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1.  Weichang’an and 5-fluorouracil suppresses colorectal cancer in a mouse model 
AIM: To examine the effect of Weichang’an (WCA) and 5-fluorouracil (5-FU) on colorectal tumor and hepatic metastasis in a mouse model.
METHODS: Quantitative determination of hesperidin, the effective component in WCA decoction, was performed using HPLC. In vitro cytotoxicity of WCA was determined by treating HCT-116 cells with WCA diluents or serum extracted from rats that received WCA by oral gavage for 1 wk and MTT assays. Forty-eight nude mice received cecum implantation with tumor blocks subcutaneously amplified from human colon cancer cell line HCT-116. Mice were randomly divided into four treatment groups: control (CON), WCA, 5-FU and combination (WCA + 5-FU). Pathological examination of tumors consisted of tissue sectioning and hematoxylin and eosin staining. Tumor weight and size were measured, and the number of metastatic lesions was counted. Serum carcinoembryonic antigen (CEA) level was determined by ELISA. The expression levels of tumor genesis and metastasis-related proteins β-catenin and matrix metalloproteinase (MMP)-7 were measured by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and immunoblotting. Cell fractionation was used to investigate intracellular distribution of β-catenin.
RESULTS: Parenchymal tumors were palpable in the abdomens of nude mice 2 wk post-implantation and orthotopic tumor formation rate was 100% in all groups. 5-FU treatment alone significantly decreased tumor weight compared to the CON group (1.203 ± 0.284 g vs 1.804 ± 0.649 g, P < 0.01). WCA treatment alone reduced the rate of metastasis (50% vs 100%, P < 0.05). Combination treatment of WCA + 5-FU was the most effective, reducing the tumor weight (1.140 ± 0.464 g vs 1.804 ± 0.649 g, P < 0.01) and size (1493.438 ± 740.906 mm3 vs 2180.259 ± 816.556 mm3, P < 0.05), the rate of metastases (40% vs 100%, P < 0.01), and serum CEA levels (31.263 ± 7.421 μg/L vs 43.040 ± 11.273 μg/L, P < 0.05). Expression of β-catenin and MMP-7 was decreased in drug-treated groups compared to controls, as detected using real-time quantitative RT-PCR, immunohistochemistry and immunoblotting, respectively. Cell fractionation assays revealed that nuclear translocation of β-catenin was reduced by WCA and/or 5-FU treatments.
CONCLUSION: Combination of WCA with 5-FU significantly inhibited colon tumor growth and hepatic metastases. Decreased expression of β-catenin and MMP-7 may be important.
PMCID: PMC4306156  PMID: 25632185
Colorectal cancer; Hepatic metastasis; Weichang’an formula; Orthotopic transplant nude mouse model; Chemotherapeutics 5-fluorouracil
2.  Maduramicin Inhibits Proliferation and Induces Apoptosis in Myoblast Cells 
PLoS ONE  2014;9(12):e115652.
Maduramicin, a polyether ionophore antibiotic derived from the bacterium Actinomadura yumaensis, is currently used as a feed additive against coccidiosis in poultry worldwide. It has been clinically observed that maduramicin can cause skeletal muscle and heart cell damage, resulting in skeletal muscle degeneration, heart failure, and even death in animals and humans, if improperly used. However, the mechanism of its toxic action in myoblasts is not well understood. Using mouse myoblasts (C2C12) and human rhabdomyosarcoma (RD and Rh30) cells as an experimental model for myoblasts, here we found that maduramicin inhibited cell proliferation and induced cell death in a concentration-dependent manner. Further studies revealed that maduramicin induced accumulation of the cells at G0/G1 phase of the cell cycle, and induced apoptosis in the cells. Concurrently, maduramicin downregulated protein expression of cyclin D1, cyclin-dependent kinases (CDK4 and CDK6), and CDC25A, and upregulated expression of the CDK inhibitors (p21Cip1 and p27Kip1), resulting in decreased phosphorylation of Rb. Maduramicin also induced expression of BAK, BAD, DR4, TRADD and TRAIL, leading to activation of caspases 8, 9 and 3 as well as cleavage of poly ADP ribose polymerase (PARP). Taken together, our results suggest that maduramicin executes its toxicity in myoblasts at least by inhibiting cell proliferation and inducing apoptotic cell death.
PMCID: PMC4274093  PMID: 25531367
3.  A Highly Selective and Sensitive Turn-On Fluorescent Chemosensor Based on Rhodamine 6G for Iron(III)** 
ChemistryOpen  2014;3(6):264-268.
Recently, more and more rhodamine derivatives have been used as fluorophores to construct sensors due to their excellent spectroscopic properties. A rhodamine-based fluorescent and colorimetric Fe3+ chemosensor 3’,6’-bis(ethylamino)-2-acetoxyl-2’,7’-dimethyl-spiro[1H-isoindole-1,9’-[9H]xanthen]-3(2H)-one (RAE) was designed and synthesized. Upon the addition of Fe3+, the dramatic enhancement of both fluorescence and absorbance intensity, as well as the color change of the solution, could be observed. The detection limit of RAE for Fe3+ was around 7.98 ppb. Common coexistent metal ions showed little or no interference in the detection of Fe3+. Moreover, the addition of CN− could quench the fluorescence of the acetonitrile solution of RAE and Fe3+, indicating the regeneration of the chemosensor RAE. The robust nature of the sensor was shown by the detection of Fe3+ even after repeated rounds of quenching. As iron is a ubiquitous metal in cells and plays vital roles in many biological processes, this chemosensor could be developed to have applications in biological studies.
PMCID: PMC4280826  PMID: 25558445
chemosensors; fluorescence; iron(III); rhodamine; selective response
4.  Fusarochromanone Induces G1 Cell Cycle Arrest and Apoptosis in COS7 and HEK293 Cells 
PLoS ONE  2014;9(11):e112641.
Fusarochromanone (FC101), a mycotoxin produced by the fungus Fusarium equiseti, is frequently observed in the contaminated grains and feedstuffs, which is toxic to animals and humans. However, the underlying molecular mechanism remains to be defined. In this study, we found that FC101 inhibited cell proliferation and induced cell death in COS7 and HEK293 cells in a concentration-dependent manner. Flow cytometric analysis showed that FC101 induced G1 cell cycle arrest and apoptosis in the cells. Concurrently, FC101 downregulated protein expression of cyclin D1, cyclin-dependent kinases (CDK4 and CDK6), and Cdc25A, and upregulated expression of the CDK inhibitors (p21Cip1 and p27Kip1), resulting in hypophosphorylation of Rb. FC101 also inhibited protein expression of Bcl-2, Bcl-xL, Mcl-1 and survivin, and induced expression of BAD, leading to activation of caspase 3 and cleavage of PARP, indicating caspase-dependent apoptosis. However, Z-VAD-FMK, a pan-caspase inhibitor, only partially prevented FC101-induced cell death, implying that FC101 may induce cell death through both caspase-dependent and -independent mechanisms. Our results support the notion that FC101 executes its toxicity at least by inhibiting cell proliferation and inducing cell death.
PMCID: PMC4226581  PMID: 25384025
5.  Schisandra Chinensis Baill, A Chinese Medicinal Herb, Alleviates High-Fat-Diet-Inducing Non-Alcoholic Steatohepatitis in Rats 
he present study aims to explore whether Schisandra chinensis Baill, a Chinese, medicinal herb can alleviates high-fat-diet-inducing non-alcoholic steatohepatitis in rats.
Materials and Methods
In the study, 24, male Wister rats with body weight between 180-220g, were included. The rats were randomly divided into four groups: model group, normal control group, rosiglitazone group, and Schisandra chinensis Baill group. The treatment lasted for 56, days. The high-fat diet used in the present study includes 25% lard, 2%, cholesterol 0.5%, sodium cholate, and 25%, Tween-80. The hepatic levels of superoxide dismutase (SOD), and malondialdehyde (MDA); the serum levels of total cholesterol (TC), and low-density lipoprotein cholesterol (LDLC), were detected.
We found that the hepatic levels of SOD were significantly lower, and the serum levels of TC, LDLC as well as, the hepatic levels of MDA in model group were significantly higher than those of normal control group; rosiglitazone group and Schisandra chinensis Baill group (P<0.05), indicates that non-alcoholic steatohepatitis rats were successfully induced by high-fat diet. Schisandra chinensis Baill group presented a significant lower serum levels of LDLC, than rosiglitazone group (P<0.05); and the hepatic levels of SOD in Schisandra chinensis Baill group were significantly lower than rosiglitazone group (P<0.05). However, no significant difference existed between Schisandra chinensis Baill group, and rosiglitazone group on the hepatic levels of MDA and the serum levels of TC (P>0.05).
It is then concluded that Schisandra chinensis Baill can significantly alleviate the non-alcoholic steatohepatitis of the rats induced by high-fat diet, and it may be used as a complementary therapy for rosiglitazone.
PMCID: PMC3957269  PMID: 24653581
Non-alcoholic steatohepatitis; high-fat diet; Schisandra chinensis Baill
6.  Biological activities of fusarochromanone: a potent anti-cancer agent 
BMC Research Notes  2014;7(1):601.
Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity.
Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT cell lines as evidenced by cell cycle profile analysis. In a mouse xenograft SCC tumor model, FC101 was well tolerated, non-toxic, and achieved a 30% reduction in tumor size at a dose of 8 mg/kg/day. FC101 is also a potent anti-angiogenenic agent. At nanomolar doses, FC101 inhibits the vascular endothelial growth factor-A (VEGF-A)-mediated proliferation of endothelial cells.
Our data presented here indicates that FC101 is an excellent lead candidate for a small molecule anti-cancer agent that simultaneously affects angiogenesis signaling, cancer signal transduction, and apoptosis. Further understanding of the underlying FC101’s molecular mechanism may lead to the design of novel targeted and selective therapeutics, both of which are pursued targets in cancer drug discovery.
PMCID: PMC4168212  PMID: 25187308
Pro-apoptotic; Anti-cancer; Anti-angiogenic; Small bioactive molecule; Fusarochromanone
7.  A Medical Manipulator System with Lasers in Photodynamic Therapy of Port Wine Stains 
BioMed Research International  2014;2014:384646.
Port wine stains (PWS) are a congenital malformation and dilation of the superficial dermal capillary. Photodynamic therapy (PDT) with lasers is an effective treatment of PWS with good results. However, because the laser density is uneven and nonuniform, the treatment is carried out manually by a doctor thus providing little accuracy. Additionally, since the treatment of a single lesion can take between 30 and 60 minutes, the doctor can become fatigued after only a few applications. To assist the medical staff with this treatment method, a medical manipulator system (MMS) was built to operate the lasers. The manipulator holds the laser fiber and, using a combination of active and passive joints, the fiber can be operated automatically. In addition to the control input from the doctor over a human-computer interface, information from a binocular vision system is used to guide and supervise the operation. Clinical results are compared in nonparametric values between treatments with and without the use of the MMS. The MMS, which can significantly reduce the workload of doctors and improve the uniformity of laser irradiation, was safely and helpfully applied in PDT treatment of PWS with good therapeutic results.
PMCID: PMC4181501  PMID: 25302297
8.  A Unique Mono- and Diacylglycerol Lipase from Penicillium cyclopium: Heterologous Expression, Biochemical Characterization and Molecular Basis for Its Substrate Selectivity 
PLoS ONE  2014;9(7):e102040.
A cDNA gene encoding a mature peptide of the mono- and diacylglycerol lipase (abbreviated to PcMdl) from Penicillium cyclopium PG37 was cloned and expressed in Pichia pastoris GS115. The recombinant PcMdl (rePcMdl) with an apparent molecular weight of 39 kDa showed the highest activity (40.5 U/mL of culture supernatant) on 1,2-dibutyrin substrate at temperature 35°C and pH 7.5. The rePcMdl was stable at a pH range of 6.5–9.5 and temperatures below 35°C. The activity of rePcMdl was inhibited by Hg2+ and Fe3+, but not significantly affected by EDTA or the other metal ions such as Na+, K+, Li+, Mg2+, Zn2+, Ca2+, Mn2+, Cu2+, and Fe2+. PcMdl was identified to be strictly specific to mono- and diacylglycerol, but not triacylglycerol. Stereographic view of PcMdl docked with substrate (tri- or diacylglycerol) analogue indicated that the residue Phe256 plays an important role in conferring the substrate selectivity. Phe256 projects its side chain towards the substrate binding groove and makes the sn-1 moiety difficult to insert in. Furthermore, sn-1 moiety prevents the phosphorus atom (substitution of carboxyl carbon) from getting to the Oγ of Ser145, which results in the failure of triacylglycerol hydrolysis. These results should provide a basis for molecular engineering of PcMdl and expand its applications in industries.
PMCID: PMC4106778  PMID: 25051359
9.  AtPRK2 Promotes ROP1 Activation via RopGEFs in the Control of Polarized Pollen Tube Growth 
Molecular Plant  2012;6(4):1187-1201.
The ROP1 GTPase-based signaling network controls tip growth in Arabidopsis pollen tubes. Our previous studies imply that ROP1 might be directly activated by RopGEF1, which belongs to a plant-specific family of Rho guanine nucleotide exchange factors (RopGEFs) and in turn may be activated by an unknown factor through releasing RopGEF1’s auto-inhibition. In this study, we found that RopGEF1 forms a complex with ROP1 and AtPRK2, a receptor-like protein kinase previously shown to interact with RopGEFs. AtPRK2 phosphorylated RopGEF1 in vitro and the atprk1,2,5 triple mutant showed defective pollen tube growth, similar to the phenotype of the ropgef1,9,12,14 quadruple mutant. Overexpression of a dominant negative form of AtPRK2 (DN-PRK2) inhibited pollen germination in Arabidopsis and reduced pollen elongation in tobacco. The DN-PRK2-induced pollen germination defect was rescued by overexpressing a constitutively active form of RopGEF1, RopGEF1(90–457), implying that RopGEF1 acts downstream of AtPRK2. Moreover, AtPRK2 increased ROP1 activity at the apical plasma membrane whereas DN-PRK2 reduced ROP1 activity. Finally, two mutations at the C-terminal putative phosphorylation sites of RopGEF1 (RopGEF1S460A and RopGEF1S480A) eliminated the function of RopGEF1 in vivo. Taken together, our results support the hypothesis that AtPRK2 acts as a positive regulator of the ROP1 signaling pathway most likely by activating RopGEF1 through phosphorylation.
PMCID: PMC3888354  PMID: 23024212
AtPRK2; RopGEF1; ROP GTPase; auto-inhibition; polarity growth.
10.  Exploring the Polyadenylated RNA Virome of Sweet Potato through High-Throughput Sequencing 
PLoS ONE  2014;9(6):e98884.
Viral diseases are the second most significant biotic stress for sweet potato, with yield losses reaching 20% to 40%. Over 30 viruses have been reported to infect sweet potato around the world, and 11 of these have been detected in China. Most of these viruses were detected by traditional detection approaches that show disadvantages in detection throughput. Next-generation sequencing technology provides a novel, high sensitive method for virus detection and diagnosis.
Methodology/Principal Findings
We report the polyadenylated RNA virome of three sweet potato cultivars using a high throughput RNA sequencing approach. Transcripts of 15 different viruses were detected, 11 of which were detected in cultivar Xushu18, whilst 11 and 4 viruses were detected in Guangshu 87 and Jingshu 6, respectively. Four were detected in sweet potato for the first time, and 4 were found for the first time in China. The most prevalent virus was SPFMV, which constituted 88% of the total viral sequence reads. Virus transcripts with extremely low expression levels were also detected, such as transcripts of SPLCV, CMV and CymMV. Digital gene expression (DGE) and reverse transcription polymerase chain reaction (RT-PCR) analyses showed that the highest viral transcript expression levels were found in fibrous and tuberous roots, which suggest that these tissues should be optimum samples for virus detection.
A total of 15 viruses were presumed to present in three sweet potato cultivars growing in China. This is the first insight into the sweet potato polyadenylated RNA virome. These results can serve as a basis for further work to investigate whether some of the 'new' viruses infecting sweet potato are pathogenic.
PMCID: PMC4047073  PMID: 24901789
11.  Acetobixan, an Inhibitor of Cellulose Synthesis Identified by Microbial Bioprospecting 
PLoS ONE  2014;9(4):e95245.
In plants, cellulose biosynthesis is an essential process for anisotropic growth and therefore is an ideal target for inhibition. Based on the documented utility of small-molecule inhibitors to dissect complex cellular processes we identified a cellulose biosynthesis inhibitor (CBI), named acetobixan, by bio-prospecting among compounds secreted by endophytic microorganisms. Acetobixan was identified using a drug-gene interaction screen to sift through hundreds of endophytic microbial secretions for one that caused synergistic reduction in root expansion of the leaky AtcesA6prc1-1 mutant. We then mined this microbial secretion for compounds that were differentially abundant compared with Bacilli that failed to mimic CBI action to isolate a lead pharmacophore. Analogs of this lead compound were screened for CBI activity, and the most potent analog was named acetobixan. In living Arabidopsis cells visualized by confocal microscopy, acetobixan treatment caused CESA particles localized at the plasma membrane (PM) to rapidly re-localize to cytoplasmic vesicles. Acetobixan inhibited 14C-Glc uptake into crystalline cellulose. Moreover, cortical microtubule dynamics were not disrupted by acetobixan, suggesting specific activity towards cellulose synthesis. Previous CBI resistant mutants such as ixr1-2, ixr2-1 or aegeus were not cross resistant to acetobixan indicating that acetobixan targets a different aspect of cellulose biosynthesis.
PMCID: PMC3991599  PMID: 24748166
12.  Mutation Spectrum of Six Genes in Chinese Phenylketonuria Patients Obtained through Next-Generation Sequencing 
PLoS ONE  2014;9(4):e94100.
The identification of gene variants plays an important role in the diagnosis of genetic diseases.
Methodology/Principal Findings
To develop a rapid method for the diagnosis of phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency, we designed a multiplex, PCR-based primer panel to amplify all the exons and flanking regions (50 bp average) of six PKU-associated genes (PAH, PTS, GCH1, QDPR, PCBD1 and GFRP). The Ion Torrent Personal Genome Machine (PGM) System was used to detect mutations in all the exons of these six genes. We tested 93 DNA samples from blood specimens from 35 patients and their parents (32 families) and 26 healthy adults. Using strict bioinformatic criteria, this sequencing data provided, on average, 99.14% coverage of the 39 exons at more than 70-fold mean depth of coverage. We found 23 previously documented variants in the PAH gene and six novel mutations in the PAH and PTS genes. A detailed analysis of the mutation spectrum of these patients is described in this study.
These results were confirmed by Sanger sequencing. In conclusion, benchtop next-generation sequencing technology can be used to detect mutations in monogenic diseases and can detect both point mutations and indels with high sensitivity, fidelity and throughput at a lower cost than conventional methods in clinical applications.
PMCID: PMC3976377  PMID: 24705691
13.  Scanning of Transposable Elements and Analyzing Expression of Transposase Genes of Sweet Potato [Ipomoea batatas] 
PLoS ONE  2014;9(3):e90895.
Transposable elements (TEs) are the most abundant genomic components in eukaryotes and affect the genome by their replications and movements to generate genetic plasticity. Sweet potato performs asexual reproduction generally and the TEs may be an important genetic factor for genome reorganization. Complete identification of TEs is essential for the study of genome evolution. However, the TEs of sweet potato are still poorly understood because of its complex hexaploid genome and difficulty in genome sequencing. The recent availability of the sweet potato transcriptome databases provides an opportunity for discovering and characterizing the expressed TEs.
Methodology/Principal Findings
We first established the integrated-transcriptome database by de novo assembling four published sweet potato transcriptome databases from three cultivars in China. Using sequence-similarity search and analysis, a total of 1,405 TEs including 883 retrotransposons and 522 DNA transposons were predicted and categorized. Depending on mapping sets of RNA-Seq raw short reads to the predicted TEs, we compared the quantities, classifications and expression activities of TEs inter- and intra-cultivars. Moreover, the differential expressions of TEs in seven tissues of Xushu 18 cultivar were analyzed by using Illumina digital gene expression (DGE) tag profiling. It was found that 417 TEs were expressed in one or more tissues and 107 in all seven tissues. Furthermore, the copy number of 11 transposase genes was determined to be 1–3 copies in the genome of sweet potato by Real-time PCR-based absolute quantification.
Our result provides a new method for TE searching on species with transcriptome sequences while lacking genome information. The searching, identification and expression analysis of TEs will provide useful TE information in sweet potato, which are valuable for the further studies of TE-mediated gene mutation and optimization in asexual reproduction. It contributes to elucidating the roles of TEs in genome evolution.
PMCID: PMC3946583  PMID: 24608103
14.  Beating in a dish: new hopes for cardiomyocyte regeneration 
Cell Research  2012;23(3):314-316.
PMCID: PMC3587704  PMID: 23184058
15.  Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes 
Protein & Cell  2014;5(1):59-68.
With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT+) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types.
Electronic supplementary material
The online version of this article (doi:10.1007/s13238-013-0016-x) contains supplementary material, which is available to authorized users.
PMCID: PMC3938846  PMID: 24474197
human cardiomyocyte; DNA methylation; microarray; heart development
16.  Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes 
Protein & Cell  2014;5(1):59-68.
With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT+) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types.
Electronic supplementary material
The online version of this article (doi:10.1007/s13238-013-0016-x) contains supplementary material, which is available to authorized users.
PMCID: PMC3938846  PMID: 24474197
human cardiomyocyte; DNA methylation; microarray; heart development
17.  Cellulose Synthesis and Its Regulation 
Cellulose, the most abundant biopolymer synthesized on land, is made of linear chains of ß (1–4) linked D-glucose. As a major structural component of the cell wall, cellulose is important not only for industrial use but also for plant growth and development. Cellulose microfibrils are tethered by other cell wall polysaccharides such as hemicellulose, pectin, and lignin. In higher plants, cellulose is synthesized by plasma membrane-localized rosette cellulose synthase complexes. Despite the recent advances using a combination of molecular genetics, live cell imaging, and spectroscopic tools, many aspects of the cellulose synthesis remain a mystery. In this chapter, we highlight recent research progress towards understanding the mechanism of cellulose synthesis in Arabidopsis.
PMCID: PMC3894906  PMID: 24465174
18.  Dissecting the molecular mechanism underlying the intimate relationship between cellulose microfibrils and cortical microtubules 
A central question in plant cell development is how the cell wall determines directional cell expansion and therefore the final shape of the cell. As the major load-bearing component of the cell wall, cellulose microfibrils are laid down transversely to the axis of elongation, thus forming a spring-like structure that reinforces the cell laterally and while favoring longitudinal expansion in most growing cells. Mounting evidence suggests that cortical microtubules organize the deposition of cellulose microfibrils, but the precise molecular mechanisms linking microtubules to cellulose organization have remained unclear until the recent discovery of cellulose synthase interactive protein 1 , a linker protein between the cortical microtubules and the cellulose biosynthesizing machinery. In this review, we will focus on the intimate relationship between cellulose microfibrils and cortical microtubules, in particular, we will discuss microtubule arrangement and cell wall architecture, the linkage between cellulose synthase complexes and microtubules, and the feedback mechanisms between cell wall and microtubules.
PMCID: PMC3952479  PMID: 24659994
cellulose synthase complex; cell wall; microtubules; CESA interactive proteins; cell expansion
19.  4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation 
Mediators of Inflammation  2013;2013:329740.
Chronic inflammatory diseases such as periodontitis have been associated with increased risk for various medical conditions including diabetes and cardiovascular disease. Endotoxin (lipopolysaccharide, LPS), derived from gram-negative periodonto-pathogens, can induce the local accumulation of mononuclear cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix metalloproteinases (MMPs). This ultimately results in the destruction of periodontal connective tissues including alveolar bone. Curcumin is the principal dyestuff in the popular Indian spice turmeric and has significant regulatory effects on inflammatory mediators but is characterized by poor solubility and low bioactivity. Recently, we developed a series of chemically modified curcumins (CMCs) with increased solubility and zinc-binding activity, while retaining, or further enhancing, their therapeutic effects. In the current study, we demonstrate that a novel CMC (CMC 2.5: 4-methoxycarbonyl curcumin) has significant inhibitory effects, better than the parent compound curcumin, on proinflammatory cytokines and MMPs in in vitro, in cell culture, and in an animal model of periodontal inflammation. The therapeutic potential of CMC 2.5 and its congeners may help to prevent tissue damage during various chronic inflammatory diseases including periodontitis and may reduce the risks of systemic diseases associated with this local disorder.
PMCID: PMC3886587  PMID: 24453415
20.  LncRNA Pathway Involved in Premature Preterm Rupture of Membrane (PPROM): An Epigenomic Approach to Study the Pathogenesis of Reproductive Disorders 
PLoS ONE  2013;8(11):e79897.
Preterm birth (PTB) is a live birth delivered before 37 weeks of gestation (GW). About one-third of PTBs result from the preterm premature rupture of membranes (PPROM). Up to the present, the pathogenic mechanisms underlying PPROM are not clearly understood. Here, we investigated the differential expression of long chain non-coding RNAs (lncRNAs) in placentas of PTBs with PPROM, and their possible involvement in the pathogenic pathways leading to PPROM. A total number of 1954, 776, and 1050 lncRNAs were identified with a microarray from placentas of PPROM (group A), which were compared to full-term birth (FTB) (group B), PTB (group C), and premature rupture of membrane (PROM) (group D) at full-term, respectively. Instead of investigating the individual pathogenic role of each lncRNA involved in the molecular mechanism underlying PPROM, we have focused on investigating the metabolic pathways and their functions to explore what is the likely association and how they are possibly involved in the development of PPROM. Six groups, including up-regulation and down-regulation in the comparisons of A vs. B, A vs. C, and A vs. D, of pathways were analyzed. Our results showed that 22 pathways were characterized as up-regulated 7 down-regulated in A vs. C, 18 up-regulated and 15 down-regulated in A vs. D, and 33 up-regulated and 7 down-regulated in A vs. B. Functional analysis showed pathways of infection and inflammatory response, ECM-receptor interactions, apoptosis, actin cytoskeleton, and smooth muscle contraction are the major pathogenic mechanisms involved in the development of PPROM. Characterization of these pathways through identification of lncRNAs opened new avenues for further investigating the epigenomic mechanisms of lncRNAs in PPROM as well as PTB.
PMCID: PMC3842261  PMID: 24312190
21.  Polarized linewidth-controllable double-trapping electromagnetically induced transparency spectra in a resonant plasmon nanocavity 
Scientific Reports  2013;3:2879.
Surface plasmons with ultrasmall optical mode volume and strong near field enhancement can be used to realize nanoscale light-matter interaction. Combining surface plasmons with the quantum system provides the possibility of nanoscale realization of important quantum optical phenomena, including the electromagnetically induced transparency (EIT), which has many applications in nonlinear quantum optics and quantum information processing. Here, using a custom-designed resonant plasmon nanocavity, we demonstrate polarized position-dependent linewidth-controllable EIT spectra at the nanoscale. We analytically obtain the double coherent population trapping conditions in a double-Λ quantum system with crossing damping, which give two transparent points in the EIT spectra. The linewidths of the three peaks are extremely sensitive to the level spacing of the excited states, the Rabi frequencies and detunings of pump fields, and the Purcell factors. In particular the linewidth of the central peak is exceptionally narrow. The hybrid system may have potential applications in ultra-compact plasmon-quantum devices.
PMCID: PMC3791453  PMID: 24096943
22.  Gametogenesis in a dish 
Cell Research  2012;22(10):1422-1425.
Recent progress in the induced pluripotent stem cell (iPSC) field as well as the establishment of germline stem cell isolation and culture methodologies may provide an in vitro platform for the study of physiological and pathological human gamete development and open new avenues for cell replacement-based personalized treatment of infertility.
PMCID: PMC3463271  PMID: 22641372
23.  Microbial Carriage State of Peripheral Blood Dendritic cells (DCs) in Chronic Periodontitis Influences DC Differentiation, Atherogenic Potential† 
The low grade oral infection chronic periodontitis (CP) has been implicated in coronary artery disease risk, but the mechanisms are unclear. Here, a pathophysiological role for blood dendritic cells (DCs) in systemic dissemination of oral mucosal pathogens to atherosclerotic plaques was investigated in humans. The frequency and microbiome of CD19−BDCA-1+DC-SIGN+ blood myeloid DCs (mDCs) were analyzed in CP subjects with, or without existing acute coronary syndrome (ACS) and in healthy controls (CTL). FACS analysis revealed a significant increase in blood mDCs in the following order: CTL
PMCID: PMC3459682  PMID: 22891282
blood dendritic cells; Porphyromonas gingivalis; atherosclerosis; chronic periodontitis; acute coronary syndrome
When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia, it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy. Here we describe a patient with a progressive dysplastic lesion in the common bile duct, which developed from moderate-high to high-grade dysplasia in approximately 2 mo. The patient refused major surgery. Therefore, endoscopic-assisted photodynamic therapy was performed. The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic. This report is the first to describe the successful treatment of high-grade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.
PMCID: PMC3761116  PMID: 24023506
Photodynamic therapy; Common bile duct; High-grade dysplasia; Choledochoscope
Plant Signaling & Behavior  2013;8(3):e23179.
In higher plants, cellulose is synthesized by cellulose synthase complexes, which contain multiple isoforms of cellulose synthases (CESAs). Among the total 10 CESA genes in Arabidopsis, recessive mutations at three of them cause the collapse of mature xylem cells in inflorescence stems of Arabidopsis (irx1cesa8, irx3cesa7 and irx5cesa4). These CESA genes are considered secondary cell wall CESAs. The others (the function CESA10 is still unknown) are thought to be specialized for cellulose synthesis in the primary cell wall. A split-ubiquitin membrane yeast two-hybrid system was used to assess interactions among four primary CESAs (CESA1, CESA2, CESA3, CESA6) and three secondary CESAs (CESA4, CESA7, CESA8). Our results showed that primary CESAs could physically interact with secondary CESAs in a limited fashion. Analysis of transgenic lines showed that CESA1 could partially rescue irx1cesa8 null mutants, resulting in complementation of the plant growth defect, collapsed xylem and cellulose content deficiency. These results suggest that mixed primary and secondary CESA complexes are functional using experimental set-ups.
PMCID: PMC3676487  PMID: 23299322
cellulose; cellulose synthase complex (CSC); primary cell wall; secondary cell wall; promoter swap

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