Utilizing benchmarked dataset and gene regulatory network to investigate hub genes in postmenopausal osteoporosis.

OBJECTIVE: The objective of this paper was to investigate hub genes of postmenopausal osteoporosis (PO) utilizing benchmarked dataset and gene regulatory network (GRN). MATERIALS AND METHODS: To achieve this goal, the first step was to benchmark the dataset downloaded from the ArrayExpress database by adding local noise and global noise. Second, differentially expressed genes (DEGs) between PO and normal controls were identified using the Linear Models for Microarray Data package based on benchmarked dataset. Third, five kinds of GRN inference methods, which comprised Zscore, GeneNet, context likelihood of relatedness (CLR) algorithm, Partial Correlation coefficient with Information Theory (PCIT), and GEne Network Inference with Ensemble of trees (Genie3), were described and evaluated by receiver operating characteristic (ROC) and precision and recall (PR) curves. Finally, GRN constructed according to the method with best performance was implemented to conduct topological centrality (closeness) for the purpose of investigate hub genes of PO. RESULTS: A total of 236 DEGs were obtained based on benchmarked dataset of 20,554 genes. By assessing Zscore, GeneNet, CLR, PCIT, and Genie3 on the basis of ROC and PR curves, Genie3 had a clear advantage than others and was applied to construct the GRN which was composed of 236 nodes and 27,730 edges. Closeness centrality analysis of GRN was carried out, and we identified 14 hub genes (such as TTN, ACTA1, and MYBPC1) for PO. CONCLUSION: In conclusion, we have identified 14 hub genes (such as TN, ACTA1, and MYBPC1) based on benchmarked dataset and GRN. These genes might be potential biomarkers and give insights for diagnose and treatment of PO.

Bone mineral density of proximal femur in adult Chinese females.

OBJECTIVE: This study was designed to establish bone mineral density (BMD) reference data of proximal femur, research the effect of age, height and weight on BMD of proximal femur, and estimate the prevalence of osteoporosis in a Chinese female population. In addition we compared the results with Lebanese and USA white women reference data. METHODS: Our study was conducted at one center, including 1578 Chinese women, aged 20-79years. We measured the BMD for proximal femur using dual-energy X-ray absorptiometry, and then established a reference database of proximal femur and set up regression equations of age, height and weight for BMD at proximal femur to research the effects of age, height and weight on BMD. After that, we calculated the standardized BMD and compared them with Lebanese and USA white women reference data. RESULTS: The peak BMD occurred in the age range 30-39 years for femoral neck and Ward's triangle, and 40-49 years for trochanter in Chinese women, which were later than in Lebanese and USA white women. The BMD of proximal femur in Chinese women were lower than Lebanese and USA white women in most age ranges. Weight profoundly influenced BMD in all age groups, and age and height mainly effected BMD in older age groups. The standardized prevalence of osteoporosis among Chinese women of 50-79 years old was 9.6% in femoral neck, which was higher than Lebanese but lower than USA white women. CONCLUSION: The BMD database of proximal femur in Chinese women we established is normative and different from Lebanese and USA white women reference data, which provides more reliable information on the prevalence of osteoporosis in China.

Intake consumption of ginsenoside Rg3, profiling of selected cytokines, and development of rectal polyps.

Background: Rectal polyps is a major risk factor for rectal cancer. There is a need to explore a panel of preventive measures, as well as reliable biomarkers for screening of rectal polyps. Patients and methods: We conducted a case control study which aimed to explore the effects of regular consumption of ginsenoside Rg3, profiling of selected cytokines, and development of rectal polyps in a Chinese population. Results: Significantly higher levels of IL-4, MIP-1ß, FasL, TGF-ß1, and RANTES were detected in rectal polyp cases. Further, we found significant dose-response relationships between quartile-categorized levels of IL-4, MIP-1ß, FasL, and TGF-ß1, and risk of rectal polyps. The strongest associations for IL-4, MIP-1ß, FasL, and TGF-ß1 were observed for the highest quartile vs the lowest quartile with an OR of 1.78, 2.70, 1.49, and 2.36, respectively. Compared with non-Rg3 consumers, regular Rg3 consumers had a significantly lower risk of rectal polyps (OR =0.71; 95% CI: 0.55-0.92; P=0.009). We also found that Rg3 consumers had significantly lower levels of IL-4, MIP-1ß, FasL, and TGF-ß1 than non-Rg3 consumers, in both rectal polyp cases and healthy controls. Conclusion: These results indicate that regular consumption of Rg3 might prevent the occurrence of rectal polyps through decreasing the serum level of selected cytokines, including IL-4, MIP-1ß, FasL, and TGF-ß1. Further clinical trials and prospective cohort studies with larger sample sizes are warranted to validate the anti-inflammatory activity and the anti-tumorigenic role of Rg3.

Wnt3a is critical for endothelial progenitor cell-mediated neural stem cell proliferation and differentiation.

The present study aimed to determine whether co-culture with bone marrow­derived endothelial progenitor cells (EPCs) affects the proliferation and differentiation of spinal cord-derived neural stem cells (NSCs), and to investigate the underlying mechanism. The proliferation and differentiation of the NSCs were evaluated by an MTT cell proliferation and cytotoxicity assay, and immunofluorescence, respectively. The number of neurospheres and the number of ß­tubulin III­positive cells were detected by microscopy. The wingless­type MMTV integration site family, member 3a (Wnt3a)/ß-catenin signaling pathway was analyzed by western blot analysis and reverse transcription­quantitative polymerase chain reaction to elucidate the possible mechanisms of EPC­mediated NSC proliferation and differentiation. The results revealed that co­culture with EPCs significantly induced NSC proliferation and differentiation. In addition, co­culture with EPCs markedly induced the expression levels of Wnt3a and ß­catenin and inhibited the phosphorylation of glycogen synthase kinase 3ß (GSK­3ß). By contrast, Wnt3a knockdown using a short hairpin RNA plasmid in the EPCs reduced EPC­mediated NSC proliferation and differentiation, accompanied by inhibition of the EPC­mediated expression of ß­catenin, and its phosphorylation and activation of GSK­3ß. Taken together, the findings of the present study demonstrated that Wnt3a was critical for EPC­mediated NSC proliferation and differentiation.

Systematic Identification, Evolution and Expression Analysis of the Zea mays PHT1 Gene Family Reveals Several New Members Involved in Root Colonization by Arbuscular Mycorrhizal Fungi.

The Phosphate Transporter1 (PHT1) family of genes plays pivotal roles in the uptake of inorganic phosphate from soils. However, there is no comprehensive report on the PHT1 family in Zea mays based on the whole genome. In the present study, a total of 13 putative PHT1 genes (ZmPHT1;1 to 13) were identified in the inbred line B73 genome by bioinformatics methods. Then, their function was investigated by a yeast PHO84 mutant complementary experiment and qRT-PCR. Thirteen ZmPHT1 genes distributed on six chromosomes (1, 2, 5, 7, 8 and 10) were divided into two paralogues (Class A and Class B). ZmPHT1;1/ZmPHT1;9 and ZmPHT1;9/ZmPHT1;13 are produced from recent segmental duplication events. ZmPHT1;1/ZmPHT1;13 and ZmPHT1;8/ZmPHT1;10 are produced from early segmental duplication events. All 13 putative ZmPHT1s can completely or partly complement the yeast Pi-uptake mutant, and they were obviously induced in maize under low Pi conditions, except for ZmPHT1;1 (p < 0.01), indicating that the overwhelming majority of ZmPHT1 genes can respond to a low Pi condition. ZmPHT1;2, ZmPHT1;4, ZmPHT1;6, ZmPHT1;7, ZmPHT1;9 and ZmPHT1;11 were up-regulated by arbuscular mycorrhizal fungi (AMF), implying that these genes might participate in mediating Pi absorption and/or transport. Analysis of the promoters revealed that the MYCS and P1BS element are widely distributed on the region of different AMF-inducible ZmPHT1 promoters. In light of the above results, five of 13 ZmPHT1 genes were newly-identified AMF-inducible high-affinity phosphate transporters in the maize genome. Our results will lay a foundation for better understanding the PHT1 family evolution and the molecular mechanisms of inorganic phosphate transport under AMF inoculation.

[Multiple derotation plus costotransversectomy for severe and rigid scoliosis].

OBJECTIVE: To explore the outcomes of multiple derotation plus costotransversectomy for patients with severe and rigid scoliosis. METHODS: Clinical analyses were conducted for the clinical data of operative duration, blood loss volume and SRS-22 scale. Radiographic data included Cobb angle of coronal curves, apical vertebral translation, coronal balance and sagittal balance. All measurements were taken pre-operation, post-operation and during the final follow-up period. RESULTS: The mean follow-up period was 4.1 ± 0.7 (3-5.5) years, mean operative duration 33 ± 8.4 min and mean blood loss volume 2303.5 ± 9.0 ml. Preoperative major curves ranged from 65° to 110° Cobb angle. Coronal plane correction of major curve from 10° to 41° Cobb angle (mean 30.8 ± 9.8°). And there was a mean loss of correction of 3.6% during the final follow-up. The magnitudes of thoracic kyphosis and lumbar lordosis were 31.1 ± 12.4°, 45.5 ± 10.5° pre-operation, 25.6 ± 5.5°, 33.43 ± 5.45° post-operation and 28.6 ± 6.1°, 35.26 ± 4.2° during the final follow-up. The apical vertebral translation of major curve was corrected by 73.2%. The coronal imbalance, sagittal imbalance and apical vertebral translation indifferently was 3.2 ± 1.1, 2.3 ± 1.1, 6.35 ± 1.65 cm pre-operation, 0.9 ± 1.0, 0.4 ± 0.5, 2.4 ± 1.2 cm post-operation and 1.2 ± 1.1, 0.6 ± 0.5, 2.6 ± 1.4 cm during the final follow-up. Incomplete thoracic nerve dysfuction occurred in one case and superficial dermatoedge necrosis in another recovered within 2 weeks. Neither malposition of pedicle screw nor complication of instrumentation was found. Excellent outcomes were obtained according to SRS-22 score. CONCLUSION: For patients with severe and rigid scoliosis, the technique of multi-rod-derotation and rib resection may achieve a good correction of scoliosis without serious complications and avoid a resection of vertebral column.