-mesenchymal transition (EndoMT) in the retinal endothelium of patients with proliferative diabetic retinopathy (PDR) at the level of retinal and vitreous specimens, and preliminary discussion of its regulatory mechanisms. Methods: Transcriptome sequencing profiles of CD31+ cells from 9 retinal fibrovascular mem-branes (FVMs) and 4 postmortem retinas were downloaded from GEO databases to analyze EndoMT-related differentially expressed genes (DEGs). Then, 42 PDR patients and 34 idiopathic macular holes (IMH) patients were enrolled as the PDR and control groups, respectively. Vitreous humor (VH) samples were collected, and the expression of EndoMT-related proteins was quantified by enzyme-linked immunosorbent assay. Results: A total of 5845 DEGs were identified, and we subsequently focused on the analysis of 24 EndoMT-related marker genes, including the trigger of EndoMT, endothelial genes, mesenchymal genes, transcription factors, inflammatory factors, and autophagy markers. Six of these genes were selected for protein assay validation in VH, showing increased mesenchymal marker (type I collagen α 2 chain, COL1A2) and decreased endothelial marker (VE-cadherin, CDH5) accompanied by increased TGFß, IL-1ß, LC3B and P62 in PDR patients. In addition, anti-VEGF therapy could enhance EndoMT-related phenotypes. Conclusions: EndoMT may underlie the pathogenesis of PDR, and the induction and regulation correlate with autophagy defects and the inflammatory response.

19.
Nucleic Acids Res ; 52(7): 3654-3666, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38300758

RESUMEN

DNA Methylation is a significant epigenetic modification that can modulate chromosome states, but its role in orchestrating chromosome organization has not been well elucidated. Here we systematically assessed the effects of DNA Methylation on chromosome organization with a multi-omics strategy to capture DNA Methylation and high-order chromosome interaction simultaneously on mouse embryonic stem cells with DNA methylation dioxygenase Tet triple knock-out (Tet-TKO). Globally, upon Tet-TKO, we observed weakened compartmentalization, corresponding to decreased methylation differences between CpG island (CGI) rich and poor domains. Tet-TKO could also induce hypermethylation for the CTCF binding peaks in TAD boundaries and chromatin loop anchors. Accordingly, CTCF peak generally weakened upon Tet-TKO, which results in weakened TAD structure and depletion of long-range chromatin loops. Genes that lost enhancer-promoter looping upon Tet-TKO showed DNA hypermethylation in their gene bodies, which may compensate for the disruption of gene expression. We also observed distinct effects of Tet1 and Tet2 on chromatin organization and increased DNA methylation correlation on spatially interacted fragments upon Tet inactivation. Our work showed the broad effects of Tet inactivation and DNA methylation dynamics on chromosome organization.


Asunto(s)
Cromatina , Islas de CpG , Metilación de ADN , Proteínas de Unión al ADN , Dioxigenasas , Proteínas Proto-Oncogénicas , Animales , Ratones , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Dioxigenasas/metabolismo , Dioxigenasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Cromatina/metabolismo , Cromatina/genética , Islas de CpG/genética , Células Madre Embrionarias de Ratones/metabolismo , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Epigénesis Genética , Regiones Promotoras Genéticas , Cromosomas/genética
20.
Foods ; 13(3)2024 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-38338634

RESUMEN

Maintaining the vibrant color of fruit is a longstanding challenge in fruit and vegetable preservation. Chitosan and selenium, known for their protective and antioxidant properties, have been applied to preserve these produce. This study aimed to investigate the influence of selenium-chitosan treatment (comprising 25 mg L-1 selenium and 1.0% chitosan) on the color of "Red Globe" grapes and to analyze the relative expression of genes associated with anthocyanin synthesis enzymes (VvCHS, VvCHI, VvF3H, VvF3'H, VvF3'5'H, VvDFR, VvLDOX, VvUFGT, VvOMT, Vv5GT, and VvGST) using RT-qPCR. Our goal was to uncover the regulatory mechanisms governing grape color. Comparing various treatments, we observed that selenium-chitosan treatment had a significant effect in reducing decay, maintaining the soluble solids content of grape flesh, and preserving the vivid color of grape. This research indicated that selenium-chitosan treatment slowed down browning and prevented the reduction in total phenolic, flavonoids, and anthocyanin in the grape. Moreover, gene expression analysis revealed that selenium-chitosan treatment increased the expression of VvCHS, VvF3H, VvF'3'H, VvLDOX, and Vv5GT, while also stabilized the expression of VvCHI, VvF3'H, and VvDFR in grape skins. These findings shed light on the potential mechanism by which selenium-chitosan impacts grape color. This study established a theoretical foundation for investigating the molecular mechanisms behind selenium-chitosan's ability to slow down grape browning and provides a novel approach to enhancing fruit and vegetable preservation techniques.

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