Profiling of exosomal microRNAs expression in umbilical cord blood from normal and preeclampsia patients.

BACKGROUND: Epidemiological and experimental studies suggest that preeclampsia has a negative impact on maternity and offspring health. Previous studies report that dysregulation in utero-environment increases risk for elderly disease such as cardiovascular disease. However, the underlying mechanisms remain elusive. Specific microRNAs (miRNAs) are packaged in exosomes may regulate microvascular dysfunction in offspring of mothers with preeclampsia. The present study aimed to identify the differential expression profiles of microRNAs in the serum exosomes between patients with preeclampsia and normal pregnancies. METHODS: A comprehensive miRNA sequence-based approach was performed to compare exosomes carry miRNAs (Exo-miRNAs) expression levels in umbilical serum between normal and preeclampsia patients. Exosomes were isolated using the ExoQuick precipitation kit. Serum exosomes were then viewed under electron microscopy, and their characteristics determined by western blotting and nanoparticle-tracking analysis. Illumina platform was used to perform sequencing. Bioinformatics analysis was used to explore differentially expressed Exo-miRNAs in umbilical serum. RESULTS: Based on sequence similarity, 1733 known miRNAs were retrieved. Furthermore, 157 mature miRNAs in serum exosomes were significantly differential expressed between PE and those control groups (P<0.05, log2|FC| > 1). Out, of the 157 miRNAs, 96 were upregulated miRNAs whereas 61 miRNAs were downregulated. The 157 differentially expressed miRNAs targeted 51,424 differentially expressed genes. Functional analysis through KEGG pathway and Gene Ontology results uncovered that target genes of miRNAs with differential expression were significantly linked to several pathways and biological processes. CONCLUSION: The findings of this study showed differential expression of umbilical serum Exo-miRNAs in normal compared with PE patients, implying that these Exo-miRNAs may associate with microvascular dysfunction in offspring of mothers with preeclampsia.

iTRAQ-based quantitative proteomic analysis of thoracic aortas from adult rats born to preeclamptic dams.

BACKGROUND: Preeclampsia and gestational hypertension can cause vascular function impairment in offspring. In our previous work, we described the protein expression profiles of umbilical artery tissues from patients with preeclampsia. METHODS: To gain insights into the mechanisms of vascular dysfunction in adult rats born to preeclamptic dams, we analyzed thoracic aorta tissues by using iTRAQ isobaric tags and 2D nano LC-MS/MS. RESULTS: By using the iTRAQ method, we analyzed 1825 proteins, of which 106 showed significantly different expression in the thoracic aortic. Ingenuity pathway analysis (IPA) showed that the majority of differentially expressed proteins (DEPs) were associated with cardiovascular function. Further analysis indicated that glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by miR-423-5p and activated by TP53, had the strongest effect on cardiovascular function. The expression of G6PD was upregulated in thoracic aorta tissues, as confirmed by Western blotting. The expression of two other vascular function-related proteins, cysteine- and glycine-rich protein 2 (CSRP2) and tubulin alpha-4 A (TUBA4A), was upregulated, as demonstrated by mass spectrometry (MS). CONCLUSIONS: Although the results require further functional validation, these data provide novel findings related to vascular function impairment in the adult offspring of preeclamptic mothers.

Prognostic and metabolic characteristics of a novel cuproptosis-related signature in patients with hepatocellular carcinoma.

Cuproptosis is a novel discovered mode of programmed cell death. To identify the molecular regulatory patterns related to cuproptosis, this study was designed for exploring the correlation between cuproptosis-related genes (CRGs) and the prognosis, metabolism, and treatment of hepatocellular carcinoma (HCC). Cancer Genome Atlas (TCGA) database was used to screen 363 HCC samples, which were categorized into 2 clusters based on the expression of CRGs. Survival analysis demonstrated that overall survival (OS) was better in Cluster 1 than Cluster 2 which might to be relevant to differences in metabolic based on functional analysis. With LASSO regression analysis and univariate COX regression, 8 prognosis-related genes were screened, a differently expressed genes (DEGs) were then constructed (HCC patients' DEGs)-based signature. The signature's stability was also validated in the 2 independent cohorts and test cohorts (GSE14520, HCC dataset in PCAWG). The 1-year, 3-year, and 5-year area under the curve (AUC) were 0.756, 0.706, and 0.722, respectively. The signature could also well predict the response to chemotherapy, targeted and transcatheter arterial chemoembolization (TACE) by providing a risk score. Moreover, the correlation was uncovered by the research between the metabolism and risk score. In conclusion, a unique cuproptosis-related signature that be capable of predicting patients' prognosis with HCC, and offered valuable insights into chemotherapy, TACE and targeted therapies for these patients has been developed.

Proteomics and bioinformatics analysis of cardiovascular related proteins in offspring exposed to gestational diabetes mellitus.

Introduction: Previous studies have demonstrated that exposed to the initial suboptimal intrauterine environment of gestational diabetes mellitus (GDM) may increase risk of cardiovascular disease in adulthood. Methods: In order to investigate the underlying mechanisms involved in the increased risk of cardiovascular diseases (CVDs) in the offspring of GDM, we applied a high-throughput proteomics approach to compare the proteomic expression profile of human umbilical vessels of normal and GDM offspring. Results: A total of significantly different 100 proteins were identified in umbilical vessels from GDM group compared with normal controls, among which 31 proteins were up-regulated, while 69 proteins were down-regulated. Differentially expressed proteins (DEPs) are validated using Western blotting analysis. The analysis of these differently expressed proteins (DEPs) related diseases and functions results, performed by Ingenuity Pathway Analysis (IPA) software. Based on "Diseases and Disorders" analysis, 17 proteins (ACTA2, ADAR, CBFB, DDAH1, FBN1, FGA, FGB, FGG, GLS, GSTM1, HBB, PGM3, PPP1R13L, S100A8, SLC12A4, TPP2, VCAN) were described to be associated with CVD, especially in Anemia, Thrombus and Myocardial infarction. Functional analysis indicated that DEPs involved in many cardiovascular functions, especially in "vasoconstriction of blood vessel" (related DEPs: ACTA2, DDAH1, FBN1, FGA, FGB, and FGG). Upstream regulator analyses of DEPs identifies STAT3 as inhibitor of ACTA2, FGA, FGB, and FGG. Conclusion: The results of this study indicate that intrauterine hyperglycemia is associated with an elevated risk of cardiovascular risk in the offspring.

[Genetic analysis of resistance to rice blast in four Japonica landraces from Taihu Lake region].

The crosses were made between four japonica rice (Oryza sativa L.) landraces Bodao, Tieganqing, Jiangnanwan and Queernuo from Taihu Lake region, which were highly resistant to the blast (Magnaporthe grisa), and a susceptible japonica variety Suyunuo to produce F1 and F2 generations. The P1 , P2, F1 and F2 generation from various combinations were inoculated separately with Japanese blast strain Hoku 1 and Chinese races ZE3 and ZG1 to study genetic patterns of resis-tance in the four landraces to the blast. Resistance in Bodao, Tieganqing or Queernuo to blast Hoku 1 might be controlled by a dominant gene, and in Jiangnanwan by two inhibiting effect genes. Resistance in Tieganqing or Queernuo to blast ZE3 might be controlled by one dominant gene, and in Bodao and Jiangnanwan by two independently dominant genes and two inhibiting effect genes, respectively. Resistance in Tieganqing to blast ZG1 might be controlled by a dominant gene, but in Bodao and Jiangnanwan by two inhibiting effect genes. The crosses were further made between landrace Bodao and 12 Japanese differential varieties possessing the known resistance genes to the blast to produce F1 and F2 generations. The plants of various generations were inoculated with strain Hoku 1 to confirm the resistance gene in Bodao was allelic with known resistance genes. The results show that the resistance gene in Bodao to strain Hoku 1 was non allelic with known resistance genes, and tentatively designated Pi-bd1(t).

[Imbalance of serum T helper 1- and 2-type cytokines in preeclampsia and gestational hypertension].

OBJECTIVE: To investigate the changes in serum levels of Th1- (IL-2 and TNF-alpha) and Th2-type cytokines (IL-10) and the ratios of Th1/Th2 (IL-2/IL-10 and TNF-alpha/IL-10) in preeclampsia and in gestational hypertension. METHODS: Levels of IL-2, IL-10 and TNF-alpha were determined with radioimmunoassay in serum samples from 22 women with preeclampsia, 15 women with gestational hypertension and 32 normal term pregnant women. The Th1/Th2 ratios were calculated accordingly. RESULT: There were no significant differences in serum levels of IL-2, IL-10 and TNF-alpha (P>0.05 for all) among normal pregnancy, gestational hypertension and preeclampsia. The ratio of serum IL-2/IL-10 was significantly higher in preeclampsia than that in controls (P < 0.05), and the ratio of TNF-alpha/IL-10 significantly higher in patients with preeclampsia than that in either controls or gestational hypertension (P<0.025 for both). CONCLUSION: Alterations of serum cytokine balance with predominance of Th1 immunity were observed in preeclampsia. These associations may offer insight into the pathogenesis of preeclampsia.