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Endoplasmic reticulum (ER) stress mediates Cd-caused germ cell apoptosis in testis. The effects of 4-phenylbutyric acid (PBA), a classical chaperone, were investigated on Cd-induced apoptosis in mouse GC-1 spermatogonia cells. The cells were pretreated with PBA before Cd exposure. TUNEL and flow cytometry assays were applied to determine apoptosis. Some key biomarkers of ER stress were analyzed using RT-PCR and western blot. as expected, the apoptotic cells exposed to Cd apparently increased. The mRNA and protein expression levels of GRP78 and ATF6α, were elevated in the Cd groups. Additional experiments displayed that Cd notably increased IRE1α and JNK phosphorylation, and upregulated XBP-1 mRNA and protein expression. Moreover, p-eIF2α and CHOP expressions were clearly elevated in the Cd groups. Interestingly, PBA almost completely inhibited ER stress and protected spermatogonia against apoptosis induced by Cd. PBA alleviated Cd-induced ER stress and spermatogonia apoptosis, and may have the therapeutic role in Cd-induced male reproductive toxicity. • CdCl 2 induced spermatogonia apoptosis in vitro. • CdCl 2 triggered spermatogonia ER stress. • 4-PBA alleviated CdCl 2 -induced spermatogonia apoptosis. [ABSTRACT FROM AUTHOR]

• 1-MCP + ethylene absorbent (EA) treatment increase shelf-life of 'Fenjiao' banana. • EA does not have the negative effect on the ripening of 'Fenjiao' banana. • 1-MCP+EA repress the enzymes activity related to fruit softening. • 1-MCP +EA modulate the expression of gene related of ripening. • 1-MCP +EA treatment is easy to promote and apply in the banana industry. The 'Fenjiao' banana (Musa ABB Pisang Awak) has a high commercial and nutritional value and is harvested when it is highly plump at between 85 and 90 % commercial maturity. The fruit are less angular at this stage. However, these fruit soften rapidly after harvest. 1-Methylcyclopropene (1-MCP) significantly delays ripening, but it can cause ripening disorders when used improperly. Ethylene absorbent (EA) is also widely used to increase the postharvest life of fruit, but it has less of an effect on 'Fenjiao' banana. This study was conducted to optimize the concentrations of 1-MCP combined with EA to increase the shelf life of these bananas. The results showed that a low concentration of 1-MCP (7 g L−1) combined with EA (2 g kg−1) significantly prolonged the shelf life of the 'Fenjiao' banana and maintained its high quality. The combination of 1-MCP and EA repressed the activities of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase, ACC synthase, pectin methylesterase, polygalacturonase and pectate lyase in the peel and pulp of 'Fenjiao' banana, as well as the corresponding levels of expression of MbACS1, MbACO1, MbPG1, MbPL1 , except for MbPME1 , which are induced by 1-MCP. This study provides a useful technique for preserving 'Fenjiao' fruit with a study on its possible physiological mechanism, which could be applied in the postharvest production of 'Fenjiao' banana. [ABSTRACT FROM AUTHOR]

Objective To evaluate whether mono (2-ethylhexyl) phthalate (MEHP) affects genomic DNA methylation and the methylation status of some specific genes such as patched gene ( PTCH ) and smoothened gene ( SMO ) in LNCaP cells. Methods LNCaP cells were treated with MEHP (0, 1, 5, 10, and 25 μmol/L) for 3 days. An ELISA assay was preformed to detect genomic methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) content. A pyrosequencing assay was applied to assess DNA methylation in PTCH and SMO gene promoters. The correlation between DNA methylation and gene expression was assessed. Results The proportion of cytosines with 5-mC methylation in LNCaP cells was significantly decreased by MEHP (1, 5, 10, and 25 μmol/L) in a dose-dependent manner ( P < 0.01). For genes in the Hedgehog pathway, there was no significant MEHP concentration-dependent difference in the DNA methylation of PTCH and SMO . Conclusion MEHP might affect the progression of prostate cancer through its effect on global DNA methylation. [ABSTRACT FROM AUTHOR]

Background This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300 m. Methods and Results The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, K a and C max of norfloxacin were significantly reduced in high altitude group (p < 0.05). However, the MRT, CL, t 1/2 and Vd were significantly increased (p < 0.05). Conclusions These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude. [ABSTRACT FROM AUTHOR]

Highlights: [•] The interferon-inducing PRRSV strain A2MC2 elicited higher neutralizing antibodies. [•] A2MC2 induced earlier onset and higher levels of the antibodies than the MLV. [•] The A2MC2-induced antibodies were able to neutralize heterologous VR-2385. [•] A2MC2 induced higher expression of IFN-γ in PAMs than the MLV. [ABSTRACT FROM AUTHOR]

Abstract: To investigate the role of liver-specific expression of glucokinase (GCK) in the pathogenesis of hyperglycemia and to identify candidate genes involved in mechanisms of the onset and progression of maturity onset diabetes of the young, type 2 (MODY-2), we examined changes in biochemical parameters and gene expression in GCK knockout (gckw/–) and wild-type (gckw/w) mice as they aged. Fasting blood glucose levels were found to be significantly higher in the gckw/– mice, compared to age-matched gckw/w mice, at all ages (P <0.05), except at 2weeks. GCK activity of gckw/– mice was about 50% of that of wild type (gckw/w) mice (P <0.05). Glycogen content at 4 and 40weeks of age was lower in gckw/– mice compared to gckw/w mice. Differentially expressed genes in the livers of 2 and 26week-old liver-specific GCK knockout (gckw/–) mice were identified by suppression subtractive hybridization (SSH), which resulted in the identification of phosphoenolpyruvatecarboxykinase (PEPCK, also called PCK1) and Sterol O-acyltransferase 2 (SOAT2) as candidate genes involved in pathogenesis. The expressions of PEPCK and SOAT2 along with glycogen phosphorylase (GP) and glycogen synthase (GS) were then examined in GCK knockout (gckw/–) and wild-type (gckw/w) mice at different ages. Changes in PEPCK mRNA levels were confirmed by real-time RT-PCR, while no differences in the levels of expression of SOAT2 or GS were observed in age-matched GCK knockout (gckw/–) and wild-type (gckw/w) mice. GP mRNA levels were decreased in 40-week old gckw/– mice compared to age-matched gckw/w mice. Changes in gluconeogenesis, delayed development of GCK and impaired hepatic glycogen synthesis in the liver potentially lead to the onset and progression of MODY2. [Copyright &y& Elsevier]

Abstract: The limitations of highly active anti-retroviral therapy (HAART) have necessitated the development of alternative therapeutics. In this study, we generated ovalbumin (OVA)-pulsed and pcDNAgp120-transfected dendritic cell (DC)-released exosomes (EXOova and EXOgp120) and ConA-stimulated C57BL/6 CD8+ T cells. OVA- and Gp120-Texo vaccines were generated from CD8+ T cells with uptake of EXOova and EXOgp120, respectively. We demonstrate that OVA-Texo stimulates in vitro and in vivo OVA-specific CD4+ and CD8+ cytotoxic T lymphocyte (CTL) responses leading to long-term immunity against OVA-expressing BL6-10OVA melanoma. Interestingly, CD8+ T cell responses are DC and CD4+ T cell independent. Importantly, Gp120-Texo also stimulates Gp120-specific CTL responses and long-term immunity against Gp120-expressing B16 melanoma. Therefore, this novel HIV-1-specific EXO-targeted Gp120-Texo vaccine may be useful in induction of efficient CTL responses in AIDS patients with DC dysfunction and CD4+ T cell deficiency. [Copyright &y& Elsevier]

Abstract: The studies presented in this manuscript focus on characterization of transcriptomic responses to anti-androgens in zebrafish (Danio rerio). Research on the effects of anti-androgens in fish has been characterized by a heavy reliance on apical endpoints, and molecular mechanisms of action (MOA) of anti-androgens remain poorly elucidated. In the present study, we examined effects of a short term exposure (24–96h) to the androgen receptor antagonists flutamide (FLU) and vinclozolin (VZ) on gene expression in gonads of sexually mature zebrafish, using commercially available zebrafish oligonucleotide microarrays (4×44K platform). We found that VZ and FLU potentially impact reproductive processes via multiple pathways related to steroidogenesis, spermatogenesis, and fertilization. Observed changes in gene expression often were shared by VZ and FLU, as demonstrated by overlap in differentially-expressed genes and enrichment of several common key pathways including: (1) integrin and actin signaling, (2) nuclear receptor 5A1 signaling, (3) fibroblast growth factor receptor signaling, (4) polyamine synthesis, and (5) androgen synthesis. This information should prove useful to elucidating specific mechanisms of reproductive effects of anti-androgens in fish, as well as developing biomarkers for this important class of endocrine-active chemicals. [ABSTRACT FROM AUTHOR]

Abstract: Neuropilin-2(Nrp2), which is a nontyrosine kinase transmembrane glycoprotein, can promote angiogenesis and is a poor prognostic factor in some human cancers. In the present study, to explore the expression and potential function of Nrp2 in salivary adenoid cystic carcinoma (SACC), immunohistochemistry was used to examine the Nrp2 expression in 50 SACCs and 20 normal salivary gland tissues nearby SACCs. The result showed that immunoreactivity for Nrp2 was detected in 47 of 50 SACCs, and its expression level had significant correlations with microvessel density, tumor size, TMN clinical stage, vascular invasion, and metastasis (P <0.05) of SACCs. In addition, inhibition of Nrp2 function by the receptor–ligand interaction-blocking antibody decreased cell migration, invasion, and angiogenic promotion without influences on the cell proliferation of Acc-3 cells. Taken together, the expression of Nrp2 protein is significantly correlated with tumor progression and angiogenesis in SACCs. These results suggest that Nrp2 may be a potential therapeutic target for SACCs. [ABSTRACT FROM AUTHOR]

Abstract: Extracellular acidic pH activated chloride channels (ICl,acid) have been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to evaluate the expression of ICl,acid in RAW264.7 monocytic-macrophage and human peripheral monocytes and to investigate the effect of simvastatin on ICl,acid. In two kinds of cells, the activation and deactivation of the current rapidly and repeatedly followed the change of the extracellular solution to pH=4.3. Compared with the outward current (pA/pF) activated at pH 4.3, the currents inhibited by simvastatin at concentrations of 0.1 μM were all decreased a little, however the currents at concentrations of 1 μM and 10 μM simvastatin were decreased significantly. The IC50 for simvastatin inhibiting ICl,acid of RAW264.7 was 13.77 μM. In summary, we report for the first time that simvastatin inhibits the ICl,acid of RAW264.7 monocytic-macrophage and human peripheral monocytes in a concentration-dependent manner. [Copyright &y& Elsevier]

Cadmium (Cd) is a common pollutant with reproductive toxicity. Our previous study revealed that Cd triggered spermatogonia ferroptosis. However, the underlying mechanisms remain unclear. Nuclear receptor coactivator 4 (NCOA4) mediates ferritinophagy and specific degradation of ferritin through lysosomes, resulting in the release of ferrous ions. Excessive autophagy can lead to ferroptosis. This study investigated the role of autophagy in Cd-triggered ferroptosis using GC-1 spermatogonial (spg) cells which exposed to CdCl 2 (5 μM, 10 μM, or 20 μM) for 24 without/with CQ. The cells which transfected with Ncoa4-siRNA were used to explore the role of NCOA4-mediated ferritinophagy in Cd-triggered ferroptosis. The results revealed that Cd caused mitochondrial swelling, rupture of cristae, and vacuolar-like changes. The Cd-treated cells exhibited more autophagosomes. Simultaneously, Cd increased intracellular iron, reactive oxygen species, and malondialdehyde concentrations while decreasing glutathione content and Superoxide Dismutase-2 activity. Moreover, Cd upregulated mRNA levels of ferritinophagy-associated genes (Ncoa4, Lc3b and Fth1), as well as enhanced protein expression of NCOA4, LC3B, and FTH1. While Cd decreased the mRNA and protein expression of p62/SQSTM1. These results showed that Cd caused ferritinophagy and ferroptosis. The use of chloroquine to inhibit autophagy ameliorated Cd-induced iron overload and ferroptosis. Moreover, Ncoa4 knockdown in spermatogonia significantly reduced intracellular iron concentration and alleviated Cd-triggered ferroptosis. In conclusion, our findings demonstrate that Cd activates the ferritinophagy pathway mediated by NCOA4, resulting in iron accumulation through ferritin degradation. This causes oxidative stress, ultimately initiating ferroptosis in spermatogonia. Our results may provide new perspectives and potential strategies for preventing and treating Cd-induced reproductive toxicity. [Display omitted] • Cd causes iron overload and triggers ferroptosis in spermatogonia. • Cd induces ferritinophagy in spermatogonia. • CQ antagonizes against Cd-caused iron overload in spermatogonia. • NCOA4-mediated ferritinophagy participates in Cd-triggered ferroptosis. [ABSTRACT FROM AUTHOR]

Abstract: Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations benefit from treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs), namely, gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. About 50% of this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as the one corresponding to T790M. In our previous study, we found that combined treatment with fulvestrant and gefitinib decreases the proliferation of H1975 NSCLC cells, compared to treatment with either fulvestrant or gefitinib alone; however, the molecular mechanism for the improved effects of the combination treatment are still unknown. In this study, we confirmed that fulvestrant increases the gefitinib sensitivity of H1975 cells and found that let-7c was most upregulated in the fulvestrant-treated cells. Our data revealed that let-7c increases gefitinib sensitivity by repressing RAS and inactivating the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. Taken together, our findings suggest that let-7c plays an important role in fulvestrant-induced upregulation of gefitinib sensitivity in H1975 cells. [Copyright &y& Elsevier]

Abstract: We conducted this study to evaluate the expression of leptin and its receptor, OB-Rb in gastric cancer and their relationship to clinicopathological features, VEGF and HER-2 expression, as well as the prognostic value. One hundred and ten gastric cancer specimens were detected for leptin, OB-Rb, VEGF and HER-2 by immunohistochemistry (IHC), and 96 specimens of normal gastric mucosa served as the control. The expression level of leptin, OB-Rb and HER-2 in gastric tissues were significantly higher than normal tissues (49.1% vs. 34.0%, 60.9% vs. 46.0%, 19.1% vs. 8.0%, P <0.05). There was a correlation between the expression of leptin and HER-2, both of which were significantly associated with invasion depth, lymph node metastasis, AJCC stage and VEGF expression. However, there was no correlation between OB-Rb expression and all clinicopathological features. Cox regression analyses showed that age, tumor size, histological grade, serosa invasion, AJCC stage, chemotherapy, leptin and HER-2 overexpression were prognostic factors. The survival of patients with leptin positive expression was significantly poorer than those with negative expression (OS: 20.0months vs. 32.5months, FPS: 12.0months vs. 18.0months, P <0.01). Leptin, rather than OB-Rb, played an important role in the progression and angiogenesis of gastric cancer, and was a prognostic factor for poor outcome. [Copyright &y& Elsevier]

Abstract: CD44 molecule plays critical role in distant malignant metastasis. It is expressed in standard form (CD44s) or variant form (CD44v). Tumor necrosis factor-α (TNF-α) is highly expressed in the cancer microenvironment. TNF-α was reported to modulate CD44 expression in several kinds of cancer. However, little is known about pathological role of TNF-α in breast cancer (BC) cells. In the current investigation, we investigated the effect of TNF-α on BC cells (MCF-7 and MDA-MB-231) viability, CD44 expression, and in vitro migration. We found that TNF-α down-regulated CD44s expression, up-regulated CD44v3 and CD44v6 expression through JNK pathway in MCF-7 cells. In MDA-MB-231 cells, TNF-α up-regulated CD44s, CD44v3 and CD44v6 expression via p38 pathway. These data indicate important role of CD44 molecule in BC pathology. [Copyright &y& Elsevier]

Abstract: Porcine reproductive and respiratory syndrome (PRRS) causes substantial economic losses to the swine industry in many countries, and current control strategies are inadequate. Previously, we explored the strategy of using peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) to inhibit PRRS virus (PRRSV) replication. PPMOs are nuclease-resistant and single-stranded DNA analogs containing a modified backbone conjugated to a cell-penetrating peptide and can act as antisense agents through steric blockade of complementary messenger RNA. A PPMO (designated 5UP2) targeting highly conserved sequence in the 5′-terminal region of the PRRSV genome was found to produce multi-log10 inhibition of PRRSV replication in cultured cells. To evaluate 5UP2 in vivo, we here administrated the PPMO to 3-week-old piglets via intranasal instillation at 24h before, and 2 and 24h after infection with PRRSV (strain VR2385). Blood samples were collected at 6, 10 and 14days post-infection (dpi) for detection of PRRSV RNA and antibodies. Necropsy was performed at 14dpi. Monitoring weight gain in all piglet groups throughout the experiment indicated that PPMO was well tolerated at the doses used. PPMO 5UP2 treatment significantly reduced PRRSV viremia at 6dpi. On day 14, piglets receiving 5UP2 had significantly less interstitial pneumonia and lower level of anti-PRRSV antibodies than untreated piglets. In alveolar macrophages isolated at the time of necropsy, the expression of antiviral genes in PPMO-treated piglets was elevated in comparison with untreated. This study provides further data indicating that the 5UP2 PPMO can be considered a candidate component for a novel PRRS control strategy. [Copyright &y& Elsevier]

Objective: To explore the possibility that local injury to the endometrium in controlled ovarian hyperstimulation cycle improves the incidence of embryo implantation and to analyze the gene expression profile in the endometria of pregnant and nonpregnant patients in in vitro fertilization/embryo transfer (IVF-ET).Design: Prospective study.Setting: A clinical assisted reproductive center of a university hospital.Patient(s): Women undergoing fresh IVF-ET cycles (n = 121), treated with a long protocol for controlled ovarian hyperstimulation, whose endometrium were diagnosed by B-ultrasound showing irregular echo.Intervention(s): Local injury to the endometrium of 60 patients in controlled ovarian hyperstimulation cycle, who were randomly selected from a total of 121 patients. Seven endometrial biopsies samples from day 10 were analyzed by Affymetrix U133 plus 2.0 gene chip.Main Outcome Measure(s): Outcomes of IVF-ET and gene expression assayed by gene chip technology.Result(s): Transfer of the same number of embryos (135 in the experimental and control patients, respectively) resulted in rates of implantation (33.33% vs. 17.78%), clinical pregnancy (48.33% vs. 27.86%), and ongoing or live births per ET (41.67% vs. 22.96%) that were higher in the experimental group compared with controls. Statistically significant differences of the expression level of 218 genes (41 up-regulated and 177 down-regulated) were detected in the endometrial biopsy samples from clinical pregnant patients and nonpregnant patients.Conclusion(s): The results suggested local injury to the endometrium during a COH cycle improved the rates of embryo implantation, clinical pregnancy and live birth in ART. We also demonstrated a statistically significant difference in the messenger RNA (mRNA) expression profiles in the endometrium of pregnant and nonpregnant patients. Further studies on the genes identified herein will assist in predicting implantation competence. [ABSTRACT FROM AUTHOR]

• Urinary extracellular vesicles miRNAs' expression pattern of RCC patients was examined. • uEV miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p were upregulated in RCC patients. • A three-uEV miRNA panel could discriminate RCC patients from controls with the AUC of 0.785. • An uEV-miRNA panel could also distinguish early-stage RCC patients with the AUC of 0.786. The potential of urinary-derived extracellular vesicle (uEV) microRNAs (miRNAs) as noninvasive molecular biomarkers for identifying early-stage renal cell carcinoma (RCC) patients is rarely explored. The present study aims to explore the possibility of uEV miRNAs as novel molecular biomarkers for distinguishing early-stage RCC. uEVs were extracted by ExoQuick-TC™ kit and miRNA concentrations were measured by RT-qPCR. ROC curves and bioinformatics analysis were employed to predict the diagnostic efficacy and regulatory mechanisms of dysregulated miRNAs. Through a multiphase case-control study on uEV miRNAs screening, training, and validation in RCC cells (ACHN, Caki-1) and control cells (HK-2) and in uEVs of 125 RCC patients and 128 age- and sex-matched controls, we successfully identified four uEVs miRNAs (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) were significantly and stably upregulated in RCC in vitro and in vivo. When adjusted with estimated glomerular filtration rate (eGFR), the AUC of the three-uEV miRNA panel (miR-135b-5p, miR-200c-3p, and miR-203a-3p) was 0.785 (95 % CI = 0.729–0.842, P < 0.0001) for discriminating RCC patients from controls. Notably, this panel exhibited similar performance in distinguishing early-stage (stage Ⅰ) RCC patients, with an AUC of 0.786 (95 %CI = 0.727–0.844, P < 0.0001). Bioinformatics analysis predicted that candidate miRNAs were involved in cancer progressing. Our study identified a four uEV miRNAs panel (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) may serve as an auxiliary noninvasive indication of early-stage RCC. [ABSTRACT FROM AUTHOR]

Highlights • Low temperature reduced banana fruity note volatiles such as esters. • Low temperatures affected volatile-related amino acids and fatty acid compositions. • Chilling temperature affected the key enzymes and genes in volatile biosynthesis. • Low temperatures repressed the LOX pathway and amino acid metabolic pathway. Abstract Banana fruit is sensitive to chilling injury, which not only causes physical damage but also dramatically reduces fruit flavor. In this work, we evaluated the influence of non-chilling low temperature (NCT, 13 °C) and chilling temperature (CT, 5 °C) storage on volatiles production in banana in comparison to control conditions (20 °C) and evaluated the possible mechanisms. We found that CT storage caused chilling injury, which negatively affected the physical appearance of the fruit and dramatically reduced volatiles production, especially fruity note volatiles, such as esters. In contrast, NCT storage only reduced the production of a few specific volatiles. Both NCT and CT affected volatile-related amino acid and biosynthetic precursors of fatty acid compositions. The expression levels of the volatiles biosynthesis-related genes, MaHPL, MaLOX, and MaAAT, were repressed by low temperature (NCT and CT), particularly chilling temperature, while MaADH and MaPDC were up-regulated. These results suggest that CT significantly reduces volatiles production by regulating different key enzymes and genes involved in volatiles biosynthetic pathways and is mainly mediated via the repression of the lipoxygenase and amino acid metabolic pathways. [ABSTRACT FROM AUTHOR]

Background Different gene expression profiles are observed in intracranial aneurysm tissues. Understanding these genes and what regulates their expression will provide insight into the pathogenesis of intracranial aneurysms. We investigated whether differences in DNA methylation regulate gene expression in intracranial aneurysms. Methods We compared 20 intracranial aneurysm tissue specimens with 20 matched specimens from the superficial temporal artery as controls. We identified the gene expression profiles in these samples using the GeneChip Human U133 Plus 2.0 array and evaluated DNA methylation modifications using the Infinium HumanMethylation450 BeadChip Kit. Results A total of 11,022 differentially methylated sites between aneurysm tissues and matched control tissues were identified, and 2142 differentially expressed gene transcripts were detected based on the 2 gene expression profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and verification analysis showed that the MYH11 , LIFR , and TLR4 genes were associated with the occurrence and development of intracranial aneurysms. These genes mainly encode cell adhesion molecules or are involved in the NF-κB, JAK-STAT, and ERK/JNK signaling pathways. Conclusions In the development of intracranial aneurysms, DNA methylation plays an important role in the regulation of genetic expression involved in immune and inflammatory reactions, cell function, cell maintenance, and cell signal transduction. [ABSTRACT FROM AUTHOR]

Gene expression is epigenetically regulated through DNA methylation and covalent chromatin modifications, such as acetylation, phosphorylation, ubiquitination, sumoylation, and methylation of histones. Histone methylation state is dynamically regulated by different groups of histone methyltransferases and demethylases. The trimethylation of histone 3 (H3K4) at lysine 4 is usually associated with the activation of gene expression, whereas trimethylation of histone 3 at lysine 27 (H3K27) is associated with the repression of gene expression. The polycomb repressive complex contains the H3K27 methyltransferase Ezh2 and controls dimethylation and trimethylation of H3K27 (H3K27me2/3). The Jumonji domain containing-3 (Jmjd3, KDM6B) and ubiquitously transcribed X-chromosome tetratricopeptide repeat protein (UTX, KDM6A) have been identified as H3K27 demethylases that catalyze the demethylation of H3K27me2/3. The role and mechanisms of both JMJD3 and UTX have been extensively studied for their involvement in development, cell plasticity, immune system, neurodegenerative disease, and cancer. In this review, we will focus on recent progresses made on understanding JMJD3 in the regulation of gene expression in development and diseases. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is known that hyperhomocysteinemia (Hhcy) is associated with the risk of restenosis after angioplasty. Folate can lower plasma homocysteine (Hcy) level and alleviate the Hhcy-induced neointima formation after balloon injury. This study aims to explore the mechanisms of folate in inhibiting neointima formation. Methods: 24 New Zealand White rabbits were randomly divided into three groups: Control, 2% methionine (Meth) and 2% methionine+folate (Meth+folate). At the end of 8 experimental weeks, all rabbits underwent the balloon injury in abdominal aorta. 4 weeks following this procedure, plasma Hcy concentration, aortic maximal neointimal thickness (NT), neointimal area (NA), medial area (MA), and ratio of neointimal area to medial area (NA/MA), ultrastructure of vascular smooth muscle cells (VSMCs), and matrix metalloproteinase-9 (MMP-9) expression were detected by high performance liquid chromatography, histomorphometric analysis, transmission electron microscope (TEM) and real-time PCR, respectively. Results: It was observed in our study that Hcy concentration, NT, NA, NA/MA and the expression of MMP-9 mRNA were higher in the Meth group than in the control. VSMCs in media exhibited typical synthetic phenotype in the Meth group compared with the transitional state between contractile phenotype and synthetic phenotype in the control group. However, in the rabbits treated with folate, Hcy concentration, NT, NA and MMP-9 mRNA expression were lower than those in the Meth group. The phenotype of VSMCs was close to that in the control group. Conclusion: This study suggested that folate could decrease the level of Hcy, reverse the Hhcy-induced exacerbation of neointima formation in rabbits following balloon injury, and the mechanisms in it may be related to the suppressive effect of folate on the expression of MMP-9 mRNA in arterial wall. [Copyright &y& Elsevier]

• It is a novel report on the effects of BPA on ovarian development in adolescent mice. • 4266 differentially expressed genes (DEGs) in the ovary of adolescent mice due to BPA exposure were identified by RNA-Seq. • BPA exposure has far-reaching effects on ovarian development in adolescent mice. Many human epidemiology and animal model studies have reported that bisphenol A (BPA) exerts adverse effects on reproduction through different regulatory mechanisms and signaling pathways in adults. In recent years, the exposure risk has increased for the general population, and little is known about how BPA affects ovarian development in adolescent animals and humans. In the present study, we aimed to investigate the effects of BPA exposure on ovarian development and the transcriptome in adolescent mice. Four-week-old ICR female mice were randomly divided into two groups and orally administered BPA (200 ng/kg/day) by gavage for 4 weeks. The BPA and estrogen (E2) levels in sera from the two groups were subsequently determined by using enzyme-linked immunosorbent assays (ELISAs). An immunohistochemical study showed that several obvious ovarian structural and developmental abnormalities were observed in the treatment group with changes in the E2 receptor gene and protein expression levels. A total of 4266 differentially expressed genes (DEGs) were identified, and the possible functions of these DEGs were explored by bioinformatics analyses based on the RNA-Seq data. The two most significant expression profiles were identified by Short Time-series Expression Miner (STEM) software, and the genes in these two profiles were enriched in actin filament-based processes, behaviour and membrane potential regulation according to Gene Ontology (GO) enrichment analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs are particularly involved in the endocrine system, the calcium and cAMP signaling pathways. [ABSTRACT FROM AUTHOR]

Flower odor is often essential for attracting pollinators, and this is especially true for species-specific mutualism such as the one between Ficus species and their pollinating wasps. Receptive figs emit a stage and species specific odor composed of a mix of volatile organic compounds (VOC) that is attractive to their pollinators. Histological studies suggest that the ostiolar bracts are the main locus of fig floral VOC synthesis. To confirm a major role of the ostiole in VOC synthesis, detect the genes involved in VOC synthesis and analyze differences between closely related species, we compare the transcriptomes of pre-receptive and receptive figs of two closely related species, F. hirta and F. triloba. The two species presented similar numbers of expressed genes and similar annotation, classification results, and their up-regulated unigenes belonged to similar biosynthetic pathways. However, phenylpropanoid and terpene synthesis were the main enriched VOC pathways in receptive figs of F. hirta while terpene and jasmonate synthesis were the main enriched VOC pathways in F. triloba. The shift in gene expression between pre-receptive and receptive figs was much more marked in the ostiolar bracts than in the flowers of F. hirta , and in the fig wall, confirming an important role of the ostiole in receptive fig odor emission. Only one unigene directly involved in VOC synthesis presented signatures of positive selection, further supporting that the source of interspecific receptive fig odor differentiation is based on gene regulation rather than on gene differentiation. Regulation based receptive fig odor differentiation between species suggests a potential for rapid evolution of this interspecific barrier. • F. hirta and F. triloba presented similar numbers of expressed genes and similar annotation. • F. hirta and F. triloba had different enriched VOC pathways related to pollinator attraction. • The important role of the ostiole in receptive fig odor emission was conformed. • The source of interspecific fig odor differentiation is based on gene regulation rather than on gene differentiation. [ABSTRACT FROM AUTHOR]