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1.
Prenat Diagn ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488843

RESUMO

OBJECTIVE: This study aimed to develop and validate a prenatal cell-free DNA (cfDNA) screening method that uses capture-based enrichment to genotype fetal autosomal recessive disorders. This method was applied in pregnancies at high risk of autosomal recessive non-syndromic hearing loss (ARNSHL) to assess its accuracy and effectiveness. METHODS: This assay measured the allele counts in both white blood cell DNA and cfDNA from the blood samples of pregnant women using a capture-based next-generation sequencing method. It then applied a binomial model to infer the fetal genotypes with the maximum likelihood. Ninety-four pregnant couples that were carriers of variants of ARNSHL in GJB2 or SLC26A4 were enrolled. The fetal genotypes deduced using this screening method were compared with the results of genetic diagnosis using amniocentesis. RESULTS: Of the 94 couples, 65 carried more than one variant, resulting in 170 single-nucleotide polymorphism (SNP) loci to be inferred in the fetuses. Of the 170 fetal SNP genotypes, 150 (88.2%) had high confidence calls and 139 (92.7%) of these matched the genotypes obtained by amniocentesis result. Out of the remaining 20 (11.8%) cases with low-confidence calls, only 14 (70.0%) were concordant with genetic diagnosis using amniocentesis. The concordance rate was 100% for sites where the maternal genotype was wild-type homozygous. The discordance was site-biased, with each locus showing a consistent direction of discordance. Genetic diagnosis identified a total of 19 wild-type homozygotes, 46 heterozygotes, 19 compound heterozygotes, and 10 pathogenic homozygotes. This screening method correctly genotyped 81.9% (77/94) of fetuses and demonstrated a sensitivity of 89.7% and a specificity of 89.2% for correctly identifying ARNSHL. CONCLUSION: This capture-based method of prenatal screening by cfDNA demonstrated strong potential for fetal genotyping of autosomal recessive disorders.

2.
Genomics ; 116(2): 110810, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38402913

RESUMO

This study generated whole genome DNA methylation maps to characterize DNA methylomes of grape (cv. 'Cabernet Franc') skins and examine their functional significance during grape skin coloration. We sampled grape skin tissues at three key stages (the early stage of grape berry swelling, the late stage of grape berry swelling and the veraison) during which the color of grape berries changed from green to red. DNA methylation levels of grape skins at the three stages were higher in transposable element regions than in the genic regions, and the CG and CHG DNA methylation levels of the genic region were higher than the CHH DNA methylation levels. We identified differentially methylated regions (DMRs) in S2_vs_S1 and S3_vs_S1. The results indicated that DMRs predominantly occurred within the CHH context during grape skin coloration. Many gene ontology (GO)-enriched DMR-related genes were involved in "nucleotide binding," "catalytic activity" and "ribonucleotide binding" terms; however, many KEGG-enriched DMR-related genes were involved in the "flavonoid biosynthesis" pathway. Our results could provide an important foundation for future research on the development mechanism of grape berries.


Assuntos
Vitis , Vitis/genética , Metilação de DNA , Frutas , Genes de Plantas , Análise de Sequência de RNA
3.
Int J Mol Sci ; 25(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38255862

RESUMO

Ethylene is one crucial phytohormone modulating plants' organ development and ripening process, especially in fruits, but its action modes and discrepancies in non-climacteric grape and climacteric peach in these processes remain elusive. This work is focused on the action mode divergences of ethylene during the modulation of the organ development and ripening process in climacteric/non-climacteric plants. We characterized the key enzyme genes in the ethylene synthesis pathway, VvACO1 and PpACO1, and uncovered that their sequence structures are highly conserved, although their promoters exhibit important divergences in the numbers and types of the cis-elements responsive to hormones, implying various responses to hormone signals. Subsequently, we found the two have similar expression modes in vegetative organ development but inverse patterns in reproductive ones, especially in fruits. Then, VvACO1 and PpACO1 were further validated in promoting fruit ripening functions through their transient over-expression/RNAi-expression in tomatoes, of which the former possesses a weaker role than the latter in the fruit ripening process. Our findings illuminated the divergence in the action patterns and function traits of the key VvACO1/PpACO1 genes in the tissue development of climacteric/non-climacteric plants, and they have implications for further gaining insight into the interaction mechanism of ethylene signaling during the modulation of the organ development and ripening process in climacteric/non-climacteric plants.


Assuntos
Climatério , Prunus persica , Vitis , Prunus persica/genética , Vitis/genética , Menopausa , Etilenos
4.
Mitochondrial DNA B Resour ; 9(1): 163-167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38274855

RESUMO

Petrocosmea qinlingensis is a protected wild plant endemic in China, inhabiting low-light limestone cliffs but the complete chloroplast genome has not been reported. In this study, we first sequenced and assembled the complete chloroplast genome of P. qinlingensis. The total size of this genome was 153,865 bp, including a large single-copy (LSC) region (84,737 bp), a small single-copy (SSC) region (18,244 bp), and two inverted repeats (IRs) regions (25,442 bp). This genome encoded 111 uniquegenes, consisted of 77 protein-coding genes, four ribosomal RNA genes, and 30 transfer RNA genes. Phylogenomic analysis based on the chloroplast protein-coding genes and showed that the genus Petrocosmea was the closest relative to Raphiocarpus. Our results will support further phylogeographic, population genetic studies of this species.

5.
Plant Signal Behav ; 18(1): 2245616, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37573563

RESUMO

Ribosome biogenesis is a fundamental process in eukaryotic cells. NOTCHLESS (NLE) is involved in 60S ribosome biogenesis in yeast, but its role in Arabidopsis (A. thaliana) remains exclusive. Here, we found that Arabidopsis NLE (AtNLE) is highly conservative in phylogeny, which encoding a WD40-repeat protein. AtNLE is expressed in actively dividing tissues. AtNLE-GFP is localized in the nucleus. AtNLE physically interacts with the MIDAS domain of AtMDN1, a protein involved in the biogenesis of the 60S ribosomal subunit in Arabidopsis. The underexpressing mutant nle-2 shows short roots and reduced cell number in the root meristem. In addition, the null mutant nle-1 is embryo lethal, and defective embryos are arrested at the early globular stage. This work suggests that AtNLE interacts with AtMDN1, and AtNLE functions in root and embryo development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Meristema/genética , Meristema/metabolismo , Núcleo Celular/metabolismo , Desenvolvimento Embrionário
6.
Sci Rep ; 13(1): 13453, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596395

RESUMO

To analyze the relationship between the composition of urinary stones and various influencing factors in the Enshi region. We used FT-IR to examine the composition of 1092 stone samples. Combined with the relevant clinical materials, the data were analyzed using both one-dimensional statistical methods and multivariate statistical methods. The study included 1092 stone samples, classified as follows: 457 (41.8%) with a single component, 453 (41.5%) with two components, 149 (13.6%) with three components, and 33 (3.0%) with four components. Stones were categorized into five types: Calcium Oxalate (CaOx) (76.4%), carbapatite (CaP) (9.3%), Struvite (ST) (8.3%), Uric Acid (UA) (4.9%), and Others (1.0%). Age, gender, urinary tract infection (UTI), family history of urinary stones (FH), hyperuricemia (HUA) and stone location were significantly associated with stone type. Logistic regression revealed that females and UTI were relative risk factors for predicting CaP and ST, while FH and HUA were relative risk factors for predicting UA. Our study indicates that the overall composition of urinary tract stones in the Enshi region is consistent with that of the entire China. Additionally, the predisposing factors for stone formation vary in terms of gender, age, FH, UTI, hyperuricemia HUA, and stone location.


Assuntos
Hiperuricemia , Cálculos Urinários , Urolitíase , Feminino , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , População do Leste Asiático , Minorias Étnicas e Raciais , Etnicidade , Estudos Retrospectivos , Grupos Minoritários
7.
FEBS J ; 290(22): 5340-5352, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37526061

RESUMO

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease worldwide and the strongest predictor of mortality in patients with diabetes. Despite its significance, the pathological mechanism underlying the onset and progression of DKD remains incompletely understood. In this study, we have shown that mitochondrial ribosomal protein L12 (MRPL12) plays a significant role in DKD by modulating mitochondrial function. We demonstrated that MRPL12 was mainly ubiquitinated at K150 in renal tubular epithelial cells. We have found that Cullin3 (CUL3), an E3 ubiquitin ligase, directly interacts with MRPL12 and induces the K63-linked ubiquitination of MRPL12, resulting in mitochondrial biosynthesis dysfunction. Moreover, under high-glucose (HG) conditions in renal tubular epithelial cells, we observed up-regulation of CUL3 expression, significant increase in CUL3-mediated ubiquitination of MRPL12 and dysregulation of mitochondrial biosynthesis. Notably, CUL3 knockdown stabilised the MRPL12 protein and protected mitochondrial biosynthesis under HG conditions. Our findings provide novel insight into how CUL3 affects mitochondrial biosynthesis in renal tubular epithelial cells through MRPL12 ubiquitination and suggest a potential therapeutic strategy for DKD in the future.


Assuntos
Nefropatias Diabéticas , Doenças Mitocondriais , Humanos , Células Epiteliais/metabolismo , Ubiquitinação , Mitocôndrias/metabolismo , Nefropatias Diabéticas/metabolismo , Doenças Mitocondriais/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Ribossômicas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Culina/genética , Proteínas Culina/metabolismo
8.
Int J Mol Sci ; 24(11)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37298429

RESUMO

In plant cells, multiple paralogs from ribosomal protein (RP) families are always synchronously expressed, which is likely contributing to ribosome heterogeneity or functional specialization. However, previous studies have shown that most RP mutants share common phenotypes. Consequently, it is difficult to distinguish whether the phenotypes of the mutants have resulted from the loss of specific genes or a global ribosome deficiency. Here, to investigate the role of a specific RP gene, we employed a gene overexpression strategy. We found that Arabidopsis lines overexpressing RPL16D (L16D-OEs) display short and curled rosette leaves. Microscopic observations reveal that both the cell size and cell arrangement are affected in L16D-OEs. The severity of the defect is positively correlated with RPL16D dosage. By combining transcriptomic and proteomic profiling, we found that overexpressing RPL16D decreases the expression of genes involved in plant growth, but increases the expression of genes involved in immune response. Overall, our results suggest that RPL16D is involved in the balance between plant growth and immune response.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteômica , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas , Fenótipo
9.
iScience ; 26(5): 106656, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37182101

RESUMO

Acute kidney injury (AKI) is a serious disease with no effective treatment. Abnormal opening of mitochondrial permeability transition pore (MPTP) is an important pathological process in ischemia reperfusion injury (IRI), the key factor of AKI. It is essential to elucidate MPTP regulation mechanism. Here, we identified mitochondrial ribosomal protein L7/L12 (MRPL12) specifically binds to adenosine nucleotide translocase 3 (ANT3) under normal physiological conditions, stabilizes MPTP and maintains mitochondrial membrane homeostasis in renal tubular epithelial cells (TECs). During AKI, MRPL12 expression was significantly decreased in TECs, and MRPL12-ANT3 interaction was reduced, leading to ANT3 conformation change, MPTP abnormal opening, and cell apoptosis. Importantly, MRPL12 overexpression protected TECs from MPTP abnormal opening and apoptosis during hypoxia/reoxygenation (H/R). Our results suggest MRPL12-ANT3 axis involves in AKI by regulating MPTP, and MRPL12 could be potential intervention target for treatment of AKI.

10.
Nat Commun ; 14(1): 812, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36781861

RESUMO

Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences.


Assuntos
Galinhas , Células Germinativas , Humanos , Masculino , Animais , Camundongos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Galinhas/genética , Galinhas/metabolismo , Células Germinativas/metabolismo , Testículo/metabolismo , Elementos de DNA Transponíveis/genética , RNA de Interação com Piwi , Mamíferos/genética
11.
Food Res Int ; 163: 112161, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36596110

RESUMO

In this study, four wine grape polysaccharides were extracted and optimized by using an efficient ultrasound-assisted extraction. A three-level, three-factor Box Behnken Design (BBD) combining with response surface methodology (RSM) was employed to optimize the extraction conditions including ultrasonic power, ultrasonic time and liquid-to-solid ratio. Furthermore, their physicochemical structures, antioxidant and liver protective activity were investigated and compared. Results revealed that the functional groups and monosaccharide compositions of these grape polysaccharides collected from different varieties were similar. Nevertheless, their molecular weights, molar ratios of monosaccharide compositions and surface morphological features were different. And the antioxidant activities of these polysaccharides were screened by free radical scavenging test. 'Beichun' (BC) and 'Benni fuji' (BF) polysaccharides possessed better antioxidant function. Further, the in vivo evaluation indicated that the polysaccharides of BC and BF have a protective effect against myocardial I/R injury in mice by inhibiting myocardial necroptosis mediated by mitochondrial ROS generation. Therefore, BC and BF grapes have potential applications in the medical and food industries.


Assuntos
Antioxidantes , Vitis , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Peso Molecular , Monossacarídeos/química
12.
J Surg Res ; 284: 318-321, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36641946

RESUMO

INTRODUCTION: Mindsets of health have been linked to different outcomes for patients with both surgical and medical conditions. A "growth" mindset, in which health is defined as malleable and subject to improvement, is associated with improved attitudes and outcomes when compared to a "fixed" mindset, in which health is defined as unchangeable. In pediatric surgery, parental growth mindsets of health have been correlated with better postoperative outcomes, including lower scores of anxiety and pain perceptions, for children. This was particularly notable in a study of postoperative outcomes for patients with pectus excavatum. In our current study, we extend our investigations to explore how health mindsets are associated with perceptions of chest wall anomalies before correction is undertaken. METHODS: Seventy-six patients (71 males, mean age 14 y, and 43 excavatum) and 18 parents were surveyed during a routine chest wall clinic visit. Demographic and clinical information as well as the Health Mindset Scale and Pectus Excavatum Evaluation Questionnaire were administered and collected pretreatment. RESULTS: Parental mindsets of health were significantly correlated with parent assessments of their children's chest pain, physical activity, and concerns about the life-time effect of the condition. A parental growth mindset was linked to lower scores of chest pain, higher ratings of activity, and lower overall level of concern. Furthermore, parental health mindsets also significantly correlated with children's own perceptions of their chest pain, physical activity, shortness of breath, and fatigue. Growth mindset also was linked to more positive ratings. CONCLUSIONS: Parental growth mindset was associated with more positive assessments of children's symptoms and limitations due to pectus deformities than fixed mindsets. Health mindset has been linked to patient perceptions of, and outcomes for, diabetes, renal disease, allergies, scoliosis, and obesity. Further study into parental and patient mindset correlation may help elucidate factors for bracing compliance, and perhaps to better prepare children and parents for corrective surgical procedures.


Assuntos
Tórax em Funil , Escoliose , Parede Torácica , Masculino , Criança , Humanos , Adolescente , Parede Torácica/cirurgia , Tórax em Funil/cirurgia , Escoliose/complicações , Dor no Peito , Pais
13.
Food Res Int ; 155: 111084, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35400460

RESUMO

Although grapevine (Vitis vinifera L.) is generally classified as a non-climacteric fruit, the regulatory mechanisms of ethylene in the ripening of non-climacteric fruit are still poorly understood. In this study, exogenous ethephon (ETH) strongly stimulated fruit color and anthocyanin accumulation, which was consistent with the increased expression of anthocyanin structural, regulatory, and transport genes. ETH application increased ABA content and decreased IAA content by coordinating ABA and auxin biosynthesis regulatory network. ETH treatment also accelerated sugar (glucose and fructose) accumulation by enhancing the gene expression involved in sugar transport and sucrose cleavage. ETH treatment blocked the synthesis of cellulose and accelerated the degradation of pectin, which was strongly associated with berry softening. To further confirm the function of ethylene biosynthesis and signaling genes, transient overexpression of VvACO4 and VvEIL3 were performed in both in tomato and strawberry fruits. These findings of the ethylene cascade add to our understanding of ethylene in non-climacteric berry ripening regulation and revealed a complex involvement of ethylene and its interplay with phytohormones during grapevine berry ripening.


Assuntos
Frutas , Transcriptoma , Antocianinas/metabolismo , Etilenos , Frutas/genética , Frutas/metabolismo , Perfilação da Expressão Gênica , Açúcares/metabolismo
14.
Sci Rep ; 12(1): 875, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042919

RESUMO

Deep coal seam mining often leads to water resource loss due to bedrock water entering the workings of the mine and is discharged adjacent to the mining area. Using the geological conditions of the Maiduoshan coal mine, this paper applied a physical simulation experiment. The specified rock above the coal seam was hydraulically fractured in advance to form a postmining grouted fracture network, followed by grouting to construct a flexible isolation layer that blocked the infiltration of groundwater from the aquifer into the water-conducting fracture zone. Stress sensors, flow sensors and strata displacement monitoring technology were deployed inside the experimental material to study the spatial distribution characteristics and evolution law of the water-conducting fracture zone in the overlying rocks. Analysis of the water-conducting fracture zone development law, stress variation, overburden evolution characteristics, fracturing and grouting sequence of the flexible isolation layer and the effect of postmining grouting on the water barrier was conducted. These experiments verified the feasibility of fracture and grouting of the flexible isolation layer. These research results will provide practical guidance for the transition from the current safe and efficient mining methods to safe and green mining methods of deep coal mining in the western mining areas of China.

15.
Cardiovasc Diabetol ; 20(1): 82, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888131

RESUMO

BACKGROUND: The triglyceride-glucose index (TyG index) has been proposed as a simple and reliable alternative insulin resistance (IR) marker, while the homeostasis model assessment for IR (HOMA-IR) is the most frequently used index. Few studies have evaluated the role of IR assessed by the TyG index and HOMA-IR on arterial stiffness in a type 2 diabetes (T2D) population with a high risk of increased arterial stiffness. We aimed to investigate the association of the TyG index and HOMA-IR with arterial stiffness in patients with T2D. METHODS: We recruited 3185 patients with T2D, who underwent brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, but without previous cardiovascular disease. Increased arterial stiffness was defined as a baPWV value greater than the 75th percentile (18.15 m/s) in the present study. The TyG index was determined as ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and the HOMA-IR was calculated as (fasting insulin [µIU/mL] × fasting glucose [mmol/L])/22.5. RESULTS: The mean age of the study participants was 54.6 ± 12.0 years, and 1954 (61.4%) were men. Seemingly unrelated regression estimation analysis demonstrated that the TyG index had stronger associations with baPWV than the HOMA-IR (all P < 0.001). In the multivariable logistic analyses, each one-unit increase in the TyG index was associated with a 1.40-fold (95% CI 1.16-1.70, P < 0.001) higher prevalence of increased arterial stiffness, but the prominent association of the HOMA-IR with the prevalence of increased arterial stiffness was not observed. Subgroup analyses showed that a more significant association between the TyG index and the prevalence of increased arterial stiffness was detected in older patients with a longer duration of diabetes and poor glycaemic control (all P < 0.05). CONCLUSIONS: Compared with the HOMA-IR, the TyG index is independently and more strongly associated with arterial stiffness in patients with T2D.


Assuntos
Glicemia/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Resistência à Insulina , Triglicerídeos/sangue , Rigidez Vascular , Adulto , Idoso , Índice Tornozelo-Braço , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Análise de Onda de Pulso , Medição de Risco
16.
ACS Nano ; 15(3): 3612-3620, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33666429

RESUMO

Extracellular vesicles (EVs) and microbubbles are nanoparticles in drug-delivery systems that are both considered important for clinical translation. Current research has found that both microbubbles and EVs have the potential to be utilized as drug-delivery agents for therapeutic targets in various diseases. In combination with EVs, microbubbles are capable of delivering chemotherapeutic drugs to tumor sites and neighboring sites of damaged tissues. However, there are no standards to evaluate or to compare the benefits of EVs (natural carrier) versus microbubbles (synthetic carrier) as drug carriers. Both drug carriers are being investigated for release patterns and for pharmacokinetics; however, few researchers have focused on their targeted delivery or efficacy. In this Perspective, we compare EVs and microbubbles for a better understanding of their utility in terms of delivering drugs to their site of action and future clinical translation.


Assuntos
Vesículas Extracelulares , Nanopartículas , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Microbolhas
17.
J Diabetes Complications ; 34(11): 107701, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32888789

RESUMO

OBJECTIVE: The study investigated the association between free triiodothyronine (FT3) and poor glycemic control with different definitions in euthyroid patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study which included 2172 patients from National Metabolic Management Center in Ruijin Hospital. The association between thyroid function and glycated hemoglobin A1c (HbA1c) was determined by multiple liner regression models. The association between FT3 and poor glycemic control was further determined by binary logistic regression models. Two definitions of poor glycemic control (HbA1c ≥ 7% and HbA1c ≥ 8%) were applied when we analyzed the association. RESULTS: Prevalence of HbA1c ≥ 7% and HbA1c ≥ 8% were 63.8% and 39.3%, respectively. After adjusting for confounding factors, FT3, rather than free tetraiodothyronine (FT4) or thyroid stimulating hormone (TSH), was independently associated with HbA1c (ß = -0.104, P = 0.002). Further analysis after gender stratification showed that the association was only found in males (ß = -0.164, P < 0.001). We further analyzed the association between FT3 quartiles and poor glycemic control. FT3 quartiles were not significantly associated with the risk of HbA1c ≥ 7% before and after adjusting for confounding factors in both genders. FT3 quartiles were negatively associated with the risk of HbA1c ≥ 8% only in males, independent of traditional risk factors for poor glycemic control (P for trend = 0.030). CONCLUSIONS: FT3 in the reference range was significantly associated with reduced risk of HbA1c ≥ 8% in males, independent of traditional risk factors for poor glycemic control.


Assuntos
Diabetes Mellitus Tipo 2 , Controle Glicêmico , Tri-Iodotironina , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hemoglobinas Glicadas , Humanos , Masculino , Fatores Sexuais , Tri-Iodotironina/sangue
18.
FASEB J ; 34(9): 13033-13048, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32777136

RESUMO

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide indicates the urgent need to develop novel and effective treatment strategies. Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has an outstanding effect in improving metabolism. However, the pharmacological action and mechanism of BA in NAFLD remain unclear. Here, we show that BA-treated high-fat diet mice and methionine-choline deficient diet-fed mice are resistant to hepatic steatosis when compared with vehicle-treated mice. BA alleviates fatty acid synthesis, fibrosis, and inflammation and promotes fatty acid oxidation. Meanwhile, fatty acid synthase (FAS) expression and activity are markedly inhibited with BA treatment both in vitro and in vivo. Moreover, BA inhibits FAS expression through transcriptional suppression of Yin Yang 1 (YY1), leading to retard hepatocytes triglyceride accumulation. Collectively, BA protects hepatocytes from abnormal lipid deposition in NAFLD through YY1/FAS pathway. Our findings establish a novel role of BA in representing a possible therapeutic strategy to reverse NAFLD.


Assuntos
Ácido Graxo Sintase Tipo I/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Triterpenos Pentacíclicos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Fator de Transcrição YY1/metabolismo , Animais , Ácidos Graxos/metabolismo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácido Betulínico
19.
Plant Cell ; 32(1): 263-284, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732704

RESUMO

In eukaryotes, autophagy maintains cellular homeostasis by recycling cytoplasmic components. The autophagy-related proteins (ATGs) ATG1 and ATG13 form a protein kinase complex that regulates autophagosome formation; however, mechanisms regulating ATG1 and ATG13 remain poorly understood. Here, we show that, under different nutrient conditions, the RING-type E3 ligases SEVEN IN ABSENTIA OF ARABIDOPSIS THALIANA1 (SINAT1), SINAT2, and SINAT6 control ATG1 and ATG13 stability and autophagy dynamics by modulating ATG13 ubiquitylation in Arabidopsis (Arabidopsis thaliana). During prolonged starvation and recovery, ATG1 and ATG13 were degraded through the 26S proteasome pathway. TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR1a (TRAF1a) and TRAF1b interacted in planta with ATG13a and ATG13b and required SINAT1 and SINAT2 to ubiquitylate and degrade ATG13s in vivo. Moreover, lysines K607 and K609 of ATG13a protein contributed to K48-linked ubiquitylation and destabilization, and suppression of autophagy. Under starvation conditions, SINAT6 competitively interacted with ATG13 and induced autophagosome biogenesis. Furthermore, under starvation conditions, ATG1 promoted TRAF1a protein stability in vivo, suggesting feedback regulation of autophagy. Consistent with ATGs functioning in autophagy, the atg1a atg1b atg1c triple knockout mutants exhibited premature leaf senescence, hypersensitivity to nutrient starvation, and reduction in TRAF1a stability. Therefore, these findings demonstrate that SINAT family proteins facilitate ATG13 ubiquitylation and stability and thus regulate autophagy.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Autofagia/fisiologia , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Transporte/metabolismo , Proteínas de Membrana , Proteínas Mitocondriais , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
20.
Int J Endocrinol ; 2019: 5069578, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781210

RESUMO

INTRODUCTION: Obesity has an unclear pathogenesis. MicroRNAs (miRNAs) may function as biologically active molecules for obesity through regulating adipocyte differentiation. This study aimed to identify how miR-129-5p (a specific miRNA) regulates adipogenesis in vitro and explore its possible role in the pathogenesis of obesity in humans. MATERIALS AND METHODS: The miR-129-5p expression was detected in obese mouse models. The effect of miR-129-5p on adipocyte differentiation was observed, and the adipose markers were analyzed. Bioinformatics and dual-luciferase reporter assay were applied to predict and confirm the target genes of miR-129-5p. The human serum samples were detected and analyzed. RESULTS: miR-129-5p is highly expressed in adipose tissues of db/db mice. Gain- and loss-of-function studies show that miR-129-5p could significantly inhibit adipocyte differentiation and white adipocyte browning in vitro and decreases the level of specific markers, such as FABP4, UCP1, and PPARγ, in mature white and brown adipocytes. miR-129-5p directly targets ATG7 which is predicted with bioinformatics and confirmed by dual-luciferase reporter assay. Serum miR-129-5p level was evidently elevated in patients with simple obesity (p < 0.01) and correlates with obesity indices, including BMI (r = 0.407, p < 0.029) and fat percentage (r = 0.394, p < 0.038). CONCLUSION: miR-129-5p might target on the ATG7-related autophagy signaling network that regulates white and brown adipogenesis. Importantly, the aforementioned results suggest serum miR-129-5p might be a potential biomarker and therapeutic target for obesity.

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