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1.  Effect of cooking temperatures on protein hydrolysates and sensory quality in crucian carp (Carassius auratus) soup 
Cooking methods have a significant impact on flavour compounds in fish soup. The effects of cooking temperatures (55, 65, 75, 85, 95, and 100 °C) on sensory properties and protein hydrolysates were studied in crucian carp (Carassius auratus) soup. The results showed that the soup prepared at 85 °C had the best sensory quality in color, flavour, amour, and soup pattern. Cooking temperature had significant influence on the hydrolysis of proteins in the soup showed by SDS-PAGE result. The contents of water soluble nitrogen (WSN) and non-protein nitrogen (NPN) increased with the cooking temperature, but the highest contents of total peptides and total free amino acids (FAA) were obtained at the cooking temperature of 85 °C. The highest contents of umami-taste active amino acid and branched-chain amino acids were also observed in the 85 °C sample. In conclusion, a cooking temperature of 85 °C was preferred for more excellent flavor and higher nutritional value of crucian carp soup.
doi:10.1007/s13197-011-0376-2
PMCID: PMC3602572  PMID: 24425950
Crucian carp; Cooking temperature; Protein; Hydrolysates; Flavour
2.  Anti-Inflammatory Effects of the Bioactive Compound Ferulic Acid Contained in Oldenlandia diffusa on Collagen-Induced Arthritis in Rats 
Objectives. This study aimed to identify the active compounds in Oldenlandia diffusa (OD) decoction and the compounds absorbed into plasma, and to determine whether the absorbed compounds derived from OD exerted any anti-inflammatory effects in rats with collagen induced arthritis (CIA). Methods. The UPLC-PDA (Ultra Performance Liquid Chromatography Photo-Diode Array) method was applied to identify the active compounds both in the decoction and rat plasma. The absorbable compound was administered to the CIA rats, and the effects were dynamically observed. X-ray films of the joints and HE stain of synovial tissues were analyzed. The levels of IL-1β and TNF-α in the rats from each group were measured by means of ELISA. The absorbed compound in the plasma of CIA rats was identified as ferulic acid (FA), following OD decoction administration. Two weeks after the administration of FA solution or OD decoction, the general conditions improved compared to the model group. The anti-inflammatory effect of FA was inferior to that of the OD decoction (P < 0.05), based on a comparison of IL-1β TNF-α levels. FA from the OD decoction was absorbed into the body of CIA rats, where it elicited anti-inflammatory responses in rats with CIA. Conclusions. These results suggest that FA is the bioactive compound in OD decoction, and FA exerts its effects through anti-inflammatory pathways.
doi:10.1155/2014/573801
PMCID: PMC4026839  PMID: 24883069
3.  Salidroside Stimulates Mitochondrial Biogenesis and Protects against H2O2-Induced Endothelial Dysfunction 
Salidroside (SAL) is an active component of Rhodiola rosea with documented antioxidative properties. The purpose of this study is to explore the mechanism of the protective effect of SAL on hydrogen peroxide- (H2O2-) induced endothelial dysfunction. Pretreatment of the human umbilical vein endothelial cells (HUVECs) with SAL significantly reduced the cytotoxicity brought by H2O2. Functional studies on the rat aortas found that SAL rescued the endothelium-dependent relaxation and reduced superoxide anion (O2∙−) production induced by H2O2. Meanwhile, SAL pretreatment inhibited H2O2-induced nitric oxide (NO) production. The underlying mechanisms involve the inhibition of H2O2-induced activation of endothelial nitric oxide synthase (eNOS), adenosine monophosphate-activated protein kinase (AMPK), and Akt, as well as the redox sensitive transcription factor, NF-kappa B (NF-κB). SAL also increased mitochondrial mass and upregulated the mitochondrial biogenesis factors, peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1α), and mitochondrial transcription factor A (TFAM) in the endothelial cells. H2O2-induced mitochondrial dysfunction, as demonstrated by reduced mitochondrial membrane potential (Δψm) and ATP production, was rescued by SAL pretreatment. Taken together, these findings implicate that SAL could protect endothelium against H2O2-induced injury via promoting mitochondrial biogenesis and function, thus preventing the overactivation of oxidative stress-related downstream signaling pathways.
doi:10.1155/2014/904834
PMCID: PMC4020198  PMID: 24868319
4.  Current Status of Pediatric Labeling in China and the near Future Efforts Needed for the Country 
Background: Children are recognized as “therapeutic orphan” in many parts of the world, one expression of this is the lack of adequate pediatric labeling information. Some research studies have been done to investigate the pediatric labeling condition in the U.S. and other countries, but no national studies had been carried out in China. This survey was conducted aiming to inquire the current situation of pediatric labeling in China.
Methods: We investigated 6020 child-applied medicines from 15 representative Chinese hospitals, and analyzed the information according to the dosage forms, therapeutic category, and label information integrity.
Results: Among all these medicines, only 238 (3.95%) are pediatric products, the rest are adult formulations with an extended use in children. The major pediatric formulations were injection (45.95%), tablet (23.69%), and capsule (4.93%), respectively. Alimentary tract/metabolism medicine (24.70%) and infections medicines (20.60%) had the most species. In prescription drugs, only 210 of 5187 (4%) medicines had adequate pediatric labeling information. The main cause of this deficiency was lack of evidence derived from pediatric clinical trials.
Conclusion: The dilemma of “therapeutic orphan” requires significant attention. Inadequate labeling information and lack of pediatric clinical trials were two prominent issues in China. It calls for more efforts from pharmaceutical industries, regulatory agencies, and legislature in China to collaborate and find solution to improve the situation.
doi:10.3389/fped.2014.00017
PMCID: PMC3972450  PMID: 24724075
pediatric; label; information; integrity; China
5.  A stochastic filtering approach to recover strain images from quasi-static ultrasound elastography 
Background
Model-based reconstruction algorithms have shown potentials over conventional strain-based methods in quasi-static elastographic image by using realistic finite element (FE) or bio-mechanical model constraints. However, it is still difficult to properly handle the discrepancies between the model constraint and ultrasound data, and the measurement noise.
Methods
In this paper, we explore the usage of Kalman filtering algorithm for the estimation of strain imaging in quasi-static ultrasound elastography. The proposed strategy formulates the displacement distribution through biomechanical models, and the ultrasound-derived measurements through observation equations. Through this filtering strategy, the discrepancies are quantitatively modelled as one Gaussian white noise, and the measurement noise of ultrasound data is modelled as another independent Gaussian white noise. The optimal estimation of kinematic functions, i.e. the full displacement and velocity field, are computed through this Kalman filter. Then the strain images can be easily calculated from the estimated displacement field.
Results
The accuracy and robustness of our proposed framework is first evaluated in synthetic data in controlled conditions, and the performance of this framework is then evaluated in the real data collected from elastography phantoms and patients with favourable results.
Conclusions
The potential of our algorithm is to provide the distribution of mechanically meaningful strain under a proper biomechanical model constraint. We address the model-data discrepancy and measurement noise by introducing process noise and measurement noise in our framework, and then the mechanically meaningful strain is estimated through the Kalman filter in the minimum mean square error (MMSE) sense.
doi:10.1186/1475-925X-13-15
PMCID: PMC3925777  PMID: 24521481
6.  The Relationship between the 24 h Blood Pressure Variability and Carotid Intima-Media Thickness: A Compared Study 
Large blood pressure variability (BPV) will not only harm the target organ but also increase the possibility of the cardiovascular events. Since the damage of vascular system always leads to the alteration of the carotid wall, the structure and function of the carotid artery have been extensively examined in previous studies. In this work we conduct a study (60 subjects, aged 33–79) to evaluate the relationship between BPV and carotid intima-media thickness (IMT) in Shenzhen, which is one large city in the southern area of China. In our study, the blood pressure (BP) was collected using the 24 h ambulatory BP monitoring, and the BPV was evaluated using standard deviation (SD), coefficient of variation (CV), and average real variability (ARV) during 24 h, daytime and nighttime. All the IMT measurements are collected by ultrasound. The results show that both the daytime, and 24 h systolic BPV evaluated by three indices are positively associated with IMT. Among them, daytime systolic BPV evaluated with ARV is the best variable to represent the increasing of carotid IMT. In addition, after adjusting by age, sex, smoking, hypertension, and mean BP and PP values, 24 h diastolic BPV evaluated with SD also presents the favorable performance.
doi:10.1155/2014/303159
PMCID: PMC3934393  PMID: 24660021
7.  High Expression of IGFBP7 in Fibroblasts Induced by Colorectal Cancer Cells Is Co-Regulated by TGF-β and Wnt Signaling in a Smad2/3-Dvl2/3-Dependent Manner 
PLoS ONE  2014;9(1):e85340.
Fibroblasts in the tumor microenvironment are a key determinant in cancer progression and may be a promising target for cancer therapy. Insulin-like growth factor binding protein 7 (IGFBP7) is known as a tumor suppressor in colorectal cancer (CRC). The present study investigated the inductive mechanism of IGFBP7 expression in fibroblasts by supernatant from the CRC cell line, SW620. The results showed that the expression of IGFBP7 was up-regulated in the fibroblasts when treated with SW620 supernatant and exogenous TGF-β1. The IGFBP7 induced by SW620 supernatant or TGF-β1 was partially inhibited by the TGF-β1 specific antibody AF and TGF-β1 receptor antagonist SB431542. The Wnt signaling-targeted genes, c-Myc, CCND1 and the proteins Dvl2/3, were all up-regulated in fibroblasts expressing high levels of IGFBP7, and the up-regulation could be inhibited both by the Wnt signaling antagonist Dickkopf-1 (DKK1) and by the TGF-β1 receptor antagonist SB431542. In conclusion, CRC cells promote the high expression of IGFBP7 in fibroblasts, most likely through the co-regulation of TGF-β and Wnt signaling in a Smad2/3-Dvl2/3 dependent manner. Taken together, these data suggest that the fibroblasts could be a novel therapeutic target in tumor therapy.
doi:10.1371/journal.pone.0085340
PMCID: PMC3888407  PMID: 24427302
8.  Cyclooxygenase-2 and B-cell lymphoma-2 expression in cystitis glandularis and primary vesicle adenocarcinoma 
BMC Urology  2014;14:2.
Background
Although cystitis glandularis (CG) is a common benign urinary bladder epithelial abnormality, it remains unclear whether CG is a premalignant lesion. Cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) overexpression has recently been reported as a potential tumor initiator or promoter. We evaluated and compared COX-2 and Bcl-2 expression in CG, chronic cystitis (CC), and primary vesicle adenocarcinoma (ADC) tissues.
Methods
We conducted a retrospective study to investigate COX-2 and Bcl-2 levels in CG and ADC. We obtained tissue samples from 75 patients (including 11 cases of CC, 30 typical cases of CG (CGTP), 30 cases of intestinal CG (CGIT), and 4 cases of ADC) between 1989 and 2009 from the Surgical Pathology Archives of the No. 2 People’s Hospital of Zhenjiang, affiliated with Jiangsu University. COX-2 and Bcl-2 immunohistochemical staining was performed on all tissues. Nine normal bladder epithelial specimens were evaluated as control samples. Correlations between COX-2 and Bcl-2 expression in CG were also analyzed.
Results
COX-2 and Bcl-2 expression was higher in the ADC group compared to other groups (p < 0.05). COX-2 and Bcl-2 levels were higher in the CGIT group compared to the CGTP group (p = 0.000 for both). The CGIT and CGTP groups both showed higher COX-2 expression compared to the CC group (p = 0.000 for both). There was no difference in Bcl-2 expression between the CGTP and CC groups (p = 0.452). Additionally, the difference in COX-2 and Bcl-2 expression between the control and CC groups was also insignificant (p = 0.668 and p = 0.097, respectively). Finally, we found that COX-2 and Bcl-2 levels were positively related (r = 0.648, p = 0.000).
Conclusion
COX-2 and Bcl-2 overexpression in the CG group suggests that CG, particularly the intestinal type, may be a premalignant lesion that converts into a tumor in the presence of carcinogens.
doi:10.1186/1471-2490-14-2
PMCID: PMC3880845  PMID: 24387269
Cyclooxygenase-2; Bcl-2; Cystitis
9.  Isolation and Structural Characterization of a Novel Antioxidant Mannoglucan from a Marine Bubble Snail, Bullacta exarata (Philippi) 
Marine Drugs  2013;11(11):4464-4477.
Bullacta exarata is one of the most economically important aquatic species in China, noted for not only its delicious taste and nutritional value, but also for its pharmacological activities. In order to explore its potential in medical applications, a mannoglucan designated as BEPS-IB was isolated and purified from the foot muscle of B. exarata after papain digestion. Chemical composition analysis indicated BEPS-IB contained mainly d-glucose and d-mannose in a molar ratio of 1:0.52, with an average molecular weight of about 94 kDa. The linkage information was determined by methylation analysis, and the anomeric configuration and chain linkage were confirmed by IR and 2D NMR. The results indicated BEPS-IB was composed of Glcp6Manp heptasaccharide repeating unit in the backbone, with occasional branch chains of mannose residues (14%) occurring in the backbone mannose. Further antioxidant assay indicated BEPS-IB exhibited positive antioxidant activity in scavenging superoxide radicals and reducing power. This is the first report on the structure and bioactivity of the mannoglucan from the B. exarata.
doi:10.3390/md11114464
PMCID: PMC3853739  PMID: 24284423
Bullacta exarata; structure; polysaccharide; mannoglucan
10.  UPLC-PDA determination of paeoniflorin in rat plasma following the oral administration of Radix Paeoniae Alba and its effects on rats with collagen-induced arthritis 
Rheumatoid arthritis (RA) is a chronic disabling autoimmune disease with characteristics of chronic, progressive inflammatory joint synovial damage, which mainly encroaches upon the synovium of the joint. The use of traditional medicine to treat RA slows the development of RA to a certain extent; however, it often has numerous side-effects. Therefore, the focus of RA research is the identification of a new, safe and effective medicine. The aim of the present study was to use an ultra performance liquid chromatography and photo diode array (UPLC-PDA) method to detect the paeoniflorin component in a Radix Paeoniae Alba decoction and in rat plasma following the oral administration of Radix Paeoniae Alba decoction. In addition, the effects of paeoniflorin on collagen-induced arthritis (CIA) in rats were investigated. The results indicate that a UPLC-PDA method for determining the presence of paeoniflorin in the Radix Paeoniae Alba decoction was successfully established. The method was fast, simple, sensitive, precise and valid. Paeoniflorin was shown to be a bioactive component of the Radix Paeoniae Alba decoction that was absorbed into rat plasma. Paeoniflorin significantly improved the disease resistant ability of RA rats and reduced the levels of the inflammatory cytokines, IL-1β and TNF-α, thereby inhibiting inflammation and bone erosion in the rats with CIA. The observations are likely to lay the foundation for further study of the mechanism of paeoniflorin in the treatment of RA.
doi:10.3892/etm.2013.1358
PMCID: PMC3861030  PMID: 24348792
ultra performance liquid chromatography; Radix Paeoniae Alba; paeoniflorin; collagen-induced arthritis; rheumatoid arthritis; bizhongxiao decoction
11.  Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain 
PLoS ONE  2013;8(8):e72943.
Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.
doi:10.1371/journal.pone.0072943
PMCID: PMC3756942  PMID: 24009718
12.  E-cadherin plays an essential role in collective directional migration of large epithelial sheets 
In wound healing and development, large epithelial sheets migrate collectively, in defined directions, and maintain tight cell–cell adhesion. This type of movement ensures an essential function of epithelia, a barrier, which is lost when cells lose connection and move in isolation. Unless wounded, epithelial sheets in cultures normally do not have overall directional migration. Cell migration is mostly studied when cells are in isolation and in the absence of mature cell–cell adhesion; the mechanisms of the migration of epithelial sheets are less well understood. We used small electric fields (EFs) as a directional cue to instigate and guide migration of epithelial sheets. Significantly, cells in monolayer migrated far more efficiently and directionally than cells in isolation or smaller cell clusters. We demonstrated for the first time the group size-dependent directional migratory response in several types of epithelial cells. Gap junctions made a minimal contribution to the directional collective migration. Breaking down calcium-dependent cell–cell adhesion significantly reduced directional sheet migration. Furthermore, E-cadherin blocking antibodies abolished migration of cell sheets. Traction force analysis revealed an important role of forces that cells in the leading rows exert on the substratum. With EF, the traction forces of the leading edge cells coordinated in directional re-orientation. Our study thus identifies a novel mechanism—E-cadherin dependence and coordinated traction forces of leading cells in collective directional migration of large epithelial sheets.
doi:10.1007/s00018-012-0951-3
PMCID: PMC3459324  PMID: 22410739
Collective cell migration; Electric fields; Galvanotaxis/electrotaxis; E-cadherin; Cell–cell adhesion; Traction force
13.  MiR-17 Partly Promotes Hematopoietic Cell Expansion through Augmenting HIF-1α in Osteoblasts 
PLoS ONE  2013;8(7):e70232.
Background
Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment, of which osteogenic cells play a crucial role. While evidence is accumulating for an important role of intrinsic miR-17 in regulating HSCs and HPCs, whether miR-17 signaling pathways are also necessary in the cell-extrinsic control of hematopoiesis hereto remains poorly understood.
Methodology/Principal Findings
Using the immortalized clone with the characteristics of osteoblasts, FBMOB-hTERT, in vitro expansion, long-term culture initiating cell (LTC-IC) and non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice repopulating cell (SRC) assay revealed that the ectopic expression of miR-17 partly promoted the ability of FBMOB-hTERT to support human cord blood (CB) CD34+ cell expansion and maintain their multipotency. It also seemed that osteoblastic miR-17 was prone to cause a specific expansion of the erythroid lineage. Conversely, deficient expression of miR-17 partly inhibited the hematopoietic supporting ability of FBMOB-hTERT. We further identified that HIF-1α is responsible for, at least in part, the promoted hematopoietic supporting ability of FBMOB-hTERT caused by miR-17. HIF-1α expression is markedly enhanced in miR-17 overexpressed FBMOB-hTERT upon interaction with CB CD34+ cells compared to other niche associated factors. More interestingly, the specific erythroid lineage expansion of CB CD34+ cells caused by osteoblastic miR-17 was abrogated by HIF-1α knock down.
Conclusion/Significance
Our data demonstrated that CB CD34+ cell expansion can be partly promoted by osteoblastic miR-17, and in particular, ectopic miR-17 can cause a specific expansion of the erythroid lineage through augmenting HIF-1α in osteoblasts.
doi:10.1371/journal.pone.0070232
PMCID: PMC3723828  PMID: 23936170
14.  In-Situ Formation of Cobalt-Phosphate Oxygen-Evolving Complex-Anchored Reduced Graphene Oxide Nanosheets for Oxygen Reduction Reaction 
Scientific Reports  2013;3:2263.
Oxygen conversion process between O2 and H2O by means of electrochemistry or photochemistry has lately received a great deal of attention. Cobalt-phosphate (Co-Pi) catalyst is a new type of cost-effective artificial oxygen-evolving complex (OEC) with amorphous features during photosynthesis. However, can such Co-Pi OEC also act as oxygen reduction reaction (ORR) catalyst in electrochemical processes? The question remains unanswered. Here for the first time we demonstrate that Co-Pi OEC does be rather active for the ORR. Particularly, Co-Pi OEC anchoring on reduced graphite oxide (rGO) nanosheet is shown to possess dramatically improved electrocatalytic activities. Differing from the generally accepted role of rGO as an “electron reservoir”, we suggest that rGO serves as “peroxide cleaner” in enhancing the electrocatalytic behaviors. The present study may bridge the gap between photochemistry and electrochemistry towards oxygen conversion.
doi:10.1038/srep02263
PMCID: PMC3719074  PMID: 23877331
15.  The identification of 14 new genes for meat quality traits in chicken using a genome-wide association study 
BMC Genomics  2013;14:458.
Background
Meat quality is an important economic trait in chickens. To identify loci and genes associated with meat quality traits, we conducted a genome-wide association study (GWAS) of F2 populations derived from a local Chinese breed (Beijing-You chickens) and a commercial fast-growing broiler line (Cobb-Vantress).
Results
In the present study, 33 association signals were detected from the compressed mixed linear model (MLM) for 10 meat quality traits: dry matter in breast muscle (DMBr), dry matter in thigh muscle (DMTh), intramuscular fat content in breast muscle (IMFBr), meat color lightness (L*) and yellowness (b*) values, skin color L*, a* (redness) and b* values, abdominal fat weight (AbFW) and AbFW as a percentage of eviscerated weight (AbFP). Relative expressions of candidate genes identified near significant signals were compared using samples of chickens with High and Low phenotypic values. A total of 14 genes associated with IMFBr, meat color L*, AbFW, and AbFP, were differentially expressed between the High and Low phenotypic groups. These genes are, therefore, prospective candidate genes for meat quality traits: protein tyrosine kinase (TYRO3) and microsomal glutathione S-transferase 1 (MGST1) for IMFBr; collagen, type I, alpha 2 (COL1A2) for meat color L*; and RET proto-oncogene (RET), natriuretic peptide B (NPPB) and sterol regulatory element binding transcription factor 1 (SREBF1) for the abdominal fat (AbF) traits.
Conclusions
Based on the association signals and differential expression of nearby genes, 14 candidate loci and genes for IMFBr, meat L* and b* values, and AbF are identified. The results provide new insight into the molecular mechanisms underlying meat quality traits in chickens.
doi:10.1186/1471-2164-14-458
PMCID: PMC3707761  PMID: 23834466
Chicken; GWAS; Meat quality traits; Abdominal fat; Candidate genes
16.  Hypothermia amplifies somatosensory evoked potentials in uninjured rats 
Temperature fluctuations significantly impact neurologic injuries in intensive care units. As benefits of therapeutic hypothermia continue to unfold, many of these discoveries are generated by studies in animal models undergoing experimental procedures under the influence of anesthetics. We studied the effect of induced hypothermia on neural electrophysiological signals of an uninjured brain in a rodent model while under isoflurane. Fourteen rats were divided into two groups (n=7 each), based on electrode placement, at either frontal-occipital (FO) or primary somatosensory (SS) cortical locations. Neural signals were recorded during normothermia (T = 36.5–37.5°C), mild hypothermia (T = 32–34°C) and hyperthermia (T = 38.5–39.5°C). Burst-suppression ratio (BSR) was used to evaluate EEGs, and amplitude-latency analysis was used to assess SSEPs. Hypothermia was characterized by an increased BSR (Mean+STD) of 0.58±0.06 in hypothermia versus 0.16±0.13 in normothermia, p<0.001 in FO; and 0.30±0.13 in hypothermia versus 0.04±0.04 in normothermia, p=0.006 in SS. There was potentiation of SSEP (2.89 ±1.24 times normothermic baseline in hypothermia, p=0.02) and prolonged peak latency (N10: 10.8±0.4 msec in hypothermia versus 9.1±0.3 msec in normothermia; P15: 16.2±0.8 msec in hypothermia versus 13.7±0.6 msec in normothermia; p<0.001), whereas hyperthermia was primarily marked by shorter peak latencies (N10: 8.6±0.2msec, P15: 12.6±0.4 msec; p<0.001). In the absence of brain injury in a rodent model, hypothermia induces significant increase to the SSEP amplitude while increasing SSEP latency. Hypothermia also suppressed EEGs at different regions of the brain by different degrees. The changes to SSEP and EEG are both reversible with subsequent rewarming.
doi:10.1097/ANA.0b013e31824ac36c
PMCID: PMC3372632  PMID: 22441433
somatosensory evoked potentials (SSEPs); EEG; burst suppression; hypothermia; anesthesia
17.  Public Place Smoke-Free Regulations, Secondhand Smoke Exposure and Related Beliefs, Awareness, Attitudes, and Practices among Chinese Urban Residents 
Objective: To evaluate the association between smoke-free regulations in public places and secondhand smoke exposure and related beliefs, awareness, attitudes, and behavior among urban residents in China. Methods: We selected one city (Hangzhou) as the intervention city and another (Jiaxing) as the comparison. A structured self-administered questionnaire was used for data collection, and implemented at two time points across a 20-month interval. Both unadjusted and adjusted logistic methods were considered in analyses. Multiple regression procedures were performed in examining variation between final and baseline measures. Results: Smoke-free regulations in the intervention city were associated with a significant decline in personal secondhand smoke exposure in government buildings, buses or taxis, and restaurants, but there was no change in such exposure in healthcare facilities and schools. In terms of personal smoking beliefs, awareness, attitudes, and practices, the only significant change was in giving quitting advice to proximal family members. Conclusions: There was a statistically significant association between implementation of smoke-free regulations in a city and inhibition of secondhand tobacco smoking exposure in public places. However, any such impact was limited. Effective tobacco control in China will require comprehensive laws implemented fully and supported by penalties and a combination of strong public health education.
doi:10.3390/ijerph10062370
PMCID: PMC3717741  PMID: 23749054
tobacco control; smoke-free regulations; secondhand smoke
18.  Intermedin Suppresses Pressure Overload Cardiac Hypertrophy through Activation of Autophagy 
PLoS ONE  2013;8(5):e64757.
Left ventricular hypertrophy is a maladaptive response to pressure overload and an important risk factor for heart failure. Intermedin (IMD), a multi-functional peptide, plays important roles in cardiovascular protection. In this study, we revealed an autophagy-dependent mechanism involved in IMD’s protection against cardiac remodeling and cardiomyocyte death in heart hypertrophy. We observed that transverse aortic contraction (TAC) induction, Ang II or ISO exposure induced remarkable increase in the expression of endogenous IMD and its receptor components, CRLR, RAMP1 and RAMP3, in mouse hearts and H9c2 cell cultures, respectively. Furthermore, the heart size, heart weight/body weight ratios, cardiomyocyte size and apoptosis, interstitial collagen, hypertrophic markers including ANP and BNP expression were also significantly increased, which were effectively suppressed by IMD supplementation. In addition, IMD induced capillary angiogenesis and improved functions in hypertrophic hearts. We further observed that IMD induced strong autophagy in hypertrophic hearts and cultured cells, which was paralleling with the decrease in cardiomyocyte size and apoptosis. Furthermore, an autophagy inhibitor, 3-MA, was used to block the IMD-augmented autophagy level, and then the protection of IMD on cardiomyocyte hypertrophy and apoptosis was almost abrogated. We also observed that IMD supplementation stirred intracellular cAMP production, and augmented the ERK1/2 phosphorylation induced by Ang II/ISO exposure in H9c2 cells. In addition, we inhibited PI3K, PKA and MAPK/ERK1/2 signaling pathways by using wortamannin, H89 and PD98059, respectively, in H9c2 cells co-incubating with both IMD and Ang II or ISO, and observed that these inhibitors effectively reduced IMD-augmented autophagy level, but only H89 and PD98059 pre-incubation abrogated the anti-apoptotic action of IMD. These results indicate that the endogenous IMD and its receptor complexes are induced in hypertrophic cardiomyocytes and proposed to play an important role in the pathogenesis of cardiac hypertrophy, and the autophagy stirred by IMD supplementation is involved in its protection against cardiomyocyte hypertrophy and apoptosis through the activation of both cAMP/PKA and MAPK/ERK1/2 pathways.
doi:10.1371/journal.pone.0064757
PMCID: PMC3667197  PMID: 23737997
19.  Scale-Free Brain Quartet: Artistic Filtering of Multi-Channel Brainwave Music 
PLoS ONE  2013;8(5):e64046.
To listen to the brain activities as a piece of music, we proposed the scale-free brainwave music (SFBM) technology, which translated scalp EEGs into music notes according to the power law of both EEG and music. In the present study, the methodology was extended for deriving a quartet from multi-channel EEGs with artistic beat and tonality filtering. EEG data from multiple electrodes were first translated into MIDI sequences by SFBM, respectively. Then, these sequences were processed by a beat filter which adjusted the duration of notes in terms of the characteristic frequency. And the sequences were further filtered from atonal to tonal according to a key defined by the analysis of the original music pieces. Resting EEGs with eyes closed and open of 40 subjects were utilized for music generation. The results revealed that the scale-free exponents of the music before and after filtering were different: the filtered music showed larger variety between the eyes-closed (EC) and eyes-open (EO) conditions, and the pitch scale exponents of the filtered music were closer to 1 and thus it was more approximate to the classical music. Furthermore, the tempo of the filtered music with eyes closed was significantly slower than that with eyes open. With the original materials obtained from multi-channel EEGs, and a little creative filtering following the composition process of a potential artist, the resulted brainwave quartet opened a new window to look into the brain in an audible musical way. In fact, as the artistic beat and tonal filters were derived from the brainwaves, the filtered music maintained the essential properties of the brain activities in a more musical style. It might harmonically distinguish the different states of the brain activities, and therefore it provided a method to analyze EEGs from a relaxed audio perspective.
doi:10.1371/journal.pone.0064046
PMCID: PMC3661572  PMID: 23717527
20.  Effects of Clostridium difficile Toxin A and B on Human T Lymphocyte Migration 
Toxins  2013;5(5):926-938.
Bacterial products such as toxins can interfere with a variety of cellular processes, leading to severe human diseases. Clostridium difficile toxins, TcdA and TcdB are the primary contributing factors to the pathogenesis of C. difficile-associated diseases (CDAD). While the mechanisms for TcdA and TcdB mediated cellular responses are complex, it has been shown that these toxins can alter chemotactic responses of neutrophils and intestinal epithelial cells leading to innate immune responses and tissue damages. The effects of C. difficile toxins on the migration and trafficking of other leukocyte subsets, such as T lymphocytes, are not clear and may have potential implications for adaptive immunity. We investigated here the direct and indirect effects of TcdA and TcdB on the migration of human blood T cells using conventional cell migration assays and microfluidic devices. It has been found that, although both toxins decrease T cell motility, only TcdA but not TcdB decreases T cell chemotaxis. Similar effects are observed in T cell migration toward the TcdA- or TcdB-treated human epithelial cells. Our study demonstrated the primary role of TcdA (compared to TcdB) in altering T cell migration and chemotaxis, suggesting possible implications for C. difficile toxin mediated adaptive immune responses in CDAD.
doi:10.3390/toxins5050926
PMCID: PMC3709270  PMID: 23645153
C. difficile toxin A and B; human T lymphocyte; cell migration; chemotaxis; microfluidic device
21.  Genome-Wide Association Study Identifies Loci and Candidate Genes for Body Composition and Meat Quality Traits in Beijing-You Chickens 
PLoS ONE  2013;8(4):e61172.
Body composition and meat quality traits are important economic traits of chickens. The development of high-throughput genotyping platforms and relevant statistical methods have enabled genome-wide association studies in chickens. In order to identify molecular markers and candidate genes associated with body composition and meat quality traits, genome-wide association studies were conducted using the Illumina 60 K SNP Beadchip to genotype 724 Beijing-You chickens. For each bird, a total of 16 traits were measured, including carcass weight (CW), eviscerated weight (EW), dressing percentage, breast muscle weight (BrW) and percentage (BrP), thigh muscle weight and percentage, abdominal fat weight and percentage, dry matter and intramuscular fat contents of breast and thigh muscle, ultimate pH, and shear force of the pectoralis major muscle at 100 d of age. The SNPs that were significantly associated with the phenotypic traits were identified using both simple (GLM) and compressed mixed linear (MLM) models. For nine of ten body composition traits studied, SNPs showing genome wide significance (P<2.59E−6) have been identified. A consistent region on chicken (Gallus gallus) chromosome 4 (GGA4), including seven significant SNPs and four candidate genes (LCORL, LAP3, LDB2, TAPT1), were found to be associated with CW and EW. Another 0.65 Mb region on GGA3 for BrW and BrP was identified. After measuring the mRNA content in beast muscle for five genes located in this region, the changes in GJA1 expression were found to be consistent with that of breast muscle weight across development. It is highly possible that GJA1 is a functional gene for breast muscle development in chickens. For meat quality traits, several SNPs reaching suggestive association were identified and possible candidate genes with their functions were discussed.
doi:10.1371/journal.pone.0061172
PMCID: PMC3630158  PMID: 23637794
22.  Low Serum Creatine Kinase Levels in Breast Cancer Patients: A Case-Control Study 
PLoS ONE  2013;8(4):e62112.
Background
Previous studies provide an ambiguous picture of creatine kinase (CK) expression and activities in malignancy. The aim of this study was to investigate the role of serum CK level in breast cancer patients.
Patients and Methods
823 female patients diagnosed with breast cancer were consecutively recruited as cases, and 823 age-match patients with benign breast disease were selected as controls. Serum CK was analyzed by commercially available standardized methods.
Results
Serum CK level was significantly associated with breast cancer (P = 0.005) and subtypes of breast cancer, including breast cancer with diameter>2 cm (P = 0.031) and stage IIIbreast cancer (P = 0.025). The mean serum CK level in patients with>2 cm tumor was significantly lower than that in≤2 cm (P = 0.0475), and the mean serum CK level of stage III breast cancer patients was significantly lower than that of stage I and II breast cancer patients (P = 0.0246). Furthermore, a significant difference (P = 0.004) was observed between serum CK level and ERBB2+breast cancer not other molecular subtypes.
Conclusions
Serum CK levels in cases was significantly lower compared with controls. Notably, our results indicated for the first time that there was a negative correlation between serum CK levels and breast cancer stage. Serum CK level, which may reflect the status of host immunity, may be an important factor in determining breast cancer development and progression.
doi:10.1371/journal.pone.0062112
PMCID: PMC3626709  PMID: 23614022
23.  Removal Efficiency and Mechanism of Sulfamethoxazole in Aqueous Solution by Bioflocculant MFX 
Although the treatment technology of sulfamethoxazole has been investigated widely, there are various issues such as the high cost, inefficiency, and secondary pollution which restricted its application. Bioflocculant, as a novel method, is proposed to improve the removal efficiency of PPCPs, which has an advantage over other methods. Bioflocculant MFX, composed by high polymer polysaccharide and protein, is the metabolism product generated and secreted by Klebsiella sp. In this paper, MFX is added to 1 mg/L sulfanilamide aqueous solution substrate, and the removal ratio is evaluated. According to literatures review, for MFX absorption of sulfanilamide, flocculant dosage, coagulant-aid dosage, pH, reaction time, and temperature are considered as influence parameters. The result shows that the optimum condition is 5 mg/L bioflocculant MFX, 0.5 mg/L coagulant aid, initial pH 5, and 1 h reaction time, and the removal efficiency could reach 67.82%. In this condition, MFX could remove 53.27% sulfamethoxazole in domestic wastewater, and the process obeys Freundlich equation. R2 value equals 0.9641. It is inferred that hydrophobic partitioning is an important factor in determining the adsorption capacity of MFX for sulfamethoxazole solutes in water; meanwhile, some chemical reaction probably occurs.
doi:10.1155/2013/568614
PMCID: PMC3588202  PMID: 23476893
24.  Hydrogen Sulfide as an Endogenous Modulator in Mitochondria and Mitochondria Dysfunction 
Hydrogen sulfide (H2S) has historically been considered to be a toxic gas, an environmental and occupational hazard. However, with the discovery of its presence and enzymatic production through precursors of L-cysteine and homocysteine in mammalian tissues, H2S has recently received much interest as a physiological signaling molecule. H2S is a gaseous messenger molecule that has been implicated in various physiological and pathological processes in mammals, including vascular relaxation, angiogenesis, and the function of ion channels, ischemia/reperfusion (I/R), and heart injury. H2S is an endogenous neuromodulator and present studies show that physiological concentrations of H2S enhance NMDA receptor-mediated responses and aid in the induction of hippocampal long-term potentiation. Moreover, in the field of neuronal protection, physiological concentrations of H2S in mitochondria have many favorable effects on cytoprotection.
doi:10.1155/2012/878052
PMCID: PMC3523162  PMID: 23304257
25.  A Low-Cost Body Inertial-Sensing Network for Practical Gait Discrimination of Hemiplegia Patients 
Telemedicine Journal and e-Health  2012;18(10):748-754.
Abstract
Gait analysis is widely used in detecting human walking disorders. Current gait analysis methods like video- or optical-based systems are expensive and cause invasion of human privacy. This article presents a self-developed low-cost body inertial-sensing network, which contains a base station, three wearable inertial measurement nodes, and the affiliated wireless communication protocol, for practical gait discrimination between hemiplegia patients and asymptomatic subjects. Every sensing node contains one three-axis accelerometer, one three-axis magnetometer, and one three-axis gyroscope. Seven hemiplegia patients (all were abnormal on the right side) and 7 asymptomatic subjects were examined. The three measurement nodes were attached on the thigh, the shank, and the dorsum of the foot, respectively (all on the right side of the body). A new method, which does not need to obtain accurate positions of the sensors, was used to calculate angles of knee flexion/extension and foot in the gait cycle. The angle amplitudes of initial contact, toe off, and knee flexion/extension were extracted. The results showed that there were significant differences between the two groups in the three angle amplitudes examined (−0.52±0.98° versus 6.94±2.63°, 28.33±11.66° versus 47.34±7.90°, and 26.85±8.6° versus 50.91±6.60°, respectively). It was concluded that the body inertial-sensing network platform provided a practical approach for wearable biomotion acquisition and was effective for discriminating gait symptoms between hemiplegia and asymptomatic subjects.
doi:10.1089/tmj.2012.0014
PMCID: PMC3523244  PMID: 22449064
gait analysis; body sensor network; hemiplegia

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