Integrated Analysis of lncRNAs and mRNAs Identifies a Potential Driver lncRNA FENDRR in Lung Cancer in Xuanwei, China.

This study was to screen out potential driver long non-coding RNAs (lncRNAs) in lung cancer in Xuanwei (LCXW) differently expressed mRNAs and lncRNAs were detected by gene expression microarrays in 23 paired lung adenocarcinoma and adjacent tissues. Combined bioinformatics analysis was performed to identify potential driver lncRNAs and their potential regulatory relationships. Transcriptome and clinical data in TCGA-LUAD were used as comparison and validation dataset. The comparison of LCXW and TCGA-LUAD revealed significant differences in expression of some genes, signaling pathways affected by differentially expressed genes, and the 5-year survival rate of patients. We identified 14 consistently deregulated mRNAs and 5 lncRNAs as candidate genes, which affected multiple cancer-related pathways and influenced patients' overall survival. By combined bioinformatics analysis, we further identified a potential driver lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) and proposed its possible regulation mechanism. The low expression of FENDRR was positively correlated with Krüppel-like factor4 (KLF4), KLF4 down-regulation may loss the activation function of cyclin-dependent kinase inhibitor 1A (CDKN1A) and cyclin-dependent kinase inhibitor 1C (CDKN1C) and the inhibition function of CyclinB1 (CCNB1), eventually cause excessive cell cycle activation and lead to lung cancer. This study revealed a potential FENDRR-KLF4-cell cycle regulation axis. These results lay an important foundation for further research on the pathogenesis of LCXW and identification of potential novel biomarkers or therapeutic targets.

Regulatory function of praja ring finger ubiquitin ligase 2 mediated by the P2rx3/P2rx7 axis in mouse hippocampal neuronal cells.

Praja2 (Pja2), a member of the growing family of mammalian RING E3 ubiquitin ligases, is reportedly involved in not only several types of cancer but also neurological diseases and disorders, but the genetic mechanism underlying the regulation of Pja2 in the nervous system remains unclear. To study the cellular and molecular functions of Pja2 in mouse hippocampal neuronal cells (MHNCs), we used gain- and loss-of-function manipulations of Pja2 in HT-22 cells and tested their regulatory effects on three Alzheimer's disease (AD) genes and cell proliferation. The results revealed that the expression of AD markers, including amyloid beta precursor protein (App), microtubule-associated protein tau (Mapt), and gamma-secretase activating protein (Gsap), could be inhibited by Pja2 overexpression and activated by Pja2 knockdown. In addition, HT-22 cell proliferation was enhanced by Pja2 upregulation and suppressed by its downregulation. We also evaluated and quantified the targets that responded to the enforced expression of Pja2 by RNA-Seq, and the results showed that purinergic receptor P2X, ligand-gated ion channel 3 and 7 (P2rx3 and P2rx7), which show different expression patterns in the critical calcium signaling pathway, mediated the regulatory effect of Pja2 in HT-22 cells. Functional studies indicated that Pja2 regulated HT-22 cells development and AD marker genes by inhibiting P2rx3 but promoting P2rx7, a gene downstream of P2rx3. In conclusion, our results provide new insights into the regulatory function of the Pja2 gene in MHNCs and thus underscore the potential relevance of this molecule to the pathophysiology of AD.

High infiltration of CD20+ B lymphocytes in extranodal natural killer/T-cell lymphoma is associated with better prognosis.

Immune cells have an uncertain function during the progression of extranodal natural killer/T-cell lymphoma (ENKTL). The present study determined the distribution, phenotype, and clinical significance of B lymphocytes in ENKTL. Immunohistochemistry indicated high infiltration of CD20+ B lymphocytes in the tumour tissues of 40% of the patients, and that a high infiltration correlated with better overall survival. Moreover, B lymphocytes had an active mature phenotype in situ and suppressed the proliferation of ENKTL cells in vitro. These results suggest that tumour infiltration of CD20+ B lymphocytes may be a new prognostic indicator for patients with ENKTL.

Novel Long Non-coding RNA Markers for Prognostic Prediction of Patients with Bladder Cancer.

Objective To explore novel long non-coding RNA (lncRNA) molecular markers related to bladder cancer prognosis and to construct a prognostic prediction model for bladder cancer patients. Methods LncRNA expression data of patients with bladder cancer were downloaded from TCGA database. Univariate Cox regression and likelihood-based survival analysis were used to discover prognosis related lncRNAs. Functional studies of prognosis related lncRNAs were conducted by co-expression analysis and pathway enrichment analysis. Multivariate Cox regression analysis was used to establish risk score model, and Receiver Operating Characteristic analysis was used to determine the optimal cut-off point of the model. The risk score model was validated through Kaplan Meier estimation method and log-rank test. Results Seven prognosis related lncRNAs (OCIAD1-AS1, RP11-111J6.2, AC079354.3, RP11-553A21.3, RP11-598F7.3, CYP4F35P and RP11-113K21.4) which can predict survival of bladder cancer patient were discovered. Co-expression analysis and pathway analysis of these novel lncRNA signature and their target genes further revealed that these lncRNAs play important roles in the occurrence and development of bladder cancer. Additionally, a seven-lncRNA signature based risk score model for prognostic prediction of bladder cancer patients was established and validated. Notably, we identified the potential significance of two tumor-related antisense lncRNAs (OCIAD1-AS1 and RP11-553A21.3) in the prognosis of bladder cancer. Conclusion Our results suggest that these lncRNA markers may serve as potential prognosis predictors for bladder cancer and deserve further functional verification studies.

[Research advances in the effect of bioactive substances in breast milk on the growth and development of infants].

There are various types of bioactive substances in human breast milk, such as active proteins, growth factors, cytokines, oligosaccharides, probiotics and cells. Many studies have shown that these bioactive substances in breast milk have important protective effects on infant growth and development, including anti-bacterial and anti-viral effects and the promotion of infant growth and development and immunologic maturation. They can also reduce the incidence rate of infectious diseases in infants, improve neural development in preterm infants, and reduce the risk of obesity and diabetes in future. However, there is still no clinical evidence for the effects of several active substances in breast milk, and their immunoregulatory mechanism remains unclear. Therefore, further studies are needed for clarification.

[Clinical features of coronavirus disease 2019 in children: a systemic review of severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019].

OBJECTIVE: To systematically summarize the clinical features of coronavirus disease 2019 (COVID-19) in children. METHODS: PubMed, Embase, Web of Science, The Cochrane Library, CNKI, Weipu Database, and Wanfang Database were searched for clinical studies on COVID-19 in children published up to May 21, 2020. Two reviewers independently screened the articles, extracted data, and assessed the risk of bias of the studies included. A descriptive analysis was then performed for the studies. Related indices between children with COVID-19 and severe acute respiratory syndromes (SARS) or Middle East respiratory syndrome (MERS) were compared. RESULTS: A total of 75 studies were included, with a total of 806 children with COVID-19. The research results showed that the age of the children ranged from 36 hours after birth to 18 years, with a male-female ratio of 1.21 : 1. Similar to SARS and MERS, COVID-19 often occurred with familial aggregation, and such cases accounted for 74.6% (601/806). The children with COVID-19, SARS, and MERS had similar clinical symptoms, mainly fever and cough. Some children had gastrointestinal symptoms. The children with asymptomatic infection accounted for 17.9% (144/806) of COVID-19 cases, 2.5% (2/81) of SARS cases, and 57.1% (12/21) of MERS cases. The children with COVID-19 and MERS mainly had bilateral lesions on chest imaging examination, with a positive rate of lesions of 63.4% (421/664) and 26.3% (5/19) respectively, which were lower than the corresponding positive rates of viral nucleic acid detection, which were 99.8% and 100% respectively. The chest radiological examination of the children with SARS mainly showed unilateral lesion, with a positive rate of imaging of 88.9% (72/81), which was higher than the corresponding positive rate of viral nucleic acid detection (29.2%). Viral nucleic acid was detected in the feces of children with COVID-19 or SARS, with positive rates of 60.2% (56/93) and 71.4% (5/7) respectively. The children with COVID-19 had a rate of severe disease of 4.6% (31/686) and a mortality rate of 0.1% (1/806), the children with SARS had a rate of severe disease of 1.5% (1/68) and a mortality rate of 0%, and those with MERS had a rate of severe disease of 14.3% (3/21) and a mortality rate of 9.5% (2/21). CONCLUSIONS: Children with COVID-19 have similar symptoms to those with SARS or MERS, mainly fever and cough. Asymptomatic infection is observed in all three diseases. Children with COVID-19 or SARS have milder disease conditions than those with MERS. COVID-19 in children often occurs with familial aggregation. Epidemiological contact history, imaging examination findings, and viral nucleic acid testing results are important bases for the diagnosis of COVID-19.

[Effect of irisin on hypoxic-ischemic brain damage in neonatal rats].

OBJECTIVE: To study the effect and mechanism of action of irisin on hypoxic-ischemic brain damage in neonatal rats. METHODS: A total of 248 7-day-old Sprague-Dawley rats were randomly divided into a sham-operation group, a model group, and low- and high-dose irisin intervention groups (n=62 each). The rats in the model and irisin intervention groups were given hypoxic treatment after right common carotid artery ligation to establish a model of hypoxic-ischemic brain damage. Those in the sham-operation group were given the separation of the right common carotid artery without ligation or hypoxic treatment. The rats in the high- and low-dose irisin intervention groups were given intracerebroventricular injection of recombinant irisin polypeptide at a dose of 0.30 µg and 0.15 µg respectively. Those in the model and sham-operation groups were given the injection of an equal volume of PBS. The water maze test was used to compare neurological behaviors between groups. TTC staining, hematoxylin-eosin staining and TUNEL staining were used to observe histopathological changes of the brain. Western blot was used to measure the expression of the apoptosis-related molecules cleaved-caspase-3 (CC3), BCL-2 and BAX. RESULTS: Compared with the sham-operation group, the model group had a significant increase in latency time and a significant reduction in the number of platform crossings (P<0.05). Compared with the model group, the high-dose irisin intervention group had a significant reduction in latency time and a significant increase in the number of platform crossings (P<0.05). Compared with the sham-operation group, the model group had massive infarction in the right hemisphere, with significant increases in karyopyknosis and karyorrhexis. Compared with the model group, the high-dose irisin intervention group had a smaller infarct area of the right hemisphere, with reductions in karyopyknosis and karyorrhexis. The model group had a significantly higher apoptosis rate of cells in the right cerebral cortex and the hippocampus than the sham-operation group. The high-dose irisin intervention group had a significantly lower apoptosis rate than the model group (P<0.05). At 24 and 48 hours after modeling, the sham-operation group had a significantly lower level of CC3 than the model group (P<0.05). Compared with the model group, the high-dose irisin intervention group had a significantly lower level of CC3 and a significantly higher BCL-2/BAX ratio (P<0.05). The low-dose irisin intervention group had similar laboratory markers and histopathological changes of the brain to the model group. CONCLUSIONS: Irisin can alleviate hypoxic-ischemic brain damage in neonatal rats in a dose-dependent manner, possibly by reducing cell apoptosis in the cerebral cortex and the hippocampus.

Gain and loss events in the evolution of the apolipoprotein family in vertebrata.

BACKGROUND: Various apolipoproteins widely distributed among vertebrata play key roles in lipid metabolism and have a direct correlation with human diseases as diagnostic markers. However, the evolutionary progress of apolipoproteins in species remains unclear. Nine human apolipoproteins and well-annotated genome data of 30 species were used to identify 210 apolipoprotein family members distributed among species from fish to humans. Our study focused on the evolution of nine exchangeable apolipoproteins (ApoA-I/II/IV/V, ApoC-I~IV and ApoE) from Chondrichthyes, Holostei, Teleostei, Amphibia, Sauria (including Aves), Prototheria, Marsupialia and Eutheria. RESULTS: In this study, we reported the overall distribution and the frequent gain and loss evolutionary events of apolipoprotein family members in vertebrata. Phylogenetic trees of orthologous apolipoproteins indicated evident divergence between species evolution and apolipoprotein phylogeny. Successive gain and loss events were found by evaluating the presence and absence of apolipoproteins in the context of species evolution. For example, only ApoA-I and ApoA-IV occurred in cartilaginous fish as ancient apolipoproteins. ApoA-II, ApoE, and ApoC-I/ApoC-II were found in Holostei, Coelacanthiformes, and Teleostei, respectively, but the latter three apolipoproteins were absent from Aves. ApoC-I was also absent from Cetartiodactyla. The apolipoprotein ApoC-III emerged in terrestrial animals, and ApoC-IV first arose in Eutheria. The results indicate that the order of the emergence of apolipoproteins is most likely ApoA-I/ApoA-IV, ApoE, ApoA-II, ApoC-I/ApoC-II, ApoA-V, ApoC-III, and ApoC-IV. CONCLUSIONS: This study reveals not only the phylogeny of apolipoprotein family members in species from Chondrichthyes to Eutheria but also the occurrence and origin of new apolipoproteins. The broad perspective of gain and loss events and the evolutionary scenario of apolipoproteins across vertebrata provide a significant reference for the research of apolipoprotein function and related diseases.

Regulatory network reconstruction of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets.

Although many of the genetic loci associated with breast cancer risk have been reported, there is a lack of systematic analysis of regulatory networks composed of different miRNAs and mRNAs on survival analysis in breast cancer. To reconstruct the microRNAs-genes regulatory network in breast cancer, we employed the expression data from The Cancer Genome Atlas (TCGA) related to five essential miRNAs including miR-21, miR-22, miR-210, miR-221, and miR-222, and their associated functional genomics data from the GEO database. Then, we performed an integration analysis to identify the essential target factors and interactions for the next survival analysis in breast cancer. Based on the results of our integrated analysis, we have identified significant common regulatory signatures including differentially expressed genes, enriched pathways, and transcriptional regulation such as interferon regulatory factors (IRFs) and signal transducer and activator of transcription 1 (STAT1). Finally, a reconstructed regulatory network of five miRNAs and 34 target factors was established and then applied to survival analysis in breast cancer. When we used expression data for individual miRNAs, only miR-21 and miR-22 were significantly associated with a survival change. However, we identified 45 significant miRNA-gene pairs that predict overall survival in breast cancer out of 170 one-on-one interactions in our reconstructed network covering all of five miRNAs, and several essential factors such as PSMB9, HLA-C, RARRES3, UBE2L6, and NMI. In our study, we reconstructed regulatory network of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets. These results may provide new insights into regulatory network-based precision medicine for breast cancer.

Identification of metabolism-associated pathways and genes involved in male and female liver cancer patients.

Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. HCC is influenced by sex and multiple metabolic abnormalities. The present study aimed to compare the overall metabolic changes between male and female HCC patients and identify key metabolic genes. Metabolic genes and pathways were identified based on analyses of publicly available data. Differential expression analysis, gene set enrichment analysis, survival analysis and transcriptional regulation analysis were employed to explore sex differences and identify key metabolic genes in HCC. The results suggested that female patients had more severe metabolic gene expression abnormalities and pathway deregulation than male patients. This study identified 9 key metabolic genes, and only upregulated ALDH1A2 independently increased overall survival risk in patients. Bioinformatic analyses suggest that upregulated GATA3 and TAL1 activate ALDH1A2 and then disrupt amino acid and carbohydrate metabolism, which may increase the risk of HCC. This study identified a novel contribution of upregulated ALDH1A2 to HCC. Future studies are needed to elucidate the potential metabolic mechanism of the role of ALDH1A2 in HCC.

Soluble CXCL16 promotes TNF-α-induced apoptosis in DLBCL via the AMAD10-NF-κB regulatory feedback loop.

We had previously identified that the co-expression of transmembrane CXCL16 (TM-CXCL16) and its receptor CXCR6 is an independent risk factor for poor survival in patients with diffuse large B-cell lymphoma (DLBCL). However, the impact of the soluble form of CXCL16 (sCXCL16) on the pathogenesis of DLBCL remains unknown. In the present study, the synergistic effect of sCXCL16 and tumor necrosis factor α (TNF-α) on apoptosis in DLBCL cell lines (OCI-LY8 and OCI-LY10) was investigated in vitro. sCXCL16 reinforced TNF-α-mediated inhibition of DLBCL cell proliferation, as determined by the cell counting kit-8 assay. The results of annexin V staining showed that sCXCL16 enhanced TNF-α-induced apoptosis in OCI-LY8 and OCI-LY10 cells through a death receptor-caspase signaling pathway. The results of gene microarray suggested a significant upregulation of differentially expressed genes in the TNF signaling pathway. sCXCL16 increased the concentration of extracellular TNF-α by binding to CXCR6 to activate the nuclear factor-κB (NF-κB) signaling pathway. TNF-α also induced the secretion of sCXCL16 by increasing the expression of ADAM10, which is known to cleave TM-CXCL16 to yield sCXCL16. Moreover, bioinformatics analysis revealed that elevated TNF-α and ADAM10 expression levels in tumor tissues predicted better survival in patients with DLBCL. Thus, our study suggests that sCXCL16 enhances TNF-α-induced apoptosis of DLBCL cells, which may involve a positive feedback loop consisting of TNF-α, ADAM10, sCXCL16, and members of the NF-κB pathway. sCXCL16 and TNF-α may be used as prognostic markers in the clinic, and their combinational use is a promising approach in the context of DLBCL therapy.

Bioinformatics Analysis Identifies Protein Tyrosine Kinase 7 (PTK7) as a Potential Prognostic and Therapeutic Biomarker in Stages I to IV Hepatocellular Carcinoma.

BACKGROUND Worldwide, hepatocellular carcinoma (HCC) accounts for 80-90% of all cases of primary liver cancer, and is one of the ten most common malignancies. This study used bioinformatics analysis to identify genes associated with patient outcome in stages I-IV HCC and the gene pathways that distinguished between normal liver and liver cells and HCC and human HCC cell lines. MATERIAL AND METHODS Target genes were defined as those that had marketed drugs or drugs under development targeting a specific gene and acquired from the Clarivate Analytics Integrity Database. Differential expression gene analysis, co-expression network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, survival analysis and receiver operating characteristic (ROC) curve analysis were used to explore the similarities and differences in gene expression profiles, functional associations, and survival in stage I-IV HCC. Normal liver cells (HL-7702) and HCC cell lines (HepaRG, HepG2, SK-Hep1, and Huh7) were studied using Western blot and quantitative reverse transcription PCR (RT-qPCR). RESULTS Hierarchical gene clustering identified target genes that distinguished between HCC and normal liver tissue. For stages I-IV HCC, there were seven commonly upregulated target genes EPHB1, LTK, NTRK2, PTK7, TBK1, TIE1, and TLR3, which were mainly involved in immune and signaling transduction pathways. PTK7 was highly expressed in stage I-IV HCC and was an independent prognostic marker for reduced overall survival (OS). CONCLUSIONS Bioinformatics analysis, combined with patient survival analysis, identified PTK7 gene expression as a potential therapeutic target and prognostic biomarker for all stages of HCC.

[Pediatric projects funded by National Natural Science Foundation of China from 2009 to 2018: retrospect and prospects].

OBJECTIVE: To perform a review and data analysis of the pediatric projects funded by National Natural Science Foundation of China from 2009 to 2018, and to investigate the changes in key support areas, research interest, and research hotspots in pediatrics. METHODS: The database of National Natural Science Foundation of China was searched to screen out pediatric research projects in 2009-2018, and the changes in funding intensity and research direction were analyzed. RESULTS: From 2009 to 2018, a total of 1 017 pediatric projects were funded by National Natural Science Foundation of China, with 485 (47.69%) General Projects, 426 (41.89%) Youth Fund Projects, 73 (7.18%) Regional Research Programs, 16 (1.57%) Key Programs, 6 (0.59%) Outstanding Youth Fund Projects, 7 (0.69%) Overseas Programs, and 4 (0.39%) other programs. There was a seven-fold increase in the total amount of subsidies, which increased from 8.42 million yuan in 2009 to 66.25 million yuan in 2018. The projects with the Primary Discipline Code of reproductive system/perinatology/neonatology, nervous system and mental illness, or circulatory system received the highest amount of fund. CONCLUSIONS: The support of pediatric projects by National Natural Science Foundation of China continues to increase in the past ten years, and the main types of projects are General Projects and Youth Fund Projects. Neonatology, nervous system/mental illness, and circulatory diseases are the main directions of funded projects.

Effects of PKM2 on global metabolic changes and prognosis in hepatocellular carcinoma: from gene expression to drug discovery.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor that threatens global human health. High PKM2 expression is widely reported in multiple cancers, especially in HCC. This study aimed to explore the effects of PKM2 on global gene expression, metabolic damages, patient prognosis, and multiple transcriptional regulation relationships, as well as to identify several key metabolic genes and screen some small-molecule drugs. METHODS: Transcriptome and clinical HCC data were downloaded from the NIH-GDC repository. Information regarding the metabolic genes and subsystems was collected from the Recon 2 human metabolic model. Drug-protein interaction data were obtained from the DrugBank and UniProt databases. We defined patients with PKM2 expression levels ≥11.25 as the high-PKM2 group, and those with low PKM2 expression (< 11.25) were defined as the low-PKM2 group. RESULTS: The results showed that the global metabolic gene expression levels were obviously divided into the high- or low-PKM2 groups. In addition, a greater number of affected metabolic subsystems were observed in the high-PKM2 group. Furthermore, we identified 98 PKM2-correlated deregulated metabolic genes that were associated with poor overall patient survival. Together, these findings suggest more comprehensive influences of PKM2 on HCC. In addition, we screened several small-molecule drugs that target these metabolic enzymes, some of which have been used in antitumor clinical studies. CONCLUSIONS: HCC patients with high PKM2 expression showed more severe metabolic damage, transcriptional regulation imbalance and poor prognosis than low-PKM2 individuals. We believe that our study provides valuable information for pathology research and drug development for HCC.

[A review on the relationship between mitochondrial dysfunction and white matter injury in preterm infants].

White matter injury in preterm infants has a complex etiology and can lead to long-term neurocognitive and behavioral deficits, but there are still no specific treatment methods for this disease at present. More and more studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of white matter injury in preterm infants and might be a common subcellular mechanism of white matter developmental disorder, which involves oxidative stress, reduced ATP synthesis, and disequilibrium of calcium homeostasis. This article reviews the role of mitochondria in brain development and the mechanism of mitochondrial dysfunction, with a hope to perform early intervention of white matter injury in preterm infants by protecting mitochondrial function, so as to provide a reference for improving the neurodevelopmental outcome of preterm infants who survive.

[A visualization analysis of current research on stem cell transplantation in the treatment of neonatal hypoxic-ischemic encephalopathy].

OBJECTIVE: To reveal the current research status on stem cell transplantation in the treatment of neonates with hypoxic-ischemic encephalopathy (HIE), and to summarize the recent hotspots of the research in this field. METHODS: Using the key words of "stem cells" and "HIE", a computerized search was performed for the articles in English published before June 1, 2018 in PubMed, EMBASE, and Web of Science. Microsoft Office Excel 2013 was used for the statistical analysis of key words. Bicomb 2.0 and VOSviewer 1.6.6 were used for the cluster analysis of hot words and plotting of knowledge maps, respectively. RESULTS: A total of 106 articles were included and 43 high-frequency key words were extracted. The words of "cell transplantation" and "hypoxia-ischemia" were in the core position of the co-word map. The cluster analysis showed that the studies of stem cell transplantation in the treatment of neonatal HIE mainly focused on umbilical cord blood cell transplantation (32.6%), mesenchymal stem cells and neural stem cells (29.5%), perinatal brain injury (28.1%), and other topics (9.8%). CONCLUSIONS: In the current studies of stem cell transplantation in the treatment of neonatal HIE, umbilical cord blood cell transplantation, mesenchymal stem cells, neural stem cells, and perinatal brain injury are popular research topics at different levels.

Comprehensive Analysis of lncRNA and mRNA Expression Profiles in Lung Cancer.

BACKGROUND: Lung cancer is one of the most common malignancies across the world. Long noncoding RNAs (lncRNAs) play an important role in the pathology. This study was to compare the lncRNA and mRNA of lung cancer. The aim of this study was to compare the lncRNA and mRNA expression profiles, their related biological functions, and pathways in lung cancer. METHODS: Human lung cancer mRNA expression datasets were searched and downloaded from NCBI-GEO. LncRNA expression profiles in lung cancer were detected by the Agilent Human LncRNA Microarray V3.0. Differential expression analysis was conducted between cases and controls in mRNA and lncRNA. The starBase web server v2.0 was used to decipher lncRNA-protein interactions. DAVID Bioinformatics Resources 6.7 was used to perform GO Biological Processes and KEGG pathway enrichment analysis of these dysregulated mRNA and lncRNA target genes. RESULTS: The study showed that differentially expressed lncRNA target genes included almost all of the differential expression genes from mRNA. Furthermore, these dysregulated lncRNAs reflected more comprehensive impairment in functional enrichment than dysregulated mRNAs. In addition, five top downregulated lncRNAs had more remarkable fold changes than top downregulated mRNAs, especially FENDRR. CONCLUSIONS: Amount of lncRNAs and mRNAs were differentially expressed in lung cancer. The degrees of difference in lncRNAs were more than mRNAs. It may provide valuable help for an effective strategy in diagnosis and prevention.

Interactions of Methylenetetrahydrofolate Reductase Gene Polymorphisms, Folate, and Homocysteine on Blood Pressure in a Chinese Hypertensive Population.

BACKGROUND: High blood pressure is related to cardiovascular diseases. We aimed to explore the interactions of methylenetetrahydrofolate reductase (MTHTR) gene C677T and A1298C mutations and folate/homocysteine (Hcy) status on blood pressure in a Chinese hypertensive population. METHODS: The clinical data in the present study derived from a previous trial (NCT00520247). Genotypes in Hcy pathway enzymes were detected by PCR-RFLP methods. Supine blood pressure was measured with a mercury sphygmomanometer. Serum Hcy was measured by high-performance liquid chromatography, and serum folate was measured by chemiluminescent immunoassay. RESULTS: This study showed that hyperhomocysteinemia independently elevated diastolic blood pressure (DBP) (ß (SE): 2.02 (0.85), p = 0.018). Furthermore, individuals with high Hcy and MTHFR1298AC + CC genotypes showed higher DBP than the normal Hcy and 1298AA carriers (ß (SE): 1.81 (0.54), p = 0.001). This correlation was verified by the trend test (p = 0.003). However, polymorphisms of MTHFR C677T, MTR A2756G or MTRR A66G do not affect baseline blood pressure level. CONCLUSIONS: The present study demonstrated that the MTHFR A1298C mutation accompanied by hyperhomocysteinemia jointly elevated DBP. Further studies are necessary to confirm the role of these genotypes and Hcy on blood pressure in a larger population.

Folate Deficiency and Gene Polymorphisms of MTHFR, MTR and MTRR Elevate the Hyperhomocysteinemia Risk.

BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). We aimed to investigate the joint effect of homocysteine metabolism gene polymorphisms, as well as the folate deficiency on the risk of HHcy in a Chinese hypertensive population. METHODS: This study enrolled 480 hypertensive patients aged 28 - 75 from six hospitals in different Chinese regions from 9/2005 - 12/2005. Known genotypes of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G were detected by PCRRFLP methods. Serum Hcy was measured by high-performance liquid chromatography and serum folate was measured by chemiluminescent immunoassay. RESULTS: MTHFR C677T and MTR A2756G can independently elevate the risk of HHcy (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA, p = 0.026, respectively), whereas MTHFR A1298C decreased HHcy risk (AC + CC vs. AA, p < 0.001) and showed a protective effect against HHcy risk. Importantly, the joint effect of these risk genotypes showed significantly higher odds of HHcy than non-risk genotypes, especially the patients with four risk genotypes. It is noteworthy that this deleterious effect was aggravated by folate deficiency. These findings were verified by generalized multifactor dimensionality reduction model (p = 0.001) and a cumulative effects model (p < 0.001). CONCLUSIONS: We have first demonstrated that the joint effect of homocysteine metabolism gene polymorphisms and folate deficiency lead to dramatic elevations in the HHcy risk.

Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study.

BACKGROUND: Dyslipidemia is a well-established risk factor for cardiovascular disease. Serum lipids were affected by several gene polymorphisms, folate, homocysteine and other metabolite levels. We aim to investigate the effects of homocysteine metabolism enzyme polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) and their interactions with folate, homocysteine on serum lipid levels in Chinese patients with hypertension. METHODS: Participants were 480 hypertensive adults that enrolled in September to December 2005 from six different Chinese hospitals (Harbin, Shanghai, Shenyang, Beijing, Xi'an, and Nanjing). Known MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G genotypes were determined by PCR-RFLP methods. Serum folate was measured by chemiluminescent immunoassay, homocysteine was measured by high-performance liquid chromatography, serum lipids parameters were determined by an automatic biochemistry analyzer, low-density lipoprotein was calculated by Friedewald's equation. Unitary linear regression model was used to assess the associations of gene polymorphisms, folate and homocysteine on serum lipid profiles. Unconditional logistic regression model was applied to test the interactions of folate, homocysteine and gene polymorphisms on dyslipidemia. RESULTS: No correlations between gene polymorphisms and homocysteine on serum lipid profiles. Compared with normal folate patients, patients with low folate showed higher odds of hypertriglyceridemia (OR = 2.02, 95 % CI: 1.25-3.25, P = 0.004) and low levels of high-density lipoprotein cholesterol (OR = 1.88, 95 % CI: 1.07-3.28, P = 0.027). Each of four gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) combined with low folate showed higher odds of hypertriglyceridemia (P for trend: 0.049, 0.004, 0.007 and 0.005, respectively). MTHFR C677T and A1298C with low folate showed higher odds of low levels of high-density lipoprotein cholesterol (P for trend: 0.008 and 0.031). CONCLUSIONS: Low folate status and homocysteine metabolism gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) may have a synergistic effect increased the incidence of dyslipidemia in Chinese hypertensive population.