Epigenetic modifications may play a relevant role in the pathogenesis of human abdominal aortic aneurysm (AAA). The aim of the study was therefore to investigate histone acetylation and expression of corresponding lysine [K] histone acetyltransferases (KATs) in AAA.

Endothelial cells (ECs) form blood vessels through angiogenesis that is regulated by coordination of vascular endothelial growth factor (VEGF), Notch, transforming growth factor β, and other signals, but the detailed molecular mechanisms remain unclear.

We employed next generation RNA sequencing analysis to reveal dysregulated long non-coding RNAs (lncRNAs) in lung cancer utilizing 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues from 3 separate institutions. We identified 281 lncRNAs with significant differential-expression between LUAD and normal lung tissue. LINC00857, a top deregulated lncRNAs, was overexpressed in tumors and significantly associated with poor survival in LUAD. knockdown of LINC00857 with siRNAs decreased tumor cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Overexpression of LINC00857 increased cancer cell proliferation, colony formation and invasion. Mechanistic analyses indicated that LINC00857 mediates tumor progression via cell cycle regulation. Our study highlights the diagnostic/prognostic potential of LINC00857 in LUAD besides delineating the functional and mechanistic aspects of its aberrant disease specific expression and potentially using as a new therapeutic target.

The diagnosis for pseudoprogression (PsP) and true tumor progression (TTP) of GBM is a challenging task in clinical practices. The purpose of this study is to identify potential genetic biomarkers associated with PsP and TTP based on the clinical records, longitudinal imaging features, and genomics data. We are the first to introduce the radiogenomics approach to identify candidate genes for PsP and TTP of GBM. Specifically, a novel longitudinal sparse regression model was developed to construct the relationship between gene expression and imaging features. The imaging features were extracted from tumors along the longitudinal MRI and provided diagnostic information of PsP and TTP. The 33 candidate genes were selected based on their association with the imaging features, reflecting their relation with the development of PsP and TTP. We then conducted biological relevance analysis for 33 candidate genes to identify the potential biomarkers, i.e., Interferon regulatory factor (IRF9) and X-ray repair cross-complementing gene (XRCC1), which were involved in the cancer suppression and prevention, respectively. The IRF9 and XRCC1 were further independently validated in the TCGA data. Our results provided the first substantial evidence that IRF9 and XRCC1 can serve as the potential biomarkers for the development of PsP and TTP.

DNA-binding proteins (DBPs) play fundamental roles in many biological processes. Therefore, the developing of effective computational tools for identifying DBPs is becoming highly desirable.

The knowledge of the tertiary structure of RNA loops is important for understanding their functions. In this work we develop an efficient approach named RNApps, specifically designed for predicting the tertiary structure of RNA loops, including hairpin loops, internal loops, and multi-way junction loops. It includes a probabilistic coarse-grained RNA model, an all-atom statistical energy function, a sequential Monte Carlo growth algorithm, and a simulated annealing procedure. The approach is tested with a dataset including nine RNA loops, a 23S ribosomal RNA, and a large dataset containing 876 RNAs. The performance is evaluated and compared with a homology modeling based predictor and an ab initio predictor. It is found that RNApps has comparable performance with the former one and outdoes the latter in terms of structure predictions. The approach holds great promise for accurate and efficient RNA tertiary structure prediction.

Docetaxel is commonly used as an effective chemotherapeutic agent in breast cancer treatment, but the underlying mechanisms of drug resistance are not fully understood. The purpose of this study was to investigate the possible role of miR-129-3p in breast cancer cell resistance to docetaxel. MiR-129 and miR-129-3p inhibitor were transfected into breast cancer cells to investigate their effects on chemoresistance to docetaxel. The function of miR-129-3p was evaluated by apoptosis, cell proliferation, and cell cycle assays. We found that miR-129-3p was up-regulated in MDA-MB-231/Doc cells, concurrent with CP110 down-regulation, compared to the parental MDA-MB-231 cells. In vitro drug sensitivity assays demonstrated that miR-129-3p inhibition sensitized MDA-MB-231/Doc and MCF-7 cells to docetaxel, whereas miR-129 overexpression enhanced MDA-MB-231 and MCF-7 cell resistance to docetaxel. Ectopic miR-129 expression reduced CP110 expression and the luciferase activity of a CP110 3' untranslated region-based reporter construct in MDA-MB-231 cells, suggesting that CP110 is a direct miR-129-3p target. We demonstrated that restoration of CP110 expression in MDA-MB-231 and MCF-7 cells by miR-129 overexpression rendered the cells sensitive to docetaxel. In a nude xenograft model, miR-129 up-regulation significantly decreased MDA-MB-231 cells' response to docetaxel. Our findings suggest that miR-129-3p down-regulation potentially sensitizes breast cancer cells to docetaxel treatment.

Buyang Huanwu Decoction (BYHWD) is a Traditional Chinese Medicine (TCM) formula for treating stroke-induced disability. Xiaoshuan enteric-coated capsule (XSECC), derived from the formula BYHWD, is a drug approved by the China Food and Drug Administration (CFDA) for stroke management. To further investigate the potential protective effects of XSECC on neurovascular functions, we endeavour to monitor the neurovascular functions using multimodal magnetic resonance imaging (MRI) and evaluated histopathological changes of neurovascular unit (NVU) after stroke.

Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored.

Disseminated candidiasis has become one of the leading causes of hospital-acquired blood stream infections with high mobility and mortality. However, the molecular basis of host defense against disseminated candidiasis remains elusive, and treatment options are limited. Here we report that the E3 ubiquitin ligase CBLB directs polyubiquitination of dectin-1 and dectin-2, two key pattern-recognition receptors for sensing Candida albicans, and their downstream kinase SYK, thus inhibiting dectin-1- and dectin-2-mediated innate immune responses. CBLB deficiency or inactivation protects mice from systemic infection with a lethal dose of C. albicans, and deficiency of dectin-1, dectin-2, or both in Cblb(-/-) mice abrogates this protection. Notably, silencing the Cblb gene in vivo protects mice from lethal systemic C. albicans infection. Our data reveal that CBLB is crucial for homeostatic control of innate immune responses mediated by dectin-1 and dectin-2. Our data also indicate that CBLB represents a potential therapeutic target for protection from disseminated candidiasis.

Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews. Moreover, the ankle brachial index, transcutaneous oxygen pressure, blood perfusion, and capillary/muscle fiber ratio were all markedly increased by the application of UC-MSCs. In addition, the conditioned culture of human umbilical vein endothelial cells using medium collected from UC-MSCs showed higher expression of angiogenic markers and improved migration ability. In short, the isolated UC-MSCs notably contributed to restoring blood supply and alleviating the symptoms of limb ischemia through enhancing angiogenesis.

We found in the present study that treatment with ox-LDL decreased the cell viability and the content of nitric oxide (NO) and the activity of nitric oxide synthase (NOS) as well as eNOS mRNA expression, while increasing the mRNA expression and content of endothelin-1 (ET-1) in human umbilical vein endothelial cells (HUVECs). However, endomorphins EM1/EM2 increased the cell viability and the content of NO and the activity of NOS as well as eNOS mRNA expression, while decreasing the mRNA expression and content of ET-1 compared with ox-LDL alone. Meanwhile, the expressions of JNK and p-JNK were enhanced by ox-LDL while being suppressed by EM1/EM2. The results suggested that EM1 and EM2 can correct the endothelial cell dysfunction induced by ox-LDL and the protective effect may be achieved by affecting the JNK pathway.

Previous studies showed that hepatitis B virus (HBV), as a latency invader, attenuated host anti-viral immune responses. miRNAs were shown to be involved in HBV infection and HBV-related diseases, however, the precise role of miRNAs in HBV-mediated immunosuppression remains unclear. Here, we observed that down-regulated RIG-I like receptors might be one critical mechanism of HBV-induced suppression of type I IFN transcription in both HBV(+) hepatoma cell lines and liver cancer tissues. Then, miR146a was demonstrated to negatively regulate the expression of RIG-I-like receptors by directly targeting both RIG-I and RIG-G. Further investigation showed that antagonizing miR146a by anti-sense inhibitors or sponge approach accelerated HBV clearance and reduced HBV load both in vitro and in a HBV-carrying mouse model. Therefore, our findings indicated that HBV-induced miR146a attenuates cell-intrinsic anti-viral innate immunity through targeting RIG-I and RIG-G, and silencing miR146a might be an effective target to reverse HBV-induced immune suppression.

Evidence suggests that exosomes can transfer genetic material between cells. However, their roles in hepatitis B virus (HBV) infection remain unclear. Here, we report that exosomes present in the sera of chronic hepatitis B (CHB) patients contained both HBV nucleic acids and HBV proteins, and transferred HBV to hepatocytes in an active manner. Notably, HBV nucleic acids were detected in natural killer (NK) cells from both CHB patients and healthy donors after exposure to HBV-positive exosomes. Through real-time fluorescence microscopy and flow cytometry, 1,1'-dioctadecyl-3,3,3',3',-tetramethylindodicarbocyanine, 4-chlorobenzenesulfnate salt (DiD)-labeled exosomes were observed to interact with NK cells and to be taken up by NK cells, which was enhanced by transforming growth factor-β treatment. Furthermore, HBV-positive exosomes impaired NK-cell functions, including interferon (IFN)-γ production, cytolytic activity, NK-cell proliferation and survival, as well as the responsiveness of the cells to poly (I:C) stimulation. HBV infection suppressed the expression of pattern-recognition receptors, especially retinoic acid inducible gene I (RIG-I), on NK cells, resulting in the dampening of the nuclear factor κB(NF-κB) and p38 mitogen-activated protein kinase pathways. Our results highlight a previously unappreciated role of exosomes in HBV transmission and NK-cell dysfunction during CHB infection.

RNA Polymerase II Elongation Factor (ELL)-associated factor 2 (EAF2) is a tumor suppressor frequently down-regulated in human prostate cancer. We previously reported that its binding partner ELL1 can enhance EAF2 protein stability and activity. Here we show that EAF2 can be polyubiquitinated and its degradation blocked by proteasome inhibitor. Co-immunoprecipitation detected EAF2 binding to SIAH2, an E3 ligase, and SIAH2 overexpression enhanced polyubiquitination of EAF2. Co-transfection of EAF2 binding partner ELL1 blocked EAF2 ubiquitination, providing a mechanism for EAF2 stabilization. Finally, EAF2K81R mutant, which exhibits reduced polyubiquitination and increased stability, was more potent than wild-type EAF2 in apoptosis induction. These findings suggest that SIAH2 is an E3 ligase for EAF2 polyubiquitination and ELL1 can enhance EAF2 level and function by blocking its polyubiquitination.

The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ± 5.95 vs -1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).

The spore germination rate and growth characteristics were compared between the citric acid high-yield strain Aspergillus niger CGMCC 5751 and A. niger ATCC 1015 in media containing antimycin A or DNP. We inferred that differences in citric acid yield might be due to differences in energy metabolism between these strains. To explore the impact of energy metabolism on citric acid production, the changes in intracellular ATP, NADH and NADH/NAD+ were measured at various fermentation stages. In addition, the effects of antimycin A or DNP on energy metabolism and citric acid production was investigated by CGMCC 5751.

The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients.

Metal nanoparticle probes were used as molecular imaging agents to detect the expression levels and spatial distributions of the CCR5 receptors on the cell surfaces. Alexa Fluor 647-labeled anti-CCR5 monoclonal antibodies (mAbs) were covalently bound to 20 nm silver nanoparticles to synthesize the mAb-metal complexes. We measured the single nanoparticle emission of the mAb-metal complexes, showing that the complexes displayed enhanced intensities and reduced lifetimes in comparison with the metal-free mAbs. Six HeLa cell lines with various CCR5 expressions were incubated with the mAb-metal complexes for the target-specific binding to the cell surfaces. Fluorescence cell images were recorded on a time-resolved confocal microscope. The collected images expressed clear CCR5 expression-dependent optical properties. Two regression curves were obtained on the basis of the emission intensity and lifetime over the entire cell images against the number of the CCR5 expression on the cells. The emission from the single mAb-metal complexes could be distinctly identified from the cellular autofluorescence on the cell images. The CCR5 spatial distributions on the cells were analyzed on the cell images and showed that the low-expression cells have the CCR5 receptors as individuals or small clusters but the high expression cells have them as the dense and discrete clusters on the cell surfaces.

The invasive phenotype of glioblastoma multiforme (GBM) is a hallmark of malignant process, yet the molecular mechanisms that dictate this locally invasive behavior remain poorly understood. Over-expression of PIAS3 effectively changes cell shape and inhibits GBM cell migration. We focused on the molecular target(s) of PIAS3 stimulated sumoylation, which play an important role in the inhibition of GBM cell motility. Here we report, through the immunoprecipitation with SUMO1 antibody, followed by proteomic analysis, the identification of vimentin (vimentin354), a nuclear component in GBM cells, as the main target of sumoylation promoted by PIAS3.