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1.  Directed Evolution of an LBP/CD14 Inhibitory Peptide and Its Anti-Endotoxin Activity 
PLoS ONE  2014;9(7):e101406.
LPS-binding protein (LBP) and its ligand CD14 are located upstream of the signaling pathway for LPS-induced inflammation. Blocking LBP and CD14 binding might prevent LPS-induced inflammation. In previous studies, we obtained a peptide analog (MP12) for the LBP/CD14 binding site and showed that this peptide analog had anti-endotoxin activity. In this study, we used in vitro directed evolution for this peptide analog to improve its in vivo and in vitro anti-endotoxin activity.
We used error-prone PCR (ep-PCR) and induced mutations in the C-terminus of LBP and attached the PCR products to T7 phages to establish a mutant phage display library. The positive clones that competed with LBP for CD14 binding was obtained by screening. We used both in vivo and in vitro experiments to compare the anti-endotoxin activities of a polypeptide designated P1 contained in a positive clone and MP12.
11 positive clones were obtained from among target phages. Sequencing showed that 9 positive clones had a threonine (T) to methionine (M) mutation in amino acid 287 of LBP. Compared to polypeptide MP12, polypeptide P1 significantly inhibited LPS-induced TNF-α expression and NF-κB activity in U937 cells (P<0.05). Compared to MP12, P1 significantly improved arterial oxygen pressure, an oxygenation index, and lung pathology scores in LPS-induced ARDS rats (P<0.05).
By in vitro directed evolution of peptide analogs for the LBP/CD14 binding site, we established a new polypeptide (P1) with a threonine (T)-to-methionine (M) mutation in amino acid 287 of LBP. This polypeptide had high anti-endotoxin activity in vitro and in vivo, which suggested that amino acid 287 in the C-terminus of LBP may play an important role in LBP binding with CD14.
PMCID: PMC4098906  PMID: 25025695
2.  Pushing the resolution of photolithography down to 15nm by surface plasmon interference 
Scientific Reports  2014;4:5618.
A deep ultraviolet plasmonic structure is designed and a surface plasmon interference lithography method using the structure is proposed to generate large-area periodic nanopatterns. By exciting the anti-symmetric coupled surface plasmon polaritons in the structure, ultrahigh resolution periodic patterns can be formed in a photoresist. The resolution of the generated patterns can be tuned by changing the refractive index and thickness of the photoresist. We demonstrate numerically that one-dimensional and two-dimensional patterns with a half-pitch resolution of 14.6 nm can be generated in a 25 nm-thick photoresist by using the structure under 193 nm illumination. Furthermore, the half-pitch resolution of the generated patterns can be down to 13 nm if high refractive index photoresists are used. Our findings open up an avenue to push the half-pitch resolution of photolithography towards 10 nm.
PMCID: PMC4085591  PMID: 25001238
3.  Isolation, plant colonization potential, and phenanthrene degradation performance of the endophytic bacterium Pseudomonas sp. Ph6-gfp 
Scientific Reports  2014;4:5462.
This investigation provides a novel method of endophyte-aided removal of polycyclic aromatic hydrocarbons (PAHs) from plant bodies. A phenanthrene-degrading endophytic bacterium Pseudomonas sp. Ph6 was isolated from clover (Trifolium pratense L.) grown in a PAH-contaminated site. After being marked with the GFP gene, the colonization and distribution of strain Ph6-gfp was directly visualized in plant roots, stems, and leaves for the first time. After ryegrass (Lolium multiflorum Lam.) roots inoculation, strain Ph6-gfp actively and internally colonized plant roots and transferred vertically to the shoots. Ph6-gfp had a natural capacity to cope with phenanthrene in vitro and in planta. Ph6-gfp degraded 81.1% of phenanthrene (50 mg·L−1) in a culture solution within 15 days. The inoculation of plants with Ph6-gfp reduced the risks associated with plant phenanthrene contamination based on observations of decreased concentration, accumulation, and translocation factors of phenanthrene in ryegrass. Our results will have important ramifications in the assessment of the environmental risks of PAHs and in finding ways to circumvent plant PAH contamination.
PMCID: PMC4071310  PMID: 24964867
4.  In Vitro Characterization of Human Adenovirus Type 55 in Comparison with Its Parental Adenoviruses, Types 11 and 14 
PLoS ONE  2014;9(6):e100665.
Human adenovirus type 55 (HAdV-B55) represents a re-emerging human pathogen, and this adenovirus has been reported to cause outbreaks of acute respiratory diseases among military trainees and in school populations around the world. HAdV-B55 has been revealed to have evolved from homologous recombination between human adenovirus type 14 (HAdV-B14) and type 11 (HAdV-B11), but it presents different clinical manifestations from parental virus HAdV-B11. In the present paper, we report the distinct biological features of HAdV-B55 in comparison with the parental viruses HAdV-B11 and HAdV-B14 in cell cultures. The results showed that HAdV-B55 replicated well in various cells, similar to HAdV-B11 and HAdV-B14, but that its processing had a slower and milder cytopathic effect in the early stages of infection. Viral fitness analysis showed that HAdV-B55 exhibited higher levels of replication in respiratory cells than did either of its parents. Cytotoxicity and apoptosis analyses in A549 cells indicated that HAdV-B55 was less cytotoxic than HAdV-B11 and HAdV-B14 were and induced milder apoptosis. Finally, thermal sensitivity analysis revealed that HAdV-B55 exhibited lower thermostability than did either HAdV-B11 or HAdV-B14, which may limit the transmission of HAdV-B55 in humans. Together, the findings described here expand current knowledge about this re-emerging recombinant HAdV, shedding light on the pathogenesis of HAdV-B55.
PMCID: PMC4067339  PMID: 24956280
5.  Tumor-Associated Mutant p53 Drives the Warburg Effect 
Nature communications  2013;4:2935.
Tumor cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Its mechanism is not well-understood. The tumor suppressor gene p53 is frequently mutated in tumors. Many tumor-associated mutant p53 (mutp53) proteins not only lose tumor suppressive function, but also gain new oncogenic functions that are independent of wild type p53, defined as mutp53 gain-of-function (GOF). Here we show that tumor-associated mutp53 stimulates the Warburg effect in cultured cells and mutp53 knock-in mice as a new mutp53 GOF. Mutp53 stimulates the Warburg effect through promoting GLUT1 translocation to plasma membrane, which is mediated by the activated RhoA and its downstream effector ROCK. Inhibition of the RhoA/ROCK/GLUT1 signaling largely abolishes mutp53 GOF in stimulating the Warburg effect. Furthermore, inhibition of glycolysis in tumor cells greatly compromises mutp53 GOF in promoting tumorigenesis. Thus, our results reveal a new mutp53 GOF and a mechanism for controlling the Warburg effect.
PMCID: PMC3969270  PMID: 24343302
6.  Combined Transoral and Endoscopic Approach for Total Maxillectomy: A Pioneering Report 
Total maxillectomy is sometimes necessary especially for malignant tumors originating from the maxillary sinus. Here we describe a combined transoral and endoscopic approach for total maxillectomy for the treatment of malignant maxillary sinus tumors and evaluate its short-term outcome. This approach was evaluated in terms of the physiological function, aesthetic outcome, and complications. Six patients underwent the above-mentioned approach for resection of malignant maxillary sinus tumors from May 2010 to June 2011. This combined transoral and endoscopic approach includes five basic steps: total sphenoethmoidectomy, sublabial incision, incision of the frontal process of the maxilla, incision of the zygomaticomaxillary fissure, and hard palate osteotomy. All patients with malignant maxillary sinus tumors successfully underwent the planned total endoscopic maxillectomy without the need for facial incision or transfixion of the nasal septum; there were no significant complications. Five patients received preoperative radiation therapy. All patients were well and had no recurrence at follow-up from 13 to 27 months. The combined approach is feasible and can be performed in carefully selected patients. The benefit of the absence of facial incisions or transfixion of the nasal septum, potential improvement in hemostasis, and visual magnification may help to decrease the morbidity of traditional open approaches.
PMCID: PMC3709934  PMID: 24436907
total maxillectomy; combined transoral and endoscopic approach; malignant tumor; maxillary sinus; endoscopic technique
7.  New Prenylxanthones from the Deep-Sea Derived Fungus Emericella sp. SCSIO 05240 
Marine Drugs  2014;12(6):3190-3202.
Four new prenylxanthones, emerixanthones A–D (1–4), together with six known analogues (5–10), were isolated from the culture of the deep-sea sediment derived fungus Emericella sp. SCSIO 05240, which was identified on the basis of morphology and ITS sequence analysis. The newstructures were determined by NMR (1H, 13C NMR, HSQC, HMBC, and 1H-1H COSY), MS, CD, and optical rotation analysis. The absolute configuration of prenylxanthone skeleton was also confirmed by the X-ray crystallographic analysis. Compounds 1 and 3 showed weak antibacterial activities, and 4 displayed mild antifungal activities against agricultural pathogens.
PMCID: PMC4071571  PMID: 24879543
prenylxanthone; Emericella; deep-sea; fungus
8.  Effects of Fermented Mushroom of Cordyceps sinensis, Rich in Selenium, on Uterine Cervix Cancer 
The purpose of this study was to investigate the effect of fermented mushroom of Cordyceps sinensis (CS), rich in selenium (Se-CS), on uterine cervical cancer in mice. The methylcholanthrene- (MCA-) induced tumor model was used in this paper. After the mice were administered Se-CS, the animals showed 40% tumor incidence (P < 0.05). Se-CS also enhanced the immune functions. Se-CS treatment showed significant (P < 0.05–0.01) restoration in the level of glutathione content, lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+/K+-ATPase activity, and glutathione S transferase activity. This finding suggested that the concomitant use of Se and CS could be a potential therapeutic approach to improve the efficacy of therapy for uterine cervical cancer.
PMCID: PMC4058183  PMID: 24971145
9.  Predicting Response to Preoperative Chemotherapy Agents by Identifying Drug Action on Modeled MicroRNA Regulation Networks 
PLoS ONE  2014;9(5):e98140.
Identifying patients most responsive to specific chemotherapy agents in neoadjuvant settings can help to maximize the benefits of treatment and minimize unnecessary side effects. Metagene approaches that predict response based on gene expression signatures derived from an associative analysis of clinical data can identify chance associations caused by the heterogeneity of a tumor, leading to reproducibility issues in independent validations. In this study, to incorporate information from drug mechanisms of action, we explore the potential of microRNA regulation networks as a new feature space for identifying predictive markers. We introduce a measure we term the CoMi (Context-specific-miRNA-regulation) pattern to represent a descriptive feature of the miRNA regulation network in the transcriptome. We examine whether the modifications to the CoMi pattern on specific biological processes are a useful representation of drug action by predicting the response to neoadjuvant Paclitaxel treatment in breast cancer and show that the drug counteracts the CoMi network dysregulation induced by tumorigenesis. We then generate a quantitative testbed to investigate the ability of the CoMi pattern to distinguish FDA approved breast cancer drugs from other FDA approved drugs not related to breast cancer. We also compare the ability of the CoMi and metagene methods to predict response to neoadjuvant Paclitaxel treatment in clinical cohorts. We find the CoMi method outperforms the metagene method, achieving area under curve (AUC) values of 0.78 and 0.66 respectively. Furthermore, several of the predicted CoMi features highlight the network-based mechanism of drug resistance. Thus, our study suggests that explicitly modeling the drug action using network biology provides a promising approach for predictive marker discovery.
PMCID: PMC4029965  PMID: 24848634
10.  Glutaminase 2 negatively regulates the PI3K/AKT signaling and shows tumor suppression activity in human hepatocellular carcinoma 
Oncotarget  2014;5(9):2635-2647.
The tumor suppressor p53 and its signaling pathway play a critical role in tumor prevention. As a direct p53 target gene, the role of glutaminase 2 (GLS2) in tumorigenesis is unclear. In this study, we found that GLS2 expression is significantly decreased in majority of human hepatocellular carcinoma (HCC). Restoration of GLS2 expression in HCC cells inhibits the anchorage-independent growth of cells and reduces the growth of HCC xenograft tumors. Interestingly, we found that GLS2 negatively regulates the PI3K/AKT signaling, which is frequently activated in HCC. Blocking the PI3K/AKT signaling in HCC cells largely abolishes the inhibitory effect of GLS2 on the anchorage-independent cell growth and xenograft tumor growth. The GLS2 promoter is hypermethylated in majority of HCC samples. CpG methylation of GLS2 promoter inhibits GLS2 transcription, whereas reducing the methylation of GLS2 promoter induces GLS2 expression. Taken together, our results demonstrate that GLS2 plays an important role in tumor suppression in HCC, and the negative regulation of PI3K/AKT signaling contributes greatly to this function of GLS2. Furthermore, hypermethylation of GLS2 promoter is an important mechanism contributing to the decreased GLS2 expression in HCC.
PMCID: PMC4058033  PMID: 24797434
p53; GLS2; tumor suppression; PI3K/AKT; Hepatocellular carcinoma
11.  Transittability of complex networks and its applications to regulatory biomolecular networks 
Scientific Reports  2014;4:4819.
We have often observed unexpected state transitions of complex systems. We are thus interested in how to steer a complex system from an unexpected state to a desired state. Here we introduce the concept of transittability of complex networks, and derive a new sufficient and necessary condition for state transittability which can be efficiently verified. We define the steering kernel as a minimal set of steering nodes to which control signals must directly be applied for transition between two specific states of a network, and propose a graph-theoretic algorithm to identify the steering kernel of a network for transition between two specific states. We applied our algorithm to 27 real complex networks, finding that sizes of steering kernels required for transittability are much less than those for complete controllability. Furthermore, applications to regulatory biomolecular networks not only validated our method but also identified the steering kernel for their phenotype transitions.
PMCID: PMC4001102  PMID: 24769565
12.  Parallel mRNA and MicroRNA Profiling of HEV71-Infected Human Neuroblastoma Cells Reveal the Up-Regulation of miR-1246 in Association with DLG3 Repression 
PLoS ONE  2014;9(4):e95272.
Human enterovirus 71 (HEV71) has emerged as the leading cause of viral encephalitis in children in most Asian countries. The roles of host miRNAs in the neurological pathogenesis of HEV71 infection remain unknown. In the present study, comprehensive miRNA expression profiling in HEV71-infected human neuroblastoma SH-SY5Y cells was performed using the Affymetrix Gene Chip microarray assay and was validated using real-time RT-PCR. Among the 69 differentially expressed miRNAs, miR-1246 was specifically induced by HEV71 infection in human neuroblastoma cells, but inhibition of miR-1246 failed to affect HEV71 replication. Parallel mRNA and microRNA profiling based on the 35 K Human Genome Array identified 182 differentially regulated genes. Target prediction of miR-1246 and network modeling revealed 14 potential target genes involved in cell death and cell signaling. Finally, a combined analysis of the results from mRNA profiling and miR-1246 target predication led to the identification of disc-large homolog 3 (DLG3), which is associated with neurological disorders, for further validation. Sequence alignment and luciferase reporter assay showed that miR-1246 directly bound with the 3′-UTR of DLG3 gene. Down-regulation of miR-1246 induced significant changes in DLG3 expression levels in HEV71-infected SHSY5Y cells. Together, these results suggested that miR-1246 might play a role in neurological pathogenesis of HEV71 by regulating DLG3 gene in infected cells. These findings provide new information on the miRNA and mRNA profiles of HEV71-infected neuroblastoma cells. The biological significance of miR-1246 and DLG3 during the course of HEV71 infection deserves further investigation.
PMCID: PMC3989279  PMID: 24739954
13.  Downregulation of Bcl-2 Expression by miR-34a Mediates Palmitate-Induced Min6 Cells Apoptosis 
Journal of Diabetes Research  2014;2014:258695.
Recent studies have demonstrated that the expression of miR-34a is significantly upregulated and associated with cell apoptosis in pancreatic β-cell treated with palmitate. Nevertheless, the underlying detailed mechanism is largely unknown. Here, we showed that miR-34a was significantly induced in Min6 pancreatic β-cell upon palmitate treatment. Elevated miR-34a promoted Min6 cell apoptosis. Intriguingly, ectopic expression of miR-34a lowered the expression of Bcl-2, an antiapoptotic protein. Luciferase reporter assay indicated the direct interaction of miR-34a with the Bcl-2 3′-UTR. Moreover, downregulated expression of Bcl-2 induced by palmitate could be restored by inhibition of miR-34a. We conclude that direct suppression of Bcl-2 by miR-34a accounts for palmitate-induced increased apoptosis rate in pancreatic β-cell.
PMCID: PMC4009326  PMID: 24829923
14.  Dental and periodontal status of 12-year-old Bulang children in China 
BMC Oral Health  2014;14:32.
Bulang is an ethnic minority group living in Yunnan in the southwestern part of China. There is little information pertaining to the oral health of Bulang children. This study aims to examine the dental caries and periodontal status of 12-year-old Bulang children in China and the factors affecting their oral-health status.
12-year-old Bulang school children in Yunnan, China, were recruited through a multi-stage cluster sampling method. Following the recommendation of the World Health Organization, caries experiences were recorded using the DMFT index and periodontal status with the CPI index. A self-completed questionnaire was used to collect information on the background and oral health-related behaviours of the children.
A total of 900 children in primary schools were invited, and 873 (97%) joined the survey. Their caries prevalence was 35%. Their caries experience in mean DMFT (±SD) score was 0.6 ± 1.1, and 94% of the carious teeth had no treatment. Most children (71%) had bleeding gums, and 58% of them had calculus. Girls and those who had visited a dentist in the previous year had higher caries risk.
Dental caries was common among the 12-year-old Bulang children in China. Most of the carious teeth were left untreated. Caries prevalence was associated with gender and dental attendance. Their periodontal condition was poor, and more than half of them had calculus.
PMCID: PMC3978202  PMID: 24708768
Caries; Children; Ethnic; Minority; China
15.  Inferring Gene Dependency Network Specific to Phenotypic Alteration Based on Gene Expression Data and Clinical Information of Breast Cancer 
PLoS ONE  2014;9(3):e92023.
Although many methods have been proposed to reconstruct gene regulatory network, most of them, when applied in the sample-based data, can not reveal the gene regulatory relations underlying the phenotypic change (e.g. normal versus cancer). In this paper, we adopt phenotype as a variable when constructing the gene regulatory network, while former researches either neglected it or only used it to select the differentially expressed genes as the inputs to construct the gene regulatory network. To be specific, we integrate phenotype information with gene expression data to identify the gene dependency pairs by using the method of conditional mutual information. A gene dependency pair (A,B) means that the influence of gene A on the phenotype depends on gene B. All identified gene dependency pairs constitute a directed network underlying the phenotype, namely gene dependency network. By this way, we have constructed gene dependency network of breast cancer from gene expression data along with two different phenotype states (metastasis and non-metastasis). Moreover, we have found the network scale free, indicating that its hub genes with high out-degrees may play critical roles in the network. After functional investigation, these hub genes are found to be biologically significant and specially related to breast cancer, which suggests that our gene dependency network is meaningful. The validity has also been justified by literature investigation. From the network, we have selected 43 discriminative hubs as signature to build the classification model for distinguishing the distant metastasis risks of breast cancer patients, and the result outperforms those classification models with published signatures. In conclusion, we have proposed a promising way to construct the gene regulatory network by using sample-based data, which has been shown to be effective and accurate in uncovering the hidden mechanism of the biological process and identifying the gene signature for phenotypic change.
PMCID: PMC3956890  PMID: 24637666
16.  Dental caries status of Bulang preschool children in Southwest China 
BMC Oral Health  2014;14:16.
Bulang is one of the 55 ethnic minorities in China with a population of around 120,000. They live mainly in Yunnan, which is a less-developed province in southwestern China. Many Bulang people live in remote villages and have little access to dental care. They like hot and sour food and chew betel nut. This study examines the caries status of 5-year-old Bulang children and factors that influence their caries status.
A sample of 5-year-old Bulang children in Yunnan was selected using a multi-stage cluster sampling method. One trained dentist examined the children using dental mirrors with intra-oral LED light and CPI probes. Caries experience was measured according to the dmft index. Oral hygiene status was recorded according to the visible plaque index (VPI). A parental questionnaire was used to study the children’s oral health-related behaviours.
A total of 775 children were invited and 723 joined the survey. The caries prevalence was 85%, and 38% of them had caries involved in pulp. The mean dmft and dt score were 5.8 ± 4.9 and 5.6 ± 4.8, respectively. Visible plaque was found on 636 children (88%). Multi-factor ANCOVA analysis found that higher dmft scores were found among the children who snacked on sweets daily, had visited a dentist within the last year and had higher VPI scores.
The caries prevalence and experience among 5-year-old Bulang children in Yunnan was high, and most of the caries were left untreated. The caries experience was associated with snacking habits, dental visit habits and oral hygiene.
PMCID: PMC3946148  PMID: 24593701
Caries; Children; Ethnic; Minority; China
17.  Early-Life Exposure to Bisphenol A Induces Liver Injury in Rats Involvement of Mitochondria-Mediated Apoptosis 
PLoS ONE  2014;9(2):e90443.
Exposure to bisphenol A (BPA), a monomer widely used to manufacture polycarbonate plastics, has been reported to be associated with abnormalities of liver function and hepatic damage. However, the molecular mechanism under the pathogenesis of hepatic injury is unclear. In this study, the effect of perinatal exposure to BPA at the reference dose of 50 µg/kg/day on the apoptotic index in the liver of rat offspring was investigated. Increased levels of ALT and enhanced cell apoptosis were observed in the liver of rat offspring at 15 and 21 weeks, and significantly increased activity of caspase-3 and caspase-9 and elevated levels of cytochrome c were also confirmed. In addition, significant change in the expression levels of Bcl-2 and Bax were found in BPA-treated offspring at 21 weeks. For in vitro experiments, liver mitochondria were isolated from neonatal rats and were treated with BPA. BPA treatment led to a significant increase in mitochondrial permeability transition. Moreover, the supernatant from BPA-treated mitochondria significantly increased apoptotic changes in nuclei isolated from liver tissue. In conclusion, the study demonstrates that BPA induces mitochondria-mediated apoptosis in hepatic cells, which may contribute to long-term hepatotoxicity induced by early-life exposure to BPA.
PMCID: PMC3938763  PMID: 24587367
18.  Ultrahigh spin thermopower and pure spin current in a single-molecule magnet 
Scientific Reports  2014;4:4128.
Using the non-equilibrium Green's function (NEGF) formalism within the sequential regime, we studied ultrahigh spin thermopower and pure spin current in single-molecule magnet(SMM), which is attached to nonmagnetic metal wires with spin bias and angle (θ) between the easy axis of SMM and the spin orientation in the electrodes. A pure spin current can be generated by tuning the gate voltage and temperature difference with finite spin bias and the arbitrary angle except of . In the linear regime, large thermopower can be obtained by modifying Vg and the angles (θ). These results are useful in fabricating and advantaging SMM devices based on spin caloritronics.
PMCID: PMC3928577  PMID: 24549224
19.  Lack of Association of P2RX7 Gene rs2230912 Polymorphism with Mood Disorders: A Meta-Analysis 
PLoS ONE  2014;9(2):e88575.
To assess the association of P2RX7 gene rs2230912 polymorphism with mood disorders using a meta-analysis.
Data were collected from the following electronic databases: PubMed, Excerpta Medica Database, Elsevier Science Direct, Cochrane Library, and Chinese Biomedical Literature Database, with the last report up to April 1, 2013. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. Dependent on the results of heterogeneity test among individual studies, the fixed effect model (Mantel–Haenszel) or random effect model (DerSimonian–Laird) was selected to summarize the pooled OR.
We identified 13 separate studies using search (6,962 cases and 9,262 controls). We detected significant between-study heterogeneity. No significant association of this polymorphism with mood disorders was found (P>0.05). We also performed disease-specific meta-analysis in unipolar depression and bipolar disorder. No significant association of this polymorphism with unipolar depression or bipolar disorder was found (P>0.05). Additionally, we performed subgroup analysis by different types of cases. No significant association of this polymorphism with mood disorders in clinical cohorts or population-based cohorts (P>0.05). A significant association of this polymorphism with mood disorders was found for the allele contrast in family-based cohorts (OR = 1.26, 95%CI = 1.05–1.50, P = 0.01).
Overall, our meta-analysis suggests that P2RX7 gene rs2230912 polymorphism may not contribute to the risk of developing mood disorders using a case-control design. Given the discordance in the subgroup analysis by different types of cases, further studies based on larger sample size are still needed.
PMCID: PMC3922924  PMID: 24533115
20.  Pretreatment of Mice with Oligonucleotide prop5 Protects Them from Influenza Virus Infections 
Viruses  2014;6(2):573-581.
Influenza A virus is a successful parasite and requires host factors to complete its life cycle. Prop5 is an antisense oligonucleotide, targeting programmed cell death protein 5 (PDCD5). In this study, we tested the antiviral activity of prop5 against mouse-adapted A/FM/1/47 strain of influenza A virus in a mouse model. Prop5 intranasally administered the mice at dosages of 10 and 20 mg/kg/d at 24 h and 30 min before infection, provided 80% and 100% survival rates and prolonged mean survival days in comparison with influenza virus-infected mice (both p < 0.01). Moreover, viral titres in mice pretreated with prop5, at dose of 10 and 20 mg/kg/d, had declined significantly on day two, four, and six post-infection compared with the yields in infected mice (p < 0.05 or p < 0.01); lung index in mice pretreated with prop5 (20 mg/kg/d) had been inhibited on day six post-infection (p < 0.05). Western blotting and immunohistochemistry showed that prop5 could down-regulate the PDCD5 protein expression levels in lung tissues of infected mice. These data indicate that antisense oligonucleotide prop5 is a promising drug for prophylaxis and control influenza virus infections and provides an insight into the host-pathogen interaction.
PMCID: PMC3939472  PMID: 24509810
influenza A virus; host factor; antisense oligonucleotide; prop5
21.  Electroacupuncture at Acupoints Reverses Plasma Glutamate, Lipid, and LDL/VLDL in an Acute Migraine Rat Model: A 1H NMR-Based Metabolomic Study 
Background. The objective of this study was to identify potential biomarkers of electroacupuncture (EA) on relieving acute migraine through metabolomic study. Methods. EA treatments were performed on both acupoints and nonacupoints on the nitroglycerin (NTG)-induced migraine rat model. NMR experiments and multivariate analysis were used for metabolomic analysis. Results. The number of head-scratching, the main ethology index of migraine rat model, was significantly increased (P < 0.01) after NTG injection. The plasma metabolic profile of model group was distinct from that of the control group. Glutamate was significantly increased (P < 0.01), whereas lipids were significantly decreased (P < 0.01) in model rats. After EA at acupoints, the metabolic profile of model rats was normalized, with decreased glutamate (P < 0.05) and increased lipids (P < 0.01). In contrast, EA at nonacupoints did not restore the metabolic profile, but with six metabolites significantly different from acupoints group. Interestingly, the number of head-scratching and glutamate level were significantly decreased (P < 0.05) after receiving EA at both acupoints and nonacupoints. Conclusions. EA at acupoints may relieve acute migraine by restoring the plasma metabolic profile and plasma glutamate, while EA at nonacupoints may modestly relieve acute migraine by decreasing plasma glutamate.
PMCID: PMC3921982  PMID: 24592282
22.  Long-term intensive management increased carbon occluded in phytolith (PhytOC) in bamboo forest soils 
Scientific Reports  2014;4:3602.
Carbon (C) occluded in phytolith (PhytOC) is highly stable at millennium scale and its accumulation in soils can help increase long-term C sequestration. Here, we report that soil PhytOC storage significantly increased with increasing duration under intensive management (mulching and fertilization) in Lei bamboo (Phyllostachys praecox) plantations. The PhytOC storage in 0–40 cm soil layer in bamboo plantations increased by 217 Mg C ha−1, 20 years after being converted from paddy fields. The PhytOC accumulated at 79 kg C ha−1 yr−1, a rate far exceeding the global mean long-term soil C accumulation rate of 24 kg C ha−1 yr−1 reported in the literature. Approximately 86% of the increased PhytOC came from the large amount of mulch applied. Our data clearly demonstrate the decadal scale management effect on PhytOC accumulation, suggesting that heavy mulching is a potential method for increasing long-term organic C storage in soils for mitigating global climate change.
PMCID: PMC3884227  PMID: 24398703
23.  Surface chemistry-mediated penetration and gold nanorod thermotherapy in multicellular tumor spheroids† 
Nanoscale  2012;5(1):143-146.
We investigated the penetration and thermotherapy efficiency of different surface coated gold nanorods (Au NRs) in multicellular tumor spheroids. The current data show that negatively charged Au NRs, other than positively charged Au NRs, can penetrate deep into the tumor spheroids and achieve a significant thermal therapeutic benefit.
PMCID: PMC3518646  PMID: 23154390
24.  Comparison of concurrent chemoradiotherapy followed by radical surgery and high-dose-rate intracavitary brachytherapy: a retrospective study of 240 patients with FIGO stage IIB cervical carcinoma 
OncoTargets and therapy  2014;7:91-100.
The aim of this study was to compare the long-term survival outcome and late toxicity in patients with FIGO (International Federation of Gynecology and Obstetrics) stage IIB cervical carcinoma after two treatment modalities, ie, concurrent chemoradiotherapy followed by radical surgery and concurrent chemoradiotherapy followed by high-dose-rate intracavitary brachytherapy.
Between November 2004 and November 2011, 240 patients with FIGO stage IIB cervical carcinoma were analyzed, comprising 119 patients treated with concurrent chemoradiotherapy followed by radical surgery (group 1) and 121 patients treated with concurrent chemoradiotherapy followed by high-dose-rate intracavitary brachytherapy (group 2). Local control, overall survival, progression-free survival, and treatment-related complications were compared between the two groups.
The median follow-up duration was 36 months. Concurrent chemoradiotherapy followed by radical surgery showed a survival benefit when comparing group 1 and group 2 (3-year overall survival, 94.9% versus 84.6%, P=0.011; 3-year progression-free survival, 91.0% versus 81.8%, P=0.049, respectively). Three-year local pelvic control was 94.6% in group 1 and 93.3% in group 2 (P=0.325). Prognostic factors in group 1 were: age (≤35 years versus >35 years), 3-year progression-free survival (74.1% versus 90.9%, P=0.037); tumor diameter (≥6 cm versus <6 cm); and 3-year progression-free survival, (60.6% versus 92.9%, P=0.004). Prognostic factors in group 2 were: tumor diameter (≥4 cm versus <4 cm); 3-year overall survival (78.0% versus 94.8%, P=0.043); tumor diameter (≥6 cm versus <6 cm); 3-year progression-free survival (42.9% versus 84.2%, P=0.032); and 3-year overall survival (42.9% versus 87.1%, P=0.013). Further, 50 patients (42.02%) in group 1 and 46 patients (38.02%) in group 2 suffered from late complications. Analysis of the difference in composition of late complications showed that the rate of leg edema was higher in group 1 (35.29% versus 4.96%, P=0.000) while the rate of radiation enteritis was higher in group 2 (30.58% versus 5.04%, P=0.000).
In patients with FIGO stage IIB cervical carcinoma, concurrent chemoradiotherapy followed by radical surgery achieved higher overall survival and progression-free survival rates in comparison with radical radiotherapy associated with concurrent chemotherapy. Tumor diameter could be a common prognostic factor in these two groups of patients.
PMCID: PMC3888351  PMID: 24421644
cervical carcinoma; preoperative concurrent chemoradiotherapy; radical radiotherapy; prognostic factors; late toxicity
25.  Profiling of MicroRNAs under Wound Treatment in Aquilaria sinensis to Identify Possible MicroRNAs Involved in Agarwood Formation 
Agarwood, a kind of highly valued non-timber product across Asia, is formed only when its resource trees -- the endangered genus Aquilaria are wounded or infected by some microbes. To promote the efficiency of agarwood production and protect the wild resource of Aquilaria species, we urgently need to reveal the regulation mechanism of agarwood formation. MicroRNAs (miRNAs) are a group of gene expression regulators with overwhelming effects on a large spectrum of biological processes. However, their roles in agarwood formation remain unknown. This work aimed at identifying possible miRNAs involved in the wound induced agarwood formation. In this study, the high-throughput sequencing was adopted to identify miRNAs and monitor their expression under wound treatment in the stems of A. sinensis. The miR171, miR390, miR394, miR2111, and miR3954 families remained at the reduced level two days after the treatment. 131 homologous miRNAs in the 0.5 h library showed over three-fold variation of read number compared with the control library, of which 12 exhibiting strong expression alterations were further confirmed by real-time quantitative PCR. Target prediction and annotation of the miRNAs demonstrated that the binding, metabolic process, catalytic activity, and cellular process are the most common functions of the predicted targets of these newly identified miRNAs in A.sinensis. The cleaveage sites of three newly predicted targets were verified by 5'RACE.
PMCID: PMC4007363  PMID: 24795531
microRNA; Agarwood; Aquilaria sinensis; wound; small RNA

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