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1.  Effects of different dietary energy and protein levels and sex on growth performance, carcass characteristics and meat quality of F1 Angus × Chinese Xiangxi yellow cattle 
Background
The experiment evaluated the effect of nutrition levels and sex on the growth performance, carcass characteristics and meat quality of F1 Angus × Chinese Xiangxi yellow cattle.
Methods
During the background period of 184 d,23 steers and 24 heifers were fed the same ration,then put into a 2 × 2 × 2 factorial arrangement under two levels of - dietary energy (TDN: 70/80% DM), protein (CP: 11.9/14.3% DM) and sex (S: male/female) during the finishing phase of 146 d. The treatments were - (1) high energy/low protein (HELP), (2) high energy/high protein (HEHP), (3) low energy/low protein (LELP) and (4) low energy/high protein (LEHP). Each treatment used 6 steers and 6 heifers, except for HELP- 5 steers and 6 heifers.
Results
Growth rate and final carcass weight were unaffected by dietary energy and protein levels or by sex. Compared with the LE diet group, the HE group had significantly lower dry matter intake (DMI, 6.76 vs. 7.48 kg DM/d), greater chest girth increments (46.1 vs. 36.8 cm), higher carcass fat (19.9 vs.16.3%) and intramuscular fat content (29.9 vs. 22.8% DM). The HE group also had improved yields of top and medium top grade commercial meat cuts (39.9 vs.36.5%). The dressing percentage was higher for the HP group than the LP group (53.4 vs. 54.9%). Steers had a greater length increment (9.0 vs. 8.3 cm), but lower carcass fat content (16.8 vs. 19.4%) than heifers. The meat quality traits (shear force value, drip loss, cooking loss and water holding capacity) were not affected by treatments or sex, averaging 3.14 kg, 2.5, 31.5 and 52.9%, respectively. The nutritive profiles (both fatty and amino acid composition) were not influenced by the energy or protein levels or by sex.
Conclusions
The dietary energy and protein levels and sex significantly influenced the carcass characteristics and chemical composition of meat but not thegrowth performance, meat quality traits and nutritive profiles.
doi:10.1186/2049-1891-5-21
PMCID: PMC4003514  PMID: 24739901
Carcass characteristics; Energy; F1 Angus × Chinese Xiangxi yellow cattle; Growth performance; Meat quality; Protein; Sex
2.  Reversal of Bortezomib Resistance in Myelodysplastic Syndrome Cells by MAPK Inhibitors 
PLoS ONE  2014;9(3):e90992.
The myelodysplastic syndromes (MDS) comprise a heterogeneous group of malignant neoplasms with distinctive clinicopathological features. Currently, there is no specific approach for the treatment of MDS. Here, we report that bortezomib (BTZ), a proteasome inhibitor that has been used to treat plasma cell myeloma, induced G2/M phase cycle arrest in the MDS cell line SKM-1 through upregulation of Wee1, a negative regulator of G2/M phase transition. Treatment by BTZ led to reduced SKM-1 cell viability as well as increased apoptosis and autophagy. The BTZ-induced cell death was associated with reduced expression of p-ERK. To elucidate the implications of downregulation of p-ERK, we established the BTZ resistant cell line SKM-1R. Our data show that resistance to BTZ-induced apoptosis could be reversed by the MEK inhibitors U0126 or PD98059. Our results suggest that MAPK pathway may play an important role in mediating BTZ resistance.
doi:10.1371/journal.pone.0090992
PMCID: PMC3946707  PMID: 24608798
3.  Association of microRNA-126 expression with clinicopathological features and the risk of biochemical recurrence in prostate cancer patients undergoing radical prostatectomy 
Diagnostic Pathology  2013;8:208.
Objective
Numerous studies have suggested that microRNA-126 (miR-126) is involved in development of various cancer types as well as in malignant proliferation and invasion. However, its role in human prostate cancer (PCa) is still unclear. The aim of this study was to investigate miR-126 expression in PCa and its prognostic value for PCa patients undergoing radical prostatectomy.
Methods
A series of 128 cases with PCa were evaluated for the expression levels of miR-126 by quantitative reverse-transcription PCR (qRT-PCR). Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between miR-126 expression and prognosis of PCa patients.
Results
Compared with non-cancerous prostate tissues, the expression level of miR-126 was significantly decreased in PCa tissues (PCa vs. non-cancerous prostate: 1.05 ± 0.63 vs. 2.92 ± 0.98, P < 0.001). Additionally, the loss of miR-126 expression was dramatically associated with aggressive clinical pathological features, including advanced pathological stage (P = 0.001), positive lymph node metastasis (P = 0.006), high preoperative PSA (P = 0.003) and positive angiolymphatic invasion (P = 0.001). Moreover, Kaplan–Meier survival analysis showed that PCa patients with low miR-126 expression have shorter biochemical recurrence (BCR)-free survival than those with high miR-126 expression. Furthermore, multivariate analysis indicated that miR-126 expression was an independent prognostic factor for BCR-free survival after radical prostatectomy.
Conclusion
These findings suggest for the first time that the loss of miR-126 expression may play a positive role in the malignant progression of PCa. More importantly, the downregulation of miR-126 may serve as an independent predictor of BCR-free survival in patients with PCa.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1740080792113255.
doi:10.1186/1746-1596-8-208
PMCID: PMC3928806  PMID: 24350576
Prostate cancer; MicroRNA-126; Clinical pathology; Prognosis
4.  DNA vaccines targeting the encoded antigens to dendritic cells induce potent antitumor immunity in mice 
BMC Immunology  2013;14:39.
Background
Although DNA vaccine holds a great potential for cancer immunotherapy, effective long-lasting antitumoral immunity sufficient to induce durable responses in cancer patients remains to be achieved. Considering the pivotal role of dendritic cells (DC) in the antigen processing and presentation, we prepared DC-targeting DNA vaccines by fusing tumor-associated antigen HER2/neu ectodomain to single chain antibody fragment (scFv) from NLDC-145 antibody specific for DC-restricted surface molecule DEC-205 (scFvNLDC-145), and explored its antitumoral efficacy and underlying mechanisms in mouse breast cancer models.
Results
In vivo targeting assay demonstrated that scFvNLDC-145 specifically delivered DNA vaccine-encoded antigen to DC. Compared with untargeted HER2/neu DNA vaccines, vaccination with scFvNLDC-145-HER2/neu markedly promoted the HER2/neu-specific cellular and humoral immune responses with long-lasting immune memory, resulting in effective protection against challenge of HER2/neu-positive D2F2/E2 breast tumor while ineffective in parental HER2/neu-negative D2F2 breast tumor. More importantly, in combination with temporary depletion of regulatory T cells (Treg) by low-dose cyclophosphamide, vaccination with scFvNLDC-145-HER2/neu induced the regression of established D2F2/E2 breast tumor and significantly retarded the development of spontaneous mammary carcinomas in transgenic BALB-neuT mice.
Conclusion
Our findings demonstrate that DC-targeted DNA vaccines for in vivo direct delivery of tumor antigens to DC could induce potent antigen-specific cellular and humoral immune responses and, if additional combination with systemic Treg depletion, was able to elicit an impressively therapeutic antitumoral activity, providing a rationale for further development of this approach for cancer treatment.
doi:10.1186/1471-2172-14-39
PMCID: PMC3751307  PMID: 23941509
DNA vaccine; DC-targeted; HER2/neu; Breast cancer; Cyclophosphamide
5.  Liver X Receptor and Peroxisome Proliferator-Activated Receptor Agonist from Cornus alternifolia 
Biochimica et biophysica acta  2012;1820(7):1021-1026.
Background
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptors superfamily and are transcription factors activated by specific ligands. Liver X receptors (LXR) belong to the nuclear hormone receptors and have been shown to play an important role in cholesterol homeostasis. From the previous screening of several medicinal plants for potential partial PPARγ agonists, the extracts of Cornus alternifolia were found to exhibit promising bioactivity. In this paper, we report the isolation and structural elucidation of four new compounds and their potential as ligands for PPAR.
Methods
The new compounds were extracted from the leaves of Cornus alternifolia and fractionated by high-performance liquid chromatography. Their structures were elucidated on the basis of spectroscopic evidence and analysis of their hydrolysis products.
Results
Three new iridoid glycosides including an iridolactone, alternosides A-C (1–3), a new megastigmane glycoside, cornalternoside (4) and 10 known compounds, were obtained from the leaves of Cornus alternifolia. Kaempferol-3-O-β-glucopyranoside (5) exhibited potent agonistic activities for PPARα, PPARγ and LXR with EC50 values of 0.62, 3.0 and 1.8 μ M, respectively.
Conclusions
We isolated four new and ten known compounds from Cornus alternifolia, and one known compound showed agonistic activities for PPARα, PPARγ and LXR.
General significance
Compound 1 is the first example of a naturally occurring iridoid glycoside containing a β-glucopyranoside moiety at C-6.
doi:10.1016/j.bbagen.2012.02.004
PMCID: PMC3482494  PMID: 22353334
Peroxisome proliferator-activated receptors; Liver X receptors; Cornus alternifolia; Iridoid glycosides
6.  Non-randomized mtDNA damage after ionizing radiation via charge transport 
Scientific Reports  2012;2:780.
Although it is well known that there are mutation hot spots in mtDNA, whether there are damage hot spots remain elusive. In this study, the regional DNA damage of mitochondrial genome after ionizing radiation was determined by real-time quantitative PCR. The mtDNA damage level was found to be dose-dependent and regional unequal. The control region was the most susceptible region to oxidative damage. GGG, as an typical hole trap during charge transport, was found to be disproportionally enriched in the control region. A total of 107 vertebrate mitochondrial genomes were then analyzed to testify whether the GGG enrichment in control region was evolutionary conserved. Surprisingly, the triple G enrichment can be observed in most of the homeothermal animals, while the majority of heterothermic animals showed no triple G enrichment. These results indicated that the triple G enrichment in control region was related to the mitochondrial metabolism during evolution.
doi:10.1038/srep00780
PMCID: PMC3483021  PMID: 23110249
7.  FliC, a Flagellin Protein, Is Essential for the Growth and Virulence of Fish Pathogen Edwardsiella tarda 
PLoS ONE  2012;7(9):e45070.
Edwardsiella tarda is a flagellated Gram-negative bacterium which causes edwardsiellosis in fish. FliC, as a flagellar filament structural protein, is hypothesized to be involved in the pathogenesis of infection. In this study, a fliC in-frame deletion mutant of a virulent isolate of E. tarda was constructed through double crossover allelic exchange by means of the suicide vector pRE112, and its virulence-associated phenotypes and pathogenicity were tested. It was found that the deletion of fliC significantly decreased the diameter of flagella filaments. In addition, the mutant showed reduced pathogenicity to fish by increasing the LD50 value for 100-fold compared to the wild-type strain, as well as showed impaired bacterial growth, reduced motility, decreased biofilm formation and reduced levels of virulence-associated protein secretion involved in the type III secretion system (TTSS). The phenotypic characteristics of the fliC deletion mutant uncovered in this investigation suggest that fliC plays an essential role in normal flagellum function, bacterial growth, protein secretion by TTSS and bacterial virulence.
doi:10.1371/journal.pone.0045070
PMCID: PMC3443227  PMID: 23024793
8.  Dynamic modeling of methylprednisolone effects on body weight and glucose regulation in rats 
Influences of methylprednisolone (MPL) and food consumption on body weight (BW), and the effects of MPL on glycemic control including food consumption and the dynamic interactions among glucose, insulin, and free fatty acids (FFA) were evaluated in normal male Wistar rats. Six groups of animals received either saline or MPL via subcutaneous infusions at the rate of 0.03, 0.1, 0.2, 0.3 and 0.4 mg/kg/h for different treatment periods. BW and food consumption were measured twice a week. Plasma concentrations of MPL and corticosterone (CST) were determined at animal sacrifice. Plasma glucose, insulin, and FFA were measured at various times after infusion. Plasma MPL concentrations were simulated by a two-compartment model and used as the driving force in the pharmacodynamic (PD) analysis. All data were modeled using ADAPT 5. The MPL treatments caused reduction of food consumption and body weights in all dosing groups. The steroid also caused changes in plasma glucose, insulin, and FFA concentrations. Hyper-insulinemia was achieved rapidly at the first sampling time of 6 h; significant elevations of FFA were observed in all drug treatment groups; whereas only modest increases in plasma glucose were observed in the low dosing groups (0.03 and 0.1 mg/kg/h). Body weight changes were modeled by dual actions of MPL: inhibition of food consumption and stimulation of weight loss, with food consumption accounting for the input of energy for body weight. Dynamic models of glucose and insulin feedback interactions were extended to capture the major metabolic effects of FFA: stimulation of insulin secretion and inhibition of insulin-stimulated glucose utilization. These models of body weight and glucose regulation adequately captured the experimental data and reflect significant physiological interactions among glucose, insulin, and FFA. These mechanism-based PD models provide further insights into the multi-factor control of this essential metabolic system.
doi:10.1007/s10928-011-9194-4
PMCID: PMC3407886  PMID: 21394487
Glucocorticoids; Methylprednisolone; Pharmacodynamics; Food intake; Body weight; Glucose; Insulin; Free fatty acids
9.  Distribution of Vibrio alginolyticus-like species in Shenzhen coastal waters, China 
Brazilian Journal of Microbiology  2011;42(3):884-896.
We investigated the distribution of vibrios in Shenzhen coastal waters in order to obtain valuable information for the aquaculture industry and a health warning system. Quantities of vibrios from surface waters ranged from 0 to 4.40×104 CFUs mL-1 in April (spring), while from 0 to 2.57×103 CFUs mL-1 in September (autumn); the abundance of V. alginolyticus-like species from surface water ranged from 0 to 6.72×103 CFUs mL-1 in April (spring) and from 0 to 1.28×103 CFUs mL-1 in September (autumn); higher counts were observed in spring. The V. alginolyticus-like species was dominant in Shenzhen coastal waters, with the highest abundance in the clean region (stations YMK001 and GDN064) in April, suggesting that Vibrio spp. were naturally occurring bacteria in marine environments. The correlation between the abundance of vibrios (including V. alginolyticus-like species) and environmental factors varied in different regions and different seasons. There were no vibrios detected when the salinity was less than 11.15‰ in the Zhujiang River estuary, which indicated that salinity played a key role in the distribution of vibrios and V. alginolyticus-like species.
doi:10.1590/S1517-83822011000300007
PMCID: PMC3768764  PMID: 24031704
Distribution; Vibrio alginolyticus-like species; season; Shenzhen coastal waters; China
10.  Complex self-assembly of pyrimido[4,5-d]pyrimidine nucleoside supramolecular structures 
Nature Communications  2014;5:3108.
Supramolecular self-assembly is not only one of the chemical roots of biological structure but is also drawing attention in different industrial fields. Here we study the mechanism of the formation of a complex flower-shaped supramolecular structure of pyrimido[4,5-d]pyrimidine nucleosides by dynamic light scattering, scanning electron microscopy, differential scanning calorimetry, nuclear magnetic resonance and X-ray analysis. Upon removing the hydroxyl group of sugars, different flower-shaped superstructures can be produced. These works demonstrate that complex self-assembly can indeed be attained through hierarchical non-covalent interactions of single molecules. Furthermore, chimerical structures built from molecular recognition by these monomers indicate their potential in other fields if combined with other chemical entities.
Supramolecular self-assembly is a fundamentally important process in fields ranging from structural biology to materials chemistry. Here, the authors report the supramolecular assembly of complex nanostructures from simple nucleosides, and probe the formation process using various in situ techniques.
doi:10.1038/ncomms4108
PMCID: PMC3916841  PMID: 24457545

Results 1-10 (10)