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Farrerol (FA) is a flavanone isolated from the Chinese herbal medicine “Man-shan-hong” (Rhododendron dauricum L.). In the present study, FA decreased the viability of SKOV3 cells in a dose- and time-dependent manner, and it induced G2/M cell cycle arrest and cell apoptosis. Cell cycle distribution analysis via flow cytometry showed that FA decreased G1 populations and increased G2/M populations in SKOV3 cells. Additionally, Western blotting confirmed an increase in the expression level of proteins involved in the cell cycle, e.g., CDK and cyclins. FA-induced apoptosis in SKOV3 cells was also investigated using a TUNEL assay, and increased expression levels of proapoptotic factors, including Caspase-3 and poly ADP ribose polymerase (PARP), through the Extracellular signal-regulated kinase (ERK)/MAPK pathway were investigated. Proinflammatory cytokines (e.g., IL-6, TNF-α, and IL-1) have been identified as a driver of the pathological mechanisms underlying involuntary weight loss and impaired physical function, i.e., cachexia, during cancer, in the present study, we showed that farrerol attenuates TNF-α-induced lipolysis and increases adipogenic differentiation in 3T3-L1 cells. Thus, farrerol could potentially be used as an anticancer agent or anticachetic drug.

Vascular smooth muscle cell (VSMC) phenotype switching from contractile to synthetic is essential for proliferation and migration in vascular pathophysiology. Connective tissue growth factor (CTGF) is a matricellular protein involved in cell adhesion, migration, and proliferation. Kahweol, a diterpene molecule in arabica coffee beans, has been reported to have anti-inflammatory, antiproliferative, and apoptotic effects in many cells. However, in VSMCs, the effects of kahweol on CTGF activities have not been investigated. Thus, in this study, the effects and associated mechanisms of kahweol in CTGF-dependent phenotype switching and migration in VSMCs were examined. Experiments were performed on primary rat aortic smooth muscle cells and a rat VSMC line, A7r5. Western blot analysis was used to determine the protein levels. The mRNA levels of synthetic markers were measured by qRT-PCR. Migration of VSMCs was evaluated by wound healing and transwell assays. Kahweol reduced the angiotensin II (Ang II)-induced CTGF expression. Further, kahweol inhibited expressions of synthetic phenotype markers of VSMC. The kahweol-reduced synthetic marker protein levels were reversed by the administration of rCTGF. However, expressions of contractile phenotype markers of VSMC were not affected. Kahweol suppressed Ang II-stimulated VSMC migration. Moreover, kahweol downregulated Ang II-induced p-FAK, p-Erk, and Yes-associated protein (YAP) protein expressions. Taken together, in Ang II-stimulated VSMCs, kahweol inhibited CTGF-dependent synthetic phenotype switching and migration, with focal adhesion kinase (FAK), Erk, and YAP involved in the underlying mechanisms of the kahweol effects. These results suggest that kahweol has a potential as a therapeutic agent to inhibit CTGF, which is a molecular target in sclerogenic vascular disease.

To determine whether spouses who only smoke cigarettes outside the home can reduce the secondhand smoke (SHS) exposure of non-smoking pregnant women to the levels of those with non-smoking spouses.In this cross-sectional survey performed between 1 October 2006 and 31 July 2007, 896 non-smoking pregnant women in their 35th gestational week were included. Hair nicotine levels and the smoking behaviour of their spouses at home were assessed.The geometric means of the hair nicotine levels of the participants with non-smoking spouses (group A), the participants with spouses who only smoked outside the home (group B), and the participants with spouses who smoked inside the home (group C) were 0.33 ng/mg (95% CI 0.30 to 0.35), 0.51 ng/mg (95% CI, 0.45 to 0.57) and 0.58 ng/mg (95% CI, 0.51 to 0.65), respectively. The mean log hair nicotine level of group A was significantly different from the other groups (p0.001, Scheffe's post hoc test). Multiple linear regression analysis of the log-transformed hair nicotine levels of the participants after adjusting for confounding showed that the mean differences (SE of the mean difference) of groups B and C compared to the reference group A were 0.43 (0.07; p0.001) and 0.44 (0.10; p0.001), respectively.Spouses who only smoked outside the home did not reduce the level of SHS exposure of pregnant women to the level of pregnant women with non-smoking spouses. A strategy based on the separation of pregnant women and the smoking activity of their spouses might be inadequate to protect pregnant women from SHS at home.

OBJECTIVE: Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Epidemiologic studies have demonstrated an association between infection and periventricular leukomalacia. The purpose of this study was to determine whether ascending intrauterine infection could cause brain white matter lesions in the fetal rabbit. STUDY DESIGN: Rabbits with timed pregnancies underwent hysteroscopy at 20 to 21 days of gestation (70%). Animals were allocated in a ratio of 2:1 for inoculation with either Escherichia coli (0.2 ml containing 103 to 104 colony-forming units) or sterile saline solution. Both groups were treated with ampicillin-sulbactam (Unasyn, 100 mg/kg per day; Pfizer, Seoul) every 8 hours until they were killed 5 to 6 days after hysteroscopy. Histologic examination of the placentas and fetal brains was conducted. RESULTS: Forty-five animals underwent hysteroscopy; 31 were inoculated with E. coli and 14 with sterile saline solution. At the time the animals were killed, the rate of intrauterine infection was higher and there were fewer live fetuses in the E. coli–inoculated animals than in the saline solution group. Histologic evidence of brain white matter damage was identified in 12 fetuses born to 10 E. coli–inoculated rabbits but none in the saline solution group (p < 0.05). All rabbits with brain white matter lesions had evidence of intrauterine infection. Evidence of white matter damage included increased karyorrhexis, rarefaction, and disorganization of white matter. Apoptosis was demonstrated in areas of white matter damage by immunohistochemical studies. CONCLUSION: Experimental ascending intrauterine infection can cause fetal brain white matter lesions. (Am J Obstet Gynecol 1997;177:797-802.)

Aims: We investigated the genital group B streptococcus (GBS) carrier rate in Korean pregnant women and the serotype distribution in face of the recent increase of late-onset GBS disease in Korea. Methods: GBS screening was performed on 4045 healthy pregnant women at 35-37 weeks' gestation. In case of positive GBS culture, serotyping was performed by using GBS typing antisera. Results: When both vaginal and anorectal culture were performed, the GBS carrier rate was 10.0% (n=121/1205), which is the highest rate ever reported in Korea. Type III was more common (36%), and type Ia (13%) and Ib (7%) were less prevalent. Conclusions: Increased maternal genital GBS carrier rate and difference in serotype distribution pattern of GBS may be related to the recent increase of late-onset GBS disease in Korea.