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4.  Pathogenic and Obesogenic Factors Associated with Inflammation in Chinese Children, Adolescents and Adults 
Influenced by pathogen exposure and obesity, inflammation provides a critical biological pathway linking changing environments to the development of cardiometabolic disease. This study tests the relative contribution of obesogenic and pathogenic factors to moderate and acute CRP elevations in Chinese children, adolescents and adults.
Data come from 8795 participants in the China Health and Nutrition Study. Age-stratified multinomial logistic models were used to test the association between illness history, pathogenic exposures, adiposity, health behaviors and moderate (1-10 mg/L in children and 3-10 mg/L in adults) and acute (>10mg/L) CRP elevations, controlling for age, sex and clustering by household. Backward model selection was used to assess which pathogenic and obesogenic predictors remained independently associated with moderate and acute CRP levels when accounting for simultaneous exposures.
Overweight was the only significant independent risk factor for moderate inflammation in children (RRR 2.10, 95%CI 1.13-3.89). History of infectious (RRR 1.28, 95%CI 1.08-1.52) and non-communicable (RRR 1.37, 95%CI 1.12-1.69) disease, overweight (RRR 1.66, 95%CI 1.45-1.89) and high waist circumference (RRR 1.63, 95%CI 1.42-1.87) were independently associated with a greater likelihood of moderate inflammation in adults while history of infectious disease (RRR 1.87, 95%CI 1.35-2.56) and overweight (RRR 1.40, 95%CI 1.04-1.88) were independently associated with acute inflammation. Environmental pathogenicity was associated with a reduced likelihood of moderate inflammation, but a greater likelihood of acute inflammation in adults.
These results highlight the importance of both obesogenic and pathogenic factors in shaping inflammation risk in societies undergoing nutritional and epidemiological transitions.
PMCID: PMC3932143  PMID: 24123588
C-reactive protein; Inflammation; Obesity; Infectious Disease; China; Life course
5.  China in the period of transition from scarcity and extensive undernutrition to emerging nutrition-related noncommunicable diseases, 1949–1992 
This study uses unique official data to document nutritional changes in the 1949–1992 period. In 1949 widespread famine, high mortality, and low life expectancy dominated. Economic progress was uneven, however, the longer-term food supply changed greatly, and hunger was conquered. Diet composition shifted greatly over this period. Cereal consumption, already high, increased from 541.2 grams per day (70.0% coarse grains) in 1952 to 645.9 grams per day (15.9% coarse grains) in 1992. Consumption of animal-source foods, half of which were pork and pork products, tripled from 30.0 grams per day to 103.0 grams per day. The proportion of energy intake from fat tripled from 7.6% to 22.5%, and that from carbohydrates decreased from 83.0% to 65.8% over the same period. Physical activity was high in all domains, but shifts were beginning to occur (e.g., the initial mechanization of work and the expansion of biking). Nutritional improvement was uneven, including increased undernutrition in the 1959–1962 period and a remarkable rebound and continued improvement thereafter. Overweight emerged only after 1982. Shifts in diet, activity, and body composition in 1949–1992 set the stage for major shifts in nutrition in the subsequent decades.
PMCID: PMC3869002  PMID: 24341754
malnutrition; food insecurity; overweight; poverty; physical activity
6.  The China Health and Nutrition Survey, 1989–2011 
The China Health and Nutrition Survey (CHNS) began in 1989 with the goal of creating a multilevel method of data collection from individuals and households and their communities to understand how the wide-ranging social and economic changes in China affect a wide array of nutrition and health-related outcomes. Initiated with a partial sample in 1989, the full survey runs from 1991 to 2011, and this issue documents the CHNS history. The CHNS cohort includes new household formation and replacement communities and households; all household members are studied. Furthermore in-depth community data are collected. The sample began with eight provinces and added a ninth, Heilongjiang, in 1997 and three autonomous cities, Beijing, Shanghai, and Chongqing, in 2011. The in-depth community contextual measures have allowed us to create a unique measure of urbanicity that captures major dimensions of modernization across all 288 communities currently in the CHNS sample. The standardized, validated urbanicity measure captures the changes in 12 dimensions: population density; economic activity; traditional markets; modern markets; transportation infrastructure; sanitation; communications; housing; education; diversity; health infrastructure; and social services. Each is based on numerous measures applicable to each dimension. They are used jointly and separately in hundreds of studies.
PMCID: PMC3869031  PMID: 24341753
Longitudinal Survey; Urbanicity; China; Nutrition
7.  Proteogenomic analysis reveals unanticipated adaptations of colorectal tumor cells to deficiencies in DNA mismatch repair 
Cancer research  2013;74(1):387-397.
A growing body of genomic data on human cancers poses the critical question of how genomic variations translate to cancer phenotypes. We employed standardized shotgun proteomics and targeted protein quantitation platforms to analyze a panel of 10 colon cancer cell lines differing by mutations in DNA mismatch repair (MMR) genes. In addition, we performed transcriptome sequencing (RNA-seq) to enable detection of protein sequence variants from the proteomic data. Biological replicate cultures yielded highly consistent proteomic inventories with a cumulative total of 6,513 protein groups with a protein FDR of 3.17% across all cell lines. Networks of co-expressed proteins with differential expression based on MMR status revealed impact on protein folding, turnover and transport, on cellular metabolism and on DNA and RNA synthesis and repair. Analysis of variant amino acid sequences suggested higher stability of proteins affected by naturally occurring germline polymorphisms than of proteins affected by somatic protein sequence changes. The data provide evidence for multi-system adaptation to MMR deficiency with a stress response that targets misfolded proteins for degradation through the ubiquitin-dependent proteasome pathway. Enrichment analysis suggested epithelial-to-mesenchymal transition (EMT) in RKO cells, as evidenced by increased mobility and invasion properties compared to SW480. The observed proteomic profiles demonstrate previously unknown consequences of altered DNA repair and provide an expanded basis for mechanistic interpretation of MMR phenotypes.
PMCID: PMC3896054  PMID: 24247723
8.  The emergence of cardiometabolic disease risk in Chinese children and adults: consequences of changes in diet, physical activity, and obesity 
Strong secular declines in physical activity, increased fat and salt intake, and increased obesity, especially abdominal obesity, mark China's recent nutrition transition. The China Health and Nutrition 2009 Survey collected anthropometry, blood pressure, and fasting blood samples from more than 9,000 individuals ≥ seven years of age. We focus on elevated blood pressure and plasma markers of diabetes, inflammation, and dyslipidemia. We used international definitions of cardiometabolic risk and estimated age- and sex-specific prevalence ratios for each outcome for high waist circumference or overweight. We used logistic regression to assess each risk factor's association with diet, physical activity, overweight, and abdominal obesity. Cardiometabolic risk prevalence was high in all age groups Prevalence ratios for most risk factors were nearly doubled for overweight or high waist circumference groups. Prevalence ratios were higher in younger than older adults. Low physical activity consistently predicted higher cardiometabolic risk across most outcomes and age-sex groups. The co-occurrence of overweight and high waist circumference was highly predictive of dyslipidemia, elevated glycated hemoglobin, and diabetes. High prevalence of cardiometabolic risk factors and their strong association with weight status and abdominal obesity in young adults portend increases in cardiometabolic morbidity and mortality. Early interventions will be required to reverse trends.
PMCID: PMC3947601  PMID: 24341758
China; cardiometabolic risk; overweight; abdominal obesity; diet; physical activity
9.  RNA-seq data analysis at the gene and CDS levels provides a comprehensive view of transcriptome responses induced by 4-hydroxynonenal 
Molecular bioSystems  2013;9(12):10.1039/c3mb70114j.
Reactive electrophiles produced during oxidative stress, such as 4-hydroxynonenal (HNE), are increasingly recognized as contributing factors in a variety of degenerative and inflammatory diseases. Here we used the RNA-seq technology to characterize transcriptome responses in RKO cells induced by HNE at subcytotoxic and cytotoxic doses. RNA-seq analysis rediscovered most of the differentially expressed genes reported by microarray studies and also identified novel gene responses. Interestingly, differential expression detection at the coding DNA sequence (CDS) level helped to further improve the consistency between the two technologies, suggesting the utility and importance of the CDS level analysis. RNA-seq data analysis combining gene and CDS levels yielded an informative and comprehensive picture of gradually evolving response networks with increasing HNE doses, from cell protection against oxidative injury at low dose, initiation of cell apoptosis and DNA damage at middle dose and significant deregulation of cellular functions at high dose. These evolving dose-dependent pathway changes, which cannot be observed by the gene level analysis alone, clearly reveal the HNE cytotoxic effect and are supported by IC50 experiments. Additionally, differential expression at the CDS level provides new insights of isoform regulation mechanisms. Taken together, our data demonstrate the power of RNA-Seq to identify subtle transcriptome changes and to characterize effects induced by HNE through the generation of high-resolution data coupled with differential analysis at both gene and CDS levels.
PMCID: PMC3864034  PMID: 24056865
10.  3D conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma 
World Journal of Gastroenterology : WJG  2014;20(45):17227-17234.
AIM: To compare transcatheter arterial chemoembolization (TACE) and 3D conformal radiotherapy (3D-CRT) with TACE monotherapy in hepatocellular carcinoma (HCC).
METHODS: We searched all the eligible studies from the Cochrane Library, PubMed, Medline, Embase, and CNKI. The meta-analysis was performed to assess the survival benefit, tumor response, and the decline in α-fetoprotein (AFP) level. According to the heterogeneity of the studies, pooled OR with 95%CI were calculated using the fixed-effects or random-effects model. An observed OR > 1 indicated that the addition of 3D-CRT to TACE offered survival benefits to patients that could be considered statistically significant. Statistical analyses were performed using Review Manager Software.
RESULTS: Ten studies met the criteria to perform a meta-analysis including 908 HCC participants, with 400 patients in the TACE/3D-CRT combination group and 508 in the TACE alone group. TACE combined with 3D-CRT significantly improved 1-, 2- and 3-year overall survival compared with TACE monotherapy (OR = 1.87, 95%CI: 1.37-2.55, P < 0.0001), (OR = 2.38, 95%CI: 1.78-3.17, P < 0.00001) and (OR = 2.97, 95%CI: 2.10-4.21, P < 0.00001). In addition, TACE plus 3D-CRT was associated with a higher tumor response (complete remission and partial remission) (OR = 3.81; 95%CI: 2.70-5.37; P < 0.00001), and decline rates of AFP level (OR = 3.24, 95%CI: 2.09-5.02, P < 0.00001).
CONCLUSION: This meta-analysis demonstrated that TACE combined with 3D-CRT was better than TACE monotherapy for patients with HCC, which needs to be confirmed by large multicenter trials.
PMCID: PMC4258595  PMID: 25493039
Hepatocellular carcinoma; Chemoembolization; Three-dimensional conformal radiotherapy; Meta-analysis
11.  A Novel RNA Motif Mediates the Strict Nuclear Localization of a Long Noncoding RNA 
Molecular and Cellular Biology  2014;34(12):2318-2329.
The ubiquitous presence of long noncoding RNAs (lncRNAs) in eukaryotes points to the importance of understanding how their sequences impact function. As many lncRNAs regulate nuclear events and thus must localize to nuclei, we analyzed the sequence requirements for nuclear localization in an intergenic lncRNA named BORG (BMP2-OP1-responsive gene), which is both spliced and polyadenylated but is strictly localized in nuclei. Subcellular localization of BORG was not dependent on the context or level of its expression or decay but rather depended on the sequence of the mature, spliced transcript. Mutational analyses indicated that nuclear localization of BORG was mediated through a novel RNA motif consisting of the pentamer sequence AGCCC with sequence restrictions at positions −8 (T or A) and −3 (G or C) relative to the first nucleotide of the pentamer. Mutation of the motif to a scrambled sequence resulted in complete loss of nuclear localization, while addition of even a single copy of the motif to a cytoplasmically localized RNA was sufficient to impart nuclear localization. Further, the presence of this motif in other cellular RNAs showed a direct correlation with nuclear localization, suggesting that the motif may act as a general nuclear localization signal for cellular RNAs.
PMCID: PMC4054287  PMID: 24732794
12.  Kismet Positively Regulates Glutamate Receptor Localization and Synaptic Transmission at the Drosophila Neuromuscular Junction 
PLoS ONE  2014;9(11):e113494.
The Drosophila neuromuscular junction (NMJ) is a glutamatergic synapse that is structurally and functionally similar to mammalian glutamatergic synapses. These synapses can, as a result of changes in activity, alter the strength of their connections via processes that require chromatin remodeling and changes in gene expression. The chromodomain helicase DNA binding (CHD) protein, Kismet (Kis), is expressed in both motor neuron nuclei and postsynaptic muscle nuclei of the Drosophila larvae. Here, we show that Kis is important for motor neuron synaptic morphology, the localization and clustering of postsynaptic glutamate receptors, larval motor behavior, and synaptic transmission. Our data suggest that Kis is part of the machinery that modulates the development and function of the NMJ. Kis is the homolog to human CHD7, which is mutated in CHARGE syndrome. Thus, our data suggest novel avenues of investigation for synaptic defects associated with CHARGE syndrome.
PMCID: PMC4239079  PMID: 25412171
13.  High Speed Railway Environment Safety Evaluation Based on Measurement Attribute Recognition Model 
In order to rationally evaluate the high speed railway operation safety level, the environmental safety evaluation index system of high speed railway should be well established by means of analyzing the impact mechanism of severe weather such as raining, thundering, lightning, earthquake, winding, and snowing. In addition to that, the attribute recognition will be identified to determine the similarity between samples and their corresponding attribute classes on the multidimensional space, which is on the basis of the Mahalanobis distance measurement function in terms of Mahalanobis distance with the characteristics of noncorrelation and nondimensionless influence. On top of the assumption, the high speed railway of China environment safety situation will be well elaborated by the suggested methods. The results from the detailed analysis show that the evaluation is basically matched up with the actual situation and could lay a scientific foundation for the high speed railway operation safety.
PMCID: PMC4241704  PMID: 25435866
14.  Integrative genomics analysis identifies candidate drivers at 3q26-29 amplicon in squamous cell carcinoma of the lung 
Chromosome 3q26-29 is a critical region of genomic amplification in lung squamous cell carcinomas (SCCs). Identification of candidate drivers in this region could help uncover new mechanisms in the pathogenesis and potentially new targets in SCC of the lung.
Experimental Design
We performed a meta-analysis of seven independent data sets containing a total of 593 human primary SCC tumor samples to identify consensus candidate drivers in 3q26-29 amplicon. Through integrating protein-protein interaction network information, we further filtered for candidates that may function together in a network. Computationally predicted candidates were validated using RNAi knock down and cell viability assays. Clinical relevance of the experimentally supported drivers was evaluated in an independent cohort of 52 lung SCC tumors using survival analysis.
The meta-analysis identified 20 consensus candidates, among which four (SENP2, DCUN1D1, DVL3 and UBXN7) were involved in a small protein-protein interaction network. Knocking down any of the four proteins led to cell growth inhibition of the 3q26-29 amplified SCC. Moreover, knocking down of SENP2 resulted in the most significant cell growth inhibition and downregulation of DCUN1D1 and DVL3. Importantly, a gene expression signature composed of SENP2, DCUN1D1 and DVL3 stratified patients into subgroups with different response to adjuvant chemotherapy.
Together, our findings show that SENP2, DCUN1D1 and DVL3 are candidate driver genes in the 3q26-29 amplicon of SCC, providing novel insights into the molecular mechanisms of disease progression and may have significant implication in the management of SCC of the lung.
PMCID: PMC3807802  PMID: 23908357
lung squamous cell carcinoma; 3q26-29 amplicon; copy number alteration; integrative genomics; candidate drivers
15.  Malignant transformation of colonic epithelial cells by a colon-derived long noncoding RNA 
Biochemical and biophysical research communications  2013;440(1):10.1016/j.bbrc.2013.09.040.
Recent progress has been made in the identification of protein-coding genes and miRNAs that are expressed in and alter the behavior of colonic epithelia. However, the role of long non-coding RNAs (lncRNAs) in colonic homeostasis is just beginning to be explored. By gene expression profiling of post-mitotic, differentiated tops and proliferative, progenitor-compartment bottoms of microdissected adult mouse colonic crypts, we identified several lncRNAs more highly expressed in crypt bottoms. One identified lncRNA, designated non-coding Nras functional RNA (ncNRFR), resides within the Nras locus but appears to be independent of the Nras coding transcript. Stable overexpression of ncNRFR in non-transformed, conditionally immortalized mouse colonocytes results in malignant transformation, as determined by growth in soft agar and formation of highly invasive tumors in nude mice. Moreover, ncNRFR appears to inhibit the function of the tumor suppressor let-7. These results suggest precise regulation of ncNRFR is necessary for proper cell growth in the colonic crypt, and its misregulation results in neoplastic transformation.
PMCID: PMC3875348  PMID: 24045012
Progenitor cells; Non-coding RNA; Colon; Intestine; Colorectal cancer; let-7
16.  Fifteen Days Microgravity Causes Growth in Calvaria of Mice 
Bone  2013;56(2):290-295.
Bone remodeling may occur in spaceflight as a response to skeletal unloading and head-ward fluid shifts. While unloading causes significant loss of bone mass and density in legs of animals exposed to microgravity, increased blood and interstitial fluid flows accompanying microgravity-induced fluid redistribution may elicit an opposite effect in the head. Seven C57BL/6 mice were randomly chosen for exposure to 15 days of microgravity on the STS-131 mission, while eight littermates served as ground controls. Upon mission completion, all 15 mice calvariae were imaged on a micro-computed tomography scanner. A standardized rectangular volume was placed on the parietal bones of each calvaria for analyses, and three parameters were determined to measure increased parietal bone volume: bone volume (BV), cross-sectional thickness (CsTh), and tissue mineral density (TMD). Microgravity exposure caused a statistically significant increase in BV of the space flight (SF) group compared to the ground control (GC) group – the mean ± SD for SF group was 10.48 ± 0.47 %, compared to 9.64 ± 0.79 % for GC group (p<0.05). CsTh demonstrated a trend of increase from 0.099 ±0.006 mm in the GC group to 0.104 ±0.005 mm in the SF group (p=0.12). TMD was similar between the two groups with 0.878 ±0.029 g/cc for GC and 0.893 ± 0.028 g/cc for SF (p=0.31). Our results indicate that microgravity causes adaptive changes in calvarial bones that do not normally bear weight. These findings suggest that fluid shifts alone accompanying microgravity may initiate bone remodeling independent of skeletal loading by tissue.
PMCID: PMC4110898  PMID: 23791778
bone; adaptation; space; microgravity
17.  The Wuhan-Zhuhai (WHZH) cohort study of environmental air particulate matter and the pathogenesis of cardiopulmonary diseases: study design, methods and baseline characteristics of the cohort 
BMC Public Health  2014;14(1):994.
Particulate air pollution has been recognized to be associated with a wide range of adverse health effects, including increased mortality, morbidity, exacerbation of respiratory conditions. However, earlier physiological or pathological changes or long-term bodies’ reaction to air pollutants have not been studied in depth in China. The Wuhan-Zhuhai (WHZH) cohort study is designed to investigate the association between air pollutants exposure and physiological or pathological reactions on respiratory and cardiovascular system.
The cohort is a community-based prospective study that includes 4812 individuals aged 18–80 years. The collections of data were conducted from April to May 2011 in Wuhan city and in May 2012 in Zhuhai city. At baseline, data on demographic and socioeconomic information, occupational history, family disease history, lifestyle, cooking mode, daily travel mode, physical activity and living condition have been collected by questionnaires. Participants underwent an extensive physical examination, including anthropometry, spirometry, electrocardiography, and measurements of blood pressure, heart rate, exhaled nitric oxide and carbon monoxide. Potential conditions in the lung, heart, liver, spleen, and skin were synchronously performed. In addition, samples of morning urine, fasting blood serum and plasma were collected during physical health examination. DNA were extracted and were stored at -80°C. Environment concentrations of particulate matter and chemicals were determined for 15 days in each of four seasons. Participants are followed for physiological or pathological changes or incidence of cardiopulmonary diseases every 3 years.
The results obtained in WHZH cohort study may increase a better understanding of the relationship between particulate air pollution and its components and possible health damages. And the potential mechanisms underlying the development of cardiopulmonary diseases has implications for the development of prevention and treatment strategies.
PMCID: PMC4247123  PMID: 25252923
Cohort study; Air pollutants; Particulate matter; Pulmonary function; Respiratory diseases; Cardiovascular diseases
18.  Desktop Transcriptome Sequencing From Archival Tissue to Identify Clinically Relevant Translocations 
Somatic mutations, often translocations or single nucleotide variations, are pathognomonic for certain types of cancers and are increasingly of clinical importance for diagnosis and prediction of response to therapy. Conventional clinical assays only evaluate 1 mutation at a time, and targeted tests are often constrained to identify only the most common mutations. Genome-wide or transcriptome-wide high-throughput sequencing (HTS) of clinical samples offers an opportunity to evaluate for all clinically significant mutations with a single test. Recently a “desktop version” of HTS has become available, but most of the experience to date is based on data obtained from high-quality DNA from frozen specimens. In this study, we demonstrate, as a proof of principle, that translocations in sarcomas can be diagnosed from formalin-fixed paraffin-embedded (FFPE) tissue with desktop HTS. Using the first generation MiSeq platform, full transcriptome sequencing was performed on FFPE material from archival blocks of 3 synovial sarcomas, 3 myxoid liposarcomas, 2 Ewing sarcomas, and 1 clear cell sarcoma. Mapping the reads to the “sarcomatome” (all known 83 genes involved in translocations and mutations in sarcoma) and using a novel algorithm for ranking fusion candidates, the pathognomonic fusions and the exact breakpoints were identified in all cases of synovial sarcoma, myxoid liposarcoma, and clear cell sarcoma. The Ewing sarcoma fusion gene was detectable in FFPE material only with a sequencing platform that generates greater sequencing depth. The results show that a single transcriptome HTS assay, from FFPE, has the potential to replace conventional molecular diagnostic techniques for the evaluation of clinically relevant mutations in cancer.
PMCID: PMC4159386  PMID: 23598961
sequencing; RNA-Seq; cancer; biomarker; archival tissue
19.  IDPQuantify: Combining Precursor Intensity with Spectral Counts for Protein and Peptide Quantification 
Journal of proteome research  2013;12(9):4111-4121.
Differentiating and quantifying protein differences in complex samples produces significant challenges in sensitivity and specificity. Label-free quantification can draw from two different information sources: precursor intensities and spectral counts. Intensities are accurate for calculating protein relative abundance, but values are often missing due to peptides that are identified sporadically. Spectral counting can reliably reproduce difference lists, but differentiating peptides or quantifying all but the most concentrated protein changes is usually beyond its abilities. Here we developed new software, IDPQuantify, to align multiple replicates using principal component analysis, extract accurate precursor intensities from MS data, and combine intensities with spectral counts for significant gains in differentiation and quantification. We have applied IDPQuantify to three comparative proteomic datasets featuring gold standard protein differences spiked in complicated backgrounds. The software is able to associate peptides with peaks that are otherwise left unidentified to increase the efficiency of protein quantification, especially for low-abundance proteins. By combing intensities with spectral counts from IDPicker, it gains an average of 30% more true positive differences among top differential proteins. IDPQuantify quantifies protein relative abundance accurately in these test datasets to produce good correlations between known and measured concentrations.
PMCID: PMC3804902  PMID: 23879310
precursor ion intensity; principal component analysis; retention time mapping; protein differentiation; comparative proteomics; quantitative proteomics; spectral counting; CPTAC
20.  The mysterious origins of coronary vessels 
Cell Research  2013;23(9):1063-1064.
The origin of the coronary vessels remains a mystery. Here we discuss recent studies that address this puzzle, including new work by Tian et al. recently published in Cell Research.
PMCID: PMC3760625  PMID: 23835479
21.  Variation in β-amylase activity and thermostability in Tibetan annual wild and cultivated barley genotypes*  
β-Amylase activity (BAA) and thermostability (BAT) are important traits for malt quality. In this study, 138 Tibetan annual wild barley accessions and 20 cultivated genotypes differing in BAA were planted and analyzed in 2009 and 2012. Significant differences were detected among genotypes in BAA and BAT. The cultivated genotypes had a mean BAA of 1137.6 U/g and a range of from 602.1 to 1407.5 U/g, while the wild accessions had a mean of 1517.9 U/g and a range of from 829.7 to 2310.0 U/g. The cultivated genotypes had a mean relative residual β-amylase activity (RRBAA) of 61.6% and a range of from 22.2% to 82.3%, while the wild barleys had a mean of 57.8% and a range of from 21.9% to 96.1%. Moreover, there was a significant difference among genotypes in the response of RRBAA to the temperature and duration of heat treatment. The wild barleys had wider variation in BAA and BAT than cultivated genotypes.
PMCID: PMC4162881  PMID: 25183034
Barley; β-Amylase activity; Thermostability; Tibet
22.  Disruption of Phosphoinositide-Specific Phospholipases Cγ1 Contributes to Extracellular Matrix Synthesis of Human Osteoarthritis Chondrocytes 
Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation including extracellular matrix (ECM) degradation and cell loss. It is known that phosphoinositide-specific phospholipase γ1 (PLCγ1) can trigger several signaling pathways to regulate cell metabolism. However, whether this kinase is expressive and active in human OA chondrocytes and its role in the pathological progression of OA have not been investigated. The current study was designed to investigate the PLCγ1 expression in human OA cartilage, and whether PLCγ1 was involved in the ECM synthesis had been further explored using cultured human OA chondrocytes. Our results indicated that PLCγ1 was highly expressed in human OA chondrocytes. In our further study using the cultured human OA chondrocytes, the results demonstrated that the disruption of PLCγ1 by its inhibitor, U73122, and siRNA contributed to the ECM synthesis of human OA chondrocytes through regulating the expression of ECM-related signaling molecules, including MMP-13, Col II, TIMP1, Sox-9, and AGG. Furthermore, PLCγ1/IP3/Ca(2+)/CaMK II signaling axis regulated the ECM synthesis of human chondrocytes through triggering mTOR/P70S6K/S6 pathway. In summary, our results suggested that PLC-γ1 activities played an important role in the ECM synthesis of human OA chondrocytes, and may serve as a therapeutic target for treating OA.
PMCID: PMC4159791  PMID: 25073093
PLC-γ1; human OA chondrocytes; ECM
23.  Mir-208 promotes cell proliferation by repressing SOX6 expression in human esophageal squamous cell carcinoma 
Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in developing countries. The prognosis and survival rate of ESCC are very poor. Recently, microRNAs (miRNAs) have emerged as important regulators of cancer cell biological processes. To better understanding the molecular mechanisms by which they regulate the behavior of cancer cells is needed.
The expression of miR-208 was examined in ESCC cell lines and tumor tissues by real-time PCR. Proliferation capability of ESCC cells upon regulation of miR-208 expression was detected by MTT assay, colony formation assay, anchorage-independent growth ability assay and flow cytometry analysis. The target of miR-208 was determined by western blotting analysis, luciferase reporter assay and real-time PCR.
miR-208 was upregulated in ESCC cell lines and tissues. Overexpression of miR-208 in ESCC cells increased cell proliferation, tumorigenicity and cell cycle progression, whereas inhibition of miR-208 reduced cells proliferation, tumorigenicity and cell cycle progression. Additionally, SOX6 was identified as a direct target of miR-208. Ectopic expression of miR-208 led to downregulation of SOX6 protein, which resulted in the downregulation of p21, upregulation of cyclin D1 and phosphorylation of Rb.
These results suggest that miR-208 represents a potential onco-miR and participates in ESCC carcinogenesis by suppressing SOX6 expression.
PMCID: PMC4107867  PMID: 25023649
miR-208; SOX6; Esophageal squamous cell carcinoma; Proliferation
24.  Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis 
AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis.
METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period.
RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 109/L vs 63.3 ± 15.7 × 109/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation.
CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.
PMCID: PMC4093718  PMID: 25024623
Autologous; Bone marrow mononuclear cells; Transplantation; Liver cirrhosis; Hepatitis B virus
25.  Enhancer-Trap Flippase Lines for Clonal Analysis in the Drosophila Ovary 
G3: Genes|Genomes|Genetics  2014;4(9):1693-1699.
The Drosophila melanogaster genetic tool box includes many stocks for generating genetically mosaic tissue in which a clone of cells, related by lineage, contain a common genetic alteration. These tools have made it possible to study the postembryonic function of essential genes and to better understand how individual cells interact within intact tissues. We have screened through 201 enhancer-trap flippase lines to identify lines that produce useful clone patterns in the adult ovary. We found that approximately 70% of the lines produced clones that were present in the adult ovary and that many ovarian cell types were represented among the different clone patterns produced by these lines. We have also identified and further characterized five particularly useful enhancer-trap flippase lines. These lines make it possible to generate clones specifically in germ cells, escort cells, prefollicle cells, or terminal filament cells. In addition, we have found that chickadee is specifically upregulated in the posterior escort cells, follicle stem cells, and prefollicle cells that comprise the follicle stem cell niche region. Collectively, these studies provide several new tools for genetic mosaic analysis in the Drosophila ovary.
PMCID: PMC4169162  PMID: 25024257
Drosophila; clonal analysis; Flp/FRT; ovary; stem cells

Results 1-25 (203)