Wnt/β-catenin signaling pathway is strictly controlled by multiple negative regulators. However, how tumor cells override the negative regulatory effects to maintain constitutive activation of Wnt/β-catenin signaling, which is commonly observed in various cancers, remains puzzling. In current study, we reported that overexpression of miR-1207 in ovarian cancer activated Wnt/β-catenin signaling by directly targeting and suppressing secreted Frizzled-related protein 1 (SFRP1), AXIN2 and inhibitor of β-catenin and TCF-4 (ICAT), which are vital negative regulators of the Wnt/β-catenin pathway. We found that the expression of miR-1207 was ubiquitously upregulated in both ovarian cancer tissues and cells, which inversely correlated with patient overall survival. Furthermore, overexpression of miR-1207 enhanced, while silencing miR-1207 reduced, stem cell-like traits of ovarian cancer cells in vitro and in vivo, including tumor sphere formation capability and proportion of SP+ and CD133+ cells. Importantly, upregulating miR-1207 promoted, while silencing miR-1207 inhibited, the tumorigenicity of ovarian cancer cells. Hence, our results suggest that miR-1207 plays a vital role in promoting the cancer stem cell-like phenotype in ovarian cancer and might represent a potential target for anti-ovarian cancer therapy.

The present study aimed to investigate the relationship between miRNAs and in spontaneously hypertensive rats (SHR) vascular remodeling and analyze the impact of the Pinggan Qianyang recipe (PQR) on miRNAs. Mammalian miRNA microarrays containing 509 miRNA genes were employed to analyze the differentially expressed miRNAs in the three groups. MiRNAs were considered to be up- or downregulated when the fluorescent intensity ratio between the two groups was over 4-fold. Validation of those miRNAs changed in SHR after PQR treatment was used by real-time quantitative RT-PCR (qRT-PCR). Compared with the normal group, a total of 32 miRNAs were differentially expressed by more than twofold; among these, 18 were upregulated and 14 were downregulated in the model group. Compared with the normal group, there were a number of 17 miRNAs which were significantly expressed by more than twofold in the different expressions of 32 miRNAs; among these, 10 were downregulated and 7 were upregulated in the PQR group. qRT-PCR verified that miR-20a, miR-145, miR-30, and miR-98 were significantly expressed in the three groups. These data show that PQR could exert its antihypertensive effect through deterioration of the vascular remodeling process. The mechanism might be associated with regulating differentially expressed miRNAs in aorta tissue.

High levels of angiogenesis and resistance to apoptosis are major clinical features of hepatocellular carcinoma (HCC), a lethal disease with a high incidence worldwide. However, the precise mechanisms underlying these malignant properties remain unclear. Here, we demonstrated that acylglycerol kinase (AGK) is markedly overexpressed in HCC cell lines and clinical tissues. Immunohistochemical analysis of 245 clinical HCC specimens revealed patients with high levels of AGK expression had poorer overall survival compared to patients with low AGK expression. Furthermore, overexpressing AGK significantly enhanced angiogenesis and inhibited apoptosis in vitro and promoted the tumorigenicity of HCC cells in vivo; silencing endogenous AGK had the opposite effects. Importantly, AGK enhanced angiogenesis and inhibited apoptosis in HCC in part via activation of NF-κB signaling. Our findings provide new evidence that AGK plays an important role in promoting angiogenesis and providing resistance to apoptosis, thus AGK may represent a novel therapeutic target for HCC.

CD147 is expressed in many tissues and is involved in many inflammatory diseases. Emerging evidence suggests that the overproduction of mucus is a malignant factor in chronic obstructive pulmonary disease (COPD), which results in severe airway obstruction and repeated airway infections. However, it is still unclear whether CD147 is involved in mucus production in COPD.

Peptide P7 specifically binds with basic fibroblast growth factor (bFGF) to inhibit the proliferation and invasion of numerous types of cancer cell. However, this effect has remained to be demonstrated in ovarian cancer-derived cell lines. In the present study, the protein P7 was used treat bFGF-stimulated SKOV3 epithelial ovarian cancer cells to explore the therapeutic potential of P7. An MTT and a scratch wound assay were used to respectively evaluate the proliferation and migration of bFGF-stimulated SKOV3 cells treated with P7. Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the gene expression of urokinase-type plasminogen activator (uPA), as well as matrix metallopeptidase (MMP)-2 and -9, which have a role in cell migration/invasion. The morphology and proliferation of SKOV3 cells were not significantly affected by different concentrations of P7. However, P7 had an obvious inhibitory effect on the proliferation and migration of bFGF-stimulated SKOV3 cells. Treatment with P7 significantly lowered the gene expression of uPA, MMP-2 and MMP-9 compared with that in the control group. In conclusion, the present results suggested that P7, which, at least in part, acts through inhibition of bFGF, may have a potential therapeutic application in epithelial ovarian cancer.

Idiopathic pulmonary fibrosis (IPF) is considered to be an ailment of the lungs that cannot be cured, wherein the lung tissues are characterized by increased thickness and stiffness, and/or scars. Despite the fact that extensive success has been achieved regarding the molecular diagnostics and pathobiology, the basic pathogenesis associated with IPF has not yet been fully elucidated and requires further clarification. In the current research, the changes in microRNA (miRNA) and mRNA expression in IPF were investigated through an integrative network technique. The authentic miRNA and mRNA expression profiling datasets were downloaded from Gene Expression Omnibus, followed by identification of differentially expressed miRNAs and mRNAs with use of the Significance Analysis of Microarrays algorithm. Expansion of the molecular targets associated with miRNAs was performed with the use of CyTargetLinker in Cytoscape, which was succeeded by validation with the use of mRNA array expression profiling. The incorporated miRNA‑mRNA network covered 27 genes, in addition to 22 miRNAs that were associated with IPF development. As revealed by the functional enrichment analysis, the cytokine‑cytokine receptor interaction and glycine, serine and threonine metabolism signalling pathways were extensively associated with IPF development. Overall, the present incorporated network illustrated the key link between miRNA and genes in IPF; in particular, it was elucidated that miR‑409‑5p and has‑miR‑376c, together with their target genes (C‑C motif chemokine ligand 20 and oncostatin M), are likely candidates involved in the promotion of IPF initiation and progression.

The paired box gene 6 (PAX6) is an essential transcription factor for eye formation. Genetic alterations in PAX6 can lead to various ocular malformations including aniridia. The purpose of this study was to identify genetic defects as the underlying cause of familial ocular coloboma in a large Chinese family.

Song control nuclei have distinct sexual differences and thus are an ideal model to address how brain areas are sexually differentiated. Through a combination of histological analysis and electrical lesions, we first identified the ventricle site for HVC progenitor cells. We then found that there were significant sex differences in the cellular proliferation activity in the ventricular zone of the HVC, the number of migrating cells along the radial cells (positive immunoreactions to vimentin) and differentiation towards neurons. Through co-culturing of male and female slices containing the developing HVC in the same well, we found that the male slices could produce diffusible substances to masculinize the female HVC. By adding estrogen, an estrogen antagonist, brain-derived neurotrophic factor (BDNF) or its antibody into the culture medium, separately or in combination, we found that these diffusible substances may include estrogen and BDNF. Finally, we found that 1) estrogen-induced BDNF upregulation could be detected 48 hr after estrogen treatment and could not be blocked by a vascular endothelial growth factor (VEGF) receptor inhibitor and 2) the amount of VEGF mRNA expressed in the developing HVC and its adjacent area did not display any significant sex differences, as did the distribution of VEGF and laminin-expressing endothelial cells in the developing HVC. Because these findings are largely different from previous reports on the adult female HVC, it is suggested that our estrogen-induced BDNF up-regulation and the resultant sexual differentiation might not be mediated by VEGF and endothelial cells, but instead, may result from the direct effects of estrogen on BDNF.

Phospholipid phosphatase 4 (PPAPDC1A or PLPP4) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to investigate the clinical significance and biological roles of PLPP4 in lung carcinoma.

The unfolded protein response, autophagy and endoplasmic reticulum (ER) stress-induced apoptosis regulate tumor cell fate and have become novel signaling targets for the development of cancer therapeutic drugs. Curcumin has been used to treat several different cancers, including ovarian cancer, in clinical trials and research; however, the role of ER stress and autophagy in the therapeutic effects of curcumin and new curcumin analogues remains unclear.

Resveratrol (RSV), a naturally occurring polyphenolic stilbenoid, is known to possess potent anti-atherogenic properties; however, the effect of RSV on hypercholesterolemia is not fully understood. We hypothesized that RSV decreases blood cholesterol levels through the activation of cholesterol 7α-hydroxylase (CYP7A1)-mediated bile acid synthetic pathway pathways in vitro and in vivo.

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, may function as a tumor suppressor or an oncogene, depending on the tumor type. We sought to determine the biological function of GSK-3β in osteosarcoma, a rare pediatric cancer for which the identification of new therapeutic targets is urgent.

SDF-1 (stromal cell derived factor-1) has been found to be widely expressed during dental pulp inflammation, while hDPSCs (human dental pulp stem cells) contribute to the repair of dental pulp. We showed that the migration of hDPSCs was induced by SDF-1 in a concentration-dependent manner and could be inhibited with siCXCR4 (C-X-C chemokine receptor type 4) and siCDC42 (cell division control protein 42), as well as drug inhibitors such as AMD3100 (antagonist of CXCR4), LY294002 (inhibitor of PI3K) and PF573228 (inhibitor of FAK). It was also confirmed that SDF-1 regulated the phosphorylation of FAK (focal adhesion kinases) on cell membranes and the translocation of β-catenin into the cell nucleus. Subsequent experiments confirmed that the expression of CXCR4 and β-catenin and the phosphorylation of FAK, PI3K (phosphoinositide 3-kinase), Akt and GSK3β (glycogen synthase kinase-3β) were altered significantly with SDF-1 stimulation. FAK and PI3K worked in coordination during this process. Our findings provide direct evidence that SDF-1/CXCR4 axis induces hDPSCs migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways, implicating a novel mechanism of dental pulp repair and a possible application of SDF-1 for the treatment of pulpitis.

PTEN plays an essential role in tumorigenesis and both its mutation and inactivation can influence proliferation, apoptosis, and cell cycle progression in tumor cells. However, the precise role of PTEN in lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutant PTEN as well as A549 cells expressing a siRNA directed toward endogenous PTEN. Overexpression of wild-type PTEN profoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase protein hTERT. In contrast, in cells expressing a PTEN directed siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, and hTERT protein expression were observed. A549 cells transfected with a PTEN mutant lacking phosphatase activity (PTEN-C124A) or an empty vector (null) did not show any effect. Furthermore, using the PI3K/AKT pathway blocker LY294002, we confirmed that the PI3K/AKT pathway was involved in mediating these effects of PTEN. Taken together, we have demonstrated that PTEN downregulates the PI3K/AKT/hTERT pathway, thereby suppressing the growth of lung adenocarcinoma cells. Our study may provide evidence for a promising therapeutic target for the treatment of lung adenocarcinoma.

Acinetobacter baumannii has emerged as an important opportunistic pathogen due to its ability to acquire resistance to most currently available antibiotics. Colistin is often considered as the last line of therapy for infections caused by multidrug-resistant A. baumannii (MDRAB). However, colistin-resistant A. baumannii strain has recently been reported. To explore how multiple drug-resistant A. baumannii responded to colistin resistance, we compared the genomic, transcriptional and proteomic profile of A. baumannii MDR-ZJ06 to the induced colistin-resistant strain ZJ06-200P5-1. Genomic analysis showed that lpxC was inactivated by ISAba1 insertion, leading to LPS loss. Transcriptional analysis demonstrated that the colistin-resistant strain regulated its metabolism. Proteomic analysis suggested increased expression of the RND efflux pump system and down-regulation of FabZ and β-lactamase. These alterations were believed to be response to LPS loss. In summary, the lpxC mutation not only established colistin resistance but also altered global gene expression.

Objective. To assess the value of bronchoscopy in the diagnosis and treatment of primary tracheobronchial amyloidosis (TBA), in order to reduce misdiagnosis rates and improve prognosis. Methods. Clinical data of 107 patients with TBA reported from 1981 to 2015 in China were retrospectively analyzed for clinical features, bronchoscopic manifestations, pathologies, treatments, and outcomes. Results. 105 of 107 TBA patients were pathologically confirmed by bronchoscopy. Main bronchoscopic manifestations of TBA were single or multiple nodules and masses within tracheobronchial lumens; local or diffuse luminal stenosis and obstruction; luminal wall thickening and rigidity; rough or uneven inner luminal walls; congestion and edema of mucosa, which was friable and prone to bleeding upon touch; and so forth. 53 patients were treated with bronchoscopic interventions, like Nd-YAG laser, high-frequency electrotome cautery, freezing, resection, clamping, argon plasma coagulation (APC), microwaving, stent implantation, drug spraying, and other treatments. 51 patients improved, 1 patient worsened, and 1 died. Conclusion. Bronchoscopic biopsy is the primary means of diagnosing TBA. A variety of bronchoscopic interventions have good short-term effects on TBA. Bronchoscopy has important value in the diagnosis, severity assessment, treatment, efficacy evaluation, and prognosis of TBA.

Chronic obstructive pulmonary disease (COPD) and squamous cell lung carcinoma (SCC) are smoking-related diseases. However, the connection between the two is poorly understood. Microarray gene expression profiles in bronchial epithelium from patients with SCC with or without COPD were downloaded from the Gene Expression Omnibus repository. Differentially expressed genes associated with COPD and SCC were identified and visualized using the Advanced Network Merger module in Cytoscape. COPD-associated genes in SCC progression were further identified using the BisoGenet plug-in in Cytoscape. The genetic interaction network was predicted using the Network Analysis function. Heat shock protein 90 α family class A member 1 (HSP90AA1), adrenoceptor β2 (ADRB2), transducin β like 1 X-linked receptor 1 (TBL1XR1) and heat shock protein family B (small) member 1 (HSPB1) were identified to be differentially expressed in SCC and COPD cases. The overall survival rate associated with the gene signatures was investigated using clinical samples from patients with SCC and COPD from the PROGgene database. The results suggest that the pathogenesis of SCC caused by COPD is regulated by HSP90AA1, ADRB2, TBL1XR1 and HSPB1. These genes may serve as potential therapeutic targets for the treatment of patients with COPD-related SCC.

Circulating factors associated with aging have been shown to be involved in the development of age-related chronic and acute brain diseases. Here, we aimed to investigate the roles and mechanisms of CCL12, a circulating factor that is highly expressed in the plasma of aged rodents after intracerebral hemorrhage (ICH) using parabiosis and ICH models. Neurological deficit score (NDS), mortality rate, brain water content (BWC), and levels of inflammatory factors were determined to assess the degree of ICH-induced brain injury. Peripheral inflammatory cell infiltration was examined using immunofluorescence and flow cytometry. After confirming that acute brain injury after ICH was aggravated with age, we found that brain and plasma CCL12 levels were markedly higher in old mice than in young mice after ICH, and that plasma CCL12 was able to enter the brain. Using CCL12-/- mice, we showed that the degree of damage in the brain-as determined by NDS, mortality rate, BWC, levels of inflammatory factors, and numbers of degenerative and apoptotic neural cells and surviving neurons was significantly attenuated compared to that observed in old wild-type (WT) mice. These effects were reversed in CCL12-treated old mice. The detrimental effects caused by CCL12 may involve its ability to recruit macrophages and T cells. Finally, the administration of an anti-CCL12 antibody markedly improved the outcomes of ICH mice. Our results are the first to indicate that elevated peripheral CCL12 levels in old mice aggravates ICH-induced brain injury by recruiting macrophages and T cells. Thus, CCL12 may be a new target for ICH treatment.

MiR-924 has been reported to be a tumor suppressor in hepatocellular carcinoma. However, the functions and mechanisms of miR-924 in non-small cell lung cancer (NSCLC) remain unclear.

Discs-large (DLG) is a member that belongs to the membrane-associated guanylate kinase (MAGUK) family. The GK domain of DLGs has evolved into a protein-protein interaction module that could bind with kinds of proteins to regulate diverse cellular functions. Previous reports have demonstrated the GK domain of DLGs functioned as a phosphor-peptide-binding module by resolving the crystal structures. Here we investigated into the interactions of DLG1 and DLG4 with their reported phosphor-peptides by molecular dynamics simulations. Post-dynamics analysis showed that DLG1/4 formed extensive interactions with phosphorylated ligands, including hydrophobic and hydrogen bonding interactions. Among them, the highly conserved residues among the DLGs in phosphor-site and β5 sheet were crucial for the binding according to the energy decomposition calculations. Additionally, the binding interactions between DLG4 and reported unphosphorylated peptides including MAP1A and designed GK inhibitory (GKI-QSF) peptides were analyzed. We found the key residues that played important roles in DLG4/unphosphorylated peptide systems were very similar as in DLG4/phosphor-peptide systems. Moreover, the molecular dynamic simulation for the complex of DLG1 and GKI-QSF was carried out and predicted that the GKI-QSF could bind with DLG1 with similar Kd value compared to DLG4/GKI-QSF, which was verified by using ITC assay (Kd = 1.20 ± 0.29 μM). Our study might be helpful for the better understanding of the structural and biological function of DLGs GK domain and encourage the discovery of new binders.