OBJECTIVE: This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1), aromatase, and rat 3β-HSD4 activities. METHODS: Human and rat placental 3β-HSDs activities were determined by converting pregnenolone to progesterone and progesterone secretion in JEG-3 cells was determined using HPLC/MS-MS, and human aromatase activity was determined by radioimmunoassay. RESULTS: PFSA inhibited human 3β-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC ₅₀: 9.03 ± 4.83 μmol/L) > perfluorodecanesulfonic acid (PFDS, 42.52 ± 8.99 μmol/L) > perfluoroheptanesulfonic acid (PFHpS, 112.6 ± 29.39 μmol/L) > perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 μmol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3β-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1-10 μmol/L PFOS and PFDS significantly reduced progesterone biosynthesis in JEG-3 cells. Docking analysis revealed that PFSA binds to the steroid-binding site of human 3β-HSD1 in a carbon chain length-dependent manner. All 100 μmol/L PFSA solutions did not affect rat 3β-HSD4 and human placental aromatase activity. CONCLUSION Carbon chain length determines inhibitory potency of PFSA on human placental 3β-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.
Humans ; Pregnancy ; Female ; Rats ; Animals ; Placenta ; Progesterone/pharmacology* ; Aromatase/pharmacology* ; Cell Line, Tumor ; Fluorocarbons ; Alkanesulfonic Acids ; Structure-Activity Relationship ; Hydroxysteroid Dehydrogenases/pharmacology*

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

Objective:To investigate the effect and mechanism of Chaihu Jia Longgu Mulitang （CJLM） on hippocampal NOD-like receptor protein 3 （NLRP3）inflammasome pathway in rats with depression. Method:Sixty male SD rats were randomly divided into a normal group，a model group， a MCC950 （1 mg·kg^-1） group， and high- （13 g·kg^-1）， medium- （6.5 g·kg^-1）， and low-dose （3.25 g·kg^-1） Chaihu Jia Longgu Mulitang groups， with 10 rats in each group．The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group. Rats were treated correspondingly for 21 days by intraperitoneal injection in the MCC950 group and gavage in other groups. The normal group and the model group received an equal volume of normal saline. The depression-like behaviors of rats were observed by sucrose preference test （SPT） and novelty-suppressed feeding test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of interleukin-1β （IL-1β） and IL-18 in the hippocampus of depressed rats. Western blot was used to detect the protein levels of NLRP3， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， and Caspase-1. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （P<0.01）， prolonged novelty-suppressed feeding time （P<0.01）， enhanced protein expression of NLRP3，ASC， and caspase-1 （P<0.05， P<0.01）， and elevated expression of IL-1β and IL-18 （P<0.01）. Conclusion:CJLM can alleviate depression-like behaviors in CUMS-induced model rats， and the underlying mechanism is related to the inhibition of the NLRP3 inflammasome pathway．

Objective:To study the effect of Chaihu Jia Longgu Mulitang on phosphatidylinositol-3-kinases （PI3K）/protein kinase B （Akt）/glycogen synthase kinase 3β （GSK3β）/β-catenin signaling pathway of hippocampus in rats with depression. Method:A total of 120 SD rats were randomly divided into normal group，model group， and low， middle and high-dose Chaihu Jia Longgu Mulitang groups（3.25，6.5，13 g·kg^-1）， and fluoxetine group， with 20 rats in each group. Except normal group， the depression model was prepared through chronic unpredictable mild stimulation（CUMS）. The normal group and the model group were given normal saline with 6.5 g·kg^-1 by gavage. Chaihu Jia Longgu Mulitang groups were intragastrically given corresponding herbal drugs 3.75，6.5，13 g·kg^-1， while fluoxetine group was intragastrically given fluoxetine 10 mg·kg^-1 for 21 days， once a day. Then the depressive behaviors of rats were observed by sucrose preference test （SPT） and forced swimming test （FST）. Western blot was used to detect the protein expressions of PI3K，Akt，GSK3β and phosphorylation level. Result:Compared with normal group，the sucrose preference index was decreased significantly，while the immobility time in FST was increased significantly（P<0.01）， the protein expressions of PI3K， p-PI3K p110， p-PI3K p85 were decreased significantly （P<0.01）， and expressions of Akt， p-Akt Thr308，p-Akt Ser473， p-GSK3β Ser9 and β-catenin were decreased significantly（P<0.01）， while the level of GSK3β， p-GSK3β Tyr216 were increased significantly in model group（P<0.05，P<0.01）. Compared with model group，Chaihu Jia Longgu Mulitang could increase sucrose preference index and decrease the immobility time in FST（P<0.01）， the protein expressions of PI3K p110 and PI3K p85 was increased significantly （P<0.01）， levels of Akt Thr308，Akt Ser473， p-GSK3β Ser9， β-catenin were increased significantly （P<0.01）， whereas levels of GSK3β， and GSK3β Tyr216 were decreased significantly. Conclusion:Chaihu Jia Longgu Mulitang could increase protein expression and activity of PI3K in rat hippocampus， activate Akt， inhibit GSK3β kinase activity and prevent β-catenin from degradation， so as to increase PI3K/Akt pathway activity in rat hippocampus， and protect hippocampal neurons.