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1.
Gene ; 736: 144422, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32007584

RESUMO

Late embryogenesis abundant (LEA) proteins are involved in plant stress responses and osmotic regulation, and they are accumulated in the late embryonic stage. There have been no previous genome-wide analyses of the LEA gene family members in wheat and its close relatives. In this study, 281, 53, 151, 89, 99, and 99 LEA genes were identified in wheat (Triticum aestivum), Triticum urartu, Triticum dicoccoides, Aegilops tauschii, barley, and Brachypodium distachyon, respectively. The wheat LEA gene family (TaLEA genes) was divided into eight subfamilies according to the conserved domains. All TaLEA genes contain very few introns (<3) and they are unevenly distributed on the 21 chromosomes. We identified 39 pairs of tandem duplication genes and 9 pairs of segmental duplication genes in the wheat LEA gene family. This proved that the tandem duplication and segmental duplication played an important role in the expansion of the TaLEA gene family. According to published transcriptome data and qRT-PCR analysis, the TaLEA genes exhibit different tissue expression patterns and they are regulated by various abiotic stresses, especially salt and cold stress. This study provides a comprehensive understanding of the wheat LEA gene family.

2.
Endocr Pract ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045287

RESUMO

Objectives: Using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria to diagnose gestational diabetes mellitus (GDM), the association between GDM and offspring's BMI gains in early childhood in China remains unclear. We aimed to assess the association between GDM diagnosed by the IADPSG criteria and the BMI gain and the risk for overweight/obesity in offspring from 1 to 4 years. Methods: This prospective cohort study was based on the healthcare records data from the Medical Birth Registry in Xiamen (MBRX), China. We included 10,412 mother-child pairs tested for GDM with IADPSG criteria. Results: A total of 1786 (17.2%) offspring were exposed to GDM. The offspring exposed to GDM had higher means of BMI Z-score (difference: 0.07 [95% CI: 0.02 to 0.12]) and risks for overweight/obesity (odds ratio: 1.22, 95% CI: 1.06 to 1.40) compared to those unexposed to GDM from 1 to 4 years of age. However, after adjustment for maternal pre-pregnancy BMI (Model 2), these associations attenuated towards the null (difference in BMI Z-score: 0.02 [95% CI: -0.03 to 0.07]; OR for overweight/obesity:1.09 [95% CI: 0.95 to 1.25]). Conclusions: The associations between GDM diagnosed using IADPSG criteria and BMI Z-score and the risk for overweight/obesity in offspring were largely explained by maternal pre-pregnancy BMI at the age of 1-4 years. Reducing the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to glycemia during pregnancy in China.

3.
Eur Radiol ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32025832

RESUMO

OBJECTIVES: To establish a quantitative MR model that uses clinically relevant features of tumor location and tumor volume to differentiate lower grade glioma (LRGG, grades II and III) and glioblastoma (GBM, grade IV). METHODS: We extracted tumor location and tumor volume (enhancing tumor, non-enhancing tumor, peritumor edema) features from 229 The Cancer Genome Atlas (TCGA)-LGG and TCGA-GBM cases. Through two sampling strategies, i.e., institution-based sampling and repeat random sampling (10 times, 70% training set vs 30% validation set), LASSO (least absolute shrinkage and selection operator) regression and nine-machine learning method-based models were established and evaluated. RESULTS: Principal component analysis of 229 TCGA-LGG and TCGA-GBM cases suggested that the LRGG and GBM cases could be differentiated by extracted features. For nine machine learning methods, stack modeling and support vector machine achieved the highest performance (institution-based sampling validation set, AUC > 0.900, classifier accuracy > 0.790; repeat random sampling, average validation set AUC > 0.930, classifier accuracy > 0.850). For the LASSO method, regression model based on tumor frontal lobe percentage and enhancing and non-enhancing tumor volume achieved the highest performance (institution-based sampling validation set, AUC 0.909, classifier accuracy 0.830). The formula for the best performance of the LASSO model was established. CONCLUSIONS: Computer-generated, clinically meaningful MRI features of tumor location and component volumes resulted in models with high performance (validation set AUC > 0.900, classifier accuracy > 0.790) to differentiate lower grade glioma and glioblastoma. KEY POINTS: • Lower grade glioma and glioblastoma have significant different location and component volume distributions. • We built machine learning prediction models that could help accurately differentiate lower grade gliomas and GBM cases. We introduced a fast evaluation model for possible clinical differentiation and further analysis.

4.
Sci Rep ; 10(1): 1549, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005877

RESUMO

The growth trajectory of Chinese preschoolers still remains unclear. Our objective was to determine whether there was an association between adverse pregnancy outcomes and overweight offspring. We analyzed population-based retrospective cohort data from the Medical Birth Registry of Xiamen, which comprised 33,157 children examined from 1 to 6 years of age. Longitudinal analyses were used to evaluate the growth trajectories of offspring body mass index (BMI). Multivariate logistic regression was used to assess the effects of two adverse pregnancy outcomes, gestational diabetes mellitus (GDM) and being large-for-gestational age (LGA), on childhood overweight. Offspring of mothers with GDM and LGA has a higher annual BMI z-score from 1 to 6 years of age (all P < 0.05). But, a higher annual BMI z-score was only observed in children aged 1-5 years in models 1-3. Overall BMI z-score of offspring aged 1-6 who were born to mothers with GDM and LGA were also higher in models 1-3 (all P < 0.05). Additionally, offspring of mothers with GDM and LGA had a higher risk for overweight in model 1, from 1 to 6 years of age (odds ratio (OR), 1.814; 95% confidence interval (CI), 1.657-1.985; P < 0.0001). However, this association was attenuated after adjusting for maternal pre-pregnancy BMI (OR, 1.270; 95% CI, 0.961-1.679; P = 0.0930). Offspring of mothers with GDM and LGA had a higher BMI z-score and increased risk for overweight. Indeed, intrauterine exposure to maternal GDM and LGA could bias offspring to overweight, whereas maternal pre-pregnancy BMI may play a key role in offspring overweight for children born to mothers with GDM and LGA.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32049640

RESUMO

BACKGROUND: Childhood obesity is associated with adverse outcomes such as metabolic syndrome, diabetes, and cardiovascular diseases in adulthood. Identifying risk factors related to excessive adiposity in early childhood is of great importance for obesity intervention. The results of studies for associations between maternal with gestational diabetes and offspring obesity are conflicting. Nonetheless, the association of maternal glucose across a spectrum of glucose values with childhood adiposity outcomes is less clear. AIM: To assess the association of maternal glucose across a spectrum of glucose values with childhood adiposity at age 5 years. METHODS: A population-based cohort study was conducted between 2011 and 2018. Using the healthcare records data were from the Medical Birth Registry in Xiamen, China. The primary outcome was offspring obese/obesity. Primary predictors were maternal oral glucose tolerance test values during pregnancy. RESULTS: 6090 mother-child pairs were analyzed. The mean age of the children at follow-up was 5.2 years. At multiple logistic regression, after adjustment for variables, including maternal pre-pregnancy body mass index (BMI), birth weight of offspring, and insulin therapy, ORs for offspring overweight/obesity were 1.13 (95% CI 0.90 to 1.42) for maternal fasting glucose levels, 1.12 (95% CI 1.04 to 1.22) for 1-hour glucose, and 1.04 (95% CI 0.95 to 1.14) for 2-hour glucose. The adjusted association of offspring BMI Z-score with maternal 1-hour glucose level remained significant. There were no significant associations between BMI Z-score and maternal fasting glucose and 2-hour glucose level. Exploratory sex-specific analyses indicated generally consistent associations for boys and girls. CONCLUSION: Maternal postload 1-hour glucose across a spectrum of glucose values during pregnancy was an independent risk for offspring weight gain at age 5 years, indicating the importance of screen and management of maternal 1-hour glucose level, except for fasting glucose and 2-hour glucose level during pregnancy in order to prevent offspring weight gain in early childhood.

6.
Diabetes Ther ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020552

RESUMO

INTRODUCTION: The aim of this study was to compare the efficacy of vildagliptin as add-on therapy to short-term continuous subcutaneous insulin infusion (CSII) with CSII monotherapy in hospitalized patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 200 hospitalized patients with inadequately controlled T2DM were randomized into groups, with one group receiving CSII monotherapy (CSII group, n =100) and the other group receiving CSII plus vildagliptin as add-on (CSII + Vig group, n = 100). Of these, 191 completed the 7-day trial (CSII group, n = 99; CSII + Vig group, n = 92) and included in the analysis. The glycemic control and variability of the patients were measured using all-day capillary blood glucose (BG) monitoring. Weight and fasting C-peptide levels were evaluated before and after the interventions. RESULTS: Mean BG concentrations during the whole treatment period were lower and the time to reach target BG was reduced in the CSII + Vig group compared with the CSII group (9.89 ± 3.37 vs. 9.46 ± 3.23 mmol/L, P < 0.01; 129 ± 4 vs. 94 ± 5 h, P < 0.01, respectively). Similarly, the indicators of glycemic variability, namely the standard deviation of BG and the largest amplitude of glycemic excursion, were significantly decreased in the CSII + Vig group compared with the CSII group (2.68 ± 1.05 vs. 2.39 ± 1.00 mmol/L, P < 0.01; 7.19 ± 2.86 vs. 6.23 ± 2.73 mmol/L, P < 0.01, respectively). CONCLUSIONS: Short-term CSII with vildagliptin as add-on therapy may be an optimized treatment for hospitalized patients with T2DM compared with short-term CSII monotherapy.

7.
Mar Biotechnol (NY) ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32030579

RESUMO

Amur ide (Leuciscus waleckii, Family Cyprinidae) is widely distributed in Northeast Asia. L. waleckii usually inhabits freshwater environments but can also survive in the Lake Dali Nur, one of the most extreme aquatic environments on the earth, with an alkalinity up to 50 mmol/L (pH 9.6). To investigate mechanisms of mitogenomic evolution underlying adaptation to extreme environments, we determined 30 complete mitogenomes that included Lake Dali Nur (alkaline environment, AL) population and Amur basin (freshwater environment, FW) population. Through phylogenetic and divergence time analysis, we found that AL and FW populations forming distinct two groups which were consistent with geographic divergence (the formation of Lake Dali Nur). In addition, we found that almost of the windows exhibited higher nucleotide diversity in FW population (avg 0.0046) than AL population (avg 0.0012). This result indicated that severe environment selection had remarkably reduced the genetic diversity of mitogenome in AL population and suggested that severe environment selection had remarkably reduced the genetic diversity of mitogenome in the AL population. Compared with the FW population (ω = 0.064), the AL population (ω = 0.092) had a larger mean ω (dN/dS ratios) value for the 13 concatenated mitochondrial protein-coding genes, indicating that the high alkaline tolerated group had accumulated more nonsynonymous mutations. These nonsynonymous mutations had resulted in slightly beneficial amino acid changes that allowed adaption to the severe conditions. This study provides an additional view to decipher the adaptive mitogenome evolution of L. waleckii of the high alkaline environment.

8.
Endocrine ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31927752

RESUMO

PURPOSE: The relationship between obstructive sleep apnea (OSA) and diabetic microvascular complications (DMC) are controversial. Whether low education is associated with increased risk of DMC independently of poor lifestyles are currently unknown. The aim of this study is to explore the independent associations of different PSG index and educational attainment with risks of DR, DKD, and DPN. METHODS: A cross-sectional study of 330 patients with T2DM who underwent overnight polysomnography (PSG) tests. Multivariable logistic regression analysis was performed to determine the associations of PSG index and educational attainments with DR, DKD, and DPN. RESULTS: The prevalence rates of DMC were 30.6% for DR, 24.9% for DKD, and 64.6% for DPN. All PSG index (AHI, REM-AHI, NREM-AHI, the severity of OSAS, ODI, MAI, and lowest SaO2) were not significantly associated with risks of DR, DKD, or DPN with adjustment for potential confounding factors. Subjects with increasing educational attainments showed significantly decreased prevalence rates of DR (42.6, 27.3, and 21.3%, p = 0.005), DKD (31.7, 25.3, and 14.7%, p = 0.035) and DPN (74.3, 63.6, and 53.3%, p = 0.015), respectively. Logistic regression analyses showed that educational attainment of primary or below showed significantly increased risks of DR (OR (95% CIs): 3.596 (1.453-8.899, p = 0.006)) and DKD (OR (95% CIs): 3.201 (1.244-8.242, p = 0.016)) as compared with that of college or above. There were significant trends of lower educational attainment with increased risks of DR and DKD (p values < 0.05). CONCLUSION: PSG index were not significantly associated with DMC. But lower education was significantly associated with increased risks of DR and DKD, and strategies to prevent DMC for those with low education should be strengthened.

9.
Sci Rep ; 10(1): 439, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949205

RESUMO

Flavanomarein (FM) is a major natural compound of Coreopsis tinctoria Nutt with protective effects against diabetic nephropathy (DN). In this study, we investigated the effects of FM on epithelial-mesenchymal transition (EMT) in high glucose (HG)-stimulated human proximal tubular epithelial cells (HK-2) and the underlying mechanisms, including both direct targets and downstream signal-related proteins. The influence of FM on EMT marker proteins was evaluated via western blot. Potential target proteins of FM were searched using Discovery Studio 2017 R2. Gene Ontology (GO) analysis was conducted to enrich the proteins within the protein-protein interaction (PPI) network for biological processes. Specific binding of FM to target proteins was examined via molecular dynamics and surface plasmon resonance analyses (SPR). FM promoted the proliferation of HK-2 cells stimulated with HG and inhibited EMT through the Syk/TGF-ß1/Smad signaling pathway. Spleen tyrosine kinase (Syk) was predicted to be the most likely directly interacting protein with FM. Combined therapy with a Syk inhibitor and FM presents significant potential as an effective novel therapeutic strategy for DN.

10.
Fish Shellfish Immunol ; 96: 190-200, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765792

RESUMO

Complement is a complex component of innate immune system, playing an important role in defense against pathogens and host homeostasis. The complement system has been comprehensively studied in mammals, however less is known about complement in teleost, especially in tetraploid common carp (Cyprinus carpio). In this study, a total of 110 complement genes were identified and characterized in common carp, which include almost all the homologs of mammalian complement genes. These genes were classified into three pathways (alternative pathways, lectin pathways and classical pathways), similar to those in mammals. Phylogenetic and selection pressure analysis showed that the complement genes were evolving-constrained and the function was conserved. Most of the complement genes were highly expressed in spleen, liver, brain and skin among the tested 12 health tissues of common carp. After Aeromonas hydrophila infection in the common carp, many members of complement genes were activated to bring about an immune response and expressed to against any pathogenic encroachment. Gene expression divergences which were found between two homoeologous genes suggested the functional divergences of the homoeologous genes after the 4R WGD event, revealing the evolutionary fate of the tetraploid common carp after the recent WGD.

11.
Br J Pharmacol ; 177(2): 432-448, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31655022

RESUMO

BACKGROUND AND PURPOSE: Growing evidence indicates targeting mitochondrial dynamics and biogenesis could accelerate recovery from renal ischemia-reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Transcription factor forkhead box O1 (FOXO1) is a key regulator of mitochondrial homeostasis and plays a pathological role in the progression of renal disease. EXPERIMENTAL APPROACH: A mouse model of renal I/R injury and a hypoxia/reoxygenation (H/R) injury model for human renal tubular epithelial cells were used. KEY RESULTS: I/R injury up-regulated renal expression of FOXO1 and treatment with FOXO1-selective inhibitor AS1842856 prior to I/R injury decreased serum urea nitrogen, serum creatinine and the tubular damage score after injury. Post-I/R injury AS1842856 treatment could also ameliorate renal function and improve the survival rate of mice following injury. AS1842856 administration reduced mitochondrial-mediated apoptosis, suppressed the overproduction of mitochondrial ROS and accelerated recovery of ATP both in vivo and in vitro. Additionally, FOXO1 inhibition improved mitochondrial biogenesis and suppressed mitophagy. Expression of PPAR-γ coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis, was down-regulated in both I/R and H/R injury, which could be abrogated by FOXO1 inhibition. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that FOXO1 inhibited PGC-1α transcription by competing with cAMP-response element binding protein (CREB) for its binding to transcriptional coactivators CREBBP/EP300 (CBP/P300). CONCLUSION AND IMPLICATIONS: These findings suggested that FOXO1 was critical to maintain mitochondrial function in renal tubular epithelial cells and FOXO1 may serve as a therapeutic target for pharmacological intervention in renal I/R injury.

12.
J Ethnopharmacol ; 250: 112479, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31846746

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithin A (UroA), the main intestinal microflora metabolite of ellagic acid of berries, pomegranate,and some other traditional chinese herbals such as emblica officinalis,etc,has been reported to exhibit anti-inflammatory, anti-oxidative, anti-tumor and pro-autophagy effects. AIM OF THE STUDY: This study evaluated the anti-diabetic and pancreas-protective effects of UroA using a mice model of type 2 diabetes and preliminarily explored its effect on autophagy as well as the mechanism involved. MATERIALS AND METHODS: Type 2 diabetes model was induced by high-fat diet (HFD; 60% energy as fat) and low-dose streptozotocin (85 mg/kg) injection. Mice were administered with UroA (50 mg/kg/d) alone or UroA-chloroquine (autophagy inhibitor) combination for 8 weeks. RESULTS: UroA improved symptoms of diabetic mice such as high water intake volume, high urine volume, significantly decreased fasting blood glucose (FBG), after-glucose-loading glucose, glycated hemoglobin (GHb) levels, plasma C-peptide, malondialdehyde (MDA) and interleukin-1 ß level, increased reduced glutathione (GSH), interleukin-10 content, and glucose tolerance. UroA also improved pancreatic function indexes such as HOMA-ß as evidenced by improved pathological and ultrastructural features of the pancreas assessed by light microscopy and transmission electron microscopy (TEM). Accordingly, UroA decreased mitochondrial swelling and myelin-like cytoplasmic inclusions. UroA significantly upregulated the protein levels of microtubule-associated protein 1 light chain 3-II (LC3II) and beclin1, downregulated sequestosome 1 (p62) accompanied by decreased expression of apoptotic protein cleaved caspase3 in pancreas of diabetic mice. In addition, it increased the phosphorylation level of protein kinase B (p-Akt) and mammalian target of rapamycin (p-mTOR). Most of these effects of UroA were reversed by treatment with autophagy inhibitor chloroquine. CONCLUSIONS: Our findings reveal that the pancreas protective effects of UroA against diabetes were partially mediated by its regulation of autophagy and AKT/mTOR signal pathway.

14.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1141-1148, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801720

RESUMO

OBJECTIVE: To explore the molecular mechanism underlying the inhibitory effects of aspirin against human breast cancer cell proliferation through bioinformatics analysis. METHODS: Drug Bank 5.1.3 was searched to identify direct protein targets (DPTs) of aspirin, and the protein-protein interaction (PPI) network of the DPTs was constructed online using STRING and the signaling pathways involved were identified. The genetic alterations of 6 DPTs associated with human breast cancer was analyzed and visualized by cBio Portal and OncoPrint, respectively. The transcriptomic data of breast cancer and normal tissues were downloaded from TCGA database, and the overexpressed genes were analyzed by DECenter. The intersection between the genes associated with the DPTs obtained by STRING analysis and the differentially over-expressed genes in TCGA was determined to confirm the candidate DPTs as a potential target of aspirin, and GO functional enrichment analysis was performed using Gene Ontology. The potential targets of aspirin against the proliferation of human breast cancer cells were verified by Western blotting. RESULTS: Eleven DPTs of aspirin were identified. KEGG pathway enrichment indicated that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2 and TP53) were associated with the occurrence and development of cancer. A total of 10 220 differentially expressed genes were identified from the TCGA database, and among them 4 genes (CDC25C, TPX2, CDC20, PLK1) were found to be the potential targets for aspirin. These genes were involved mostly in the regulation of cell cycle and cell division. Western blotting showed that aspirin could down-regulate the expression levels of several pivotal proteins that regulated cell cycle and cell division, including CDC25C, TPX2, CDC20 and PLK1. CONCLUSIONS: CDC25C, TPX2, CDC20 and PLK1 may be potential targets for aspirin to inhibit the proliferation of human breast cancer cells, by affecting the progress of cell cycle and cell division.


Assuntos
Aspirina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Biologia Computacional , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Cdc20 , Proteínas de Ciclo Celular , Proliferação de Células , Perfilação da Expressão Gênica , Humanos , Proteínas Associadas aos Microtúbulos , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas , Fosfatases cdc25
15.
EPMA J ; 10(4): 395-414, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832114

RESUMO

Background: Non-functional pituitary adenoma (NFPA) is highly heterogeneous with different hormone expression subtypes. Of them, follicle-stimulating hormone (FSH)-positive expression is an important subtype of NFPAs. It is well-known that FSH exerted its functions through binding its receptor. However, the expression rate of FSH receptor was significantly higher in aggressive pituitary adenomas. This study aimed to investigate the molecular characteristics of FSH-positive NFPAs for effective stratification of patient, target treatment, prognostic assessment, and personalized treatment of FSH-positive NFPAs. Methods: Tandem mass tag (TMT)-based quantitative proteomics was used to investigate differentially expressed proteins (DEPs) between FSH-positive and negative NFPAs. Gene ontology and KEGG pathway enrichment analyses were used to analyze the DEPs. Differentially expressed genes (DEGs) between invasive and non-invasive NFPAs from GEO database were analyzed with pathway enrichment analysis. Protein-protein interaction (PPI) networks were constructed based on DEPs in excetral cellular matrix (ECM)-receptor interaction, focal adhesion, and PI3K-Akt pathways. Cytoscape was used to obtain most significant modules. Western blot was used to validate the expressions of upregulated proteins (ITGA1, ITGA6, and ITGB4), the expression and phosphorylated status of Akt in PI3K-Akt pathway, and the expression of FSH receptors in FSH-positive relative to negative NFPAs. Results: A total of 594 DEPs (374 upregulated and 220 downregulated) were identified between FSH-positive and negative NFPAs. Nineteen KEGG pathway networks were identified to involve DEPs, and reveal molecular differences between FSH-positive and negative NFPAs, including three important pathways that were significantly associated with tumor invasiveness and aggressiveness: ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways. Further, focal adhesion pathway was also confirmed with invasiveness-related NFPA DEG data that were derived from GEO database. Moreover, the significantly upregulated DEPs (ITGA1, ITGA6, and ITGB4) that were associated with tumor invasiveness and aggressiveness were confirmed by immunoaffinity analysis in FSH-positive vs. negative NFPAs. Also, the phosphorylation level but not its expression level of AKT in PI3K-AKT signaling was significantly increased, and the expression level of FSH receptor was significantly increased in FSH-positive relative to negative NFPAs. Also, overlapping analysis of 594 DEPs and 898 DEGs revealed 45 invasiveness-related DEPs, including 11 upregulated DEPs (ITGA6, FARP1, PALLD, PPBP, LIMA1, SCD, UACA, BAG3, CLU, PLEC, and GATM) that were also upregulated genes in invasive NFPAs, and 8 downregulated DEPs (ALCAM, HP, FSTL4, IL13RA2, NPTX2, DPP6, CRABP2, and SLC27A2) that were also downregulated genes in invasive NFPAs. Conclusions: FSH-positive expression was an important NFPA subtype. It was the first time for this study to reveal FSH-related proteomic variations and the corresponding molecular network alterations in FSH-positive relative to negative NFPAs. Also, three signaling pathways (ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways) and involved upregulated proteins (ITGA1, ITGA6, ITGB4, pAKT, and FSHR) were significantly associated with tumor invasiveness and aggressiveness, and a set of invasiveness-related DEPs were identified with overlapping analysis of 594 DEPs in FSH-positive vs. negative NFPAs and 898 DEGs in invasive vs. non-invasive NFPAs. These findings offered the scientific evidence to in-depth understand molecular characteristics of FSH-positive NFPAs, and effectively stratify the post-surgery patients for personalized prognostic assessment and targeted treatment of FSH-positive NFPAs.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31707005

RESUMO

Myostatin, through type I receptor (kinase 4, 5, ALK4/5), functions to participate in the immune system and negatively regulate muscle growth in mammals. However, the role of myostatin (mstn) in the immune system of teleosts is largely unknown. In a previous study, we cloned the mstn1 cDNA encoding myostatin in Qi river crucian carp (Carassius auratus). In the present study, we have cloned mstn2 cDNA, which was characterized and analyzed together with mstn1. Tissue distribution analysis showed that both mstn genes are expressed in numerous tissues, with mstn1 dominantly expressed in the muscle and brain, whereas mstn2 is mainly expressed in the brain. During embryogenesis, mstn1 and mstn2 exhibit different expression patterns. Both mstn1 and mstn2 expression increased stepwise in the brain at different developmental stages. Furthermore, both genes are differentially regulated during different periods of fasting/re-feeding. Following the exposure of C. auratus to polyI:C, lipopolysaccharide (LPS), and Aeromonas hydrophila, both genes were upregulated in different tissues, which indicated that they might be involved in the immune response against pathogenic invasion. Blocking the Mstn signal pathway with SB-431542 (a chemical inhibitor of ALK4/5) resulted in significantly increased body length and weight. However, the mortality of SB-431542-treated fish was higher after A. hydrophila challenge. Moreover, decreased expression of lysozymes (lyz), complement component 3 (c3), ß-defensin 3 (defb3), and interferon γ (ifnγ) were exhibited in treated fish, compared with the controls. Furthermore, the expression of nf-κb1, three pro-inflammatory cytokines (il1ß, il6, and tnfα), and inflammatory cytokines (il8 and il10) were significantly increased in both the SB-431542-treated group and the control after A. hydrophila infection, suggesting that the NF-κB pathway was not suppressed in the SB-431542-treated fish. Taken together, our data suggest that both mstn1 and mstn2 play important roles in early body development, muscle growth, and the immune system by acting downstream of the NF-κB signal pathway.

17.
Sci Rep ; 9(1): 15998, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690787

RESUMO

Our aim is to assess the optimal cutoff value of fasting plasma glucose (FPG) in Chinese women at 24-28 weeks' gestation by performing oral glucose tolerance test (OGTT) to improve diagnostic rate of gestational diabetes mellitus (GDM). Data were derived from the Medical Birth Registry of Xiamen. A FPG cutoff value of 5.1 mmol/L confirmed the diagnosis of GDM in 4,794 (6.10%) pregnant women. However, a FPG cutoff value of 4.5 mmol/L should rule out the diagnosis of GDM in 35,932 (45.73%) pregnant women. If we use this cutoff value, the diagnosis of GDM to about 27.3% of pregnant women will be missed. Additionally, a 75-g OGTT was performed in pregnant women with FPG values between 4.5 and 5.1 mmol/L, avoiding the performance of formal 75-g OGTT in about 50.37% pregnant women. Meanwhile, according to maternal age and pre-pregnancy BMI categories, with FPG values between 4.5 mmol/L and 5.1 mmol/L, which had high sensitivity, to improve the diagnostic rate of GDM in all groups. Further researches are needed to present stronger evidences for the screening value of FPG in establishing the diagnosis of GDM in pregnant women.

18.
J Cancer ; 10(22): 5536-5548, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632497

RESUMO

Glioblastoma (GBM) is one of the lethal tumors with poor prognosis. However, prognostic prediction approaches need to be further explored. Therefore, we developed an evaluation system that could be used for prognostic prediction of GBM patients. Published mRNA expression datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) were analyzed. Quantitative Realtime-PCR of signature genes and molecular aberrations of 178 Xiangya GBM patients were used for confirmation. Gene set enrichment analysis (GSEA) was performed for functional annotation. As a result, we established a 13-gene signature which named Combined Therapy Sensitivity Index (CTSI). Based on a cutoff point, we divided patients into high-risk group and low-risk group. Based on Kaplan-Meier analysis and multivariate Cox regression analysis, we found that patients in the high-risk group had a shorter overall survival time than patients in the low-risk group (p<0.001 in TCGA and CGGA datasets, p=0.047 in GSE4271 dataset, p=0.008 in Xiangya GBM cohort, HR: 1.65-3.42). By comparing the status of IDH mutation, TERT promoter mutation (TERTp-mut) and MGMT promoter methylation, CTSI was predictable in IDH wild-type (IDH-wt)/MGMT promoter unmethylated (MGMTp-unmeth) patients (p=0.037 in IDH-wt/TERTp-mut/MGMTp-unmeth subgroup, HR: 1.98; p=0.032 in IDH-wt/TERTp-wt/MGMTp-unmeth subgroup, HR: 2.09). Based on GESA, the Gene Ontology (GO) gene sets were enriched differently between CTSI high-risk and low-risk groups. Our results showed CTSI risk score can predict the prognosis of IDH-wt/MGMTp-unmeth GBM patients. Based on CTSI, combined with the status of IDH mutation, TERT promoter mutation and MGMT promoter methylation, a stepwise prognosis evaluation system which can provide precise prognosis prediction for GBM patients was established.

19.
Front Cell Dev Biol ; 7: 217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632968

RESUMO

Background: LncRNAs have been shown to play essential roles in cancer therapeutic response. However, the detailed mechanism of lncRNAs in temozolomide (TMZ) resistance in glioblastoma (GBM) remain to be elucidated. Methods: To elucidate the mechanism maintaining TMZ resistance, we constructed two TMZ-resistant GBM cell lines (T98G-R/U118-R). LncRNAs from four public datasets were reanalyzed, and the candidate lncRNA ADAMTS9-AS2 was evaluated in TMZ-treated GBM patients and in vitro cell lines. Results: Reanalysis of lncRNA expression profiles identified ADAMTS9-AS2 as significantly overexpressed in TMZ-resistant GBM cells and as positively associated with the IC50 of TMZ in GBM cells. Overexpression of ADAMTS9-AS2 was also significantly associated with poor TMZ response and shorter progression-free survival (PFS) in TMZ-treated GBM patients. Knockdown of ADAMTS9-AS2 inhibited proliferation and attenuated the IC50 of TMZ, as well as mitigating invasion and migration in TMZ-resistant GBM cells. Subsequent investigations indicated that reduced expression of ADAMTS9-AS2 significantly suppressed expression of the FUS protein, which was predicted as a direct substrate of ADAMTS9-AS2. Expression trends of FUS were directly correlated with those of ADAMTS9-AS2, as shown by increasing concentrations and prolonged treatment with TMZ. RNA pull-down and RIP assays indicated that both endogenous and exogenous ADAMTS9-AS2 directly binds to the RRM and Znf_RanBP2 domains of FUS, consequently increasing FUS protein expression. Knockdown of ADAMTS9-AS2 reduced the half-life of FUS and decreased FUS protein stability via K48 ubiquitin degradation. Moreover, the E3 ubiquitin-protein ligase MDM2 interacts with and down regulates FUS, while the RRM and Znf_RanBP2 domains of FUS facilitate its binding with MDM2. ADAMTS9-AS2 decreased the interaction between MDM2 and FUS, which mediates FUS K48 ubiquitination. Additionally, knockdown of the ADAMTS9-AS2/FUS signaling axis significantly alleviated progression and metastasis in TMZ-resistant cells. Conclusion: ADAMTS9-AS2 possessed a novel function that promotes TMZ resistance via upregulating the FUS/MDM2 axis in GBM cells. The RRM or Znf_RanBP2 domains of FUS facilitate the combination of ADAMTS9-AS2 and FUS, competitively inhibiting MDM2-dependent FUS K48 ubiquitination and resulting in enhanced FUS stability and TMZ resistance. Our results suggest that the ADAMTS9-AS2/FUS/MDM2 axis may represent a suitable prognostic biomarker and a potential target in TMZ-resistant GBM therapy.

20.
Front Genet ; 10: 960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649731

RESUMO

The largemouth bass is an important species, and its culture has risen sharply with the surge in fish aquaculture in China. Due to the lack of selective breeding technology for the largemouth bass, the growth rate and disease resistance are low, its sexual maturation is slow, and other serious problems are contributing to a sharp decline in the safety and quality of largemouth bass products in recent decades. Therefore, comprehensive breeding programs to improve the economic performance and promote the modern industrial development of largemouth bass must be considered a priority. Here, a total of 152 adult largemouth bass, including two parents and 150 progenies, were selected to produce the genetic mapping family. Then, a high-density linkage map was constructed based on restriction site-associated DNA sequencing using 6,917 single-nucleotide polymorphisms (SNPs) located in 24 linkage groups (LGs). The total genetic length of the linkage map was 1,261.96 cM, and the length of each LG varied from 24.72 cM for LG02 to 117.53 cM for LG16, with an average length of 52.58 cM and an average SNP number of 286. Thirteen significant quantitative trait loci (QTLs) for sex determination were located on LG04, LG05, LG08, LG12, LG15, LG21, and LG23. An informative QTL cluster that included six QTLs was detected on LG12. However, one notable QTL, which accounted for 71.48% of the total phenotypic variation, was located in the region of 1.85 cM on LG05. In addition, 32 identified QTLs were related to growth, including body weight, body length, body height, and head length. The QTLs for these growth-related traits are located in 13 LG regions and have little effect on phenotypic variation. This high-density genetic linkage map will enable the fine-mapping of economic traits and support the future genome assembly of the largemouth bass. Additionally, our study will be useful for future selective culture of largemouth bass and could potentially be used in molecular-assisted breeding of largemouth bass for aquaculture.

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