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Osmundacetone (OSC) is a bioactive phenolic compound isolated from Phellinus igniarius and that was shown to exert cytotoxic effects on cancer cells in our previous work. The antiproliferative impact of OSC on non-small cell lung cancer (NSCLC) and the underlying mechanisms, however, have not been studied.This study aimed to explore the antiproliferative effect of OSC on NSCLC cells and the mechanisms involved.Cell viability, colony formation and cell cycle distribution were measured following exposure to OSC in vitro. The anticancer activity of OSC was also examined using a xenograft growth assay in vivo. Furthermore, serum metabolomics analysis by GC-MS was done to detect alterations in the metabolic profile. Next, expression of GLS1 and GLUD1, the key enzymes in glutamine metabolism, was evaluated using RT-PCR and western blot. α-KG and NADH metabolites were assessed by ELISA. Mitochondrial functions and morphology were evaluated using the JC-1 probe and transmission electron microscopy, respectively. The ATP production rate in mitochondria of cells with OSC treatment was determined using a Seahorse XFe24 Analyzer.OSC selectively reduced the proliferation of A549 and H460 cells. OSC triggered G2/M cell cycle arrest and decreased the cell clone formation. A mouse xenograft model revealed that OSC inhibited tumor growth in vivo. Findings of serum metabolomics analyses indicated that the anticancer function of OSC was related to disorders of glutamine metabolism. Such a speculation was further verified by the expression level of GLUD1, which was downregulated by OSC treatment. Concentrations of the related metabolites α-KG and NADH were reduced in response to OSC treatment. Moreover, OSC led to disorganization of the mitochondrial ultrastructure and a decrease in mitochondrial membrane potential. OSC also decreased ATP production via oxidative phosphorylation (OXPHOS) but did not affect glycolysis in NSCLC cells.The key role of OSC in mitochondrial energy metabolism in NSCLC cells is to suppress tumor development and cell proliferation downregulating GLUD1 to inhibit the glutamine/glutamate/α-KG metabolic axis and OXPHOS. It indicats that OSC might be a potential natural agent for personalized medicine and an anticancer metabolic modulator in NSCLC chemotherapy.

Orcinol Glucoside (OG), a phenolic glucoside isolated from C. orchioides, showed the antidepressant-like effect on chronic unpredictable mild stress (CUMS)-induced rats previously. This study was designed to determine whether OG could improve the depressive-like symptoms of perimenopausal depression (PMD) and the possible mechanisms involved. This research was performed on a PMD mice model established by a two-steps method of ovariectomy (OVX) followed CUMS. OG treatment effectively improved the depressive-like behaviors of OVX-CUMS mice, as indicated by increased sucrose intake in sucrose preference test (SPT), reduced immobility time in forced swimming test (FST), and tail suspension test (TST), lower frequency of grooming and defecation, increased actions of rearing, and prolonged duration in the center in open field test (OFT). OG treatment alleviated the OVX-CUMS induced dysfunction of hypothalamic-pituitary-ovarian (HPO) axis by increased serum estradiol (E2) and decreased ovarian hormones follicle stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing hormone (GnRH) in serum. Meanwhile, OG reversed the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis as evidenced by decreased CORT and ACTH in serum, reduced as well as the mRNA and protein expression of corticotropin-releasing hormone (CRH) in hypothalamus and hippocampus. Moreover, OG up-regulated the protein expression of BDNF, TrkB, and phosphorylation level of CREB and ERK1/2 in hippocampus. These findings demonstrated that OG improves depressive behaviors of OVX-CUMS mice by modulating of HPO/HPA axis dysfunction, and activating BDNF-TrkB-CREB signaling pathway.

Background Interferon regulatory factor 6 (IRF6) exhibits tumor-suppressive functions in several cancer types. In the present study, the antitumor properties and related pathway mechanism of IRF6 were investigated in cervical cancer. Methods Forty-one pairs of cervical cancer specimens and para-carcinoma tissues were collected to evaluate IRF6 expression using immunohistochemical staining and miR-587. The effects of miR-587 and IRF6 on cervical cancer cell growth were explored by MTT assays and in a HeLa tumor xenograft mouse model. The migration and invasion of cervical cancer cells were monitored using transwell assays. Results IRF6 expression in cervical cancer specimens and cell lines was significantly reduced compared to that in the corresponding control group. In addition, IRF6 expression was negatively correlated with miR-587 in cervical cancer tissues. Bioinformatics algorithms and luciferase assays revealed that IRF6 is a potential target of miR-587, and miR-587 mimic transfection led to a significant repression of IRF6 protein levels in cervical cancer cells. We also discovered that the antineoplastic properties of IRF6 could be reversed by overexpressing miR-587 in cervical cancer cells. The up-regulation of miR-587 was correlated with poor overall survival in cervical cancer. In an in vivo experiment, miR-587 silencing induced HeLa tumor growth inhibition, which was associated with the up-regulation of IRF6 protein in the tumor. Conclusions miR-587 post-transcriptionally represses IRF6 protein expression to abrogate the antineoplastic activity of IRF6. The miR-587/IRF6 signaling pathway plays a crucial role in the progression of cervical cancer and serves as a potential therapeutic target for the treatment of cervical cancer.

This study aimed to assess human papilloma virus (HPV) 16 18/45 typing test results combined with cytology for cervical exfoliated cells from women who screened positive in an HPV E6/E7 mRNA assay (Aptima HPV, AHPV).In total, 3257 AHPV-positive women aged 25-65 years were underwent AHPV 16 18/45 Genotype assay (AHPV-GT) testing with cytology. Women were referred for colposcopy and further biopsy if indicated. Different triaging strategies were compared.Overall, 624 women (19.2%) tested AHPV-GT positive. When identifying CIN2+, compared with cytology, AHPV-GT achieved a similar AUC (0.72 vs. 0.69, P = 0.158) but a higher specificity (85.1% vs. 79.3%, P 0.001) and positive predictive value (PPV) (29.6% vs. 23.2%, P 0.001). When identifying CIN2+, compared with cytology, the cotesting strategy (cytology combined with AHPV-GT) increased the AUC from 0.69 to 0.76 (P 0.001), with a higher sensitivity (84.6% vs. 59.5%, P 0.001), higher NPV (97.6% vs. 94.9%, P 0.001) and similar PPV (21.6% vs. 23.2%, P = 0.054). When identifying CIN2+, the results of combination strategy (AHPV-GT genotyping plus reflex cytology in women positive for the 11 other hrHPV genotypes) were consistent with those of the cotesting strategy. Similar results were achieved when identifying CIN3 + .The AHPV-GT test may be a promising triage approach with high specificity in women receiving AHPV-positive primary screening tests. Although a combination strategy and cotesting strategy detected the same CIN2+ and CIN3+ cases, the former required significantly fewer screening tests.

OBJECTIVE To investigate the relationship of ventriculomegaly (VM) with postnatal neurological development. METHODS Fetuses with isolated VM on MRI (n = 160; VM group) were separated into three subgroups according to lateral ventricle width: subgroup A (10.0-12.0 mm; n = 113), subgroup B (12.1-15.0 mm; n = 37), and subgroup C (>15.0 mm; n = 10). Fifty normal fetuses formed a control group. Post-delivery changes in ventricular width and neurological development were assessed with MRI/ultrasonography and the Gesell Development Schedules (GDS), respectively, at 3, 6, 12, and 18 months. RESULTS GDS scores of subgroup A and subgroup B did not differ from that of the controls at 3 and 6 months. Subgroup B scores differed significantly from the control scores at 12 and 18 months. Subgroup C scores differed from the control scores at all-time points (all P

To screen for genomic copy number variants (CNVs) in a fetus with cardiac abnormalities and intrauterine growth retardation through single nucleotide polymorphism microarray (SNP array) and karyotyping analysis.The fetus and its parents were subjected to conventional G banding and SNP-array analysis. The results were confirmed with fluorescence in situ hybridization (FISH).G-banding analysis showed that the fetus has a karyotype of 47,XX,+mar. The father has a karyotype of 46,XY,t(4;18) (p15.2q11.2), while the mother showed a normal karyotype. SNP-array detected two microduplications at 18p11.32q11.2 (20.5 Mb) and 4p16.3p15.2 (24.7 Mb) in the fetus. The supernumerary marker chromosome carried by the fetus has derived from the balanced translocation carried by its father. The result was confirmed by FISH.Based on the two microduplications, the fetus was diagnosed as Wolf-Hirschhorn syndrome in conjunction with Edward syndrome. Verification of the origin of the supernumerary marker chromosome by SNP-array has provided a basis for prenatal genetic diagnosis.

To screen for genomic copy number variants (CNVs) in a fetus with one sibling affected with Prader-Willi syndrome using single nucleotide polymorphism (SNP) array.The fetus and its parents were subjected to chromosomal karyotyping and SNP array analysis.A 5p15.33 microdeletions was identified in the fetus and its phenotypically normal mother with a size of 344 kb (113 576 to 457 213). The father was normal for both testing. Analysis of literature and CNVs database indicated the above CNV to be variant of unclear significance. The couple decided to continue with the pregnancy and gave birth to a healthy boy at full-term. No abnormalities were found during the follow-up.This study may provide further data for the phenotype-genotype correlation of 5p15.33 microdeletion, which differs from Cri du Chat syndrome.

PURPOSE Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer. METHODS We searched public databases to explore associations between UCK2 gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with UCK2 gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets. RESULTS We found that UCK2 mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High UCK2 levels were correlated with estrogen receptor negativity (p