Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease in reproductive women, and the endocrine levels are also affected by diseases. The aim of this study was to determine the effect of thrombospondin-1 (TSP-1) on PCOS rat model. METHODS: We established the PCOS rat model, the serum hormones including TSP-1 expression were determined and morphological characteristics were investigated to evaluate the model. These above endocrine and morphological features were investigated again to evaluate the effect of TSP-1 treatment. RESULTS: In the PCOS model group, the serum hormones change (higher luteinizing hormone, testosterone and estrogen) and decreased TSP-1 expression levels were found compared with the control group. Besides, the morphological characteristics of PCOS were also observed in the model group. After TSP-1 treatment, the higher TSP-1, ANGPT2, PDGFB and PDGFD expression levels, the lower LH and T levels, decreased vessel density as well as VEGFA and ANGPT1 expression levels were found compared with the control group, and the ovary morphological changes were also observed in the TSP-1 experimental group. CONCLUSIONS: TSP-1 delivery system might be an alternative therapy for PCOS treatment.

Spectroscopic investigation of the anticancer alkaloid piperlongumine binding to human serum albumin from the viewpoint of drug delivery.

Piperlongumine (PL) is a very promising natural agent with a high potential for cancer treatment. To overcome the poor water solubility of PL, there is a need to develop a novel water-soluble formulation in which PL is non-covalently bound to human serum albumin (HSA). PL binding to HSA was studied by various spectroscopic techniques under simulated physiological conditions. Spectroscopic evidence showed that the interaction of PL with HSA could form a PL-HSA complex. The binding constant (Ka ) values increased with increasing temperature, and a similar dependence was observed for the number of binding sites (n) values. The number of PL molecules bound to HSA reached 8.1 when the temperature was raised to 308 K. Thermodynamic calculation results suggested that the binding reaction occurred spontaneously but was an entropy-driven process, and hydrophobic forces played a major role in stabilizing the complex. Furthermore, PL binding induced conformational and microenvironmental changes in HSA. Displacement studies indicated that PL and warfarin had separate binding regions in site I. Therefore, it would be possible to develop a novel water-soluble formulation involving PL and HSA. This study may provide some valuable information in terms of improving the poor water solubility of PL.

Sleep Deprivation and Late Bedtime Impair Sperm Health Through Increasing Antisperm Antibody Production: A Prospective Study of 981 Healthy Men.

BACKGROUND The aim of this study was to investigate the effects of sleep duration and bedtime on sperm health, and the possible mechanism involved. MATERIAL AND METHODS We randomly divided 981 healthy Chinese men into groups according to research-set bedtimes (A=8-10 PM, B=after 10 PM, and C=after midnight) and sleep durations: group 1=<6.0 h (short), group 2=7.0-8.0 h (average), and group 3=>9.0 h (long). Sperm morphology, count, survival, and motility were examined according to sleep patterns. Antisperm antibody (ASA) production in semen was determined. RESULTS Sperm counts and their survival rates were lower in the short sleepers as compared to others within each group (all P<0.01). The lower counts and survival rates were observed in different bedtimes, with significant differences found between measurements of C1 vs. A1 and C2 vs. A2 or B2 (all P<0.05 or 0.01). Semen motility was lower in the short sleepers as compared to the average and long sleepers (all P<0.01). There were differences in the bedtime-related results between measurements of C1 vs. A1 or B1 (P<0.05 or 0.01). Additionally, the population proportion for the ASA-positive participates and incidence of the ASA-expressed population obviously increased in the short sleepers as compared to others within each group (all P<0.05). CONCLUSIONS Short and long sleep durations and late bedtime were associated with impaired sperm health in the study cohort, partly through increasing ASA production in the semen.

Iodine status and its association with prevalence of thyroid diseases in adults from Jiangxi Province, China.

BACKGROUND: Iodine is an essential element for the biosynthesis of thyroid-stimulating hormone (TSH). Both excessive and deficient iodine are major risk factors for thyroid diseases, including thyroid dysfunction, thyroid nodules, and thyroid autoimmunity (TAI). This study aimed to elucidate the relationship between iodine status and the prevalence of thyroid diseases through a national cross-sectional epidemiological survey in Jiangxi province (China). METHODS: This population-based, cross-sectional study enrolled 2636 Chinese local inhabitants who aged over 18 years old from April to August in 2015. Physical examination was performed and biochemical indices, urinary iodine concentration (UIC), and TSH level were measured. The Chi-square test, nonparametric test, and 4 multivariate logistic regression models adjusted for risk factors were applied to analysis. Spearman correlation coefficients were calculated to investigate the relationship between iodine intake level and the prevalence of thyroid diseases. RESULTS: The median UIC was 176.4 µg/L, and a significant difference was found in median UIC between men (182.45 µg/L) and women (169.25 µg/L) (P = 0.03). Among these study subjects, 14.4%, 44.5%, 26.1%, and 15.0% had deficient, adequate, more than adequate, and excessive iodine concentrations, respectively. The prevalence rates of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, thyroid nodules, and TAI were 0.91%, 0.57%, 0.34% and 7.89%, 9.45%, and 12.7%, respectively. Significant differences were found in iodine status, waist circumstance, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), TSH, thyroid nodules, and TAI between men and women (P < 0.05). Compared with those with adequate UIC, subjects with excessive UIC had higher prevalence rates of thyroid dysfunction (odds ratio (OR) = 1.74, 95% confidence interval (CI): 1.40-2.54) and thyroid nodules (OR = 3.33, 95%CI 1.32-8.42). In addition, subjects with deficient and excessive UIC were at the higher risk of TAI compared with those with adequate UIC (OR = 1.68, 95%CI: 1.19-2.60; OR = 1.52, 95%CI: 1.04-2.96, respectively). UIC was positively correlated with the prevalence rates of thyroid nodules (r = -0.44, P < 0.01) and TAI (r = -0.055, P < 0.01). On the contrary, UIC was negatively correlated with the risk of thyroid dysfunction (r = -0.24, P > 0.05). CONCLUSION: Adult inhabitants from Jiangxi province in the TIDE study were in the adequate iodine status. Excessive iodine status was noted as a risk factor for thyroid dysfunction and thyroid nodules. In addition, both iodine deficiency and excessive iodine were risk factors for TAI.

[Clinical value of anti-adhesion agents used in laparotomy in obstetrics and gynecology].

OBJECTIVE: To investigate clinical value of anti-adhesion agent:chitosan in preventing adhesions followed by laparotomy surgery in obstetrics and gynecology. METHODS: From Jan. 2006 to Dec. 2009, 770 patients underwent laparotomy surgery at Department of Obstetrics and Gynecology in the Second Affiliated Hospital of Harbin Medical University. One hundred and twenty-five patients underwent secondary surgery due to disease recurrence or cesarean section, the previous surgery were 18 cases with myomectomy, 20 cases with endometriosis surgery, 5 cases with resection of pelvic abscess, 20 cases with ectopic pregnancy surgery, 27 cases with benign adnexal neoplasm resection, 9 cases with cyto-reductive surgery in ovarian cancer, 26 cases with variable infertility surgery. Those 125 patients were managed by different agents washing before abdomen closure, which were assigned into two groups, including 59 cases washed by saline in control group and 66 cases washed by chitosan in study group. The abdomen adhesion in secondary surgery was evaluated by adhesion classification system. RESULTS: In study group, 37 patients without adhesions, 20 patients with degree I adhesion, 6 patients with degree II adhesion, 3 patients with degree III adhesion, and no patients with degree IV adhesion were observed. While in control group, there were 11 patients without adhesions, 23 patients with degree I adhesion, 14 patients with degree II adhesion, 8 patients with degree III adhesion, and 3 patients with degree IV adhesion. The distribution of adhesion reached statistical significance between the two groups (χ(2) = 20.9999, P = 0.0003). Twenty-six patients in previous surgeries due to infertility included 17 cases in control group and 9 cases in study group. They all were managed by cesarean section in secondary surgery, it was found that 15 cases without adhesion and 2 cases with degree I adhesion were in study group and 2 cases without adhesion and 7 cases with degree I adhesion were in control group. It reached statistical difference (P = 0.0016). CONCLUSION: Anti-adhesion agent could prevent adhesion followed by surgery in obstetrics and gynecology effectively.

Comparative proteomics elucidates the dynamics of ovarian development in the Chinese mitten crab Eriocheir sinensis.

Ovarian development is a complex physiological process for crustacean reproduction that is divided into the oogonium proliferation stage, endogenous vitellogenic stage, exogenous vitellogenic stage, and oocyte maturation stage. Proteomics analysis offers a feasible approach to reveal the proteins involved in the complex physiological processes of any organism. Therefore, this study performed a comparative proteomics analysis of the ovary and hepatopancreas at three key ovarian stages, including stages I (oogonium proliferation), II (endogenous vitellogenesis) and IV (exogenous vitellogenesis), of the Chinese mitten crab Eriocheir sinensis using a label-free quantitative approach. The results showed that a total of 2,224 proteins were identified, and some key proteins related to ovarian development and nutrition metabolism were differentially expressed. The 26 key proteins were mainly involved in the ubiquitin/proteasome pathway (UPP), cyclic AMP-protein kinase A (cAMP-PKA) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway during oogenesis. Fifteen differentially abundant proteins (DAPs) were found to participate in vitellogenesis and oocyte development, such as vitelline membrane outer layer protein 1 homolog, vitellogenin, vitellogenin receptor, heat shock 70 kDa protein cognate 3 and farnesyl pyrophosphate synthase. Forty-seven DAPs related to nutrition metabolism were identified, including the protein digestion, fatty acid metabolism, prostaglandin metabolism, lipid digestion and transportation, i.e. short-chain specific acyl-CoA dehydrogenase, acyl-CoA desaturase, fatty acid-binding protein, long-chain fatty acid CoA ligase 4, and hematopoietic prostaglandin D synthase. These results not only indicate proteins involved in ovarian development and nutrient deposition but also enhance the understanding of the regulatory pathways and physiological processes of crustacean ovarian development.

Diammonium glycyrrhizinate lipid ligand ameliorates lipopolysaccharide-induced acute lung injury by modulating vascular endothelial barrier function.

The aim of the present study was to investigate the effects of diammonium glycyrrhizinate lipid ligand (DGLL) treatment on acute lung injury (ALI) and pulmonary edema induced by lipopolysaccharide (LPS) in Sprague-Dawley rats. Rats orally received 30, 60 and 120 mg/kg DGLL. After 1 h, the rat ALI model was established by LPS (10 mg/kg) intraperitoneal injection. After 6 h, lung injury was evaluated using hematoxylin and eosin staining techniques. Pulmonary edema was evaluated using lung wet-dry weight ratio, protein concentrations in the bronchoalveolar lavage fluid (BALF) and Evans blue (EB) extravasation in lung tissue. The expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in lung tissues were measured using ELISA. Myeloperoxidase (MPO) expression levels were detected by immunohistochemical staining. Western blotting was used to measure the expression level changes of intercellular adhesion molecule (ICAM)-1, as well as adherent and tight junction proteins, including vascular endothelial (VE)-cadherin, zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM)-1 that were associated with pulmonary inflammation and microvascular permeability. DGLL treatment significantly alleviated ALI induced by LPS, which was demonstrated by reduction of MPO-positive cells and expression levels of TNF-α, IL-1ß and ICAM-1 in rat lung tissues. In addition, DGLL abrogated LPS-induced pulmonary edema, decreased the protein concentration in BALF and reduced EB extravasation. DGLL also reversed the reduced expression of VE-cadherin and tight junction proteins, including ZO-1, occludin and JAM-1 in the lung tissues caused by LPS. In conclusion, DGLL exhibits a protective effect on LPS-induced rat ALI, which is associated with the inhibition of inflammatory cell infiltration and microvascular barrier disruption. The present results provide a theoretical basis for the application of DGLL for the potential clinical treatment of ALI.

Ibrolipim increases ABCA1/G1 expression by the LXRα signaling pathway in THP-1 macrophage-derived foam cells.

AIM: To determine the effects and potential mechanisms of ibrolipim on ATP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1) expression from human macrophage foam cells, which may play a critical role in atherogenesis. METHODS: Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RT-PCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays. RESULTS: Ibrolipim 5 and 50 µmol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXRα was also upregulated by the ibrolipim treatment. In addition, LXRα small interfering RNA completely abolished the promotion effect that was induced by ibrolipim. CONCLUSION: Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRα signaling pathway.

Variations in the Profiles of Vascular-Related Factors Among Different Sub-Types of Polycystic Ovarian Syndrome in Northern China.

Recently, a growing body of evidence has suggested that abnormal ovarian angiogenesis, secondary to the imbalance between various angiogenic markers, is involved in the pathogenesis of PCOS, and this has led to the use of various interventions (such as Diane-35) to restore the normal ovarian angiogenesis. Therefore, we conducted the current investigation to determine the role of such markers (endothelial growth factor (VEGF), endostatin (ES), and thrombospondin-1 (TSP-1)) in the pathogenesis of PCOS along with the associated changes in ovarian blood flow in patients with PCOS compared to healthy controls, both before and after a course of oral contraception. A total of 381 patients with PCOS and 98 healthy females of childbearing age were recruited from July 2014 to June 2017 at the Reproductive Center of the Second Affiliated Hospital of Harbin Medical University. The serum levels of VEGF, ES, and TSP-1 were determined by enzyme-linked immunosorbent assay, while ovarian perfusion was measured by the pulsatility index (PI) and resistance index (RI) by using transvaginal color Doppler ultrasound. Repeated analyses were carried out after 3 months of Diane-35 treatment. Post-treatment serum levels of luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio of patients with PCOS decreased significantly (P <0.05). The RI values of most PCOS patients increased after treatment (P<0.05), while PI was significantly increased in all patients (P<0.05). However, variable changes in the serum levels of TSP-1, VEGF, and ES after treatment were observed. Serum VEGF levels showed a negative correlation with serum LH/FSH ratio, T concentration, and ES (P <0.05), while ES levels were negatively correlated with serum T concentrations only (P<0.05). The markers of angiogenesis (VEGF, ES, and TSP-1) were expressed differently among PCOS patients, who also responded differently to the same course of Diane-35 treatment. This field still warrants further investigation to reach a more definitive conclusion.

Silencing CCAT2 inhibited proliferation and invasion of epithelial ovarian carcinoma cells by regulating Wnt signaling pathway.

Long non-coding RNA CCAT2 (colon cancer-associated transcript 2) is dysregulated in varieties of human tumors. However, the role of CCAT2 in epithelial ovarian carcinoma (EOC) is not yet known clearly. The aim of this study is to investigate the effects of CCAT2 on proliferation and invasion of EOC cells and the potential mechanisms by which CCAT2 functions. In the present paper, we found that knockdown of CCAT2 impaired cell proliferation and invasion in vitro. Furthermore, we also studied the role of CCAT2 in the modulation of Wnt/ß-catenin signaling pathway. Our results showed that knockdown of CCAT2 inhibited the expression of ß-catenin and the activity of TCF/LEF (T-cell factor/lymphoid enhancer factor) acting as a key transcription factor of Wnt/ß-catenin signaling pathway. In addition, we found that silencing CCAT2 down-regulated the expression of c-MYC and MMP-7. But, that was reversed by the treatment with LiCl (lithium chloride) which could activate canonical Wnt/ß-catenin signaling pathway. Taken together, these results indicate that CCAT2 may promote ovarian cancer progression, at least partly, through Wnt/ß-catenin signaling pathway. Thus, CCAT2 might represent a novel therapeutic target for ovarian cancer.

ERCC1 and XRCC1 but not XPA single nucleotide polymorphisms correlate with response to chemotherapy in endometrial carcinoma.

Our study aimed to investigate the correlation between single nucleotide polymorphisms of ERCC1/XRCC1/XPA genes and postoperative chemotherapy efficacy and prognosis of endometrial carcinoma. Our study included 108 patients with endometrial carcinoma and 100 healthy participants. ERCC1 rs11615/XRCC1 rs25487/XPA rs1800975 gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Then the chemotherapy efficacy and toxic effects of the patients were assessed. The genotype and allele frequency of ERCC1 rs11615/XRCC1 rs25487 in the case group were significantly different from that in the control group (all P<0.05). The patients with AA + GA in ERCC1 rs11615 had an increased risk of endometrial carcinoma than those with GG, and the risk of endometrial carcinoma for patients with AA + GA was also higher in comparison with patients with GG genotype in XRCC1 rs25487 (all P<0.05). GG on both ERCC1 rs11615/XRCC1 rs25487 had a higher effective rate of chemotherapy than GA + AA (all P<0.05). ERCC1 rs11615/XRCC1 rs25487 gene polymorphisms were linked with toxic effects in liver, kidney, and nervous system. ERCC1 rs11615/XRCC1 rs25487, muscular invasion, and tumor stage were independent risk factors for the prognosis of endometrial carcinoma (all P<0.05). However, no significant associations were observed between XPA rs1800975 polymorphism and chemotherapy efficacy and prognosis of endometrial carcinoma (all P>0.05). These results indicated that ERCC1 and XRCC1 but not XPA polymorphisms correlate with response to chemotherapy in endometrial carcinoma.

[Study on the expression of the gene deleted in colorectal carcinoma in ovarian carcinoma].

OBJECTIVE: The purpose of this study was to explore the relationship between the loss of the gene deleted in colorectal carcinoma (DCC) gene expression in ovarian carcinoma and the transformation, progression of the tumor and its clinicopathological factors. METHODS: DCC gene mRNA expression were examined by reverse transcription polymerase chain reaction (RT-PCR) in 34 malignant, 10 benign and 10 normal ovarian samples. To clarify the expression of DCC gene by the DNA cloning and the DNA sequencing analysis in normal ovarian sample. RESULTS: The expression of DCC gene was lost in no normal ovarian tissues, in 2 (2/10) benign lesions, while the loss of DCC gene expression was found in 19 (19/34, 56%) carcinomas (P < 0.05). Similar findings were also noted when subdivision was into serous (14/18) and mucinous (4/11) categories (P < 0.05). The percentage of the loss of DCC gene expression in stage III - IV was 68%, in stage I - II was 22%, as well as 42% in grade I - II and 90% in grade III. 61% of the carcinoma with metastasis presented the loss of DCC gene expression, then there was 33% in which without metastasis. CONCLUSIONS: In ovarian carcinomas, loss of DCC gene expression was significantly related to the serous phenotype, a high histological grade and a more advanced stage. The results indicated that loss of DCC gene expression may play an important role in ovarian carcinomas and its progression.

Expression and effects of JMJD2A histone demethylase in endometrial carcinoma.

Previous studies have demonstrated that JMJD2A is a potential oncogene and is overexpressed in human tumors. However, its role in the endometrial carcinoma remains largely unknown. In this study, we discovered that JMJD2A was overexpressed in endometrial carcinoma, using immunohistochemistry, quantitative real- time polymerase chain reaction, and western blotting. Downregulation of JMJD2A led to reduced endometrial carcinoma RL95-2 and ISK cell proliferation, invasion and metastasis as asessed with cell counting kit-8, cell migration and invasive assays. Collectively, our results support that JMJD2A is a promoter of endometrial carcinoma cell proliferation and survival, and is a potential novel drug target.