Nanoparticle-Encapsulated Liushenwan Could Treat Nanodiethylnitrosamine-Induced Liver Cancer in Mice by Interfering With Multiple Critical Factors for the Tumor Microenvironment.

We previously isolated an ethanol fraction of LSW (Liushenwan pill, a traditional Chinese medicine) which has been shown to prevent and treat liver cancer induced by nanodiethylnitrosamine (nanoDEN) in mice. In the present study, we utilized a high-pressure microfluidics technique to generate LSW lipid nanoparticles (nano-LSW) to reduce its toxicity, and enhance its inhibitory effect on tumor growth, and further evaluate its therapeutic effect using a nanoDEN-induced mouse model of liver cancer. Our in vitro results indicated that nano-LSW-low could induce apoptosis in HepG2 cells, but exhibited low toxicity in L02 cells. Furthermore, the in vivo results indicated that nano-LSW-low exerted minimal or no damage to normal hepatocytes, kidney, and small intestine tissues. In addition, our results showed that at the 20th week, the inflammatory infiltration in the mice in the model group increased severely, and partial pimelosis and fibrosis occurred. In contrast, the liver tissues in the mice treated with nano-LSW exhibited only slight inflammatory infiltration, without pimelosis and fibrosis. At the 30th week, 4 out of 5 liver tissues in the model group showed hyperplastic nodules by hematoxylin and eosin (H&E) staining. However, the liver tissues in the nano-LSW treatment group did not showed hyperplastic nodules. Immunohistochemical staining showed that, in contrast to the model group, the levels of COX-2, PCNA, ß-catenin, and HMGB1 protein expressions were significantly lower in the nano-LSW-low group at the 20th and 30th week. Compared to model group, the COX-2, TNF-α, Smad-2, and TGF-ß1 mRNA levels obviously decreased in the liver tissue after the nano-LSW-low treatment. Taken together, nano-LSW-low may serve as a potent therapeutic agent for preventing liver cancer by interfering with multiple critical factors for the tumor microenvironment during oncogenesis.

[Effect of PI3K/AKT inhibitor on benign prostate hyperplasia and its mechanism: an experimental study].

OBJECTIVE: To explore the effect of the phosphoinositide 3-kinase/protein kinase B (PI3K/PKB or PI3K/AKT) signaling pathway inhibitor on benign prostate hyperplasia (BPH) and its mechanism. METHODS: Forty-eight SD male adult rats aged 12 weeks were equally randomized to 4 groups: sham operation control, BPH model, 50 mg LY294002 and 100 mg LY294002. The BPH models were made by muscular injection of testosterone propionate at 10 mg/kg/d for 30 days following castration. The LY294002 groups were treated with the PI3K/AKT signaling pathway inhibitor LY294002 at 50 and 100 mg/kg every other day for 30 days. The prostates of the rats were weighed and the structural changes of the prostatic histiocytes observed under the light microscope. The expressions of Ki-67, anti-apoptotic Bcl-2 and apoptotic Bax were detected by immunohistochemistry, and the apoptosis of prostatic cells determined by terminal de-oxynucleotidyl transferase-mediated dUTP nick end labeling. RESULTS: The prostate wet weight and prostatic index were (551 +/- 10.8) mg and 1.61 +/- 0.05 in the sham operation group, (687 +/- 13.8) mg and 2.15 +/- 0.12 in the BPH model group, (623 +/- 23.5) mg and 1.95 +/- 0.11 in the LY294002 50 mg group (P < 0.05 versus the BPH models) and (561 +/- 12.6) mg and 1.71 +/- 0.18 in the LY294002 100 mg group (P < 0.01 versus the BPH models). The expressions of apoptotic Bax and anti-apoptotic Bcl-2 were 16.7% and 16.7% in the sham operation group, 16.7% and 58.3% in the BPH model group, 33.3% and 33.3% in the LY294002 50 mg group (P < 0.05 versus the BPH models), and 50.0% and 25.0% in the LY294002 100 mg group (P < 0.01 versus the BPH models). The proliferative and apoptotic indexes were 14.2 +/- 6.4 and 6.5 +/- 1.8 in the epithelial and 7.6 +/- 2.6 and 2.5 +/- 0.3 in the interstitial tissue of the sham operation group, 50.9 +/- 12.8 and 2.7 +/- 1.4 in the epithelial and 16.5 +/- 5.7 and 1.3 +/- 0.8 in the interstitial tissue of the BPH models, 32.0 +/- 13.8 and 6.2 +/- 2.5 in the epithelial and 12.1 +/- 3.8 and 1.6 +/- 1.1 in the interstitial tissue of the LY294002 50 mg group (P < 0.05 versus the BPH models), and 17.8 +/- 14.7 and 7.4 +/- 3.6 in the epithelial and 9.5 +/- 3.4 and 2.2 +/- 1.3 in the interstitial tissue of the LY294002 100 mg group (P < 0.01 versus the BPH models). CONCLUSION: The increased proliferation and decreased apoptosis of prostatic cells in the BPH animal models might be involved in the development and progression of BPH. The PI3K/AKT signaling pathway plays an important role in the development of BPH, which could be inhibited by blocking the PI3K/AKT signaling pathway.

[Cytogenetic analysis and phenotype location analysis on the karyotype of a ring chromosome 21 syndrome].

OBJECTIVE: To search the forming cause and the correlation between the clinical phenotype and chromosome band by the cytogenetic analysis on a case of ring chromosome 21 syndrome. METHODS: Identification and location of 21 ring chromosome were performed with the G-banding, C-banding, N-banding, high-resolution banding and fluorescence in situ hybridization (FISH) techniques. RESULTS: It was found that the karyotypes of the patient's parents are normal. The patient's karyotype is 46,XY, r(21)[91]/46,XY,r(21;21)(p11q22.3;p11q22.3) [5]/45,XY,-21[4]. CONCLUSION: The clinical phenotype of ring chromosome 21 syndrome is related to the deletion of distal segment of 21q, and the abnormal sexual development of male is related with the deletion of 21q22.3.