In this study, a water-soluble polysaccharide (PPS) from Dictyophora indusiata was purified and investigated through a combination of gel chromatography (Sephadex G-200), infrared (IR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The results indicated that PPS has a backbone of β-conformation, mainly consist of glucose (98.58%). And the antioxidant activities of PPS were investigated in vitro including reducing power, hydroxyl assay, superoxide radical assay and DPPH scavenge activity. The results showed that PPS has antioxidant activities in all these assay systems, suggesting it may be explored as a novel natural antioxidant with potential therapeutic properties in mammalian systems.

Endoplasmic reticulum (ER) stress plays a key role in the development of neurodegenerative diseases, including Parkinson's disease (PD). Sulforaphane (SF) is a natural drug derived from isothiocyanate found in cruciferous vegetables. Although there are reports indicating that SF is a potential candidate for PD treatment, there have been no reports on the effects of SF on ER stress in PD. In this study, we investigated the cytoprotective effects of SF on 6-hydroxydopamine (6-OHDA)-induced ER stress in rat PC12 cells. Pre-treatment with SF elicited cytoprotection against 6-OHDA-induced cytotoxicity. Consistent with its cytoprotective action, SF significantly inhibited subsequent ER stress, including the expression of Bip and the C/EBP homologous protein. We also found that transfection with NF-E2-related factor-2 (Nrf2) siRNA reversed the inhibitory effects of SF on 6-OHDA-induced ER stress responses. In conclusion, our results show that SF can prevent ER stress response induced by 6-OHDA through the activation of Nrf2. SF may be a therapeutic candidate for the treatment of ER stress-associated neural diseases, including PD.

The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male.

Piwi- interacting RNAs (piRNAs), a new class of small RNAs discovered from mammalian testes, are involved in transcriptional silencing of retrotransposons and other genetic elements in germ line cells. In order to identify a full transcriptome set of piRNAs expressed in the sexually mature porcine testes, small RNA fractions were extracted and were subjected to a Solexa deep sequencing. We cloned 6,913,561 clean reads of Sus Scrofa small RNAs (18-30 nt) and performed functional characterization. Sus Scrofa small RNAs showed a bimodal length distribution with two peaks at 21 nt and 29 nt. Then from 938,328 deep-sequenced small RNAs (26-30 nt), 375,195 piRNAs were identified by a k-mer scheme and 326 piRNAs were identified by homology searches. All piRNAs predicted by the k-mer scheme were then mapped to swine genome by Short Oligonucleotide Analysis Package (SOAP), and 81.61% of all uniquely mapping piRNAs (197,673) were located to 1124 defined genomic regions (5.85 Mb). Within these regions, 536 and 501 piRNA clusters generally distributed across only minus or plus genomic strand, 48 piRNA clusters distributed on two strands but in a divergent manner, and 39 piRNA clusters distributed on two strands in an overlapping manner. Furthermore, expression pattern of 7 piRNAs identified by homology searches showed 5 piRNAs displayed a ubiquitous expression pattern, although 2 piRNAs were specifically expressed in the testes. Overall, our results provide new information of porcine piRNAs and their specific expression pattern in porcine testes suggests that piRNAs have a role in regulating spermatogenesis.

Background:  Current treatment of acute peripheral artery or bypass graft occlusion utilizes catheter-directed thrombolysis of a plasminogen activator (PA). Plasmin is a direct-acting thrombolytic with a striking safety advantage over PA in pre-clinical models. Objectives:  We report the first use of purified plasmin for acute lower extremity arterial or bypass graft thrombosis in a Phase I, dose-escalation study of catheter-delivered agent. Methods:  Eighty-three patients with non-embolic occlusion of infrainguinal native arteries or bypass grafts were enrolled (safety population) into seven sequential dose cohorts to receive 25-175 mg of plasmin by intra-thrombus infusion over 5 hours. Arteriograms were performed at baseline, 2 and 5 hours and subjects were monitored for 30 days for clinical outcomes and laboratory parameters of systemic fibrinolysis. Results:  Major bleeding occurred in 4 patients (4.8%), minor bleeding alone in 13 (15.7%), with no trend towards more bleeding at higher dosages of plasmin. There was a trend towards lower plasma concentrations of fibrinogen, α(2)-antiplasmin, and α(2)-macroglobulin with increasing doses of plasmin, but the nadir fibrinogen was >350 mg/dL at the highest plasmin dose. Individual nadir values were above 200 mg/dL in 82 of 83 subjects, and were not different in patients with or without bleeding. Thrombolysis (≥50%) occurred in 79% of subjects receiving 125-175 mg of plasmin, compared with 50% who received 25-100 mg. Conclusions:  Catheter-delivered plasmin is safely administered to patients with acute lower extremity arterial occlusion at dosages of 25 to 175 mg. © 2012 International Society on Thrombosis and Haemostasis.

Robust reversible watermarking (RRW) methods are popular in multimedia for protecting copyright, while preserving intactness of host images and providing robustness against unintentional attacks. However, conventional RRW methods are not readily applicable in practice. That is mainly because 1) they fail to offer satisfactory reversibility on large-scale image datasets; 2) they have limited robustness in extracting watermarks from the watermarked images destroyed by different unintentional attacks; and 3) some of them suffer from extremely poor invisibility for watermarked images. Therefore, it is necessary to have a framework to address these three problems, and further improve its performance. This paper presents a novel pragmatic framework, wavelet-domain statistical quantity histogram shifting and clustering (WSQH-SC). Compared with conventional methods, WSQH-SC ingeniously constructs new watermark embedding and extraction procedures by histogram shifting and clustering, which are important for improving robustness and reducing run-time complexity. Additionally, WSQH-SC includes the property inspired pixel adjustment (PIPA) to effectively handle overflow and underflow of pixels. This results in satisfactory reversibility and invisibility. Furthermore, to increase its practical applicability, WSQH-SC designs an enhanced pixel-wise masking (EPWM) to balance robustness and invisibility. We perform extensive experiments over natural, medical, and synthetic aperture radar (SAR) images to show the effectiveness of WSQH-SC by comparing with the histogram rotation (HR)-based and histogram distribution constrained (HDC) methods.

BACKGROUND/AIM Second generation antipsychotics (SGAs) are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapine-induced obesity. METHODOLOGY/RESULTS Levels of pro-opiomelanocortin (POMC), neuropeptide Y (NPY) and glutamic acid decarboxylase (GAD(65), enzyme for GABA synthesis) mRNA expression, and cannabinoid CB1 receptor (CB1R) binding density (using [(3)H]SR-141716A) were examined in the arcuate nucleus (Arc) and dorsal vagal complex (DVC) of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (3×/day, 14-days). Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD(65) mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. CONCLUSIONS Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly by altering POMC transmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug.

BACKGROUND: Aberrant expressions of microRNAs, including upregulation of miR-141, are closely associated with the tumorigenesis of prostate cancer (PCa). The orphan receptor small heterodimer partner (Shp) is a co-repressor to androgen receptor (AR) and represses AR-regulated transcriptional activity. METHODS: Here, we investigated the correlation of Shp expression with the cellular level of miR-141 and its effects on AR transcriptional activity in non-malignant and malignant human prostate epithelial cell lines. RESULTS: We found that Shp was downregulated in multiple PCa cell lines. The mature form of miR-141 was upregulated in PCa cells. miR-141 could target 3'-untranslated region of Shp mRNA resulting in translational suppression and RNA degradation. Moreover, enforced expression of Shp or inhibition of miR-141 function by anti-miR-141 attenuated AR-regulated transcriptional activity in AR-responsive LNCaP cells. Phenethyl isothiocyanate, a natural constituent of many edible cruciferous vegetables, increased Shp expression, downregulated miR-141, and inhibited AR transcriptional activity in LNCaP cells. CONCLUSIONS: Shp is a target for miR-141 and it is downregulated in cultured human PCa cells with the involvement of upregulation of miR-141, which promotes AR transcriptional activity. Moreover, Shp and miR-141 could be targets for chemoprevention for PCa. Prostate © 2012 Wiley Periodicals, Inc.

TAL1/SCL is a hematopoietic-specific oncogene and its activity is regulated by associated transcriptional co-activators and corepressors. Dysregulation of TAL1 activity has been associated with T-cell leukemogenesis. However, it remains unclear how the interactions between TAL1 and corepressors versus co-activators are properly regulated. Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis. Knockdown of TAL1 or LSD1 led to a derepression of the TAL1 target genes in T-cell acute lymphoblast leukemia (T-ALL) Jurkat cells, which is accompanied by elevating promoter H3K4 methylation. Similarly, treatment of PKA activator forskolin resulted in derepression of target genes by reducing its interaction with LSD1 while PKA inhibitor H89 represses them by suppressing H3K4 methylation levels. Consistent with the dual roles of TAL1 in transcription, TAL1-associated LSD1 is decreased while recruitment of hSET1 is increased at the TAL1 targets during erythroid differentiation. This process is accompanied by a dramatic increase in H3K4 methylation. Thus, our data revealed a novel interplay between PKA phosphorylation and TAL1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis.Oncogene advance online publication, 6 February 2012; doi:10.1038/onc.2012.8.

Biomarkers are currently widely used to diagnose diseases, monitor treatments, and evaluate potential drug candidates. Research of differential Omics accelerate the advancements of biomarkers' discovery. By extracting biological knowledge from the 'omics' through integration, integrative system biology creates predictive models of cells, organs, biochemical processes and complete organisms, in addition to identifying human disease biomarkers. Recent development in high-throughput methods enables analysis of genome, transcriptome, proteome, and metabolome at an unprecedented scale, thus contributing to the deluge of experimental data in numerous public databases. Several integrative system biology approaches have been developed and applied to the discovery of disease biomarkers from databases. In this review, we highlight several of these approaches and identify future steps in the context of the field of integrative system biology.