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1.
Endocrine ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782862

RESUMEN

BACKGROUND: Metabolic diseases are associated with thyroid disorders. Insulin resistance is the common pathological basis of metabolic diseases. We explored the relationship between the triglyceride-glucose (TyG) index, a simple insulin-resistance marker, and thyroid disorders. METHODS: Eligible TIDE (Thyroid Diseases, Iodine Status and Diabetes Epidemiology) subjects (n = 47,710) were screened with inclusion/exclusion criteria. Thyroid disorder prevalence among different TyG index groups was stratified by sex. Logistic regression evaluated the correlation between the TyG index and thyroid disorders. Multiple linear regression evaluated the association between the TyG index and TSH. Additionally, two-sample Mendelian randomization (MR) using published genome-wide association study data evaluated causality in the association between the TyG index and TSH. RESULTS: Men and women with greater TyG indices had a significantly greater prevalence of thyroid disorders than individuals with the lowest quartile (Q1) of TyG index (p < 0.05). Following adjustment for confounding factors, we observed that a greater TyG index significantly increased the risk of subclinical hypothyroidism in men and women (men: Q2: odds ratio (OR) [95% confidence interval (CI)] = 1.22 [1.07-1.38], p = 0.002; Q3: OR [95% CI] = 1.28 [1.12-1.45], p < 0.001; Q4: OR [95% CI] = 1.29 [1.12-1.50], p = 0.001; women: Q2: OR [95% CI] = 1.25 [1.12-1.39], p < 0.001; Q3: OR [95% CI] = 1.47 [1.31-1.64], p < 0.001; Q4: OR [95% CI] = 1.61 [1.43-1.82], p < 0.001). Only among women was the highest TyG index quartile associated with hypothyroidism (OR [95% CI] = 1.70 [1.15-2.50], p = 0.007). Additionally, in men, the association exists only in the more than adequate iodine intake population. In women, the relationship between the TyG index and thyroid disorders disappears after menopause. Furthermore, the TyG index exhibited a linear positive correlation with TSH levels. The MR analysis results revealed a causal relationship between a genetically determined greater TyG index and increased TSH (inverse-variance weighting (IVW): OR [95% CI] = 1.14 [1.02-1.28], p = 0.020); however, this causal relationship disappeared after adjusting for BMI in multivariable MR (MVMR) analysis (MVMR-IVW: OR 1.03, 95% CI 0.87-1.22, p = 0.739). CONCLUSIONS: A greater TyG index is associated with hypothyroidism and subclinical hypothyroidism and varies by sex and menopausal status. MR analysis demonstrated that the causal relationship between a genetically determined greater TyG index and elevated TSH levels is confounded or mediated by BMI.

2.
BMC Plant Biol ; 24(1): 258, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594637

RESUMEN

BACKGROUND: Weed control is essential for agricultural floor management in vineyards and the inter-row mulching is an eco-friendly practice to inhibit weed growth via filtering out photosynthetically active radiation. Besides weed suppression, inter-row mulching can influence grapevine growth and the accumulation of metabolites in grape berries. However, the complex interaction of multiple factors in the field challenges the understanding of molecular mechanisms on the regulated metabolites. In the current study, black geotextile inter-row mulch (M) was applied for two vintages (2016-2017) from anthesis to harvest. Metabolomics and transcriptomics analysis were conducted in two vintages, aiming to provide insights into metabolic and molecular responses of Cabernet Sauvignon grapes to M in a semi-arid climate. RESULTS: Upregulation of genes related to photosynthesis and heat shock proteins confirmed that M weakened the total light exposure and grapes suffered heat stress, resulting in lower sugar-acid ratio at harvest. Key genes responsible for enhancements in phenylalanine, glutamine, ornithine, arginine, and C6 alcohol concentrations, and the downward trend in ε-viniferin, anthocyanins, flavonols, terpenes, and norisoprenoids in M grapes were identified. In addition, several modules significantly correlated with the metabolic biomarkers through weighted correlation network analysis, and the potential key transcription factors regulating the above metabolites including VviGATA11, VviHSFA6B, and VviWRKY03 were also identified. CONCLUSION: This study provides a valuable overview of metabolic and transcriptomic responses of M grapes in semi-arid climates, which could facilitate understanding the complex regulatory network of metabolites in response to microclimate changes.


Asunto(s)
Vitis , Vino , Vitis/metabolismo , Transcriptoma , Antocianinas/metabolismo , Microclima , Granjas , Frutas , Vino/análisis
3.
Front Plant Sci ; 15: 1356799, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38533403

RESUMEN

Kolor is a teinturier grape cultivar, that accumulates flavonoids in the skin and pulp. However, the concentrations and proportions of flavonoids in Kolor skin and pulp differ, suggesting tissue specificity in teinturier grapes. Light conditions significantly influence the evolution of flavonoids. Moreover, studies on the mechanisms governing flavonoid accumulation in light response sensitivity of teinturier grapes are limited. In the three consecutive years of study, the exposure of Kolor clusters was altered by bagging from pre-veraison to harvest. QqQ/MS and RT‒qPCR wereused to determine the individual anthocyanin contents and the relative gene expression. There was a significant decrease in the total anthocyanins and flavonols in the Kolor berries, with flavonols showing greater sensitivity to bagging. Bagging did not exert a consistent impact on the flavan-3-ols in Kolor berries. The sensitivities of anthocyanins in Kolor skin and pulp differed under light exclusion conditions. The concentration of trihydroxy-substituted anthocyanins in the skin decreased, while the proportion of dihydroxy-substituted anthocyanins in the pulp significantly increased, but the anthocyanin concentration in the pulp did not change significantly after bagging. The contents of malvidins and quercetins in the skin, and myricetins and quercetins in the pulp, were significantly reduced after bagging. The expression of flavonoid synthesis genes in Kolor skin and pulp was tissue-specific. After bagging, UFGT expression increased in the pulp and decreased in the skin. In addition, LDOX, FLS-1, CHI-1, CHI-2, F3H-1, F3H-2, and MYB4a exhibited sensitive light responses in both the skin and pulp. This study offers new insights into the regulation of flavonoids in Kolor grapes under light exclusion conditions.

4.
Curr Issues Mol Biol ; 46(3): 2301-2319, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38534763

RESUMEN

Increases in litter size, which are influenced by ovulation, are responsible for between 74% and 96% of the economic value of genetic progress, which influences selection. For the selection and breeding of highly prolific goats, genetic mechanisms underlying variations in litter size should be elucidated. Here, we used single-nucleus RNA sequencing to analyze 44,605 single nuclei from the ovaries of polytocous and monotocous goats during the follicular phase. Utilizing known reference marker genes, we identified 10 ovarian cell types characterized by distinct gene expression profiles, transcription factor networks, and reciprocal interaction signatures. An in-depth analysis of the granulosa cells revealed three subtypes exhibiting distinct gene expression patterns and dynamic regulatory mechanisms. Further investigation of cell-type-specific prolificacy-associated transcriptional changes elucidated that "downregulation of apoptosis", "increased anabolism", and "upstream responsiveness to hormonal stimulation" are associated with prolificacy. This study provides a comprehensive understanding of the cell-type-specific mechanisms and regulatory networks in the goat ovary, providing insights into the molecular mechanisms underlying goat prolificacy. These findings establish a vital foundation for furthering understanding of the molecular mechanisms governing folliculogenesis and for improving the litter size in goats via molecular design breeding.

5.
Environ Sci Pollut Res Int ; 30(59): 123657-123678, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37991615

RESUMEN

As a new economic form that has emerged from the technological and digital revolution, the digital economy has great benefits to the green development of the economy, protection of the ecological environment, and improvement in social well-being. This study examines whether the digital economy affects the inclusive green growth (IGG). Measurement index system for the digital economy and IGG from 2013 to 2020 in China was constructed and the entropy evaluation method and super-efficiency epsilon-based measure (Super-EBM) model was used to evaluate them. We examined the direct effect, mediation effect, and spatial spillover effect of the digital economy on IGG using the basic regression model, mediating effect model, and the spatial Durbin model. Our results revealed that the development of the digital economy has clear regional differences. The role of digital economy on IGG has positive direct effects and positive spatial spillover effects. The digital economy affects IGG through industrial structure upgrading, so industrial structure upgrading has a significant intermediary effect. By comparing the coefficients, we found that the spatial spillover effects are stronger than the direct effects. Absorbing the spillover of the digital economy in surrounding areas is particularly important for promoting IGG. Heterogeneity analysis revealed that the digital economy is better for IGG and releases more digital dividends in eastern China. Finally, the research conclusions of this paper provide reference for the Chinese government to formulate relevant policies to deepen the integration of digital information technology and IGG, and promote the coordinated development of regional digital economy and IGG.


Asunto(s)
Ambiente , China , Ciudades , Desarrollo Económico , Entropía
6.
Org Lett ; 25(43): 7895-7899, 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37874766

RESUMEN

Herein, we report a Cu-catalyzed redox isomerization-reductive deuteration sequence, providing facile access to a range of α-deuterated amino acid esters featuring an Z-configured alkene moiety with high yields. The advantages of this sequence include mild conditions, broad substrate scope, and excellent stereoselectivity. This research also represents a rare example of the Z-selective redox isomerization of propargyl amines.

7.
J Nutr Biochem ; 117: 109351, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37087074

RESUMEN

Resveratrol (RES) is one of the best-known bioactive polyphenols that has received much attention in recent years because of its importance to anti-obesity. However, the exact mechanism underlying this effect and whether it can improve lipid metabolism by regulating the long-chain noncoding RNA (lncRNA) remains unclear. In this study, 24 healthy crossbred castrated boars were fed a basal diet (control) and a basal diet supplemented with 200 mg, 400 mg or 600 mg RES per Kilogram (kg) of feed for 41 d, respectively. We found that 400 mg/kg and 600 mg/kg RES-supplemented diet did not affect growth rate, but reduced significantly subcutaneous adipose thickness, carcass fat rate, greater dramatically the serum concentration of adiponectin and high-density lipoprotein in pigs. Further, we verified that RES could inhibit the formation and accumulation of lipid droplets by AdipoQ-AdipoR1-AMPKα and AdipoQ-AdipoR2-PPARα signal pathway in vivo and vitro (3T3-L1 preadipocytes). Transcriptome analyses found that 5 differently expressed (DE) lncRNAs and 77 mRNAs in subcutaneous adipose between control group and 400 mg/kg RES group, which mainly involved in "adipocytokine signaling pathway," "Wnt signaling pathway," "PI3K-Akt signaling pathway" and "MAPK signaling pathway." In conclusion, RES can inhibit the formation and accumulation of lipid droplets through AdipoQ signal pathway and lipid metabolism-related lncRNAs. Our results provide a new insight on the molecular mechanism of RES as a nutritional agents to the prevention and treatment for obesity.


Asunto(s)
Metabolismo de los Lípidos , ARN Largo no Codificante , Masculino , Animales , Porcinos , Metabolismo de los Lípidos/genética , ARN Largo no Codificante/genética , Resveratrol/farmacología , Gotas Lipídicas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Obesidad/metabolismo , Transducción de Señal
8.
Thyroid ; 33(5): 603-614, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36924297

RESUMEN

Background: The relationship between isolated hypothyroxinemia (IH) in pregnancy and adverse pregnancy outcomes is controversial, with no consensus on the need for treatment. Summary: We conducted a systematic review and meta-analysis examining adverse pregnancy and neonatal outcomes in women with IH in pregnancy. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for publications from inception to December 2022. Randomized clinical trials and cohort studies were included. Random-effects meta-analyses were used to estimate pooled relative risks (RRs) for each outcome. We included 21 articles, of which 19 investigated the relationship between IH and maternal and neonatal outcomes and 4 investigated the efficacy of levothyroxine (LT4) treatment. Compared with euthyroid pregnancies, IH pregnancies were associated with an increased risk of preterm birth (RR 1.35 [confidence interval, CI, 1.16-1.56]; I2 = 9%), premature rupture of membranes (RR 1.41 [CI 1.08-1.84]; I2 = 0%), gestational diabetes (RR 1.34 [CI 1.07-1.67]; I2 = 76%), macrosomia (RR 1.62 [CI 1.31-2.02]; I2 = 42%), and fetal distress (RR 1.72 [CI 1.15-2.56]; I2 = 0%). However, no statistically significant differences were noted in adverse outcomes according to LT4 treatment status. Conclusions: There is evidence suggesting that IH in pregnancy may be associated with an increased risk of adverse pregnancy and neonatal outcomes. However, it is unclear whether LT4 may mitigate the risk of these adverse outcomes.


Asunto(s)
Diabetes Gestacional , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Nacimiento Prematuro/epidemiología , Resultado del Embarazo , Tiroxina/uso terapéutico
9.
Genes (Basel) ; 14(2)2023 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-36833242

RESUMEN

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate several pathway intermediates and affect the skeletal muscle development in mice, pigs, sheep, and cattle. However, to date, only a small number of miRNAs have been reported in the muscle development of goats. In this report, the longissimus dorsi transcripts of one- and ten-month-old goats were analyzed by sequencing RNAs and miRNAs. The results showed that the ten-month-old Longlin goats had 327 up- and 419 down-regulated differentially expressed genes (DEGs) compared with the one-month-old. In addition, 20 co-up-regulated and 55 co-down-regulated miRNAs involved in the muscle fiber hypertrophy of goats were identified in ten-month-old Longlin and Nubian goats compared with one-month-old. Five miRNA-mRNA pairs (chi-let-7b-3p-MIRLET7A, chi-miR193b-3p-MMP14, chi-miR-355-5p-DGAT2, novel_128-LOC102178119, novel_140-SOD3) involved in the goat skeletal muscle development were identified by miRNA-mRNA negative correlation network analysis. Our results provided new insight into the functional roles of goat muscle-associated miRNAs, allowing a deeper understanding of the transformation of miRNA roles during mammalian muscle development.


Asunto(s)
MicroARNs , Porcinos , Animales , Bovinos , Ratones , Ovinos/genética , MicroARNs/genética , Perfilación de la Expresión Génica , ARN Mensajero/genética , Cabras/genética , Fibras Musculares Esqueléticas/metabolismo , Hipertrofia
10.
Food Res Int ; 163: 112165, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36596113

RESUMEN

The ionic elements in wine and in vineyards are gaining attention due to characterization of the wine traits, wine origin tracing, and vine nutrient judging. In this experiment, 19 elements were detected by inductively coupled plasma mass spectrometry (ICP-MS) in 69 wine samples from 4 regions, 3 vintages, and 3 grape maturity levels. Furthermore, the elements related to vine development, such as N, P, K, Ca, Mg, Cu, Fe, Zn and Cu in the vineyard soil and petioles were determined. Two orthogonal partial least squares discriminant analysis (O2PLS-DA) showed that K, Mn, Co, Sr, B, Si, Pb, Ni, Cu, and Zn were important elements in distinguishing the regions. High-temperature vintages can bring wines with high levels of Sr in wine. Na, Ca, K, Mg, Rb, Al, Rb, Pb and Fe can be used as signature elements to distinguish wines made from 2 grape maturities. And Cu, Zn, and Mn were the key elements used to differentiate the petioles in the 4 regions. Partial square regression (PLSR) analysis showed that soil pH was positively correlated with Al, B, Ba, K, Pb, Mn, Sr and Rb in wine, and K in wine was significantly positively correlated with element K in the soil. In conclusion, the elemental contents in wine are shaped by the combination of origin, vintage and grape maturity, while some key elements can be used as indicators of origin traceability.


Asunto(s)
Oligoelementos , Vitis , Oligoelementos/análisis , Vitis/química , Espectrometría de Masas , Plomo/análisis , Suelo
11.
Environ Sci Pollut Res Int ; 30(6): 16017-16035, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36178653

RESUMEN

Inclusive Green Growth (IGG) has important reference value for China's ecological civilization construction and transformation of economic development. Therefore, this study assesses China's IGG level from the perspective of relative efficiency. The IGG efficiency (IGGE) was measured at the provincial level in China from 2000 to 2020 by using Super-Epsilon-Based Measure (EBM) model that considers undesirable outputs. The spatiotemporal pattern of IGGE was analyzed by kernel density estimation and spatial autocorrelation. The results indicate a fluctuating trend from 2000 to 2020 for the IGGE of China, and significant differences between regional and interprovincial IGGE were observed. On average, the eastern region presented the highest efficiency, while the level in the central regions was lowest. There is a positive spatial autocorrelation in the IGGE distribution, and the agglomeration of spatial distribution fluctuated during the study period. The IGGE has spatial spillover effects at the provincial level according to the spatial Durbin model. Among the influencing factors, the spatial spillover effects of industrial structure, government administrative capability, and industrialization level are significant. The regression results also confirm the Environmental Kuznets Curve effect between IGG and economic growth in China. Finally, some implicit policies can be established based on the empirical analysis.


Asunto(s)
Desarrollo Industrial , Industrias , China , Desarrollo Económico , Eficiencia , Inmunoglobulina G
12.
J Gene Med ; 25(3): e3468, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36518003

RESUMEN

BACKGROUND: It is difficult to distinguish between arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM) because of their similar clinical manifestations. This study aimed to develop a novel diagnostic algorithm for distinguishing ACM from DCM. METHODS: Two public datasets containing human ACM and DCM myocardial samples were used. Consensus clustering, non-negative matrix factorization and principal component analysis were applied. Weighted gene co-expression network analysis and machine learning methods, including random forest and the least absolute shrinkage and selection operator, were used to identify candidate genes. Receiver operating characteristic curves and nomograms were performed to estimate diagnostic efficacy, and Spearman's correlation analysis was used to assess the correlation between candidate genes and cardiac function indices. RESULTS: Both ACM and DCM showed highly similar gene expression patterns in the clustering analyses. Hub gene modules associated with cardiomyopathy were obtained using weighted gene co-expression network analysis. Thirteen candidate genes were selected using machine learning algorithms, and their combination showed a high diagnostic value (area under the ROC curve = 0.86) for distinguishing ACM from DCM. In addition, TATA-box binding protein associated factor 15 showed a negative correlation with cardiac index (R = -0.54, p = 0.0054) and left ventricular ejection fraction (R = -0.48, p = 0.0015). CONCLUSIONS: Our study revealed an effective diagnostic model with key gene signatures, which indicates a potential tool to differentiate between ACM and DCM in clinical practice. In addition, we identified several genes that are highly related to cardiac function, which may contribute to our understanding of ACM and DCM.


Asunto(s)
Cardiomiopatías , Cardiomiopatía Dilatada , Humanos , Cardiomiopatía Dilatada/genética , Volumen Sistólico , Función Ventricular Izquierda , Perfilación de la Expresión Génica , Algoritmos , Aprendizaje Automático
13.
Gene ; 851: 146967, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36261092

RESUMEN

With the development of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system in gene editing, the catalytic site in Cas9 has been mutated to dead Cas9 (dCas9) to regulate target gene's expression with the guidance of single guide RNA (sgRNA) in many organisms. When dCas9 was navigated to the region close to the transcription start site, duo to sterical hindrance, it could downregulate the expression level of target gene specifically without genomic alteration. Furthermore, the fusion of synthetic transcriptional repressor domain (TRD) to dCas9 could improve the gene silencing efficiency dramatically, the above all was also known as CRISPR interference system (CRISPRi). Till now, SRDX repressor domain was the most frequently used TRD in plant. Nevertheless, its incomplete repression limited the application of CRISPRi system. Hereafter, in this study, we identified three more effective TRDs, DLN144, DLS and MIX in plant. To dissect the transcriptional repressing activity of DLN144, DLS and MIX in plant, first and foremost, we proved their transcriptional repression efficiency in transient transformed Nicotiana benthamiana leaves. Then, their intrinsic transcriptional repressing activity was corroborated in stable transgenic wheat and N. benthamiana. These three functional TRDs, DLN144, DLS and MIX, provide more options for the application of CRISPRi in plant and shed new light on the advancement of more robust TRDs by combining different individual effective repressor domain in plant which will facilitate the application of CRISPRi when higher repression efficiency is required.


Asunto(s)
ARN Guía de Sistemas CRISPR-Cas , Transcripción Genética , Sistemas CRISPR-Cas , Silenciador del Gen , Plantas/genética , ARN Guía de Sistemas CRISPR-Cas/genética
14.
Front Plant Sci ; 13: 978497, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36051296

RESUMEN

Rootstocks are commonly utilized owing to their resistance to abiotic and biotic stress in viticulture. This study evaluated the effects of three rootstocks (1103P, SO4, and 5A) on the Cabernet Sauvignon (CS) vine growth, and their berries and wines flavonoids profiles in four consecutive vintages. The results showed that 1103P increased the pruning weight of CS and decreased the anthocyanin concentration in berries and wines, especially in the vintages with more rainy and cloudy days. 5A tended to decrease the pruning weight of CS and increase the anthocyanin concentration in berries and wines. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed that the concentrations of total anthocyanins, F3'H-anthocyanins, malvidin-3-O-glucoside (Mv-glu), and malvidin-3-O-acetylglucoside (Mv-acglu) were the key substances affected by the rootstocks in CS berries and were significantly decreased by 1103P. Total anthocyanins, pinotins, Mv-glu, epicatechin, and vitisins were the rootstock-sensitive compounds that commonly differed in wines among the three comparison groups in the two vintages. Furthermore, 1103P brought more brightness to the wine and 5A gave the wine more red tones. In conclusion, rootstock 5A was recommended in the rainy and cloudy climate regions with regard to the berry flavonoids accumulation and the wine color.

15.
Foods ; 11(17)2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-36076875

RESUMEN

Resveratrol (RES) has a wide range of biological and pharmacological activities with various health benefits for humans as a food additive. In animal production, RES has been considered a potential functional feed additive for producing high-quality pork. Long noncoding RNAs (lncRNAs) have emerged as essential regulators of fat metabolism, and phytochemicals can regulate fat metabolism through lncRNA. However, it is unclear whether RES can improve back-fat thickness by regulating lncRNA. In this study, we identified a novel lncRNA, which was named a long intergenic non-protein coding RNA, a regulator of fat metabolism (LincRNA-ROFM), from our previous lncRNA sequencing data. LincRNA-ROFM can inhibit adipocyte proliferation and differentiation. In-depth analyses showed that LincRNA-ROFM acts as a molecular sponge for miR-133b, and adiponectin (AdipoQ) is a direct target of miR-133b in porcine preadipocytes. In addition, the expression of LincRNA-ROFM was positively correlated with AdipoQ. RES can promote the expression of LincRNA-ROFM by PPARα and C/EBPα. Altogether, our research showed that LincRNA-ROFM acts as a ceRNA to sequester miR-133b and is upregulated by RES, leading to heightened AdipoQ expression, and thus decreased adipocyte proliferation and differentiation, which reduces back-fat thickness of pigs. Taken together, the RES/LincRNA-ROFM/miR-133b/AdipoQ regulatory network preliminarily explains the mechanism of action of RES in inhibiting fat deposition, which provides new insight into the downstream mechanism of RES inhibition of fat deposits by regulating the lncRNA.

16.
J Immunol Res ; 2022: 1345971, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35935577

RESUMEN

IL-28B, belonging to type III interferons (IFN-λs), exhibits a potent antitumor activity with reduced regulated T cells (Tregs) population, yet the effect of IL-28B on the tumor microenvironment (TME) and if IL-28B can downregulate Tregs directly in vitro are still unknown. In this study, we investigated the effects of IL-28B on Tregs in the spleen and TME in H22 tumor-bearing mice and verified the downregulation of IL-28B on Tregs in vitro. We found that rAd-mIL-28B significantly inhibited tumor growth and reduced the frequency of splenic CD4+Foxp3+ T cells. The levels of CXCL13, ICAM-1, MCP-5, and IL-7 in the serum, and the levels of IL-15 and sFasL in the tumor tissue decreased significantly after rAd-mIL-28B treatment relative to rAd-EGFP. Furthermore, the percentage of CD8+ cells in the TME was significantly increased in the rAd-mIL-28B group compared with the untreated group. In vitro, splenocytes were stimulated with anti-CD3/CD28 and IL-2 in the presence of TGF-ß with or without IL-28B for three days and followed by flow cytometric, RT-PCR, and IL-10 production analysis. The results showed that IL-28B significantly reduced the proportion of induced Foxp3+ cells. It demonstrated that IL-28B may be used as a promising immunotherapy strategy against cancer.


Asunto(s)
Neoplasias , Microambiente Tumoral , Animales , Factores de Transcripción Forkhead , Ratones , Neoplasias/patología , Linfocitos T Reguladores , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/farmacología
17.
Hum Mol Genet ; 31(20): 3504-3520, 2022 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-35666215

RESUMEN

Mutations in genes encoding subunits of the BAF (BRG1/BRM-associated factor) complex cause various neurodevelopmental diseases. However, the underlying pathophysiology remains largely unknown. Here, we analyzed the function of Brahma-related gene 1 (Brg1), a core ATPase of BAF complexes, in the developing cerebral cortex. Loss of Brg1 causes several morphological defects resembling human malformations of cortical developments (MCDs), including microcephaly, cortical dysplasia, cobblestone lissencephaly and periventricular heterotopia. We demonstrated that neural progenitor cell renewal, neuronal differentiation, neuronal migration, apoptotic cell death, pial basement membrane and apical junctional complexes, which are associated with MCD formation, were impaired after Brg1 deletion. Furthermore, transcriptome profiling indicated that a large number of genes were deregulated. The deregulated genes were closely related to MCD formation, and most of these genes were bound by Brg1. Cumulatively, our study indicates an essential role of Brg1 in cortical development and provides a new possible pathogenesis underlying Brg1-based BAF complex-related neurodevelopmental disorders.


Asunto(s)
Cromatina , ADN Helicasas/metabolismo , Malformaciones del Desarrollo Cortical , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Animales , Humanos , Ratones
18.
Thyroid ; 32(8): 983-989, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35651276

RESUMEN

Objective: The use of antithyroid drugs (ATDs) carries potential risk for teratogenic effects. For women with well-controlled hyperthyroidism on a low dose of ATDs, drug withdrawal upon pregnancy is recommended by international medical guidelines. Therefore, it is necessary to determine the characteristics of patients suitable for ATD withdrawal, subsequent changes in thyroid function after ATD discontinuation, and its impact on pregnancy and offspring outcomes. Methods: This prospective study recruited 63 pregnant women with well-controlled Graves' hyperthyroidism who had stopped ATDs during early pregnancy. Patients were followed up until the end of pregnancy and data on pregnancy outcomes were collected. Results: Overall, 20 patients (31.7%) had rebound of hyperthyroidism. Patients with either subnormal thyrotropin (TSH) levels (TSH <0.35 mIU/L, odds ratio [OR] = 5.12, confidence interval [CI = 1.29-20.34], p = 0.03) or positive thyrotropin receptor antibody (TRAb) (TRAb >1.75 IU/L, OR = 3.79, [CI = 1.17-12.30], p = 0.02) at the time of ATDs withdrawal presented a higher risk of rebound than those with either normal TSH levels or negative TRAb. Patients with both subnormal TSH and positive TRAb at the time of ATD withdrawal were more likely to experience rebound (83.3%, 5/6) than those with both normal TSH and negative TRAb (13%, 3/23, OR = 33.33, [CI = 2.83-392.60], p = 0.003). The prevalence of adverse pregnancy outcomes was significantly higher in patients who experienced rebound compared with those who did not (55.0% vs. 9.3%, OR = 11.92, [CI = 3.08-46.18], p = 0.0002). Conclusions: Subnormal TSH levels and TRAb positivity at the time of ATD withdrawal in early pregnancy may be associated with rebound of Graves' hyperthyroidism. Rebound of hyperthyroidism during pregnancy may increase the risk of adverse pregnancy outcomes. Larger prospective studies are needed to confirm these findings.


Asunto(s)
Enfermedad de Graves , Hipertiroidismo , Antitiroideos/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Hipertiroidismo/inducido químicamente , Hipertiroidismo/tratamiento farmacológico , Inmunoglobulinas Estimulantes de la Tiroides , Embarazo , Estudios Prospectivos , Receptores de Tirotropina , Tirotropina
19.
Endocr Pract ; 28(6): 578-585, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35278704

RESUMEN

OBJECTIVE: Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment. METHODS: Women were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly. RESULTS: After delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery. CONCLUSION: For patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.


Asunto(s)
Hipotiroidismo , Complicaciones del Embarazo , Neoplasias de la Tiroides , Femenino , Humanos , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Periodo Posparto , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Neoplasias de la Tiroides/tratamiento farmacológico , Tirotropina/uso terapéutico , Tiroxina/uso terapéutico
20.
Foods ; 11(4)2022 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-35206074

RESUMEN

This study investigated the effects of resveratrol (RES) supplementation on the growth performance, carcass and meat quality, blood lipid levels and ruminal bacterial microbiota of fattening goats. A total of forty castrated Nubian goats (28.25 ± 0.26 kg body weight) were randomly divided into four groups and provided with diets containing different levels of RES (0, 150, 300 and 600 mg/kg) for 120 d. The results showed that RES increased redness and intramuscular fat content, whilst reducing shear force in the longissimus dorsi muscle of goats (p < 0.05). In addition, the final weight, average daily gain, hot carcass weight, net meat weight, carcass lean percentage and eye muscle area of goats were significantly increased in the 150 mg/kg RES group compared with the other three groups, while those in the 600 mg/kg RES group significantly decreased (p < 0.05). RES significantly decreased serum triacylglycerol and LDL-C contents (p < 0.05), and increased HDL-C content and the HDL-C/TC ratio (p < 0.05). Supplementation with 150 mg/kg RES also increased the proportion of Acetitomaculum and Moryella, genera comprising short-chain fatty acid-producing bacteria. The present study indicated that an appropriate supplemental level of RES could improve the growth performance, neat percentage, meat quality, ruminal microbiota and serum lipid levels of fattening goats.

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