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Rapamycin has been proven to effectively inhibit the activation of primordial follicles while cisplatin-induced the loss of primordial follicles due to the over-activation of the primordial follicle stockpile. Whether rapamycin could inhibit the loss of primordial follicles induced by cisplatin is still unknown. The ovaries of neonatal Sprague Dawley rats were cultured in vitro in different doses of rapamycin (0.08, 0.16, and 0.32 μg/ml) and cisplatin (0.1, 0.4, and 0.8 μg/ml). The immature BALB/c mice were administered cisplatin with or without rapamycin by intraperitoneal injection. Ovaries were collected to analyze the histomorphology, the messenger RNA (mRNA) expression of anti-Mullerian hormone (AMH), growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15) and the expression of key proteins of mammalian target of rapamycin (mTOR) pathway. Growing follicle counts of ovaries cultured in vitro in the R0.16 and R0.32 groups were decreased and the ratio of growing to primordial follicles was also decreased in a dose-dependent manner. In the C0.8 group, growing follicles were decreased compared with the other groups while the ratio was substantially increased in the C0.4 and C0.8 group. Co-treatment attenuated primordial follicle loss and reduced the upregulated ratio induced by cisplatin. Ovarian follicle dynamics in vivo was consistent with the in vitro results. Primordial follicles counts were statistically increased and the ratio was reduced in the rapamycin group compared with the control group. Primordial follicle counts were dramatically reduced in the cisplatin group whereas co-treatment with rapamycin slightly recovered its counts. There was no obvious difference in the number of growing follicles between the cisplatin group and other groups. The ratio was significantly increased in cisplatin-treated mice whereas decreased in the co-treatment group. The apoptosis rate of antral follicles in cisplatin-treated mice was higher than the other groups while the apoptosis rate was decreased in the co-treatment group in vivo. Compared with the control and rapamycin group, the mRNA expression of AMH, GDF9, and BMP15 were downregulated in the cisplatin group. The co-treatment group recovered the mRNA expression of BMP15. In addition, the expression of key protein of mTOR pathway rpS6 and its phosphorylated forms were increased in the cisplatin-treated group while co-treatment decreased their expression. Rapamycin attenuated the loss of primordial follicles induced by cisplatin through the inhibitory effect of rapamycin on the mTOR pathway. These results suggest that rapamycin may be an effective drug for the protection of ovarian function during chemotherapy.

Callicarpa siongsaiensis Metcalf is a drought resistance shrub with ornamental potential. In this study, Illumina sequencing data were used to assemble the complete chloroplast genome of Callicarpa siongsaiensis. The length of the circular genome is 154,144 bp. It contains a total of 130 genes, including 87 protein-coding, 36 tRNA, and seven rRNA genes. The GC content of the chloroplast genome of C. siongsaiensis is 38.09%. The phylogenetic analysis fully resolved C. siongsaiensis in a clade with C. formosana.

Casearia glomerata Roxb. is classified in Salicaceae and has a high economic value. Herein, we report the complete chloroplast (cp) genome of C. glomerata using Illumina sequence data. The cp genome is 156,809 bp in length and contains a large single-copy (LSC) region of 84,888 bp and a small single-copy (SSC) region of 17,039 bp separated by two inverted repeat (IR) regions of 27,441 bp each. It contained a total of 123 genes, with an overall GC content of 36.81%. The phylogenetic analysis showed that C. glomerata is closely related to Casearia velutina. This study provides important sequence information for species identification and its phylogenetic relationship in the Salicaceae.

Background Primordial follicular depletion has thought to be a common adverse effect of chemotherapy especially for female of reproductive age. The study aimed to evaluate the protective effect of rapamycin on the primordial follicles and its potential mechanism for patients receiving chemotherapy. Methods 8-week old BALB/c female mice were randomly assigned into four groups (control; rapamycin; cyclophosphamide; and rapamycin combined with cyclophosphamide). Hematoxylin staining, immunohistochemical, TUNEL, western blotting and ELISA were employed to assess inter-group differences using Student’s t-test and Mann-Whitney test. Results Cyclophosphamide depleted the follicular reserve and induced the phosphorylation of the key proteins of PI3K/Akt/mTOR pathway in mice in a dose-dependent manner. Co-treatment with rapamycin significantly reduced primordial follicle loss at all cyclophosphamide dose groups and prevent the follicle growth wave caused by cyclophosphamide treatment (P

Epidermolytic hyperkeratosis (EHK) is a rare dominantly inherited skin disorder with erythroderma and hyperkeratosis. Mutations have been found in keratin 1 (K1) or keratin 10 (K10) gene. In the present study, we reported three sporadic and one familial Chinese EHK patients with their mutation findings. All the mutations turned out to be single heterozygous point substitutions. A novel mutation designated as E477K of K1 was identified in one patient, and previous reported mutations in codon 156 of K10, i.e. R156S, R156P, R156H were found in other patients. This is the first report of the keratin mutations in Chinese kindreds. The results showed that the possible correlation between the genotype and phenotype in these patients was complex, not only depended on the position of the mutation but also on the actual amino acid substitution. And palmoplantar keratoderma (PPKD) can be an accompanied symptom caused by either K1 or K10 mutation.