Proopiomelanocortin and its potential functions in the pathological synovium of patients with osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a chronic degenerative disease of the joints, adversely affecting the quality of life for the patients. To better understand the mechanisms underlying the pathological changes in osteoarthritis and identify the key genes associated with osteoarthritis pathogenesis, we utilized a comprehensive bioinformatics approach to analyze the transcriptome between osteoarthritis synovial and control samples with public microarray datasets. MATERIALS AND METHODS: First, the GSE82107 microarray dataset containing ten osteoarthritis synovial and seven control samples were selected from the Gene Expression Omnibus (GEO) database. RESULTS: A total of 52 overlapped differentially expressed genes (DEGs) in GSE82107 and OA-associated genes in the Comparative Toxicogenomics Database were identified. These OA-associated DEGs were further incorporated into a protein-protein interaction (PPI) network. Gene proopiomelanocortin (POMC) was identified in the largest cluster of PPI network with Cytoscape. GO and KEGG analyses suggested that these genes were associated with multiple functions. Other GEO datasets of osteoarthritis synovial tissues, including GSE55235 and GSE55457, were used to validate the expression level of POMC. Quantitative polymerase chain reaction and western blot analyses were also used to test the expression levels of POMC in our osteoarthritis samples. We found POMC was positively associated with transporter complex, ion channel activity, and G protein-coupled receptor signaling pathway. CONCLUSIONS: This study highlighted the OA-associated gene POMC, and its related biological pathways, suggesting it served as a potential treatment target in osteoarthritis.

[Evaluation of estimation of prevalence ratio using bayesian log-binomial regression model].

To evaluate the estimation of prevalence ratio (PR) by using bayesian log-binomial regression model and its application, we estimated the PR of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea in their infants by using bayesian log-binomial regression model in Openbugs software. The results showed that caregivers' recognition of infant' s risk signs of diarrhea was associated significantly with a 13% increase of medical care-seeking. Meanwhile, we compared the differences in PR's point estimation and its interval estimation of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea and convergence of three models (model 1: not adjusting for the covariates; model 2: adjusting for duration of caregivers' education, model 3: adjusting for distance between village and township and child month-age based on model 2) between bayesian log-binomial regression model and conventional log-binomial regression model. The results showed that all three bayesian log-binomial regression models were convergence and the estimated PRs were 1.130(95%CI: 1.005-1.265), 1.128(95%CI: 1.001-1.264) and 1.132(95%CI: 1.004-1.267), respectively. Conventional log-binomial regression model 1 and model 2 were convergence and their PRs were 1.130(95% CI: 1.055-1.206) and 1.126(95% CI: 1.051-1.203), respectively, but the model 3 was misconvergence, so COPY method was used to estimate PR, which was 1.125 (95%CI: 1.051-1.200). In addition, the point estimation and interval estimation of PRs from three bayesian log-binomial regression models differed slightly from those of PRs from conventional log-binomial regression model, but they had a good consistency in estimating PR. Therefore, bayesian log-binomial regression model can effectively estimate PR with less misconvergence and have more advantages in application compared with conventional log-binomial regression model.

Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry

Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.

Although 17ß-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

Graphene mode-locked femtosecond laser at 2 µm wavelength.

We experimentally demonstrated a passively mode-locked femtosecond laser by using a graphene-based saturable absorber mirror (graphene SAM) in the spectral region of 2 µm. The graphene SAM was fabricated by transferring chemical-vapor-deposited, high-quality, and large-area graphene on a highly reflective plane mirror. Stable mode-locked laser pulses as short as 729 fs were obtained with a repetition rate of 98.7 MHz and an average output power of 60.2 mW at 2018 nm.

Diode-pumped mode-locked femtosecond Tm:CLNGG disordered crystal laser.

A diode-end-pumped passively mode-locked femtosecond Tm-doped calcium lithium niobium gallium garnet (Tm:CLNGG) disordered crystal laser was demonstrated for the first time to our knowledge. With a 790 nm laser diode pumping, stable CW mode-locking operation was obtained by using a semiconductor saturable absorber mirror. The disordered crystal laser generated mode-locked pulses as short as 479 fs, with an average output power of 288 mW, and repetition rate of 99 MHz in 2 µm spectral region.

Highly efficient 2 µm Tm:YAG ceramic laser.

We have experimentally demonstrated a highly efficient diode-pumped Tm:YAG ceramic laser operating at 2 µm wavelength. The maximum output power of 6.05 W was realized with a slope efficiency as high as 65%. As far as we know, it is the highest slope efficiency reported for Tm:YAG ceramic laser. The wavelength tuning experiment of Tm:YAG ceramic laser was carried out and the results suggest that Tm:YAG ceramic laser could operate simultaneously at multiple wavelengths in a wide range of 1884-2017 nm.

Effect of trychostatin A treatment on gene expression in cloned mouse embryos.

Histone deacetylation occurs upon the transfer of somatic nuclei into enucleated oocytes, but its role in reprogramming somatic chromatin to the totipotent state is unknown. To investigate the importance of histone deacetylation in reprogramming, we constructed embryos by electrofusing breast cancer cells with enucleated mouse oocytes. The reconstructed embryos were then cultured before and/or after activation for 6h in the presence of trychostatin A (TSA), a potent inhibitor of histone deacetylase. Total RNA was isolated from these TSA-treated and untreated embryos and real-time reverse transcription PCR was conducted to monitor transcription of ErbB2, Muc1, eIF-4C, MuERV-L, and c-mos genes. The nuclear-cytoplasmic interaction inhibited typical expression of ErbB2 and Muc1 in the somatic cells. Moreover, the inhibition of histone deacetylation prior to activation did not increase the levels of eIF-4C, MuERV-L, and c-mos expression in the nuclear transfer (NT) embryos (P>0.05), whereas additional treatment with 100nM TSA beyond the activation point improved expression of these genes (P<0.05). Trychostatin A treatment also improved the development rates of NT embryos at the 2-cell, 4-cell, and blastocyst stages (78.6% vs. 90.2%, 45.2% vs. 68.9%, and 16.7% vs. 30.3%, respectively, P<0.05). We hypothesized that the reprogramming of gene expression in NT embryos is independent of somatic histone deacetylation, and that hyperacetylation may have a positive effect on NT embryo development.