Effect of nourishing and purging fire Chinese herbal mixture on delaying light-induced premature puberty in rats.

OBJECTIVE: To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture (NYPF) in delaying light-induced premature puberty in rats. METHODS: Twenty-one days old female Sprague-Dawley rats were randomly assigned to normal group (N), long light exposure group (L), NYPF and normal saline group (NS). Rats in the L, NYPF and NS groups were exposed to 16 h: 350 lux light/8 h: dark, while rats in the N group were exposed to 12 h: 50 lux light/12 h: dark. NYPF and normal saline was administered to the rats in the NYPF group or NS group, respectively, from day 21. Five rats in every group were sacrificed at 9 p.m. on day 28 (P28), on the day when rat's vulva opened in the L group (L-VO), on the day when the first estrous interphase occurred in rats of L group (L-E1), and on the day when the second estrous interphase occurred in rats of L group (L-E2), respectively. RESULITS: On day 34, all rats in the L group, 80% of rats in the NS group, 40% of rats in the N group, and 20% of rats in the NYPF group showed complete opening of the vulva. At P28, mRNA level of hypothalamic kisspeptin (Kiss-1) in the L group was significantly higher than that in the N group (P < 0.05). The rats in the L and NS groups had significantly lower hypothalamic arginine-phenylalanine-amide (RFamide)-related peptide 3 (RFRP-3) mRNA levels than those in the N group (P < 0.05), whereas RFRP-3 mRNA level was significantly higher in the NYPF group than that in the L group (P < 0.05). At L-VO, the ovarian index of the L and NS groups was significantly higher than that of the N group (P < 0.05) and estradiol (E2) level of the NYPF group was significantly lower than that of the N and NS groups (P < 0.05); hypothalamic Kiss-1 mRNA level in the L and NS groups was significantly higher than that in the N and NYPF groups (P < 0.05), whereas hypothalamic RFRP-3 mRNA level in the L, NYPF, and NS groups was significantly lower than that in the N group (P < 0.05). At L-E1, E2 level of the L and NS groups was significantly higher than that of the N group (P < 0.01), whereas it was significantly lower in the NYPF group than that of the N, L, and NS groups (P < 0.01), and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group (P < 0.05); levels of serum melatonin and ovarian melatonin receptor 1 (MT-1) mRNA in the L, NYPF, and NS groups were significantly lower than those in the N group (P < 0.05). At L-E2, the uterine organ index of the NYPF group was significantly lower than that of the L group (P < 0.05); and ovarian MT-1 mRNA level of the L and NS groups was significantly lower than that in the N group (P < 0.05). CONCLUSIONS: NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration, and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.

Correlation of Ki-67 and gelsolin expression to clinical outcome in renal clear cell carcinoma.

OBJECTIVES: To analyze the expression levels of Ki-67 and gelsolin in renal cell carcinoma (RCC) and determine their prognostic value in association with other clinicopathologic factors using tissue microarray technology. Histologic nuclear grade, performance status, and clinical stage are important prognostic factors in RCC. Because patients with tumors of similar grade, performance status, and stage may show a wide variation in biologic behavior and clinical outcome, additional biomarkers for RCC are needed to provide further prognostic information and possibly offer insight into the mechanisms of the disease. METHODS: Using a renal cancer tissue microarray, we correlated the expression of Ki-67, a marker of cell proliferation, and gelsolin, an actin-binding protein, with grade, stage, and survival in patients with clear cell RCC. RESULTS: In Cox multivariate regression analysis, stage (pT) was the most significant predictor of cancer-specific survival (P <0.0001), followed by Ki-67 (P = 0.0216). In univariate analysis, increased Ki-67 expression predicted poor cancer-specific survival (P = 0.0006) when a cutoff value for Ki-67 staining was applied. In patients with grade 2 tumors, increased Ki-67 expression and decreased gelsolin expression in the same tumor was suggestive of poor cancer-specific survival (P = 0.0507). CONCLUSIONS: Our findings support the utility of Ki-67 as a prognostic biomarker for RCC and suggest a role for gelsolin in renal carcinogenesis.