Targeting Effect of Betulinic Acid Liposome Modified by Hyaluronic Acid on Hepatoma Cells In Vitro.

Betulinic acid (BA) is a natural pentacyclic triterpenoid with broad-spectrum anticancer activity, which has great development potential as an anti-cancer drug. In this study, a novel hyaluronic acid (HA)-modified BA liposome (BA-L) was developed for use in targeted liver cancer therapy. The size, polymer dispersity index (PDI), zeta potential, and entrapment efficiency were measured. Cell viability, cell migration and clonogenicity, cellular uptake, immunohistochemistry of CD44, and protein expression of ROCK1/IP3/RAS were also investigated. BA, BA-L, and HA-BA-L had no inhibitory effect on the activity of LO2 normal hepatocytes, but they inhibited the proliferation of HepG2 and SMMC-7721 cells in a dose- and time-dependent manner, with HA-BA-L exhibiting the most prominent inhibitory effect. Compared with the BA-L group, the expression of CD44 in HepG2 cells in the HA-BA-L group was decreased. The results of WB showed that BA, BA-L, and HA-BA-L downregulated the expression of ROCK1, IP3, and RAS in HepG2 cells, and the expression level in the HA-BA-L group was significantly decreased. The easily prepared HA-BA-L was demonstrated to be an excellent CD44-mediated intracellular delivery system capable of targeting effects. Further mechanistic research revealed that the inhibition of HA-BA-L on HepG2 cells may be mediated by blocking the ROCK1/IP3/RAS signaling pathways.

Therapeutic Antidepressant Potential of NONHSAG045500 in Regulating Serotonin Transporter in Major Depressive Disorder.

BACKGROUND Major depressive disorder (MDD) is a chronic, life-threatening, highly disabling disease. Standardized treatment with fewer adverse effects, quick onset, and long-term maintenance of the effects of brief treatment for MDD is always being pursued. Long non-coding RNAs (lncRNAs) are highly expressed in the central nervous system and are involved in the occurrence and development of neurodegenerative and psychiatric diseases. This study aimed to investigate whether the overexpression and interference of 3 differentially down-regulated lncRNAs (NONHSAT142707, NONHSAG045500, and ENST00000517573) in MDD can affect the expression of central neurotransmitter serotonin (5-hydroxytryptamine) transporter (SERT) in vitro. MATERIAL AND METHODS First, we synthesized and validated the effect of 3 lncRNA plasmids and small interfering RNAs (siRNAs); next, we transfected the plasmids and siRNAs that caused significant overexpression or interference in SK-N-SH cells, and tested the expression of SERT by qRT-PCR. RESULTS The results showed that 3 lncRNA plasmids and siRNAs2 caused overexpression and interference, respectively. Only the overexpression of NONHSAG045500 could significantly inhibit the expression of SERT; interference with NONHSAG045500 could significantly strengthen the expression of SERT. CONCLUSIONS This study indicated that the expression of SERT could be regulated by up-regulating or down-regulating NONHSAG045500 expression and suggested that NONHSAG045500 could potentially be established as a new therapeutic target of MDD. Future work may be needed to definitively determine the correlation between NONHSAG045500 and SERT in vivo.

[Vulvar intraepithelial neoplasia: a clinicopathologic study of twenty cases].

OBJECTIVE: To investigate the clinical, pathological and immunohistochemical features of vulvar intraepithelial neoplasia (VIN). METHODS: According to the 2004 modified terminology of International Society for the Study of Vulvovaginal Diseases (ISSVD), the cases were diagnosed as VIN from patients who had performed vulvar biopsy in Beijing Wuzhou Women's Hospital from February 2009 to December 2011, which were reclassified as usual VIN and differentiated VIN. The clinical and pathological studies were conducted respectively. MaxVision immunohistochemical staining was used to detect the expression of Ki-67, p16 and p53 proteins. RESULTS: There were 20 cases of VIN in 237 patients, and the incidence of VIN was 8.4% in all of contemporary vulvar biopsy. In 17 cases of usual VIN, mean age was 29.6 years, the lesion typically presented with atypical cells involving almost all layers of the epithelium, which was equivalent to the high-grade squamous intraepithelial neoplasia of cervix. Immunohistochemistry for Ki-67 and p16 was strongly positive in usual VIN. High risk human papillomavirus (HPV) detection was also positive. The incidence of differentiated VIN was less than usual VIN, and there were only 3 cases in this study. In differentiated VIN, patients aged over 50 years, with mean of 53.7 years, and the lesion most commonly presented with lichen sclerosis background. There were epithelial thickening and extending, and parakeratosis, and atypia was strictly confined to the basal and parabasal layers of the epithelium where the cells enlarged with abundant eosinophilic cytoplasm, presented with prominent nucleoli, increased cellularity and abnormal keratinization. In differentiated VIN, p53 was strongly positive, Ki-67 and p16 immunohistochemical expression was confined to the basal layer only. CONCLUSIONS: VIN is a precursor of invasive squamous cell carcinoma of the vulva. The modified terminology of ISSVD classifies VIN as high-grade lesions. Definitive pathological diagnosis of VIN plays an important role in its timely treatment and the prevention of vulvar carcinoma.