Network Pharmacological Screening of Herbal Monomers that Regulate Apoptosis-Associated Genes in Acute Pancreatitis.

OBJECTIVES: In this study, we screened for differentially expressed genes in acute pancreatitis and the herbal monomers that regulate these genes. METHODS: Gene expression profile data were downloaded from the Gene Expression Omnibus database (GSE3644). We used the Human Protein Reference Database to determine the protein-protein interaction network and CFinder software (Department of Biological Physics of Eötvös University, Budapest, Hungary) to identify several functional modules. Then, we used Database for Annotation, Visualization and Integrated Discovery software (Frederick, Md) to perform a gene ontology-biological process functional enrichment analysis. Based on a database of herbal monomers and a literature search, we constructed a gene-herbal monomer regulatory network using Cytoscape software (San Diego, Calif), and we analyzed the relationships between apoptosis, genes, and herbal monomers. RESULTS: A total of 1745 differentially expressed genes were identified. Nine modules were identified, and the main function of module 3 was closely related to apoptosis. Within module 3, we selected 13 genes that were closely related to apoptosis for further analysis. In the gene-herbal monomer regulatory network, 18 herbal monomers that regulate multiple target genes were selected as the focus of this study. CONCLUSIONS: These herbal monomers regulate multiple target genes to induce apoptosis and may potentially be used as new drugs for acute pancreatitis treatment in the future.

Database screening of herbal monomers regulating autophagy by constructing a "disease-gene-drug" network.

BACKGROUND: Studies suggest an important role of autophagy as a target for cancer therapy. We constructed a "disease-gene-drug" network using the modular approach of bioinformatics and screened herbal monomers demonstrating functions related to autophagy regulation. METHODS: Based on the microarray results of the gene expression omnibus (GEO) database (GSE2435 and GSE31040, starvation-induced autophagy model), we used the human protein reference database (HPRD) to obtain the protein-protein interaction (PPI) network. In addition, we used the CFinder software to identify several functional modules, performed gene ontology-biological process (GO-BP) functional enrichment analysis using the DAVID software, constructed a herbal monomer-module gene regulatory network using literature search and the Cytoscape software, and then analyzed the relationships between autophagy, genes, and herbal monomers. RESULTS: We screened 544 differentially expressed genes related to autophagy, 375 pairs of differentially expressed genes, and 7 gene modules, wherein the functions of module 3 (composed of 7 genes) were enriched in "cell death". Using the constructed herbal monomer-module gene regulatory network, we found that 30 herbal monomers can simultaneously regulate these 7 genes, indicating a potential regulatory role in autophagy. CONCLUSIONS: Database screening using the disease-gene-drug network can provide new strategies and ideas for the application of herbal medicines in cancer therapy.

Bioinformatics screening regarding herbal components that targetedly regulate the function of tumour-associated macrophages.

As an important component of tumour stroma, tumour-associated macrophages (TAMs) promote tumour development and progression. Herbs have been increasingly used in anticancer therapies due to their wide-ranging anticancer effects and minor side-effects. However, no herb-based treatments targeting TAMs have yet been proposed. To address this issue, screening using modular analysis bioinformatics techniques found 6 core functional modules for TAMs that contain 46 total genes. Moreover, 15 potential new anticancer drugs that regulate the genes in the 6 core modules were identified through bioinformatics techniques and Fisher's exact test. Our results provide a new research avenue for targeting TAMs in anticancer therapies.

[Effects of Astragalus polysaccharides and Cordyceps sinensis mycelium mixture on the transforming growth factor-beta1 expression in chronic rejection of artery transplantation: experiment with rats].

OBJECTIVE: To explore the effect of Astragalus polysaccharides (APS) and Cordyceps sinensis (CP) mycelium mixture on the chronic rejection of artery transplantation. METHODS: The abdominal arteries of 180 Wistar rats were isolated and transplanted to 180 SD rats whose with their abdominal arteries resected. The 180 recipient SD rats were randomly divided into blank control group (n = 20), APS group (n = 40, receiving gastric perfusion of APS 1 mg/kg bid), APS + low-dose CP group (n = 40, receiving APS and CP mycelium powder 1.25 g/d), APS + medium-dose CP group (n = 40, receiving APS and CP mycelium powder 2.5 g/d), and APS + high-dose CP group (n = 40, receiving APS and CP mycelium powder 5 g/d). Thirty days later the SD rats were killed with the transplanted abdominal arteries taken out to undergo microscopy. The expression of transforming growth factor (TGF)-beta(1) in the transplanted artery was examined by immunohistochemistry. RESULTS: In the control group, overexpression of TGF-beta(1) was observed in the intimal smooth muscle cells, monocytes, arterial endothelial cells, and arteriole, venule, and blood capillary endothelial cells in extima. However, the expression levels of TGF-beta(1) in the APS group and the 3 mixture administration groups were all significantly lower, especially in the medium- and high-dose groups (all P < 0.01). Severe edema of arterial endothelial cells and proliferation of monocytes were observed microscopically in the control group. Under electron microscope, rough endoplasmic reticulum and Golgi body were abundant in the control group. While in the mixture administration groups these changes were either weakened or absent. CONCLUSION: Astragalus polysaccharides and Cordyceps sinensis mycelium polysaccharides mixture can decrease the expression of TGF-beta(1) and inhibit the synthesis of collagen in the transplanted arteries.

[Effect of electroacupuncture on myoelectric activity of Jejunal limb After Roux-en-Y esophagojejunostomy].

OBJECTIVE: To explore the effect of electroacupuncture on myoelectric activity of Jejunal limb after Roux-en-Y esophagojejunostomy. METHODS: Fourteen health young pigs were randomly divided into 2 groups, an experimental group (total gastrectomy and Roux-en-Y esophagojejunostomy was carried out) and a control group (the abdominal cavity was closed after the electrode was placed), 7 pigs in each group. Electroacupunture was given at "Zusanli" (ST 36) in the experimental group. The changes of myoelectrogram of the jejunal limb was investigated. RESULTS: Compared with the control group, the amplitude and the frequency of the slow wave, and the amplitude and incidence rate of the spike potential in the experimental group were changed significantly; the duration of migrating motor complex (MMC) phase III was (2.6 +/- 0.7) minutes in the experimental group, which was significantly shorter than (7.1 +/- 1.1) minutes in the control group. Electroacupuncture did not significantly influence the amplitude and the frequency of the slow wave, but could increased significantly the incidence rate and the amplitude of the spike potential; after electroacupuncture, the duration of MMC phase III was (5.7 +/- 0.9) minutes, which was significantly longer than (2.6 +/- 0.7) minutes before electroacupuncture. CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) can relieve the Roux-en-Y stasis syndrome through influencing myoelectric activity of the jejunum.

Arterial chemotherapy of 5-fluorouracil and mitomycin C in the treatment of liver metastases of colorectal cancer.

AIM: Regional chemotherapy using hepatic artery catheters is a good method of treating patients with colorectal cancer liver metastases. We investigated the survival of patients with liver metastases from colorectal cancer using 5-fluorouracil (5-FU) and mitomycin C Cthrough implantable hepatic arterial infusion port. METHODS: Seventy-five patients with inoperable liver metastases from colorectal cancer were included between March, 1992 and November, 2001. We placed implantable hepatic arterial catheter (HAC) port by laparotomy. 5-FU, 1 000 mg/ m(2)/d continuous infusion for five days every four weeks, was delivered in the hepatic arterial catheter through the port. Mitomycin C, 30 mg/m(2)/d infusion in the first day every cycle through the port. Response to the treatment was evaluated by serial determinations of plasma CEA and imaging techniques consisting of computerized tomography and sonography of liver. RESULTS: Sixty-eight were performed hepatic artery chemotherapy and fifty-six were followed up among seventy-five HAC patients. Twenty-six patients(46.4 %) have responded and 4 complete remission were achieved. Eight patients (14.3 %) had stable liver metastases. Twenty-two patients (39.3 %) were progressed with increased tumor size and number. Twenty-nine patients(51.8%) had a decreased serum CEA level, while 10 patients (17.9 %) were stable and 17 patients (30.4 %) had an increased serum CEA level. There were no operative death in this series. Complications, which occurred in 18 patients (32.1 %), were as followed: hepatic artery thrombosis in 11, Upper gastric and intestinal bleeding in 3, liver abscess in 1, pocket infection in 1, cholangitis in 1, and hepatic artery pseudo-aneurysm in one patient. CONCLUSION: Combined infusion of 5-FU and mitomycin C by hepatic artery catheter port is an effective treatment for liver metastases from colorectal cancer. The high response and lower complication rates prove the adjuvant treatment of colorectal cancer with this treatment.