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1.  KISS1 methylation and expression as predictors of disease progression in colorectal cancer patients 
World Journal of Gastroenterology : WJG  2014;20(29):10071-10081.
AIM: To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer (CRC) and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target.
METHODS: KISS1 promoter methylation, mRNA expression and protein expression were detected by methylation-specific polymerase chain reaction (PCR), real-time quantitative PCR and Western blotting, respectively, in 126 CRC tissues and 142 normal colorectal tissues. Human CRC cells with KISS1 promoter hypermethylation and poor KISS1 expression were treated in vitro with 5-aza-2’-deoxycytidine (5-Aza-CdR). After treatment, KISS1 promoter methylation, KISS1 mRNA and protein expression and cell migration and invasion were evaluated.
RESULTS: Hypermethylation of KISS1 occurred frequently in CRC samples (83.1%, 105/126), but was infrequent in normal colorectal tissues (6.34%, 9/142). Moreover, KISS1 methylation was associated with tumor differentiation, the depth of invasion, lymph node metastasis and distant metastasis (P < 0.001). KISS1 methylation was also associated with low KISS1 expression (P < 0.001). Furthermore, we observed re-expression of the KISS1 gene and decreased cell migration after 5-Aza-CdR treatment in a CRC cell line.
CONCLUSION: These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC.
doi:10.3748/wjg.v20.i29.10071
PMCID: PMC4123336  PMID: 25110434
Colorectal cancer; KISS1; Methylation; 5-aza-2’-deoxycytidine; Metastasis
2.  Real-Time Hand Gesture Recognition Using Finger Segmentation 
The Scientific World Journal  2014;2014:267872.
Hand gesture recognition is very significant for human-computer interaction. In this work, we present a novel real-time method for hand gesture recognition. In our framework, the hand region is extracted from the background with the background subtraction method. Then, the palm and fingers are segmented so as to detect and recognize the fingers. Finally, a rule classifier is applied to predict the labels of hand gestures. The experiments on the data set of 1300 images show that our method performs well and is highly efficient. Moreover, our method shows better performance than a state-of-art method on another data set of hand gestures.
doi:10.1155/2014/267872
PMCID: PMC4099175  PMID: 25054171
3.  Enantioselective Syntheses of FR901464 and Spliceostatin A: Potent Inhibitors of Spliceosome 
Organic letters  2013;15(19):10.1021/ol4024634.
Enantioselective syntheses of FR901464 and Spliceostatin A, potent spliceosome inhibitors are described. The synthesis of FR901464 has been accomplished in a convergent manner in 10 linear steps (20 total steps). The synthesis of the A-tetrahydropyran ring was constructed from (R)-isopropylidene glyceraldehyde. The functionalized tetrahydropyran B-ring was synthesized utilizing a Corey-Bakshi-Shibata reduction, an Achmatowicz reaction, and a stereoselective Michael addition as the key steps. Coupling of A- and B-ring fragments was accomplished via cross-metathesis.
doi:10.1021/ol4024634
PMCID: PMC3827971  PMID: 24050251
4.  Characterization of Interstitial Cajal Progenitors Cells and Their Changes in Hirschsprung’s Disease 
PLoS ONE  2014;9(1):e86100.
Interstitial cells of Cajal (ICC) are critical to gastrointestinal motility. The phenotypes of ICC progenitors have been observed in the mouse gut, but whether they exist in the human colon and what abnormal changes in their quantity and ultrastructure are present in Hirschsprung’s disease (HSCR) colon remains uncertain. In this study, we collected the surgical resection of colons, both proximal and narrow segments, from HSCR patients and normal controls. First, we identified the progenitor of ICC in normal adult colon using immunofluorescent localization techniques with laser confocal microscopy. Next, the progenitors were sorted to observe their morphology. We further applied flow cytometry to examine the content of ICC progenitors in these fresh samples. The ultrastructural changes in the narrow and proximal parts of the HSCR colon were observed using transmission electron microscopy (TEM) and were compared with the normal adult colon. The presumed early progenitor (c-KitlowCD34+Igf1r+) and committed progenitor (c-Kit+CD34+Igf1r+) of ICC exist in adult normal colon as well as in the narrow and proximal parts of the HSCR colon. However, the proportions of mature, early and committed progenitors of ICC were dramatically reduced in the narrow segment of the HSCR colon. The proportions of mature and committed progenitors of ICC in the proximal segment of the HSCR colon were lower than in the adult normal colon. Ultrastructurally, ICC, enteric nerves, and smooth muscle in the narrow segment of the HSCR colon showed severe injury, including swollen vacuola or ted mitochondria, disappearance of mitochondrial cristae, dilated rough endoplasmic reticulum, vesiculation and degranulation, and disappearance of the caveolae on the ICC membrane surface. The contents of ICC and its progenitors in the narrow part of the HSCR colon were significantly decreased than those of adult colon, which may be associated with HSCR pathogenesis.
doi:10.1371/journal.pone.0086100
PMCID: PMC3901676  PMID: 24475076
5.  Prevention of allergic airway hyperresponsiveness and remodeling in mice by Astragaliradix Antiasthmatic decoction 
Background
Astragali radix Antiasthmatic Decoction (AAD), a traditional Chinese medication, is found effective in treating allergic diseases and chronic cough. The purpose of this study is to determine whether this medication could suppress allergen-induced airway hyperresponsiveness (AHR) and remodeling in mice, and its possible mechanisms.
Methods
A mouse model of chronic asthma was used to investigate the effects of AAD on the airway lesions. Mice were sensitized and challenged with ovalbumin (OVA), and the extent of AHR and airway remodeling were characterized. Cells and cytokines in the bronchoalveolar lavage fluid (BALF) were examined.
Results
AAD treatment effectively decreased OVA-induced AHR, eosinophilic airway inflammation, and collagen deposition around the airway. It significantly reduced the levels of IL-13 and TGF-β1, but exerted inconsiderable effect on INF-γ and IL-10.
Conclusions
AAD greatly improves the symptoms of allergic airway remodeling probably through inhibition of Th2 cytokines and TGF-β1.
doi:10.1186/1472-6882-13-369
PMCID: PMC3922862  PMID: 24367979
Astragalus Antiasthmatic Decoction; Airway hyperresponsiveness; Airway remodeling
6.  Characterization of Bacterial Polysaccharide Capsules and Detection in the Presence of Deliquescent Water by Atomic Force Microscopy 
We detected polysaccharide capsules from Zunongwangia profunda SM-A87 with atomic force microscopy (AFM). The molecular organization of the capsules at the single-polysaccharide-chain level was reported. Furthermore, we found that with ScanAsyst mode the polysaccharide capsules could be detected even in the presence of deliquescent water covering the capsule.
doi:10.1128/AEM.00207-12
PMCID: PMC3346466  PMID: 22344657
7.  Antimicrobial Peptide Trichokonin VI-Induced Alterations in the Morphological and Nanomechanical Properties of Bacillus subtilis 
PLoS ONE  2012;7(9):e45818.
Antimicrobial peptides are promising alternative antimicrobial agents compared to conventional antibiotics. Understanding the mode of action is important for their further application. We examined the interaction between trichokonin VI, a peptaibol isolated from Trichoderma pseudokoningii, and Bacillus subtilis, a representative Gram-positive bacterium. Trichokonin VI was effective against B. subtilis with a minimal inhibitory concentration of 25 µM. Trichokonin VI exhibited a concentration- and time-dependent effect against B. subtilis, which was studied using atomic force microscopy. The cell wall of B. subtilis collapsed and the roughness increased upon treatment with trichokonin VI. Nanoindentation experiments revealed a progressive decrease in the stiffness of the cells. Furthermore, the membrane permeabilization effect of trichokonin VI on B. subtilis was monitored, and the results suggest that the leakage of intracellular materials is a possible mechanism of action for trichokonin VI, which led to alterations in the morphological and nanomechanical properties of B. subtilis.
doi:10.1371/journal.pone.0045818
PMCID: PMC3458079  PMID: 23049870
8.  Autophagic Protein LC3B Confers Resistance against Hypoxia-induced Pulmonary Hypertension 
Rationale: Pulmonary hypertension (PH) is a progressive disease with unclear etiology. The significance of autophagy in PH remains unknown.
Objectives: To determine the mechanisms by which autophagic proteins regulate tissue responses during PH.
Methods: Lungs from patients with PH, lungs from mice exposed to chronic hypoxia, and human pulmonary vascular cells were examined for autophagy using electron microscopy and Western analysis. Mice deficient in microtubule-associated protein-1 light chain-3B (LC3B−/−), or early growth response-1 (Egr-1−/−), were evaluated for vascular morphology and hemodynamics.
Measurements and Main Results: Human PH lungs displayed elevated lipid-conjugated LC3B, and autophagosomes relative to normal lungs. These autophagic markers increased in hypoxic mice, and in human pulmonary vascular cells exposed to hypoxia. Egr-1, which regulates LC3B expression, was elevated in PH, and increased by hypoxia in vivo and in vitro. LC3B−/− or Egr-1−/−, but not Beclin 1+/−, mice displayed exaggerated PH during hypoxia. In vitro, LC3B knockdown increased reactive oxygen species production, hypoxia-inducible factor-1α stabilization, and hypoxic cell proliferation. LC3B and Egr-1 localized to caveolae, associated with caveolin-1, and trafficked to the cytosol during hypoxia.
Conclusions: The results demonstrate elevated LC3B in the lungs of humans with PH, and of mice with hypoxic PH. The increased susceptibility of LC3B−/− and Egr-1−/− mice to hypoxia-induced PH and increased hypoxic proliferation of LC3B knockdown cells suggest adaptive functions of these proteins during hypoxic vascular remodeling. The results suggest that autophagic protein LC3B exerts a protective function during the pathogenesis of PH, through the regulation of hypoxic cell proliferation.
doi:10.1164/rccm.201005-0746OC
PMCID: PMC3081281  PMID: 20889906
autophagy; hypoxia; hypertension, pulmonary
9.  Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease 
PLoS ONE  2008;3(10):e3316.
Background
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.
Methodology and Principal Findings
Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1−/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.
Conclusions
We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.
doi:10.1371/journal.pone.0003316
PMCID: PMC2552992  PMID: 18830406
10.  Identifying targets for COPD treatment through gene expression analyses 
Despite the status of chronic obstructive pulmonary disease (COPD) as a major global health problem, no currently available therapies can limit COPD progression. Therefore, an urgent need exists for the development of new and effective treatments for COPD. An improved understanding in the molecular pathogenesis of COPD can potentially identify molecular targets to facilitate the development of new therapeutic modalities. Among the best approaches for understanding the molecular basis of COPD include gene expression profiling techniques, such as serial analysis of gene expression or microarrays. Using these methods, recent studies have mapped comparative gene expression profiles of lung tissues from patients with different stages of COPD relative to healthy smokers or non-smokers. Such studies have revealed a number of differentially-regulated genes associated with COPD progression, which include genes involved in the regulation of inflammation, extracellular matrix, cytokines, chemokines, apoptosis, and stress responses. These studies have shed new light on the molecular mechanisms of COPD, and suggest novel targets for clinical treatments.
PMCID: PMC2629979  PMID: 18990963
COPD; gene expression; therapeutic targets

Results 1-10 (10)