Circulating chemerin levels in women with polycystic ovary syndrome: a meta-analysis.

OBJECTIVE: The present meta-analysis was conducted to investigate the association between circulating chemerin levels and polycystic ovary syndrome (PCOS) in women. METHODS: Relevant studies published up to May 2020 were searched from PubMed, Ovid, the Cochrane Library, and Clinical Trial Database. A random effects model was used to measure the strength of association between PCOS and chemerin by using the standardized mean difference (SMD) and 95% confidence interval (CI). All data were analyzed using Stata 12.0 (version 12; Stata-Corp, College Station, TX). RESULTS: The final meta-analysis included eight studies with 15 results including a total of 897 participants (524 patients with PCOS and 373 controls). The circulating chemerin levels were higher in patients with PCOS (random effects SMD = 1.07; 95% CI: 0.55-1.59; p < .001) than in controls. However, considerable heterogeneity across studies was not eliminated in subgroup analyses. The meta-regression analysis further suggested that region is the main source of heterogeneity (p = .001). CONCLUSIONS: Our meta-analysis indicated that women with PCOS have significantly higher circulating chemerin levels than in healthy women, indicating that chemerin may be involved in the pathogenesis of PCOS.

Comparative study on pharmacological effects of DM-phencynonate hydrochloride and its optical isomers.

AIM: The 3-azabicyclo(3,3,1)nonanyl-9-alpha-yl-alpha-cyclopentyl-alpha-phenyl-alpha-glycolate (DM-phencynonate hydrochloride, DMCPG) is a demethylated metabolite of 3-methyl-3-azabicyclo(3,3,1)nonanyl-9-alpha-yl-alpha-cyclopentyl-alpha-phenyl-alpha-glycolate (phencynonate hydrochloride, CPG). (+/-)DMCPG had one chiral center and two enantiomers [R(-) and S(+)DMCPG]. Here we carried out a comparative study of the pharmacological profiles of these optical isomers. METHODS: Affinity and relative efficacy were tested using a radioligand-binding assay with muscarinic acetylcholine receptors from the rat cerebral cortex. Pharmacological activity was assessed in three individual experiments: (1) potentiating the effect of a sub-threshold hypnotic dose of sodium pentobarbital; (2) inhibiting oxotremorine-induced salivation; and (3) inhibiting the contractile response to carbachol. RESULTS: In the competitive binding assay, R(-)DMCPG (K(i)=763.75 nmol/L) was 4- and 2-fold more potent than (+/-)DMCPG (K(i)=3186 nmol/L) and S(+)DMCPG (K(i)=1699 nmol/L) in inhibiting the binding of [(3)H]QNB. The R(-) and S (+) configurations showed positive cooperation (n(H)>1) with the muscarinic receptor, whereas (+/-)DMCPG had a negative cooperation (n(H)<1) relationship with the muscarinic receptor in a radio-binding assay. Both the R(-) and S(+) configurations could potentiate the effect of sub-threshold hypnotic dose of sodium pentobarbital in a dose-dependent manner (the ED(50) values were 2.53 and 18.65 mg/kg, respectively), but (+/-)DMCPG did not display significant central depressant effects at doses from 10 to 29.15 mg/kg (P>0.05). (+/-)DMCPG and its optical isomers suppressed the guinea pig ileum contractile response to carbachol. The IC(50) values were 7.78 x 10(-9), 1.88 x 10(-7), and 1.038 x 10(-7) nmol/L, respectively. In the anti-salivation study, (+/-)DMCPG and its enantiomers depressed oxotremorine- induced salivation in a dose-dependent manner, and the order of potency was R(-)DMCPG (ED(50)=0.44 mg/kg) > (+/-)DMCPG (ED(50)=2.88 mg/kg) >S(+)DMCPG (ED(50)=5.05 mg/kg). CONCLUSION: (+/-)DMCPG and its optical isomers have differences in their pharmacological potencies as anticholinergic agents, and the R(-) configuration is more active than the S(+) configuration.