Xiao Han

Effects of compound K on hyperglycemia and insulin resistance in rats with type 2 diabetes mellitus.

Compound K (CK) is a final metabolite of panaxadiol ginsenosides from Panax ginseng. Although anti-diabetic activity of CK has been reported in recent years, the molecular mechanism of CK in the treatment of diabetes mellitus remains unclear. In the present investigation, we established a rat model of type 2 diabetes mellitus (T2DM) with insulin resistance using high-fat diet (HFD) and streptozotocin (STZ), and attempted to verify more details and exact mechanisms in the treatment of T2DM. CK was administered orally at three doses [300, 100 and 30 mg/kg bodyweight (b.w.)] to the diabetic rats. Bodyweight, food-intake, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity (ISI), total glycerin (TG), total cholesterol (TC), as well as oral glucose tolerance test (OGTT) were evaluated in normal and diabetic rats. According to our results, CK could improve bodyweight and food-intake of diabetic rats. CK exhibited dose-dependent reduction of FBG, TG and TC of diabetic rats. CK treatment also enhanced FINS and ISI. Meanwhile, the glucose tolerance observed in the present study was improved significantly by CK. It is concluded from the results that CK may have improving effects on hyperglycemia and insulin resistance of diabetic rats. Furthermore, research showed that CK could promote the expression of InsR, IRS1, PI3Kp85, pAkt and Glut4 in skeletal muscle tissue of diabetic rats. These results indicate that the hypoglycemic activity of CK is mediated by improvement of insulin sensitivity, which is closely related to PI3K/Akt signaling pathway.

GHGKHKNK octapeptide (P-5m) inhibits metastasis of HCCLM3 cell lines via regulation of MMP-2 expression in in vitro and in vivo studies.

P-5m, an octapeptide derived from domain 5 of HKa, was initially found to inhibit the invasion and migration of melanoma cells. The high metastatic potential of melanoma cells was prevented by the HGK motif in the P-5m peptide in vitro and in an experimental lung metastasis model, suggesting that P-5m may play an important role in the regulation of tumor metastasis. The aim of this study was to measure the effect of P-5m on tumor metastasis of human hepatocarcinoma cell line (HCCLM3) in vitro and in vivo in a nude mouse model of hepatocellular carcinoma (HCC), and detect the mechanisms involved in P-5m-induced anti-metastasis. By gelatin zymography, matrix metallo-proteinases 2 (MMP-2) activity in HCCLM3 was dramatically diminished by P-5m peptide. In addition, the migration and metastasis of HCCLM3 cells was also inhibited by the peptide in vitro. In an orthotopic model of HCC in nude mice, P-5m treatment effectively reduced the lung metastasis as well as the expression of MMP-2 in the tumor tissues. Overall, these observations indicate an important role for P-5m peptide in HCC invasion and metastasis, at least partially through modulation MMP-2 expression. These data suggests that P-5m may have therapeutic potential in metastatic human hepatocarcinoma.

Screening for the protective effect target of deproteinized extract of calf blood and its mechanisms in mice with CCl4-induced acute liver injury

Liver injury is a common pathological basis of various liver diseases, and long-term liver injury is often an important initiation factor leading to liver fibrosis and even liver cirrhosis and hepatocellular carcinoma (HCC). It has been reported that deproteinized extract of calf blood (DECB) can inhibit the replication of hepatitis B virus and confers a protective effect on the liver after traumatic liver injury. However, few studies on the regulatory factors and mechanisms of DECB have been reported. In this current study, an acute mouse liver injury model was established with carbon tetrachloride (CCl4). The differentially expressed genes and related cell signal transduction pathways were screened using mRNA expression microarray. STEM software V1.3.6 was used for clustering gene functions, and the DAVID and KEGG databases were applied for the analysis. A total of 1355 differentially expressed genes were selected, among which nine were validated by RT-qPCR. The results showed that the Fas, IL1b, Pik3r1, Pik3r5, Traf2, Traf2, Csf2rb2, Map3k14, Pik3cd and Ppp3cc genes were involved in the regulation of DECB in an acute mouse liver injury model. Targets of the protective effects of DECB and its related mechanisms were found in mice with acute liver injury induced by carbon tetrachloride, which may provide an important theoretical basis for further DECB research.

mRNA chip-based analysis on transcription factor regulatory network central nodes of protection targets of Deproteinized Extract of Calf Blood on acute liver injury in mice

&NA; Our previous study found that Deproteinized Extract of Calf Blood (DECB) could protect the acute liver injury induced by carbon tetrachloride in mice, but the target‐related transcription factors and their regulatory networks were not comprehensively studied. Based on the mRNA expression microarray data obtained in the previous study, the mRNA transcription factor regulatory networks were constructed by screening the transcription factors of differentially expressed genes and their corresponding target proteins, and the analysis on the functions and pathways of the regulatory network central nodes was performed. Eight genes Ltf, Tnf, Il6, Jun, Il12b, Stat3, Rel and Crem could regulate the inflammatory factors, and TNF signaling pathway and Jak‐STAT signaling pathway might play an important role in the mechanism through which DECB protected the liver of mice. DECB can not only inhibit the apoptosis of hepatocytes, but also inhibit the inflammatory cytokines.

Combined antitumor effects of P‑5m octapeptide and 5‑fluorouracil on a murine model of H22 hepatoma ascites

The present study has demonstrated that P-5m octapeptide (P-5m) has therapeutic potential in metastatic human hepatocarcinoma, possibly through the modulation of matrix metalloproteinase-2 expression. The purpose of the present study was to evaluate the antitumor effect of P-5m combined with 5-fluorouracil (5-Fu) on the treatment of hepatoma 22 (H22) hepatocarcinoma malignant ascites in a mouse model. The inhibitory effect on the growth of mouse ascites tumors was monitored by measuring body weight gain, survival time, ascites volume, numbers of tumor cells, DNA synthesis and peritoneal capillary permeability analysis. The present data revealed a significant reduction in ascites volume and cell count in mice that were treated with P-5m plus 5-Fu. Furthermore, the median survival time in mice in the combination group was prolonged compared with the disease control group. Moreover, a significant reduction in the total H22 ascites cell count in mice from the combination group was observed when compared with the disease control group. P-5m plus 5-Fu was able to induce the cell cycle arrest and inhibit the peritoneal capillary permeability of the mice. To conclude, the present study indicated that P-5m may have therapeutic potential in ascites caused by hepatocellular carcinoma.

High-Throughput Screening of Escherichia coli O157:H7 Pathogenic Genes via Pathway Enrichment and Operon Analysis

BACKGROUND About thirty thousand people globally die every day from infectious diarrhea, mostly caused by pathogenic Escherichia coli (E. coli) O157:H7. METHODS In order to search for clinical diagnostic biomarkers and novel drug targets for infectious diarrhea, we used a bibliometric method to collect pathogenic genes of E. coli O157:H7 and performed a functional analysis of the important pathogenic genes by pathway enrichment and operon analysis. RESULTS We found 364 pathogenic genes which may be involved in infection with E. coli O157:H7 including 50 new specific pathogenic genes. It is possible that these newly found pathogenic genes will be of great importance in the treatment of E. coli O157:H7 infected diseases and the discovery of novel diagnostic biomarkers. CONCLUSIONS Our findings also lay a theoretical foundation for the control, diagnosis, and prognosis of pathogenic E. coli related diseases.

Anti-Fatigue Effect of Ginseng and Acanthopanax Senticosus Extracts

The aim of study was to optimize the extraction process of ginsenosides and investigate the anti-fatigue effect of ginseng and acanthopanax extracts. Orthogonal test was used to optimize the extraction process, loading swimming experiment was used to observe the ant-fatigue effect, and BUN, LDH, CK, glycogen, T-SOD, MDA, GSH-Px and LD were taken as the anti-fatigue indeses to be observed. The yield of ginsenoside was 3.8%. The swimming time of mice in the treatment group was significantly prolonged compared with that in the control group (P< 0.05). The hepatic glycogen storage, LDH, GSH-PX and SOD in the treatment groups were obviously increased (P<0.05). Serum MDA and LD levels in the treatment groups were decreased, but no statistical significance compared with those in the control group. The serum BUN was significantly decreased in the middle-dose group (P<0.05). There was no significant difference in the serum CK between the treatment groups and the control group.LDH levels in the middle-dose and high-dose groups were significantly different from those in the control group. The ginseng and acanthopanax extracts can exert its anti-fatigue effect through increasing the amount of liver glycogen reserve and reducing the damage of negative metabolic products caused by an excessive exercise to the body.

Necessity of Bioinformatics in the Setting of Pharmacy

In the wake ofthe gradual improvement of peoples living standards and the growing demand for health, new drug developments are becoming more and more needed. On the basis of the coming of post-genomic era and the development of computer technology, bioinformatics comes into the world as an efficient technology. In recent years, bioinformatics has been wildly used in novel drug design. Besides, bioinformatics has been merged into medical application, especially, together with the rapid development of molecular biology technology and the coming of post-genomicera; the research of drug resource is also facing a challenge of massive data. The application of cloud computing into the drug resource study has been an inevitable tendency. In this article, we discussed the importance and necessity of bioinformatics in the setting of pharmacy