[Jujing Gouju Granules promote reproductive function in rats with spermatozoa].

OBJECTIVE: To observe the intervention effect of Jujing Gouju Granules (JGG) on teratozoospermia (TZ) in rats and explore its action mechanism. METHODS: Thirty-two male SD rats were randomly divided into four groups of an equal number: normal control, TZ model control, high-dose JGG and low-dose JGG. The TZ model was established in the latter three groups of rats by intragastric administration of methyl methanesulfonate at 4 mg/100 g body weight/day for 7 consecutive days. After successful modeling, the animals in the high- and low-dose JGG groups were treated with JGG at 0.288 and 0.072g/100 g body weight/d, respectively, while the normal controls with the same dose of normal saline, all for 48 days. At two days after medication, all the rats were sacrificed and the right epididymides harvested for sperm counting, sperm motility analysis, observation the sperm morphology, and determination of contents of fructose, zinc, α-glucosidase and superoxide dismutase (SOD) in the epididymal suspension, the levels of IL-6, IL-8 and TNF-α in the seminal plasma, and that of reactive oxygen species (ROS) in the sperm. RESULTS: Both sperm concentration and motility were significantly increased and the percentage of morphologically abnormal sperm decreased in the JGG groups compared with the model controls, even more significantly in the high- than in the low-dose JGG group (P < 0.05). No statistically significant difference was found in the contents of fructose and zinc in the epididymal suspension among the four groups, but that of α-glucosidase was remarkably lower in the TZ model than in the normal controls (ï¼»50.31 ± 2.12ï¼½ vs ï¼»67.23 ± 3.54ï¼½ U/L, P < 0.05), but higher in the high- and low-dose JGG groups (ï¼»79.36 ± 2.35ï¼½ and ï¼»56.25 ± 3.44ï¼½ U/L) than in the model control group (P < 0.05). The level of ROS was markedly higher and that of SOD lower in the TZ model than in the normal controls, while the former was lower and the latter was higher in the JGG groups than in the TZ model controls (P < 0.05), even more significantly in the in the high- than in the low-dose JGG group (P < 0.05). Compared with the TZ model controls, the rats in the JGG groups showed dramatically decreased levels of IL-6, IL-8 and TNF-α in the seminal plasma, even more significantly in the high- than in the low-dose JGG group (P < 0.05). CONCLUSIONS: Jujing Gouju Granules can improve sperm morphology in teratozoospermia rats, possibly by regulating oxidative stress and inflammation-related factors.

Integrated analysis of comprehensive metabolomics and network pharmacology to reveal the mechanisms of abelmoschus manihot (L.) medik. in the treatment of cisplatin-induced chronic kidney disease.

Background: Abelmoschus manihot (L.) Medik ("Huangkui" in Chinese, HK) has been widely used for the treatment of kidney diseases. Nephrotoxicity is the side effect of cisplatin (CDDP), which greatly limits its clinical application. Therefore, CDDP could be used to establish the chronic kidney disease (CKD) model. However, the protective effects of HK on CDDP-induced CKD have not been investigated. Purpose: To explore the protective effect and underlying mechanisms of HK on multiple low-dose CDDP-induced CKD in rats by the integrated analysis of serum, kidney, and urine metabolomics and network pharmacology. Methods: The CKD model was induced by multiple low-dose CDDP. Body weight, organ index, serum biochemical, and kidney histology were examined to evaluate the effect of HK. Serum, kidney, and urine were collected and profiled by HILIC/RPLC-Q-TOF/MS-based metabolomics. Potential biomarkers (PBs) were screened according to the criteria of VIP >1, p < 0.01, and FC > 2, and then identified or assigned. The pathway analysis and PBs enrichment were conducted by MetaboAnalyst and ChemRICH. Furthermore, network pharmacology was adopted to dig out the active components and targets. Finally, the results from metabolomics and network pharmacology were integrated to confirm each other. Results: HK could recover the CDDP-induced abnormal pharmacological and metabolic profile changes. A total of 187 PBs were screened and identified from the serum, kidney, and urine metabolomics. Pathway analysis showed that multiple metabolic pathways, mainly related to amino acid and lipid metabolisms, were involved in the nephroprotective effect of HK, and especially, HK could significantly alleviate the disorder of tryptophan metabolism pathway in serum, kidney, and urine. Meanwhile, network pharmacology analysis revealed that 5 components in HK and 4 key genes could be responsible for the nephroprotection of HK, which also indicated that the metabolism of tryptophan played an important role in HK against CKD. Conclusion: HK has a nephroprotection on CDDP-induced CKD, mainly by restoring the dysregulation of tryptophan metabolism. Integrated analysis of serum, kidney, and urine metabolomics and network pharmacology was a powerful method for exploring pharmacological mechanisms and screening active components and targets of traditional Chinese medicine.

The Clinical Study of Urokinase-Type Plasminogen Activator and Vascular Endothelial Growth Factor in Gastric Cancer.

The aim of this study is to explore the expression and significance of urokinase-type plasminogen activator (u-PA) and vascular endothelial growth factor (VEGF) in gastric cancer, providing a novel insight for the diagnosis and treatment of gastric cancer. The gastric cancer specimens, which were excised from 87 patients and confirmed during July, 2012-July, 2014, were selected as observation group, and the normal tissue next to the tumor (more than 5 cm from the edge of the tumor) from 45 patients were randomly selected as control. u-PA and VEGF were detected by immunohistochemistry for the analysis of the correlation of u-PA and VEGF in two groups. The positive rates of u-PA and VEGF in gastric cancer tissue were 81.61 and 79.31 %, respectively, which were 6.67 and 8.89 % in the control group, respectively. The positive rates in the observation group were obviously higher than those in the control group, and the difference was statistically significant (P < 0.05). Among the 87 gastric cancer tissue samples from the observation group, the positive rates of u-PA and VEGF in the gastric cancer with poor differentiation, lymphatic metastasis, invasion up to serosal layer, and TNM stage III + IV were obviously higher than those in the gastric cancer with high differentiation, non-lymphatic metastasis, invasion not up to the serosal layer, and TNM stage I + II, and the difference was statistically significant (P < 0.05). Among the 87 gastric cancer tissue samples from the observation group, u-PA and VEGF were found to be positive in 60 cases and negative in 7 cases. By comparing the two groups, u-PA and VEGF were positively correlated in gastric cancer tissue (P < 0.05). u-PA and VEGF were highly expressed in gastric cancer tissue, which could be used as the molecular biological indicators to predict the invasion and metastasis potential of gastric cancer. The combination of two factors plays a guiding role in early diagnosis and treatment of gastric cancer.

Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma (HCC) still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. METHODS: Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR) and protein (Western blot) levels. The phosphorylation status of cyclin-dependent kinases (CDKs) and retinoblastoma (Rb) protein was also examined using Western blot analysis. RESULTS: Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1), pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. CONCLUSION: Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.