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Heart transplantation is the gold standard for treating patients with advanced heart failure. Although improvements in immunosuppressive therapies have significantly reduced the frequency of cardiac graft rejection, the incidences of T cell-mediated rejection (TCMR) and antibody-mediated rejection remain almost unchanged. A four-archetype analysis (4AA) model, developed by Philip F. Halloran, illustrated this problem well. It provided a new dimension to improve the accuracy of diagnoses and an independent system for recalibrating the histology guidelines. However, this model was based on the invasive method of endocardial biopsy, which undoubtedly increased the postoperative risk of heart transplant patients. Currently, little is known regarding the associated genes and specific functions of the different phenotypes. We performed bioinformatics analysis (using machine-learning methods and the WGCNA algorithm) to screen for hub-specific genes related to different phenotypes, based Gene Expression Omnibus accession number GSE124897. More immune cell infiltration was observed with the ABMR, TCMR, and injury phenotypes than with the stable phenotype. Hub-specific genes for each of the four archetypes were verified successfully using an external test set (accession number GSE2596). Logistic-regression models based on TCMR-specific hub genes and common hub genes were constructed with accurate diagnostic utility (area under the curve > 0.95). RELA, NFKB1, and SOX14 were identified as transcription factors important for TCMR/injury phenotypes and common genes, respectively. Additionally, 11 Food and Drug Administration-approved drugs were chosen from the DrugBank Database for each four-archetype model. Tyrosine kinase inhibitors may be a promising new option for transplant rejection treatment. KRAS signaling in cardiac transplant rejection is worth further investigation. Our results showed that heart transplant rejection subtypes can be accurately diagnosed by detecting expression of the corresponding specific genes, thereby enabling precise treatment or medication. [ABSTRACT FROM AUTHOR]

Cantharidin (CTD) is a well-established defensive toxin synthesized by blister beetles, displaying both therapeutic potential and toxicity. Among these beetles, Hycleus cichorii and Hycleus phaleratus are the two most commercially significant species due to their capacity to produce CTD in males. In this investigation, we conducted a gene expression profiling analysis of male and female individuals of these two species, utilizing the Illumina Hiseq4000 platform. We identified 7,983 expressed genes, including 2,823 differentially expressed genes (DEGs) shared by both male and female blister beetles. Nineteen genes related to CTD biosynthesis in the terpenoid backbone biosynthesis pathway were identified, including hydroxymethylglutaryl-CoA reductase (HMGR; EC:1.1.1.34), which demonstrated a significant correlation with CTD content. Furthermore, hydroxymethylglutaryl-CoA synthase (HMGS; EC:2.3.3.10) and isopentenyl-diphosphate Delta-isomerase (IDI; EC:5.3.3.2) were also found to be significantly up-regulated in males. Comparative analysis revealed that NADP+-dependent farnesol dehydrogenase (FOHSDR; EC:1.1.1.216) and farnesyl diphosphate synthase (FDPS; EC:2.5.1.1) had the highest copy number in these beetles, significantly higher than the copy number of the other four non-Meloidae insects. The analysis of the protein-protein interaction network of genes related to CTD biosynthesis revealed that the acetyl-CoA C-acetyltransferase (ACAT; EC:2.3.1.9) gene was the central gene, exhibiting greater expression in male blister beetles than in females. This study offers novel insights into the mechanisms of CTD biosynthesis in blister beetles and enhances our comprehensions of the association between particular genes and CTD content. [ABSTRACT FROM AUTHOR]

Background: To determine whether there is a correlation between stiffness measured by strain elastography and the severity of dysmenorrhea and to determine the value of elastography in evaluating severe dysmenorrhea in patients with adenomyosis. Methods: The correlation between tissue stiffness and dysmenorrhea was analyzed by performing elastography on premenopausal women diagnosed with adenomyosis. Expression levels of transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), and protein gene product 9.5 (PGP9.5) were detected by immunohistochemistry; the correlation of TGF-β and α-SMA levels with the tissue stiffness and the degree of fibrosis was further analyzed. Also, the relationship of the PGP9.5 expression level with the tissue stiffness and degree of dysmenorrhea was determined. Results: The degree of dysmenorrhea was significantly positively correlated with lesion stiffness in patients with adenomyosis but not with the uterine or lesion volume. The cutoff for the strain ratio was > 1.36 between the adenomyosis and control groups, with an area under the curve (AUC) of 0.987. For severe dysmenorrhea, the cutoff for the strain ratio was > 1.65 in patients with adenomyosis, with an AUC of 0.849. TGF-β, α-SMA, and PGP9.5 expression levels were higher in adenomyotic lesions than in the endometrium of the adenomyosis and control groups. Both TGF-β and α-SMA levels were positively correlated with the tissue stiffness and degree of fibrosis. Additionally, the expression level of PGP9.5 showed a positive correlation with the tissue stiffness and degree of dysmenorrhea. Conclusions: Elastography can be used to evaluate the degree of dysmenorrhea; the greater the tissue stiffness, the greater the degree of dysmenorrhea. In addition, elastography performed well in the diagnosis of adenomyosis and the evaluation of severe dysmenorrhea in patients with adenomyosis. [ABSTRACT FROM AUTHOR]

Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial effects on cardiac function and ventricular remodeling. The present study aimed to investigate the expression of ghrelin and the growth hormone (GH) secretagogue receptor 1a (GHSR-1a), and the association with cardiac remodeling in rats with myocardial infarction (MI). Twenty-four hours after ligation of the anterior descending artery (LAD), adult male Sprague–Dawley rats were randomized to 3 d, 7 d and 28 d group. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. Expression of both ghrelin and GHSR-1a was assessed by means of immunohistochemistry and real-time PCR. Plasma ghrelin levels were measured by ELISA kit. In addition, cardiac remodeling was assessed by echocardiographic and hemodynamic measurements. Plasma and cardiac expression of ghrelin decreased on days 3, 7 and 28 compared with the sham group (P < 0.05). In contrast the GHSR-1a mRNA levels increased during the same days (P < 0.05). Decreased positive immunoreaction for ghrelin and increased positive GHSR-1a were also observed in the infarcted heart. Interestingly, plasma ghrelin correlated negatively with left ventricular end-diastolic pressure (r = − 0.59, P = 0.002) and left ventricular end-diastolic dimension (r = − 0.73, P < 0.01). The ghrelin system may play an important role regulating cardiac remodeling after MI and present as a potential significant target for pharmacological modulation and treating cardiac remodeling. [ABSTRACT FROM AUTHOR]

Summary With the prevalence of gene expression studies and the relatively low reproducibility caused by insufficient sample sizes, it is natural to consider joint analysis that could combine data from different experiments effectively to achieve improved accuracy. We present in this article a model-based approach for better identification of differentially expressed genes by incorporating data from different studies. The model can accommodate in a seamless fashion a wide range of studies including those performed at different platforms by fitting each data with different set of parameters, and/or under different but overlapping biological conditions. Model-based inferences can be done in an empirical Bayes' fashion. Because of the information sharing among studies, the joint analysis dramatically improves inferences based on individual analysis. Simulation studies and real data examples are presented to demonstrate the effectiveness of the proposed approach under a variety of complications that often arise in practice. [ABSTRACT FROM AUTHOR]

Ghrelin is a peptide hormone, originally identified from the stomach, that functions as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) and promotes growth hormone (GH) release and food intake. Increasing reports point out ghrelin's role in cancer progression. We previously characterized ghrelin's prognostic significance in the clear cell subtype of renal cell carcinoma (ccRCC), and its pro-metastatic ability via Snail-dependent cell migration. However, ghrelin's activity in promoting cell invasion remains obscure. In this study, an Ingenuity Pathway Analysis (IPA)-based investigation of differentially expressed genes in Cancer Cell Line Encyclopedia (CCLE) dataset indicated the potential association of Aurora A with ghrelin in ccRCC metastasis. In addition, a significant correlation between ghrelin and Aurora A expression level in 15 ccRCC cell line was confirmed by variant probes. ccRCC patients with high ghrelin and Aurora A status were clinically associated with poor outcome. We further observed that ghrelin upregulated Aurora A at the protein and RNA levels and that ghrelin-induced ccRCC in vitro invasion and in vivo metastasis occurred in an Aurora A-dependent manner. Furthermore, MMP1, 2, 9 and 10 expressions are associated with poor outcome. In particular, MMP10 is significantly upregulated and required for the ghrelin-Aurora A axis to promote ccRCC invasion. The results of this study indicated a novel signaling mechanism in ccRCC metastasis. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death 5 (PDCD5) expression is reduced in various human tumor cells, and the protein concentration and nuclear translocation of PDCD5 is also observed during tumor cell apoptosis. Aims: The purpose of this study was to investigate the differential expression of PDCD5 in six gastric cell lines, and to explore the changes of biological behavior mechanism underlying enhanced apoptosis-inducing effects of cisplatin by PDCD5 over-expression on gastric cancer BGC823 cells. Methods: RT-PCR and real-time PCR were used to determine PDCD5 expression. BGC823/PDCD5 cells were assessed the cellular proliferating ability by MTT assay, soft agar cloning experiments and tumorigenicity in nude mice experiments in vivo. The effects of cisplatin in combination with PDCD5 on the proliferation and apoptosis were measured by MTT, Annexin-V-FITC/PI dual labeling and cell cycle analysis, respectively. Immunofluorescence was used to detect co-localization of p53 and PDCD5 protein to explore the mechanism underlying the synergistic therapeutic effect of PDCD5 with cisplatin (5 μg/ml for 24 h). Results: PDCD5 had the highest expression level in the GES1 cell among other cell lines. The growths of BGC823 cells transfected with PDCD5 for six (6th) or 17 (17th) days were both slower than that of BGC823 and BGC823/Neo ( P < 0.01). The stable transfection of PDCD5 demonstrated G2/M cell cycle arrest, increased apoptosis and nuclear translocation of PDCD5 and p53 after cisplatin treatment. Conclusions: Stable transfection of the PDCD5 gene can inhibit the growth of the BGC823 cell line and notably improve apoptosis-inducing effects of cisplatin, indicating a novel strategy for better chemotherapeutic effects on gastric cancer. [ABSTRACT FROM AUTHOR]

In the genetic system that regulates complex traits, metabolites, gene expression levels, RNA editing levels and DNA methylation, a series of small and linked genes exist. To date, however, little is known about how to design an efficient framework for the detection of these kinds of genes. In this article, we propose a genome-wide composite interval mapping (GCIM) in F2. First, controlling polygenic background via selecting markers in the genome scanning of linkage analysis was replaced by estimating polygenic variance in a genome-wide association study. This can control large, middle and minor polygenic backgrounds in genome scanning. Then, additive and dominant effects for each putative quantitative trait locus (QTL) were separately scanned so that a negative logarithm P -value curve against genome position could be separately obtained for each kind of effect. In each curve, all the peaks were identified as potential QTLs. Thus, almost all the small-effect and linked QTLs are included in a multi-locus model. Finally, adaptive least absolute shrinkage and selection operator (adaptive lasso) was used to estimate all the effects in the multi-locus model, and all the nonzero effects were further identified by likelihood ratio test for true QTL identification. This method was used to reanalyze four rice traits. Among 25 known genes detected in this study, 16 small-effect genes were identified only by GCIM. To further demonstrate GCIM, a series of Monte Carlo simulation experiments was performed. As a result, GCIM is demonstrated to be more powerful than the widely used methods for the detection of closely linked and small-effect QTLs. [ABSTRACT FROM AUTHOR]

Chemical hepatotoxicity, especially alcoholic liver injury (ALI), commonly occurs in young and middle-aged people who drink heavily. ALI is extremely harmful and can induce severe disease states, such as hepatitis, liver fibrosis, cirrhosis, or liver cancer, which are similar to CCl 4 -induced liver disease states in animals. In recent studies, the pathological changes of hepatocytes and the hepatic stellate cell have shown a significant connection between endoplasmic reticulum (ER) stress and the development of liver pathology in patients. However, the detailed pathological mechanism needs to be further studied. Schisandra chinensis , (S. chinensis) , a fruit-bearing vine used in Traditional Chinese Medicine (TCM), has been used to treat chronic or acute diseases, including liver disease. S. chinensis -derived lignans (SCDLs) in particular have been shown to alleviate liver pathological changes. This study sought to elucidate the mechanisms underlying SCDL-mediated hepatoprotection. We first used in silico target prediction and computational simulation methods to identify putative lignan-binding targets relative to the hepatoprotective effect. A gene microarray analysis was performed to identify differently expressed genes that might have significance in the disease pathological process. We then used histological analyses in a mice hepatotoxicity model to test the effectiveness of SCDLs in vivo , and a hepatocellular toxicity model to analyze the candidate-compound-mediated hepatoprotection and expression states of the key targets in vitro. The in silico analysis results indicated that endothelin receptor B (ETBR/EDNRB) is likely a significant node during the liver pathological change process and a promising key target for the SCDL compound schisantherin D on the hepatoprotective effect; experimental studies showed that schisantherin D alleviated the EtOH- and ET-1-induced HL-7702 cell (belongs to liver parenchymal cell lines) injury ratio, decreased the expression of ETBR, and inhibited ECMs and ET-1 secretion in LX-2 cells (one form of hepatic stellate cells). SCDLs ameliorated EtOH- and CCl 4 -induced fibrosis formation in mice liver tissue. Liver tissue western blots of SCDL-treated mice showed downregulated α-SMA, ETBR, PLCβ, CHOP, Bax, and the apoptotic factors of cleaved-caspase 12, cleaved-caspase 9, and cleaved-caspase 3 hinted at an anti-apoptosis and hepatoprotective effect. The SCDL treatment also elevated serum glutathione (GSH) and reduced the serum-transforming growth factor-β1 (TGF-β1) level. The findings indicated that SCDLs prevent hepatotoxicity via their anti-fibrotic, anti-oxidant, and anti-apoptosis properties. ETBR may be the key factor in promoting chemical hepatotoxicity. Image 1 • ETBR was confirmed to be a promising alcoholic liver injury treating target. • In silico analysis and experimental validation was used to illustrate SCDLs mediated hepatotoxicity protection. • Schisantherin D showed potential hepatotoxicity protective effect via blocking ETBR. [ABSTRACT FROM AUTHOR]

Given mitochondrion is the 'energy and oxygen usage factories', adaptive signatures of mitochondrial genes have been extensively investigated in vertebrates from different altitudes, but few studies focus on insects. Here, we sequenced the complete mitochondrial genome (mitogenome) of Dolycoris. baccarum living in the Tibetan Plateau (DBHC, ∼3200 m above sea level (asl)) and conducted a detailed comparative analysis with another D. baccarum mitogenome (DBQY) from relatively low altitude (∼1300 m asl). All the 37 mitochondrial genes were highly conserved and under purifying selection, except for two mitochondrial protein-coding genes (MPCGs) (atp6 and nad5) that showed positively selected signatures. We therefore further examined non-synonymous substitutions in atp6 and nad5, by sequencing more individuals from three populations with different altitudes. We found that these non-synonymous substitutions were polymorphic in these populations, likely due to relaxed selection constraints in different altitudes. Purifying selection in all mitochondrial genes may be due to their functional importance for the precision of ATP production usually. Length difference in mitochondrial control regions between DBHC and DBQY was also conversed at the population level, indicating that sequence size adjustments in control region may be associated with adaptation to divergent altitudes. Quantitatively real-time PCR analysis for 12 MPCGs showed that gene expression patterns had a significant change between the two populations, suggesting that expression levels of MPCGs could be modulated by divergent environmental pressures (e.g. oxygen content and ambient temperature). These results provided an important guide for further uncovering genetic mechanisms of ecological adaptation in insects. [ABSTRACT FROM AUTHOR]

Abstract Background NK cells are presented in tumor microenvironments and acts as an essential defense line against multiple malignancies. Recently, miRNAs are reported to involve in the development of natural killer (NK) cells via negatively regulating gene expression. Here, we aim to explore the function and mechanism underlying how miR-20a modulated the killing effect of NK cells to cervical cancer cells. Methods Abundances of miR-20a and runt-related transcription factor 1 (RUNX1) in NK cells from cervical cancer patients and healthy donors were detected by qRT-PCR and western blot. The releases of IFN-γ and TNF-α were determined by ELISA. The cytotoxicity of NK cells against cervical cancer cells was measured by CytoTox 96 non-radioactive cytotoxicity assay. Luciferase reporter, western blot, and RNA immunoprecipitation (RIP) assays were performed to assess the interaction between miR-20a and RUNX1. Result miR-20a was upregulated while RUNX1 was downregulated in NK cells from cervical cancer patients compared to healthy donors. IL-2 stimulated the releases of IFN-γ and TNF-α, and the killing effect of NK cells to cervical cancer cells, which was overturned by miR-20a introduction. RUNX1 was identified to be a target of miR-20a. Restoration of RUNX1 abolished the inhibitory effects of miR-20a on the secretions of IFN-γ and TNF-α, as well as the killing effect of NK cells to colorectal cancer cells. Conclusion miR-20a attenuated the killing effect of NK cells to cervical cancer cells by directly targeting RUNX1. Highlights • MiR-20a was upregulated while RUNX1 was downregulated in NK cells from cervical cancer patients. • MiR-20a attenuated the natural killing effect of NK cells to cervical cancer cells. • RUNX1 was targeted by miR-20a. • MiR-20a inhibited the natural killing effect of NK cells to cervical cancer cells via targeting RUNX1. [ABSTRACT FROM AUTHOR]

Color polymorphism is an ecologically important trait, which is related to local adaptation and ecological speciation. The pea aphid Acyrthosiphon pisum shows color polymorphism: the red and green color morphs where differences in ecological adaptation have been observed. Here, we measured genome-wide gene expression profiles of two color morphs in natural populations of A. pisum to explore the genetic basis of differentiated ecological adaptation. The results showed that only 32 genes were significantly differentially expressed between the two morphs, of which 18 had functional annotations. Among them, 13 genes were up-regulated [e.g. genes encoding protoheme IX farnesyltransferase (LOC100570971), carotene dehydrogenase ( tor ) and V-type proton ATPase subunit B (LOC100169462)] and 5 genes were down-regulated in the red morph (e.g. genes encoding transcription factors and heat shock proteins). To assess the functional importance of these differentially expressed genes (DEGs), we selected three highly expressed DEGs (LOC100169462, LOC100570971 and tor ) with functional annotations and analyzed their expression levels in the red morph under three low temperatures (1 °C, 4 °C, and 8 °C) for 24 h. These three DEGs showed an interesting expression response to the cold acclimating conditions which resulted in an obvious phenotypic change of the red individuals to be greenish variants. This study suggests a link between gene expressions and body color polymorphisms in the pea aphid and provides important clues for further studying molecular mechanisms of ecological adaptation in aphids. [ABSTRACT FROM AUTHOR]

Changes in gene expression patterns can reflect the adaptation of organisms to divergent environments. Quantitative real-time PCR ( qRT- PCR) is an important tool for ecological adaptation studies at the gene expression level. The quality of the results of qRT- PCR analysis largely depends on the availability of reliable reference genes ( RGs). To date, reliable RGs have not been determined for adaptive evolution studies in insects using a standard approach. Here, we evaluated the reliability of 17 candidate RGs for five Gynaephora populations inhabiting various altitudes of the Tibetan Plateau ( TP) using four independent (geNorm, NormFinder, BestKeeper, and the deltaCt method) and one comprehensive (RefFinder) algorithms. Our results showed that EF1-α, RPS15, and RPS13 were the top three most suitable RGs, and a combination of these three RGs was the most optimal for normalization. Conversely, RPS2, ACT, and RPL27 were the most unstable RGs. The expression profiles of two target genes ( HSP70 and HSP90) were used to confirm the reliability of the chosen RGs. Additionally, the expression patterns of four other genes ( GPI, HIF1A, HSP20, and USP) associated with adaptation to extreme environments were assessed to explore the adaptive mechanisms of TP Gynaephora species to divergent environments. Each of these six target genes showed discrepant expression patterns among the five populations, suggesting that the observed expression differences may be associated with the local adaptation of Gynaephora to divergent altitudinal environments. This study is a useful resource for studying the adaptive evolution of TP Gynaephora to divergent environments using qRT- PCR, and it also acts as a guide for selecting suitable RGs for ecological and evolutionary studies in insects. [ABSTRACT FROM AUTHOR]

The Indian meal moth Plodia interpunctella (Lepidoptera: Pyralidae) is a worldwide pest that causes serious damage to stored foods. Although many efforts have been conducted on this species due to its economic importance, the study of genetic basis of development, behavior and insecticide resistance has been greatly hampered due to lack of genomic information. In this study, we used high throughput sequencing platform to perform a de novo transcriptome assembly and tag-based digital gene expression profiling (DGE) analyses across four different developmental stages of P. interpunctella (egg, third-instar larvae, pupae and adult). We obtained approximate 9 gigabyte (GB) of clean data and recovered 84,938 unigenes, including 37,602 clusters and 47,336 singletons. These unigenes were annotated using BLAST against the non-redundant protein databases and then functionally classified based on Gene Ontology (GO), Clusters of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes databases (KEGG). A large number of differentially expressed genes were identified by pairwise comparisons among different developmental stages. Gene expression profiles dramatically changed between developmental stage transitions. Some of these differentially expressed genes were related to digestion and cuticularization. Quantitative real-time PCR results of six randomly selected genes conformed the findings in the DGEs. Furthermore, we identified over 8000 microsatellite markers and 97,648 single nucleotide polymorphisms which will be useful for population genetics studies of P. interpunctella . This transcriptomic information provided insight into the developmental basis of P. interpunctella and will be helpful for establishing integrated management strategies and developing new targets of insecticides for this serious pest. [ABSTRACT FROM AUTHOR]

The adaptive evolution of animals to high-elevation environments has been extensively studied in vertebrates, while few studies have focused on insects. Gynaephora species (Lepidoptera: Lymantriinae) are endemic to the Qinghai-Tibetan Plateau (QTP) and represent an important insect pest of alpine meadows. Here, we present a detailed comparative analysis of the mitochondrial genomes (mitogenomes) of two Gynaephora species inhabiting different high-elevation environments: G. alpherakii and G. menyuanensis . The results indicated that the general mitogenomic features (genome size, nucleotide composition, codon usage and secondary structures of tRNAs) were well conserved between the two species. All of mitochondrial protein-coding genes were evolving under purifying selection, suggesting that selection constraints may play a role in ensuring adequate energy production. However, a number of substitutions and indels were identified that altered the protein conformations of ATP8 and NAD1, which may be the result of adaptive evolution of the two Gynaephora species to different high-elevation environments. Levels of gene expression for nine mitochondrial genes in nine different developmental stages were significantly suppressed in G. alpherakii , which lives at the higher elevation (~ 4800 m above sea level), suggesting that gene expression patterns could be modulated by atmospheric oxygen content and environmental temperature. These results enhance our understanding of the genetic bases for the adaptive evolution of insects endemic to the QTP. [ABSTRACT FROM AUTHOR]

Seed oils provide a renewable source of food, biofuel and industrial raw materials that is important for humans. Although many genes and pathways for acyl-lipid metabolism have been identified, little is known about whether there is a specific mechanism for high-oil content in high-oil plants. Based on the distinct differences in seed oil content between four high-oil dicots (20~50%) and three low-oil grasses (<3%), comparative genome, transcriptome and differential expression analyses were used to investigate this mechanism. Among 4,051 dicot-specific soybean genes identified from 252,443 genes in the seven species, 54 genes were shown to directly participate in acyl-lipid metabolism, and 93 genes were found to be associated with acyl-lipid metabolism. Among the 93 dicot-specific genes, 42 and 27 genes, including CBM20-like SBDs and GPT2, participate in carbohydrate degradation and transport, respectively. 40 genes highly up-regulated during seed oil rapid accumulation period are mainly involved in initial fatty acid synthesis, triacylglyceride assembly and oil-body formation, for example, ACCase, PP, DGAT1, PDAT1, OLEs and STEROs, which were also found to be differentially expressed between high- and low-oil soybean accessions. Phylogenetic analysis revealed distinct differences of oleosin in patterns of gene duplication and loss between high-oil dicots and low-oil grasses. In addition, seed-specific GmGRF5, ABI5 and GmTZF4 were predicted to be candidate regulators in seed oil accumulation. This study facilitates future research on lipid biosynthesis and potential genetic improvement of seed oil content. [ABSTRACT FROM AUTHOR]

We investigated the effect of exposure to acute and chronic high-altitude hypoxia (AHH and CHH) on the activity and expression of CYP1A2, CYP2D6, CYP2C9, CYP2C19 and NAT2 in rats. The rats were divided into plain (400 m), acute middle-altitude hypoxia (2,800 m), chronic middle-altitude hypoxia (2,800 m), AHH (4,300 m) and CHH (4,300 m). After probe drugs had been orally administered to the rats of the 5 groups, the serum or urine concentration of the probe drug and its metabolite was determined by reversed-phase HPLC. The activity of cytochrome P450 isozyme and NAT2 was evaluated by the ratio of the metabolite to the probe drug. The ELISA and real-time PCR were used to analyze the protein and mRNA expression of cytochrome P450 isozyme and NAT2, respectively. AHH and CHH caused significant decreases in the activity and protein and mRNA expression of rat CYP1A2 in vivo. AHH downregulates the activity and mRNA expression of rat NAT2 in vivo, and CHH upregulates the activity and protein and mRNA expression of rat CYP2D6. AHH and CHH did not change the expression of CYP2C9 and CYP2C19 in rats. This study found significant changes in the activity and protein and mRNA expression of CYP1A2, CYP2D6 and NAT2 in rats in the special environment of high-altitude hypoxia. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background MicroRNAs (miRNAs), small noncoding RNA molecules can function as oncogenes or tumor suppressors in tumorigenesis. Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide with a 5-year survival rate of approximately 50%. Methods The expression of microRNA-99a (miR-99a) in OSCC tissues and cell lines was investigated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. The functions of miR-99a in migration/invasion and lung colonization were determined by transwell and tail vein injection assays, respectively. Specific targets of miR-99a were determined by software prediction, correlation with target protein expression, and luciferase reporter assay. The signaling pathways involved in regulation of miR-99a were investigated using the kinase inhibitors. Results We observed reduced levels of miR-99a, identified as one of the most downregulated miRNA in OSCC and all tested OSCC cell lines compared to normal oral keratinocytes. Ectopic miR- 99a expression in OSCC cells markedly reduced migration and invasion in vitro as well as lung colonization in vivo. When evaluating the specific targets of miR-99a, we found that ectopic miR-99a expression downregulates insulin-like growth factor 1 receptor (IGF1R) protein and that the expression of miR-99a correlates negatively with IGF1R protein in OSCC cells. Insertion of the 3'UTR of IGF1R mRNA into the 3'UTR of a reporter gene markedly reduced luciferase activity in OSCC cells expressing miR-99a, suggesting that miR-99a reduces luciferase activity by targeting the 3'UTR of IGF1R mRNA. When evaluating the mechanisms of miR-99a downregulation, we observed the upregulation of miR-99a expression in serum-starved conditions and its suppression in response to insulin-like growth factor (IGF1) stimulation. Inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) kinase inhibited IGF1-induced suppression of miR-99a, suggesting the negative regulation of miR-99a expression by IGF1R signaling. Conclusion Overall, results indicate that miR-99a functions as a tumor metastasis suppressor in OSCC cells and mutually regulates IGF1R expression in a reciprocal regulation. [ABSTRACT FROM AUTHOR]

Abstract: Cyclooxygenase-2 (COX-2) has been found to be over-expressed in esophageal carcinoma (EC) and it could be considered as a potential tumor-associated antigen (TAA). In the present study, six candidate peptides from COX-2 were firstly predicted and synthesized. Among them, P479 had the highest affinity and stability toward both HLA-A∗0201 and HLA-A∗03 molecules and it could significantly promote the IFN-γ release. The cytotoxic T lymphocytes (CTLs) induced by P479 could specifically lyse COX-2-expressed EC cell lines, EC-1 (HLA-A3 supertype) and EC-9706 (HLA-A2 supertype). These results suggested that P479 as a novel broad-spectrum T cell epitope would be very useful in immunotherapy against esophageal carcinoma. [Copyright &y& Elsevier]

Abstract  Trichomoniasis caused by Trichomonas vaginalis is the most common sexual transmitted infection in the world. The 170-MB genome of this protozoan contains 60,000 genes, the largest number of genes ever identified in protozoan. High-throughput expression sequenced tag analysis showed that at least 4,000 genes were expressed in the trophozoite stage. In the present study, we use two-dimensional electrophoresis combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis to profile, identify, and characterize proteins expressed in the trophozoite stage of T. vaginalis. A total of 247 spots representing 164 different proteins were identified. The identified proteins with known sequence or motif/domain homologies were further classified into groups according to their biological functions. Among them, proteins related to carbohydrate metabolism represented the most abundant category in the T. vaginalis proteome. This study presented the most extensive proteomic analysis of T. vaginalis to date and provided a reference proteome database for future comparative proteomic studies. [ABSTRACT FROM AUTHOR]