Elucidation of the Anti-Lung Cancer Mechanism of Xiao'ai Jiedu Prescription Based on Network Pharmacology and Molecular Docking.

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

Aitongping patch could alleviate cancer pain via suppressing microglia activation and modulating the miR-150-5p/CXCL12 signaling.

PURPOSE: We aimed to investigate the pharmacological effects and mechanisms of the Aitongping formula for treating cancer pain. METHODS: We enrolled 60 cancer patients with Numeric Rating Scale above 4 and grouped them randomly as a Control group (N = 30) and a Patch group (N = 30). We also established bone cancer mice models via tumor implantation. And the animal groups were established as a Sham group, a tumor cell implantation (TCI) group, a TCI + Patch group, and a Patch group. RESULTS: After the validation of successful tumor implantation, we identified candidate miRNAs and genes that were dysregulated in TCI mice and compared their expressions between different mice groups. We also observed the effect of Aitongping patch in vitro in mice primary microglia. The time to disease progression and cancer stability were prolonged by Aitongping patch in cancer patients. And the daily morphine dose was lower, and patients' quality of life was improved in the Patch group. Moreover, Aitongping patch alleviated cancer pain and inhibited microglia activation after the successful implantation of bone tumor in TCI mice. We also observed the dysregulation of miR-150-5p and chemokine CXC motif ligand 12 (CXCL12) mRNA in TCI mice. And CXCL12 was found to be targeted by miR-150-5p. Aitongping patch was found to upregulate miR-150-5p and downregulate CXCL12 in vivo and in vitro. CONCLUSION: Aitongping patch could alleviate cancer pain via suppressing microglia activation, and the downregulation of miR-150-5p, as well as the upregulation of CXCL12 mRNA and protein, induced by tumor implantation or lipopolysaccharide stimulation, was restored by Aitongping treatment.

Maimendong and Qianjinweijing Tang combined with cisplatin suppressed lung cancer through targeting lncRNA-p21.

ETHNOPHARMACOLOGICAL RELEVANCE: Maimendong and Qianjinweijing Tang (Jin formula) is a traditional Chinese medicine formula that has been proven effective in the treatment of lung cancer in long-term clinical practice. AIM OF THE STUDY: To evaluate the anti-tumor effects of Jin formula combined with cisplatin (JIN + DDP) in vivo and in vitro, as well as to explore the role of long non-coding RNA (lncRNA) in the anti-lung cancer mechanism of its action. MATERIALS AND METHODS: A Lewis lung cancer model was established in C57 BL/6 mice to study the in vivo anti-tumor effect of Jin formula combined with cisplatin. TUNEL staining and western blot were applied to study the effects of Jin formula combined cisplatin on apoptosis. The in vitro anti-cancer function of Jin formula combined with cisplatin was explored by cell viability assay, flow cytometry, wound healing assay and transwell assay. The changes in lncRNA expression profiles were determined by lncRNA microarray, and the differentially expressed lncRNA-p21 was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. The expression differences of lncRNA-p21 in tumor and normal tissues were analyzed by bioinformatics, and the expression differences of lncRNA-p21 in tumor cells and normal cells were detected by qRT-PCR. The role of lncRNA-p21 in the anti-cancer effect of Jin formula combined cisplatin was investigated by knockdown or overexpression of lncRNA-p21 and a series of cell experiments. The expression of MAPK pathway-related proteins was analyzed by western blot. RESULTS: Jin formula combined with cisplatin (JIN + DDP) can suppress tumor growth and promote apoptosis in Lewis lung cancer mouse model. LncRNA-p21 was significantly up-regulated in the JIN and JIN + DDP groups, and the expression of lncRNA-p21 in lung cancer tissues and cells was lower than that in normal tissues and cells. In vitro, JIN + DDP significantly induced apoptosis and inhibited the proliferation, migration, and invasion of H460 and H1650 lung cancer cells. The above effects can be enhanced by the overexpression of lncRNA-p21 and eliminated by knock-down of lncRNA-p21. Further studies revealed that JIN + DDP inhibited the expression of mitogen-activated protein kinase (MAPK) pathway-related proteins, whereas knock-down of lncRNA-p21 abrogated the inhibition of the MAPK signaling pathway. CONCLUSIONS: This study showed that Jin formula combined with cisplatin could effectively inhibit the progression of lung cancer partially through targeting lncRNA-p21.

Banxia Xiexin Decoction Prevents HT22 Cells From High Glucose-Induced Neurotoxicity via JNK/SIRT1/Foxo3a Signaling Pathway.

BACKGROUND: Type 2 diabetes-associated cognitive dysfunction (DCD) is a chronic complication of diabetes that has gained international attention. The medicinal compound Banxia Xiexin Decoction (BXXXD) from traditional Chinese medicine (TCM) has shown potential in improving insulin resistance, regulating endoplasmic reticulum stress (ERS), and inhibiting cell apoptosis through various pathways. However, the specific mechanism of action and medical value of BXXXD remain unclear. METHODS: We utilized TCMSP databases to screen the chemical constituents of BXXXD and identified DCD disease targets through relevant databases. By using Stitch and String databases, we imported the data into Cytoscape 3.8.0 software to construct a protein-protein interaction (PPI) network and subsequently identified core targets through network topology analysis. The core targets were subjected to Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The results were further validated through in vitro experiments. RESULTS: Network pharmacology analysis revealed the screening of 1490 DCD-related targets and 190 agents present in BXXXD. The topological analysis and enrichment analysis conducted using Cytoscape software identified 34 core targets. Additionally, GO and KEGG pathway analyses yielded 104 biological targets and 97 pathways, respectively. BXXXD exhibited its potential in treating DCD by controlling synaptic plasticity and conduction, suppressing apoptosis, reducing inflammation, and acting as an antioxidant. In a high glucose (HG) environment, the expression of JNK, Foxo3a, SIRT1, ATG7, Lamp2, and LC3 was downregulated. BXXXD intervention on HT22 cells potentially involved inhibiting excessive oxidative stress, promoting neuronal autophagy, and increasing the expression levels of JNK, SIRT1, Foxo3a, ATG7, Lamp2, and LC3. Furthermore, the neuroprotective effect of BXXXD was partially blocked by SP600125, while quercetin enhanced the favorable role of BXXXD in the HG environment. CONCLUSION: BXXXD exerts its effects on DCD through multiple components, targets, levels, and pathways. It modulates the JNK/SIRT1/Foxo3a signaling pathway to mitigate autophagy inhibition and apoptotic damage in HT22 cells induced by HG. These findings provide valuable perspectives and concepts for future clinical trials and fundamental research.

A Network Pharmacology Approach for Uncovering the Mechanism of 'Kouchuangling' in Radiation-induced Oral Mucositis Treatment.

BACKGROUND: Radiation-induced oral mucositis (RIOM) is an intractable inflammatory disease whose pathogenesis needs to be clarified. "Kouchuangling" (KCL), a traditional Chinese medicine formula, is composed of Lonicerae Japonicae Flos, Radix Paeoniae Rubra, and Radix Sanguisorbae. Although all of them are Chinese folk medicines which have long been utilized for ameliorating inflammation, the mechanism of KCL to RIOM remains unclear. PURPOSE: To predict the active ingredients of KCL and identify the mechanism of KCL on RIOM. MATERIALS AND METHODS: We identified the chemical ingredients in KCL using TCM Systems Pharmacology (TCMSP), TCM@Taiwan, PubChem, and SuperPred databases and used the oral bioavailability (OB), drug-like properties (DL) and Degree of compounds for screening. Targets for oral mucositis were obtained from the Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), PharmGKB, and DrugBank databases. Cytoscape 3.7.0 was used to visualize the compound-target-disease network for KCL and RIOM. The biological processes of target gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed using DAVID. RESULTS: Based on OB≥30%, DL≥0.18 and Degree≥3, 24 active ingredients and 960 targets on which the active components acted were identified. A total of 1387 targets for oral mucositis were screened. GO enrichment and KEGG pathway analyses resulted in 43 biological processes (BPs), 3 cell components (CCs), 5 molecular functions (MFs), and 32 KEGG pathways, including leishmaniasis, Toll-like receptor signaling, TNF signaling, and Influenza A pathways. CONCLUSION: This experiment preliminarily verified that the active ingredients of KCL play a role in the treatment of RIOM through multiple targets and pathways, providing a reference for further study of the pharmacological mechanism of Chinese herbal medicine.

Celastrol induces caspase-dependent apoptosis of hepatocellular carcinoma cells by suppression of mammalian target of rapamycin.

OBJECTIVE: To investigate the efficacy of celastrol treatment of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to propose a mechanism of action. METHODS: A human HepG2 liver cancer cell line and a xenograft tumor model were used to investigate the effects of celastrol on HCC in vitro and in vivo. A CCK-8 kit was used to detect cell viability. Flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining were used to detect apoptosis. Western blotting and immunohistochemistry were used to detect the expression of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, mammalian target of rapamycin (mTOR), and p-mTOR. Hematoxylin-eosin staining was used to observe the tissue morphology. RESULTS: Celastrol decreased the viability of HepG2 cells and induced apoptosis. Western blot assays indicated that celastrol up-regulated cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, and cleaved-PARP by inhibiting the phosphorylation of mTOR in HepG2 cells. Moreover, celastrol inhibited the tumor growth in a xenograft model. Celastrol also induced caspase-dependent apoptosis (up-regulation of cleaved-caspase- 3, -8, -9, and cleaved-PARP) and inhibited the activation of mTOR in vivo. CONCLUSION: Celastrol induces caspase-dependent apoptosis in HCC cells by inhibiting the activation of mTOR.

Maimendong and Qianjinweijing Tang (Jin formula) suppresses lung cancer by regulation of miR-149-3p.

ETHNOPHARMACOLOGICAL RELEVANCE: Maimendong and Qianjinweijing Tang (Jin formula), a classic Chinese formula, can enhance therapeutic efficacy and reduce adverse effects in patients with lung cancer. AIM OF THE STUDY: To evaluate the anti-lung cancer effect of Jin formula in vivo and in vitro, and to explore the role of microRNA (miRNA) in the anti-lung cancer mechanism of Jin formula. MATERIALS AND METHODS: Cell survival was determined via a colorimetric method, and apoptotic condition was revealed by flow cytometric analysis. Cell migration and invasion were detected by scratch and transwell assays. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was applied to measure the changes of miRNA expression. Pathological histology of lung tissues were assessed by hematoxylin-eosin (HE) staining. Immunohistochemistry and immunoblotting were used to detect the expression of marker proteins of Wnt/ß-catenin pathway. The relationship between miR-149-3p and MYC associated zinc finger protein (MAZ) was verified using a dual-luciferase reporter assay system. RESULTS: Our findings demonstrated the anti-cancer effect of Jin formula in vitro, and revealed that Jin formula could suppress the proliferation, migration and invasion of human lung cancer A549 and H1299 cells. We also confirmed the capability of Jin formula to reduce tumor growth through the up-regulation of miR-149-3p and down-regulation of Wnt/ß-catenin signaling in animal models. qRT-PCR analysis in vitro further confirmed a dose-dependent increase of miR-149-3p by treatment with Jin formula. Functional studies identified MAZ as a downstream target of miR-149-3p. Overexpression of miR-149-3p inhibited cell proliferation, migration, invasion and induced apoptosis in A549 and H1299 cells, similar to our findings on the effects of Jin formula treatment. In contrast, inhibiting the expression of miR-149-3p reversed the anti-cancer effects of Jin formula. Additionally, we revealed that miR-149-3p was involved in the anti-cancer effects of Jin formula, at least in part, by inhibiting MAZ expression and the Wnt/ß-catenin signaling cascade. CONCLUSION: Our study illustrated that Jin formula suppressed the development of lung cancer and the mechanism may be associated with the miR-149-3p/MAZ/Wnt/ß-catenin axis.

Xiaoai Jiedu Recipe Inhibits Proliferation and Metastasis of Non-Small Cell Lung Cancer Cells by Blocking the P38 Mitogen-Activated Protein Kinase (MAPK) Pathway.

BACKGROUND Lung cancer is the leading cause of cancer deaths in the world. Its major histopathological subtype is non-small cell lung cancer (NSCLC). Xiaoai Jiedu recipe (XJR) is a traditional Chinese medicine formula that can suppress growth and invasion of tumor cells. Here, we assessed the antitumor effect of XJR on NSCLC explored the underlying mechanisms. MATERIAL AND METHODS Three concentrations of XJR (low, middle, and high) were used to treat A549 cells. Cell Counting Kit-8 and colony formation assay were used to measure proliferation of A549 cells. Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry. The expression of apoptosis-associated proteins was measured by Western blot analysis. Transwell and scratch wound healing assay were used to assess invasion and migration, respectively, of A549 cells. The expression of p38 MAPK pathway-associated proteins were measured using Western blot analysis. RESULTS XJR suppressed proliferation and promoted apoptosis of A549 cells, especially in the high-dose group. The expression of Bcl-2 was reduced with increasing expression of Bax, cleaved caspase-3, and cleaved caspase-9. Invasion and migration abilities of A549 cells were inhibited after XJR treatment. XJR treatment decreased the expression levels of phosphorylated p38 (p-p38), p-ERK, and p-JNK in a dose-dependent manner. CONCLUSIONS The results demonstrated that XJR can inhibit proliferation, invasion, and migration, and induce apoptosis of NSCLC by blocking the p38 MAPK pathway, which shows the potential of XJR as a new treatment of NSCLC.

2-Hydroxy-3-methylanthraquinone inhibits lung carcinoma cells through modulation of IL-6-induced JAK2/STAT3 pathway.

BACKGROUND: 2-hydroxy-3-methylanthraquinone (HMA), an anthraquinone monomer in traditional Chinese medicine Hedyotis diffusa, has been reported to inhibit the growth of several types of cancer, but its effect on lung cancer has not been adequately investigated. HYPOTHESIS/PURPOSE: This study aimed to test the hypothesis that HMA inhibit the growth, migration, and invasion of lung cancer cells in part via downregulation of interleukin (IL)-6-induced JAK2/STAT3 pathway. METHODS: Growth and apoptosis of lung cancer cells were quantitated by CCK-8 assay and Annexin V-FITC/PI flow cytometric analysis, respectively. Migration and invasion of A549 cells were determined by wound-healing assay and transwell invasion assay, respectively. The effect of HMA on cytokines expression in A549 cells was evaluated by the cytokine antibody array assay. Gene expression and protein levels of related molecular markers were quantitated by real time-PCR and Western blot analysis, respectively. RESULTS: HMA significantly inhibited IL-6-stimulated growth and colony formation of A549 cells, increased the number of apoptotic cells, and inhibited invasion associated with downregulation of expression of IL-6-induced MMP-1, MMP-2, and MMP-9 genes. IL-6 increased the levels of tyrosine phosphorylation of JAK2 and STAT3 in A549 cells, which was reversed by HMA treatment. In addition, HMA reduced the expression of a series of inflammation-related cytokines in A549 cells supernatant, including IL-6, G-CSF, IL-6R, IL-8, MCP-1, RANTES, TNF-α. CONCLUSION: These results suggest that HMA may inhibit the growth and invasion of lung cancer cells in part via downregulation of IL-6-induced JAK2/STAT3 pathway.

Ophiopogonin B suppresses the metastasis and angiogenesis of A549 cells in vitro and in vivo by inhibiting the EphA2/Akt signaling pathway.

Lung adenocarcinoma is the most common metastatic cancer, and is associated with high patient mortality. Therefore, investigation of anti­metastatic treatments for lung adenocarcinoma is crucial. Ophiopogonin B (OP­B) is a bioactive component of Radix Ophiopogon Japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease. Screening of transcriptome and digital gene expression (DGE) profiling data in NSCLC cell lines showed that OP­B regulated the epithelial­mesenchymal transition (EMT) pathway in A549 cells. Further results showed that 10 µmol/l OP­B downregulated EphA2 expression and phosphorylation (Ser897) in A549 cells but upregulated them in NCI­H460 cells. Meanwhile, the Ras/ERK pathway was unaffected in A549 cells and stimulated in NCI­H460 cells. More importantly, detection of the EMT pathway showed that OP­B treatment increased the epithelial markers ZO­1 and E­cadherin and decreased the expression of the mesenchymal marker N­cadherin and the transcriptional repressors Snail, Slug and ZEB1. Furthermore, through Transwell migration and scratch wound healing assays, we found that 10 µmol/l OP­B significantly reduced the invasion and migration of A549 cells. In vivo, we found that 75 mg/kg OP­B inhibited A549 cell metastasis in a pulmonary metastasis nude mouse model. In addition, we also found that 10 µmol/l OP­B significantly inhibited tube formation in EA.hy926 cells. The expression of VEGFR2 and Tie­2, the phosphorylation of Akt (S473) and PLC (S1248), and the levels of EphA2 and phosphorylated EphA2 (S897) were all inhibited by OP­B in this cell line. In vivo, using a Matrigel plug assay, we found that OP­B inhibited angiogenesis and the hemoglobin content of A549 transplanted tumors. Taken together, OP­B inhibited the metastasis and angiogenesis of A549 cells by inhibiting EphA2/Akt and the corresponding pathway. The investigation gives new recognition to the anticancer mechanism of OP­B in NSCLC and this compound is a promising inhibitor of metastasis and angiogenesis of lung adenocarcinoma cells.

Inhibition of hepatocellular carcinoma tumorigenesis by curcumin may be associated with CDKN1A and CTGF.

This study aimed to explore crucial genes, transcription factors (TFs), and microRNAs (miRNAs) associated with the effects of curcumin against hepatocellular carcinoma (HCC). We downloaded data (GSE59713) from Gene Expression Omnibus to analyze differentially expressed genes (DEGs) between curcumin-treated and untreated HCC cell lines. Then, we identified the disease ontology (DO) and functional enrichment analysis of these DEGs and analyzed their protein-protein interactions (PPIs). Additionally, we constructed TF-target gene and miRNA-target gene regulatory networks and explored the potential functions of these DEGs. Finally, we detected the expression of CDKN1A, CTGF, LEF1 TF and MIR-19A regulated by curcumin in PLC/PRF/5 cells using RT-PCR. In total, 345 upregulated and 212 downregulated genes were identified. The main enriched pathway of upregulated genes was the TNF signaling pathway. The downregulated genes were significantly enriched in TGF-beta signaling pathway. In addition, most DEGs were significantly enriched in DO terms such as liver cirrhosis, hepatitis, hepatitis C and cholestasis (eg., CTGF). In the constructed PPI network, CDKN1A and CTGF were the key proteins. Moreover, LEF1, CDKN1A, and miR-19A that regulated CTGF were highlighted in the regulatory networks. Furthermore, the expression of CDKN1A, CTGF, LEF1 TF and miR-19A regulated by curcumin in PLC/PRF/5 cells was consistent with the aforementioned bioinformatics analysis results. To conclude, curcumin might exert its protective effects against HCC tumorigenesis by downregulating LEF1 and downregulating CTGF regulated by MIR-19A and upregulating CDKN1A expression.

Study on Inhibitory Effect of MaiMenDong Decoction and WeiJing Decoction Combination with Cisplatin on NCI-A549 Xenograft in Nude Mice and Its Mechanism.

MaiMenDong Decoction and WeiJing Decoction (Jin formula) is a traditional Chinese medication that consists of 8 medicinal plants, which recorded in the classical TCM literature Jin Kui Yao Lue and has been utilized in the treatment of lung diseases for hundreds of years in China. The present study aimed to determine the anti-tumor activity and the underlying mechanisms of Jin formula combined with cisplatin in the treatment of non-small cell lung cancer (NSCLC). Xenograft model of NCI-A549 was established in Balb/c nude mice. Five groups, including normal, MOCK, Jin, cisplatin (DDP), and Jin+DDP were included in the study. We found that Jin formula ameliorated the body weight loss caused by DDP 15 days after drug administration. Moreover, the combination of Jin with DDP enhanced the anti-tumor function of DDP. Microarray analysis showed that Jin suppressed gene expression of certain pathways which regulating cell cycle and apoptosis. Furthermore, DDP mainly decreased the gene expression level of angiogenesis associated factors, such as VEGFA, TGF-ß and MMP-1. Moreover, co-treatment with Jin and DDP not only down-regulated Bcl-2 and E2F1, but also decreased the expression of MYC, MET, and MCAM. In addition, co-formula decreased the levels of p-AKT (thr308) and p-PTEN, increased Bax/Bcl-2 value, and resulted in apoptosis of tumor cells. Taken together, Jin+DDP significantly inhibited the growth of A549 cell transplanted solid tumor with slight side effect compared to the treatment by DDP only, and had a better effect than the Jin group. The mechanisms may be mainly associated with inactivation of PI3K/AKT pathway and apoptosis induction.

Effect of Aidi injection plus transarterial chemoembolization on primary hepatic carcinoma: a systematic review and Meta-analysis.

OBJECTIVE: To assess the efficacy and safety of Aidi injection plus transarterial chemoembolization (TACE) in patients with primary hepatic carcinoma. METHODS: A comprehensive research of seven electronic databases was performed for comparative studies evaluating Aidi injection combined with TACE for primary hepatic carcinoma until September 2016. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool from the Cochrane Handbook version 5.1.0. Data was synthesized by using RevMan 5.3 software. RESULTS: Forty-nine studies involving 3435 patients met the inclusion criteria, most of which were low methodological quality. Compared with TACE alone, Aidi injection plus TACE can significantly improve the efficiency rate [RR = 1.33, 95%CI (1.24, 1.43), P < 0.000 01], clinical beneficial rate [RR = 1.25, 95% CI (1.17, 1.33), P < 0.000 01], survival rate [6 months, RR = 1.19, 95% CI (1.09, 1.29), P < 0.0001], 12 months, [RR = 1.37, 95% CI (1.24, 1.52), P < 0.000 01], 18 months, [RR = 2.00, 95% CI (1.26, 3.20), P < 0.004], 24 months, [RR = 1.44, 95% CI (1.22, 1.70), P < 0.0001], 36 months, [RR = 1.50, 95% CI (1.07, 2.11), P = 0.02 < 0.05], quality of life [RR = 1.84, 95% CI (1.64, 2.05), P < 0.000 01] and immune function [CD3+, MD = 11.12, 95% CI (7.93, 14.30), P < 0.000 01], CD4+, [MD = 10.37, 95% CI (7.29, 13.45), P < 0.000 01], CD4+/CD8+, [MD = 0.30, 95% CI (0.07, 0.53), P = 0.01 < 0.05], NK, [MD = 7.49, 95% CI (6.64, 8.34), P < 0.000 01]. A significant improvement was also found in improvement of symptoms [RR = 1.64, 95%CI (1.38, 1.94), P < 0.000 01], leukopenia [RR = 0.60, 95% CI (0.54, 0.66), P < 0.000 01], thrombocytopenia [RR = 0.46, 95% CI (0.34, 0.61), P < 0.000 01], nausea and vomiting incidence [RR = 0.66, 95% CI (0.54, 0.81), P < 0.0001), liver damage rate [RR = 0.57, 95% CI (0.42, 0.77), P = 0.0003 < 0.05), and kidney damage rate [RR = 0.18, 95% CI (0.05, 0.68), P = 0.01 < 0.05]. CONCLUSION: The results suggested that Aidi injection plus TACE significantly improve the clinical effect of TACE, and reduce the incidence of adverse events. However, rigorous multicenter trials with larger size are warranted to further confirm the findings.

Aqueous Oldenlandia diffusa extracts inhibits colorectal cancer cells via activating AMP-activated protein kinase signalings.

Here we evaluated the anti-cancer activity of aqueous Oldenlandia diffusa (OD) extracts (ODE) in colorectal cancer (CRC) cells. We showed that ODE exerted potent anti-proliferative, cytotoxic and pro-apoptotic activities against a panel of established CRC lines (HCT-116, DLD-1, HT-29 and Lovo) and primary (patient-derived) human CRC cells. ODE activated AMP-activated protein kinase (AMPK) signaling, which led to subsequent mTORC1 inhibition and Bcl-2/HIF-1α downregulation in CRC cells. In ODE-treated CRC cells, AMPKα1 formed a complex with p53. This might be important for p53 activation and subsequent cancer cell apoptosis. Inhibition of AMPK signaling, though dominant negative (dn) mutation or shRNA/siRNA knockdown of AMPKα1 attenuated ODE-exerted CRC cytotoxicity. In vivo, i.p. administration of ODE inhibited HCT-116 xenograft tumor growth in SCID mice. In addition, AMPK activation, mTORC1 inhibition and p53 activation were observed in ODE-treated HCT-116 xenograft tumors. These results suggest that ODE inhibits CRC cells in vitro and in vivo, possibly via activation of AMPK-dependent signalings.

Combination Efficacy of Astragalus membranaceus and Curcuma wenyujin at Different Stages of Tumor Progression in an Imageable Orthotopic Nude Mouse Model of Metastatic Human Ovarian Cancer Expressing Red Fluorescent Protein.

BACKGROUND/AIM: The present study determined the efficacy of extracts of Astragalus membranaceus (AM) and Curcuma wenyujin (CW), a traditional Chinese medicine herbal mixture, at different tumor stages of an orthotopic nude mouse model of human ovarian cancer expressing red fluorescent protein. MATERIALS AND METHODS: The tumor-bearing mice were treated with cisplatinum (CDDP), AM, CW, or a combination of AM and CW in each of three tumor stages, using the same regimen. Group 1 received saline as negative control. Group 2 received CDDP i.p. as positive control with a dose of 2 mg/kg, every three days. Group 3 received AM daily via oral gavage, at a dose of 9120 mg/kg. Group 4 received CW daily via oral gavage, at a dose of 4560 mg/kg. Groups 5, 6 and 7 received combinations of AM and CW daily via oral gavage at low (AM, 2280 mg/kg; CW, 1140 mg/kg), medium (AM, 4560 mg/kg; CW 2280 mg/kg), and high (AM, 9120 mg/kg; CW, 4560 mg/kg) doses. The expression of angiogenesis- and apoptosis-related genes in the tumors were analyzed by immunohistochemistry for matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) fibroblast growth factor 2 (FGF-2), B-cell lymphoma 2 (Bcl-2) and cyclooxygenase 2 (Cox-2), and by polymerase chain reaction for MMP-2, FGF-2 and Bcl-2. RESULTS: CDDP, AM, and its combination with CW-induced significant growth inhibition of Stage I tumors. Strong efficacy of the combination of AM and CW at high dose was observed. Monotherapy with CDDP, AM, CW, and the combination treatments did not significantly inhibit Stage II and III tumors. The expression of MMP-2, VEGF, FGF-2, and Cox-2 was significantly reduced in Stage I tumors treated with AM, CW, and their combination, suggesting a possible role of these angiogenesis- and apoptosis-related genes in the observed efficacy of the agents tested. CONCLUSION: This study is the first report on the efficacy of anticancer agents at different stages of ovarian cancer in an orthotopic mouse model. As the tumor progressed, it became treatment-resistant, similar to the clinical situation, further demonstrating the utility of the model and the need for agents acrtive in advanced-stage ovarian cancer.

[Effect of xiaoai jiedu recipe on gene expression profiles in H22 tumor-bearing mice].

OBJECTIVE: To explore the mechanism of Xiaoai Jiedu Recipe (XJR) for fighting against tumors by detecting tumor gene expression profiles of H22 tumor-bearing mice. METHODS: H22 tumor-bearing mice were randomly divided into the normal control group, the low dose XJR group, the medium dose XJR group, the high dose XJR group, and the Cisplatin group. The differentially expressed genes of tumor tissues in H22 tumor-bearing mice were detected by using gene chip technique. The antitumor mechanism of XJR associated signaling pathways and gene expressions were found out by pathway analysis. The chemokine signaling pathways were analyzed. RESULTS: XJP could significantly affect multiple signaling pathways associated with tumor growth, apoptosis, and immunity. XJP also could decrease expressions of CCL3 and CXCL2 in the chemokine signaling pathway. CONCLUSION: XJP could inhibit the growth and invasion of tumor cells possibly by affecting expressions of some genes in the chemokine signaling pathway.

[Systems biology is a bridge of integrated traditional Chinese and Western medicine].

The integration of Chinese medicine (CM) and Western medicine (WM) is the only way for the development of medicine, and it is the best form for unifying systems theory and reductionism. In this paper, systems biology and its application in medical research were discussed. The authors put forward that systems biology may possibly interpret the scientific connotation of the complex theoretic systems of CM, which will make WM to well know the human body and disease. We hold that systems biology is a bridge of integrated CM and WM.

Effect of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome.

OBJECTIVE: To investigate the effects of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome induced by mutifactor stimuli. METHODS: SD rats were divided into control, model, Liangxuehuayu Recipe (high, middle and low dose, 18, 9, 4.5 g/kg accordingly). Except the control group, blood stasis model was established in the rest groups. The hemorheological parameters were measured and compared. RESULTS: Blood viscosity at high, moderate and low level in rats with blood stasis significantly increased (P<0.05), but blood viscosity at high level and plasma viscosity was significantly decreased in rats induced by some stimuli after Liangxuehuayu Recipe were intra-gastrically administered for 1 weeks (P<0.01, P<0.05). CONCLUSIONS: Liangxuehuayu Recipe is effective in improving hemorheology, and has important application value in the prevention of occurrence and development of ischemic stroke.

[The establishment of research inherit mode of famous academic thoughts].

To study and summarize the academic thoughts of famous Chinese medicine doctors is the main pathway of developing Chinese medicine theories. It is of important significance in enriching and developing the Chinese medicine theories by combining traditional and modern research methods, merging multiple disciples to study the research inherit mode of famous academic thoughts. The major study links include: (1) To refine scientific hypotheses from huge amount of clinical case records; (2) To find the literature sources; (3) To embody the practice significance of the innovative theories by clinical studies; (4) To reveal the scientific connotation of Chinese medicine theories by experimental studies. We hope to reach the goal of innovating and developing Chinese medicine theories on the basis of inheritance by integrating clinical case records, tracing the literature sources, clinical and experimental studies.

[Viewing from the toll-like receptor/nuclear factor-kappaB signaling pathway to explore the immunomodulatory mechanism of Chinese drugs].

Many Chinese drugs (CHD) have showed their significant effects of integral immune-regulation, and lots of researches have conducted in recent years for exploring their mechanism from different levels, like cytological, molecular and genetic levels. In this paper, the relation between immune-regulation of CHD and Toll-like receptors/nuclear factor-kappaB (TLRs/NF-kappaB) signaling pathway was introduced in brief based upon the achievements of previous researches. It was pointed out that the two are closely related, to explore mechanism of CHD in this way is meaningful not only for further deepening the theoretical understanding of CHD's pharmacological immunoregulation, but also be practically facilitate for enhancing therapeutic efficacy of CHD and developing new CHD.