Interplay Between Long Noncoding RNA ZEB1-AS1 and miR-200s Regulates Osteosarcoma Cell Proliferation and Migration.

In our previous study, we found long noncoding RNA ZEB1-AS1 is upregulated and functions as an oncogene in osteosarcoma. MiR-200 family (miR-200s) functions as tumor suppressor via directly targeting ZEB1 in various cancers. In this study, we further investigate the potential interplay between ZEB1-AS1, miR-200s, and ZEB1 in osteosarcoma. Our results showed that ZEB1-AS1 functions as a molecular sponge for miR-200s and relieves the inhibition of ZEB1 caused by miR-200s. ZEB1-AS1 and miR-200s reciprocally negatively regulate each other. MiR-200s are downregulated in osteosarcoma tissues, and negatively correlated with ZEB1-AS1 and ZEB1 expression levels in osteosarcoma. Functional experiments showed that consistent with ZEB1-AS1 depletion, miR-200s overexpression and ZEB1 depletion both inhibit osteosarcoma cell proliferation and migration. Overexpression of miR-200s partially abolished the effects of ZEB1-AS1 on osteosarcoma cell proliferation and migration. Moreover, the combination of ZEB1-AS1 depletion and miR-200s overexpression significantly inhibits osteosarcoma cell proliferation and migration. In conclusion, this study revealed a novel regulatory mechanism between ZEB1-AS1, miR-200s, and ZEB1. The interplay between ZEB1-AS1 and miR-200s contributes to osteosarcoma cell proliferation and migration, and targeting this interplay could be a promising strategy for osteosarcoma treatment. J. Cell. Biochem. 118: 2250-2260, 2017. © 2017 Wiley Periodicals, Inc.

The tumor-promoting function of ECRG4 in papillary thyroid carcinoma and its related mechanism.

This study aimed to explore the tumor-promoting function of esophageal cancer-related gene 4 (ECRG4) in the papillary thyroid cancer and its related mechanism. ECRG4 Messenger RNA (mRNA) and protein expression analysis in papillary thyroid cancer tissues was performed by quantitative real-time PCR (Q-RT-PCR), Western blot, and immunohistochemistry methods. Ten pairs of fresh samples from the papillary thyroid carcinoma patients were analyzed for ECRG4 promoter CpG island methylation status by bisulfite sequencing analysis. We also transfected ECRG4 into papillary thyroid cancer cell lines W3 and K1 with lentivirus and analyzed ECRG4 functions through evaluating the changes of the proliferation activity, the cell cycle, and the cell apoptosis rate of these transformed cells. We found that ECRG4 expression was upregulated in most papillary thyroid cancer samples (70.0%, 28 out of 40 papillary thyroid cancer samples) on the protein level, and the ECRG4 mRNA level was also enhanced in tumor tissues compared to their matched nontumor tissues. CpG islands around the ECRG4 promoter region were demethylated in the papillary thyroid cancer samples. At the same time, the upregulated expression of ECRG4 in papillary thyroid cancer cell lines W3 and K1 could promote both the proliferation activity and the cell cycle transition from the G1 phase into the G2 but could not affect the cell apoptosis rate. The expression of ECRG4 is frequently upregulated in a papillary thyroid carcinoma through the demethylation mechanism of CpG islands in the gene promoter region, and the ECRG4 has a tumor-promoting function through inducing the cell cycle transition from the G1 phase to the G2 in papillary thyroid carcinoma cells.

The apoptotic effect of shikonin on human papillary thyroid carcinoma cells through mitochondrial pathway.

This study aims to explore the apoptotic function of shikonin on the papillary thyroid cancer cells and the related mechanism. The papillary thyroid cancer cell lines K1 and W3 and thyroid follicular epithelial cells NTHY-ORI 3-1 were treated with different concentrations of shikonin. Cell proliferation was tested. Morphological changes of the apoptotic cells were observed by Hoechst 33342 staining. The apoptosis rate of the papillary thyroid cancer cells was measured with flow cytometry. Changes of the cell cycle were explored. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Bcl-2 family proteins and caspase-3 expression with shikonin treatment was analyzed by real-time fluorescence polymerase chain reaction (PCR). Cell proliferation of K1 and W3 was inhibited by shikonin, and the inhibition was dose-time dependent. Papillary thyroid carcinoma cells treated by shikonin had no obvious cell cycle arrest but were observed with the higher apoptosis rate and the typical apoptotic morphological changes of the cell nucleus. JC-1 staining showed that shikonin reduced the mitochondrial membrane potential of papillary thyroid carcinoma cells. Real-time PCR results showed that shikonin significantly increased Bax and caspase-3 expression and upregulated Bcl-2 expression in a dose-dependent manner in papillary thyroid carcinoma cells. However, the NTHY-ORI 3-1 was almost not affected by shikonin treatment. Shikonin can inhibit K1 and W3 cell proliferation in a dose- and time-dependent manner, enhance Bax levels, reduce anti-apoptotic protein Bcl-2 levels, result in decreasing mitochondrial membrane potential and activating caspase-3 enzyme, and finally lead to apoptosis.

The apoptotic effect of apigenin on human gastric carcinoma cells through mitochondrial signal pathway.

This study aims to explore the apoptotic function of apigenin on the gastric cancer cells and the related mechanism. The gastric cancer cell lines HGC-27 and SGC-7901, and normal gastric epithelial cell line GES1 were treated with different concentrations of apigenin. Cell proliferation was tested. Morphological changes of the apoptotic cells were observed after Hoechst33342 staining. The apoptosis rate of the gastric cancer cells were measured with flow cytometry. Changes of the cell cycle were explored. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Bcl-2 family proteins and caspases-3 expression with apigenin treatment was analyzed by real-time PCR. Cell proliferation of HGC-27 and SGC-7901 was inhibited by apigenin, and the inhibition was dose-time-dependent. Gastric carcinoma cells treated by apigenin had no obvious cell cycle arrest, but were observed with the higher apoptosis rate and the typical apoptotic morphological changes of the cell nucleus. JC-1 staining showed that apigenin could reduce mitochondrial membrane potential of gastric carcinoma cells. Real-time PCR results showed that apigenin significantly increased caspase-3 and Bax expression level, and down-regulated Bcl-2 expression in a dose-dependent manner in gastric carcinoma cells. However, the GES1 was almost not affected by apigenin treatment. Apigenin can inhibit cell lines HGC-27 and SGC-7901 proliferation in a time and dose-dependent manner, reduce anti-apoptotic protein Bcl-2 levels, enhance apoptosis-promoting protein Bax level, result in mitochondrial membrane potential decreasing and caspase-3 enzyme activating, then lead to cell apoptosis.

The interaction between smoking and GSTM1 variant on lung cancer in the Chinese population.

Smoking and the deletion of GSTM1 variant are two risk factors of lung cancer. This meta-analysis was performed to examine the GSTM1-smoking interaction on lung cancer in the Chinese population. PubMed, Web of Science, and other Chinese databases were searched to include all the related studies. The number of subjects with two GSTM1 genotypes across different smoking status was extracted. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated using fixed- or random-effect model. A total of 4,345 cases and 5,031 controls from 30 studies were included in the meta-analysis. Compared with nonsmokers having power GSTM1, the pooled ORs with 95 % CIs for lung cancer in smokers with power GSTM1, in nonsmokers with null GSTM1, and in smokers with null GSTM1 were 2.24 (1.82-2.76), 1.48 (1.23-1.79), and 4.18 (3.38-5.16), respectively. This meta-analysis showed that there was an interaction between the GSTM1 and smoking on the risk of lung cancer in the Chinese. Further studies are needed to examine the interactions between other environmental factors and GSTM1 on the risk of lung cancer.

XRCC3 T241M polymorphism is associated risk of hepatocellular carcinoma in the Chinese.

The X-ray repair cross-complementing group 3 (XRCC3) gene has been suggested to play an important role in the pathogenesis of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of XRCC3 Thr241Met variant with HCC. The published literature from PubMed, Chinese National Knowledge Infrastructure, and Wan Fang data was retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed or random effects model. A total of five studies (1,531 HCC cancer cases and 1,952 controls) for XRCC3 Thr241Met variant were included in the meta-analysis. The meta-analysis showed that XRCC3 Thr241Met variant was associated with HCC risk under homogeneous codominant model (OR = 3.99, 95 % CI = 1.74-9.13) and recessive model (OR = 5.22, 95 % CI = 3.65-7.48), but not under heterogeneous codominant model (OR = 1.18, 95 % CI = 0.68-2.05) and dominant model (OR = 1.37, 95 % CI = 0.73-2.57). Subgroup analysis by ethnicity suggested that XRCC3 Thr241Met variant was associated with HCC risk in Chinese population, but not in Pakistani population. The present meta-analysis supported the positive association of XRCC3 Thr241Met variant with HCC in the Chinese. Further large-scale studies with the consideration for gene-gene/gene-environment interactions should be conducted to investigate the association.

Glycyrrhiza polysaccharide induces apoptosis and inhibits proliferation of human hepatocellular carcinoma cells by blocking PI3K/AKT signal pathway.

To study the antitumor effect of glycyrrhiza polysaccharide (GPS) on human hepatocellular carcinoma cells and its mechanism, GPS was extracted and identified with phenol-sulfuric acid assay, Limulus amebocytes lysate assay, gel permeation chromatography, and infrared spectroscopy analysis. To study its antitumor function, 4-5-week-old imprinting control region mice were subcutaneously implanted with H22 cells and intragastrically subjected to 1 ml GPS (25, 50, and 75 mg/kg/day), 150 mg/kg cyclophosphamide in a dose of 150 mg/kg, or equal volume of phosphate buffered saline as control. Tumor weights were detected 10 days later. Apoptosis of intraperitoneally cultured and GPS-treated H22 cells was identified by flow cytometry and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide. In vitro, the function of GPS on cell proliferation was applied on BEL7402 cells and confirmed by 4,6-diamidino-z-phenylindole staining. Assessment of the effect of GPS on P53 gene was analyzed by real-time PCR and Western blot, and the effects of GPS on phosphatidylinositol-3 kinase (PI3K), AKT, p-PI3K, and p-AKT were analyzed by Western blot. We extracted the GPS, and it dose-dependently inhibited the tumorigenicity of hepatocellular carcinoma cells in nude mice. GPS treatment resulted in a significant (P<0.05) dose-dependent increase in the number of apoptotic cells in vivo and a significant (P<0.05) dose-dependent decrease in hepatocellular carcinoma cell proliferation in vitro. GPS modified multiple key enzymes (p-PI3K, p-AKT, and P53) in P53/PI3K/AKT signaling pathways on DNA or protein levels. Taken together, we extracted the GPS successfully and our findings suggest that GPS functions as a tumor suppressor through influencing the P53/PI3K/AKT pathway in the carcinogenesis of hepatocellular carcinoma and may have therapeutic implications for the clinical management of hepatocellular carcinoma patients.

Glutathione S-transferase P1 Ile105Val polymorphism and oral cancer risk: a meta-analysis.

Objective The glutathione S-transferase P1 (GSTP1) gene has been suggested to play an important role in the pathogenesis of oral cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of GSTP1 Ile105Val polymorphisms with oral cancer risk. Methods Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Results 13 studies (1803 oral cancer cases and 2998 controls) for GSTP1 Ile105Val polymorphism were included in the meta-analysis. The results indicated that there was no significant association between GSTP1 Ile105Val polymorphism and oral cancer in the overall population (OR=1.30, 95%CI=0.92-1.38, I(2)=48.0%, p for heterogeneity=0.027). Further subgroup analysis by ethnicity suggested that GSTP1 Ile105Val polymorphism was significantly associated with oral cancer only in East Asians (OR=1.64, 95%CI=1.16-2.31, I(2)=0.0%, p for heterogeneity=0.525), but not in Caucasians (OR=1.16, 95%CI=0.73-1.82, I(2)=7.5%, p for heterogeneity=0.299), Africans (OR=1.10, 95%CI=0.37-3.28), South Asians (OR=1.20, 95%CI=0.69-2.08, I(2)=74.3%, p for heterogeneity=0.021) and mixed population (OR=0.91, 95%CI=0.70-1.20, I(2)=39.7%, p for heterogeneity=0.174). Conclusions The present meta-analysis has limited evidence to support the association of GSTP1 Ile105Val polymorphism with HCC risk in the overall population. However, GSTP1 Ile105Val polymorphism might be associated with risk of oral cancer in East Asians.

Diagnostic roles of neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein, and cancer antigen 125 for ovarian cancer.

OBJECTIVE: To compare the diagnostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP) level, and cancer antigen 125 (CA125) level for ovarian cancer (OC). METHODS: Data of 72 patients with OC, 50 patients with benign ovarian disease, and 46 healthy controls were retrospectively analyzed, and receiver operating characteristic analysis was performed. RESULTS: The platelet count was higher in patients with a tumor diameter of ≥10 vs. <10 cm. The absolute lymphocyte count was significantly higher in patients with stage I/II OC than in those with multiple and stage III/IV OC. The absolute monocyte count, NLR, MLR, and CA125 were significantly higher in patients with multiple and stage III/IV OC than in those with single and stage I/II OC. The NLR, PLR, MLR, fibrinogen, D-dimer, CRP, and CA125 were useful for distinguishing between the OC and healthy control groups. CONCLUSIONS: Our analysis showed that the following combinations have practical diagnostic value in OC: NLR + PLR + MLR + CA125, NLR + PLR + MLR + CA125 + CRP, NLR + MLR +PLR + CA125 + CRP + fibrinogen, and NLR + MLR + PLR + CA125 + CRP + fibrinogen + D-dimer.

CYP2E1 PstI/RsaI polymorphism and interaction with alcohol consumption in hepatocellular carcinoma susceptibility: evidence from 1,661 cases and 2,317 controls.

Many studies have suggested that cytochrome P450 2E1 (CYP2E1) gene might be involved in the development of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the association between Pst I/Rsa polymorphism in the CYP2E1 gene and HCC risk. PubMed and China National Knowledge Infrastructure were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. Fifteen studies (1,661 HCC cases and 2,317 controls) were identified for the data analysis. The overall result showed that there was no statistically significant association between CYP2E1 Pst I/Rsa polymorphism and HCC risk (c2/c2 vs. c1/c1, OR = 0.73, 95% CI 0.50-1.06; c1/c2 vs. c1/c1, OR = 1.00, 95% CI 0.76-1.33; c2/c2+ c1/c2 vs. c1/c1, OR = 0.99, 95% CI 0.77-1.26; c2/c2 vs. c1/c2+ c1/c1, OR = 0.73, 95% CI 0.50-1.06). Further stratified analyses indicated that the habitual alcohol drinkers with c2 alleles were more likely to develop HCC (OR = 1.73, 95% CI 1.19-2.51), compared with the non-habitual drinkers with c1 homozygote. The meta-analysis indicated that CYP2E1 Pst I/Rsa polymorphism was not associated with HCC risk, while the interaction between Pst I/Rsa polymorphism and alcohol consumption increased the risk of HCC.

Pooled analyses of the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk.

BACKGROUND: The GRK4 and EMILIN1 genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk. METHODS: Published literature from PubMed and Embase databases were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. RESULTS: Five studies for polymorphisms in the GRK4 gene and five studies for polymorphisms in the EMILIN1 gene were identified. The results suggested that rs1801058 polymorphism in the GRK4 gene was inversely associated with hypertension among East Asians (TT vs. CC: OR=0.39, 95%CI 0.28-0.55) and positively associated with hypertension among Europeans (TT vs. CC: OR= 2.38, 95%CI 1.38-4.10). Rs2960306 polymorphism in the GRK4 gene was significantly associated with hypertension among Europeans (TT vs. GG: OR=1.92, 95%CI 1.13-3.27). The significant associations were also observed for rs2011616 and rs2304682 polymorphisms in the EMILIN1 gene among Japanese (rs2011616: AA vs. GG: OR=0.38, 95%CI 0.18-0.82; rs2304682: GG vs. CC: OR=0.37, 95%CI 0.17-0.81) but not among Chinese. CONCLUSIONS: This meta-analysis suggested that rs1801058 polymorphism in the GRK4 gene was associated with hypertension in East Asians and Europeans. The significant association was also found for rs2960306 polymorphism in the GRK4 gene among Europeans. In addition, there were significant associations of rs2011616 and rs2304682 polymorphisms in the EMILIN1 gene with hypertension among Japanese.

Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast cancer risk: a meta-analysis.

Common genetic variations in the leptin (LEP), leptin receptor (LEPR), and paraoxonase 1 (PON1) genes have been considered to be implicated in the development of breast cancer. However, the results were inconsistent. In this study, a meta-analysis was performed to assess the associations of five polymorphisms, including LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, and PON1 Q192R polymorphisms, with breast cancer risk. Published literature from PubMed, ISI Web of Science, Embase databases, CNKI, and Wanfang Data were retrieved. All studies evaluating the association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, or PON1 Q192R polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Three studies (2,003 cases and 1,967 controls) for LEP G2548A polymorphism, nine studies (4,627 cases and 5,476 controls) for LEPR Q223R polymorphism, five studies (2,759 cases and 2,573 controls) for LEPR Lys109Arg polymorphism, four studies (1,517 cases and 1,379 controls) for PON1 L55M polymorphism, and five studies (1,575 cases and 2,283 controls) for PON1 Q192R polymorphism were included in the meta-analysis. Overall, the results showed null significant association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, or PON1 Q192R polymorphism and breast cancer risk; however, PON1 L55M was significantly associated with breast cancer risk overall (MM vs. LL: OR = 2.16; 95% CI, 1.76-2.66). For LEPR Q223R polymorphism, further subgroup analysis suggested that the association was only statistically significant in East Asians (OR = 0.50; 95% CI, 0.36-0.70) but not in Caucasians (OR = 1.06; 95% CI, 0.77-1.45) or Africans (OR = 1.30; 95% CI, 0.83-2.03). The present meta-analysis suggested that LEPR Q223R polymorphism might be implicated in the development of breast cancer in East Asians; PON1 L55M might increase breast cancer risk. However, given the limited sample size, the findings warrant further investigation.

Effect of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on identifying biomarkers of laryngeal carcinoma.

The aim is to study the serum protein fingerprint of patients with laryngeal carcinoma (LC) and to screen for protein molecules closely related to LC during the onset and progression of the disease with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Serum samples from 68 patients with LC and 117 non-cancer control samples (75 healthy volunteers and 42 Vocal fold polyps). Q10 protein chips and PBSII-C protein chips reader (Ciphergen Biosystems Inc.) were used. The protein fingerprint expression of all the Serum samples and the resulting profiles between cancer and non-cancer groups were analyzed with Biomarker Wizard system. A group of proteomic peaks were detected. Three differently expressed potential biomarkers were identified with the relative molecular weights of 5,915, 6,440 and 9,190 Da. Among the three peaks, the one with m/z 6,440 was down-regulated, and the other two peaks with m/z 5,915 and 9,190 were up-regulated in LC. This diagnostic model could distinguish LC patients from controls with a sensitivity of 92.1% and a specificity of 91.9%. Moreover, blind test data showed a sensitivity of 86.7% and a specificity of 89.1%. The data suggested that SELDI technology could be used to screen proteins with altered expression levels in the serum of LC patients. These protein peaks were considered as specific serum biomarkers of LC and have the potential value for further investigation.

The application of SELDI-TOF-MS in clinical diagnosis of cancers.

Cancer diagnosis is important, and the early diagnosis of cancers could predict a more successful treatment. The proteomic studies emerged to be useful in combined analyses of samples from patients and provide more accurate diagnosis when compared to the single-factor-based diagnosis. In recent years, cancer detection with surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS) is flourishing and brought significant progress in this area. This paper summarizes some recent results with this technique for cancer diagnosis.

New serum biomarkers for detection of tuberculosis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: New technologies for the early detection of tuberculosis (TB) are urgently needed. Pathological changes within an organ might be reflected in proteomic patterns in serum. The aim of the present study was to screen for the potential protein biomarkers in serum for the diagnosis of TB using proteomic fingerprint technology. METHODS: Proteomic fingerprint technology combining protein chips with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to profile the serum proteins from 50 patients with TB, 25 patients with lung disease other than TB, and 25 healthy volunteers. The protein fingerprint expression of all the serum samples and the resulting profiles between TB and control groups were analyzed with the Biomarker Wizard system. RESULTS: A total of 30 discriminating m/z peaks were detected that were related to TB (p<0.01). The model of biomarkers constructed by the Biomarker Patterns Software based on the three biomarkers (2024, 8007, and 8598 Da) generated excellent separation between the TB and control groups. The sensitivity was 84.0% and the specificity was 86.0%. Blind test data indicated a sensitivity of 80.0% and a specificity of 84.2%. CONCLUSIONS: The data suggested a potential application of SELDI-TOF MS as an effective technology to profile serum proteome, and with pattern analysis, a diagnostic model comprising three potential biomarkers was indicated to differentiate people with TB and healthy controls rapidly and precisely.

MALDI-TOF MS combined with magnetic beads for detecting serum protein biomarkers and establishment of boosting decision tree model for diagnosis of colorectal cancer.

The aim of present study is to study the serum protein fingerprint of patients with colorectal cancer (CRC) and to screen protein molecules that are closely related to colorectal cancer during the onset and progression of the disease with Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Serum samples from 144 patients with CRC and 120 healthy volunteers were adopted in present study. Weak cation exchange (WCX) magnetic beads and PBSII-C protein chips reader (Ciphergen Biosystems Ins.) were used. The protein fingerprint expression of all the Serum samples and the resulted profiles between cancer and normal groups were analyzed with Biomarker Wizard system. Several proteomic peaks were detected and four potential biomarkers with different expression profiles were identified with their relative molecular weights of 2870.7 Da, 3084 Da, 9180.5 Da, and 13748.8 Da, respectively. Among the four proteins, two proteins with m/z 2870.7 and 3084 were down-regulated, and the other two with m/z 9180.5 and 13748.8 were up-regulated in serum samples from CRC patients. The present diagnostic model could distinguish CRC from healthy controls with the sensitivity of 92.85% and the specificity of 91.25%. Blind test data indicated a sensitivity of 86.95% and a specificity of 85%. The result suggested that MALDI technology could be used to screen critical proteins with differential expression in the serum of CRC patients. These differentially regulated proteins were considered as potential biomarkers for the patients with CRC in the serum and of the potential value for further investigation.

Clustering of cardio-metabolic risk factors and pre-diabetes among U.S. adolescents.

Few studies have assessed the association between clustering of cardio-metabolic risk factors (CMRFs) and pre-diabetes in children or adolescents. We aimed to examine the association between clustering of CMRFs and pre-diabetes among U.S. adolescents. Data were available for 5,633 U.S. adolescents aged 12-19 years from the National Health and Nutrition Examination Surveys 1999-2014. Pre-diabetes was defined as impaired fasting glucose (IFG) (fasting plasma glucose 100-125 mg/dL), impaired glucose tolerance (IGT) (2-h plasma glucose 140-199 mg/dL) or elevated hemoglobin A1c (HbA1c) (HbA1c 5.7-6.4%). The individual CMRFs considered in the present study were as follows: waist-to-height ratio, blood pressure, triglycerides, and high-density lipoprotein cholesterol. CMRFs were defined based on the modified National Cholesterol Education Program (NCEP) criteria or the modified International Diabetes Federation (IDF) criteria. Logistic regression analysis was used to examine the association between clustering of CMRFs and pre-diabetes with adjustment for potential covariates. Among 5633 adolescents, 11.4% had IFG, 4.7% had IGT, 4.5% had elevated HbA1c and 16.1% had pre-diabetes. Compared with adolescents with no CMRFs, the odds ratios (ORs) with 95% confidence intervals (CIs) for pre-diabetes across the clustering of CMRFs (i.e., 1, 2, 3, and 4) were 1.32 (1.03-1.68), 2.07 (1.55-2.76), 2.52 (1.69-3.76), and 5.41 (3.14-9.32), respectively, based on the modified NCEP criteria. The corresponding ORs with 95% CIs were 1.16 (0.89-1.51), 1.78 (1.35-2.36), 3.07 (1.89-4.98) and 12.20 (3.93-37.89), respectively, based on the modified IDF criteria. The present study suggests that the clustering of CMRFs is associated with increased pre-diabetes among U.S. adolescents. It might be necessary for effective strategies and measures targeting adolescents with clustering of CMRFs, including those with less than 3 risk factors.

[Detection of differentially expressed proteins in the semen of oligospermia patients by SELDI-TOF-MS technology].

OBJECTIVE: To analyze the spectrometric semen protein profiling of oligospermia patients and healthy controls by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), and to establish a semen marker pattern for the diagnosis of oligospermia. METHODS: Semen samples of 33 oligospermia patients and 31 healthy controls were collected on the CM01O proteinchip. The spectrometric protein profiling was detected by SELDI-TOF-MS and the data analyzed by Biomarker Pattern Software provided by Ciphergen Corp. A primary diagnostic model of oligospermia was established and evaluated by blind test with the 33 patients and 31 healthy controls. RESULTS: A total of 185 protein peaks were detected at the molecular range of 2000-20,000, among which 23 showed significant differences between oligospermia patients and healthy controls (P < 0.05). The diagnostic model consisted of 3 protein peaks, with a sensitivity of 90.9% (30/33) and a specificity of 93.6% (29/31). And the double-blind test generated a sensitivity of 87.8% (29/33) and a specificity of 90.3% (28/31). CONCLUSION: The diagnostic model was successfully established by SELDI-TOF-MS, which could be applied to the differentiation of the spectrometric protein profiling patterns of oligospermia patients and healthy controls.