Identification of Hub Genes Related to Carcinogenesis and Prognosis in Colorectal Cancer Based on Integrated Bioinformatics.

The high mortality of colorectal cancer (CRC) patients and the limitations of conventional tumor-node-metastasis (TNM) stage emphasized the necessity of exploring hub genes closely related to carcinogenesis and prognosis in CRC. The study is aimed at identifying hub genes associated with carcinogenesis and prognosis for CRC. We identified and validated 212 differentially expressed genes (DEGs) from six Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) database. We investigated functional enrichment analysis for DEGs. The protein-protein interaction (PPI) network was constructed, and hub modules and genes in CRC carcinogenesis were extracted. A prognostic signature was developed and validated based on Cox proportional hazards regression analysis. The DEGs mainly regulated biological processes covering response to stimulus, metabolic process, and affected molecular functions containing protein binding and catalytic activity. The DEGs played important roles in CRC-related pathways involving in preneoplastic lesions, carcinogenesis, metastasis, and poor prognosis. Hub genes closely related to CRC carcinogenesis were extracted including six genes in model 1 (CXCL1, CXCL3, CXCL8, CXCL11, NMU, and PPBP) and two genes and Metallothioneins (MTs) in model 2 (SLC26A3 and SLC30A10). Among them, CXCL8 was also related to prognosis. An eight-gene signature was proposed comprising AMH, WBSCR28, SFTA2, MYH2, POU4F1, SIX4, PGPEP1L, and PAX5. The study identified hub genes in CRC carcinogenesis and proposed an eight-gene signature with good reproducibility and robustness at the molecular level for CRC, which might provide directive significance for treatment selection and survival prediction.

Uniconazole and diethyl aminoethyl hexanoate increase soybean pod setting and yield by regulating sucrose and starch content.

BACKGROUND: Uniconazole (S3307) and diethyl aminoethyl hexanoate (DA-6) are known plant growth regulators (PGRs). However, it is unknown if their regulation of sucrose and starch content can affect pod setting and yield in soybean. Herein, S3307 and DA-6 were foliar sprayed on soybean Hefeng50 and Kangxian6 at the beginning of the bloom cycle in field tests conducted over two years. RESULTS: PGRs promoted the accumulation and distribution of plant biomass and significantly improved leaf photosynthetic rates. Sucrose and starch content increased after PGR treatment across organs and varieties. Accumulation and allocation of sucrose and starch content in soybean source organs are enhanced by PGRs, which supply high levels of assimilate to sink organs. Moreover, sucrose and starch contents in source and sink organs are positively correlated. S3307 and DA-6 also significantly increased pod setting rates and reduced flower and pod abscission rates, leading to increased yield. CONCLUSION: S3307 and DA-6 promoted the accumulation and availability of sucrose and starch content in source organs and increased sucrose and starch content in flowers and pods or seeds, thereby maintaining the balance between source and sink organs and contributing to increased pod setting rates and soybean yield. © 2018 Society of Chemical Industry.

[Retracted] Polyphenol­rich extract of Saliva chinensis exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G0/G1­phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that several figures (Figs. 3, 4 and 6) contained apparent anomalies, including repeated patternings of data within the same figure panels. Furthermore, Fig. 6 contained data that bore striking similarities to data published in Fig. 8 in another paper published in Molecular Medicine Reports, which has now been retracted [Zhu Y­Y, Huang H­Y and Wu Y­L: Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells. Mol Med Rep 12: 5012­5018, 2015]. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original articles was published in Molecular Medicine Reports 12: 4843­4850, 2015; DOI: 10.3892/mmr.2015.4074].

Exploring the Pharmacological Mechanism of the Herb Pair "HuangLian-GanJiang" against Colorectal Cancer Based on Network Pharmacology.

Since the herb pair Huang Lian-Gan Jiang (HL-GJ) was put forward as conventional compatibility for cold-heat regulation in the middle energizer in the theory of Traditional Chinese Medicine (TCM), their therapeutic effects were observed on the prevention and treatment of intestinal inflammation and tumors including colorectal cancer (CRC). However, the active compounds, crucial targets, and related pathways of HL-GJ against CRC remained unclear. The purpose of this research was to establish a comprehensive and systemic approach that could identify the active compounds, excavate crucial targets, and reveal anti-CRC mechanisms of HL-GJ against CRC based on network pharmacology. We used methods including chemical compound screening based on absorption, distribution, metabolism, and excretion (ADME), compound target prediction, CRC target collection, network construction and analysis, Gene Ontology (GO), and pathway analysis. In this study, eight main active compounds of HL-GJ were identified, including Gingerenone C, Isogingerenone B, 5,8-dihydroxy-2-(2-phenylethyl) Chromone, 2,3,4-trihydroxy-benzenepropanoic acid, 3,4-dihydroxyphenylethyl Alcohol Glucoside, 3-carboxy-4-hydroxy-phenoxy Glucoside, Moupinamide, and Obaculactone. HRAS, KRAS, PIK3CA, PDE5A, PPARG, TGFBR1, and TGFBR2 were identified as crucial targets of HL-GJ against CRC. There were mainly 500 biological processes and 70 molecular functions regulated during HL-GJ against CRC (P < 0.001). There were mainly 162 signaling pathways contributing to therapeutic effects (P < 0.001), the top 10 of which included DAP12 signaling, signaling by PDGF, signaling by EGFR, NGF signaling via TRKA from the plasma membrane, signaling by NGF, downstream signal transduction, DAP12 interactions, signaling by VEGF, signaling by FGFR3, and signaling by FGFR4. The study established a comprehensive and systematic paradigm to understand the pharmacological mechanisms of multiherb compatibility such as an herb pair, which might accelerate the development and modernization of TCM.

Systematic Investigation of Scutellariae Barbatae Herba for Treating Hepatocellular Carcinoma Based on Network Pharmacology.

As the fifth most common type of malignant cancers globally, hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. As a long-time medicinal herb in Traditional Chinese Medicine (TCM), Scutellariae Barbatae Herba (SBH) has also been used for treating various cancers including HCC, but its underlying mechanisms have not been completely clarified. Presently, an innovative network-pharmacology platform was introduced to systematically elucidate the pharmacological mechanisms of SBH against HCC, adopting active ingredients prescreening, target fishing, and network analysis. The results revealed that SBH appeared to work on HCC probably through regulating 4 molecular functions, 20 biological processes, and hitting on 21 candidate targets involved in 40 pathways. By in-depth analysis of the first-ranked signaling pathway and hit genes, only TTR was highly and specially expressed in the liver tissue. TTR might play a crucial role in neutrophil degranulation pathway during SBH against HCC. Hence, TTR might become a therapeutic target of HCC. The study investigated the anti-hepatoma mechanisms of SBH from a holistic perspective, which provided a theoretical foundation for further experimental research and rational clinical application of SBH.

Polyphenol-rich extract of Salvia chinensis exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G0/G1-phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells.

Pancreatic cancer (PC) is one of the most aggressive types of human malignancy, which has an overall 5-year survival rate of <2%. PC is the fourth most common cause of cancer­associated mortality in the western world. At present, there is almost no effective treatment available for the treatment of PC. The aim of the present study was to evaluate the anticancer potential of a polyphenol enriched extract obtained from Salvia chinensis, a Chinese medicinal plant. An MTT assay was used to evaluate the cell viability of five cancer cell lines and one normal cell line. In addition, the effects of the extract on apoptotic induction, cell cycle phase distribution, DNA damage and loss of mitochondrial membrane potential (ΛΨm) were evaluated in MiapaCa­2 human PC cells. The effects of the extract on cell cycle phase distribution and ΛΨm were assessed by flow cytometry, using propidium iodide and rhodamine­123 DNA­binding fluorescent dyes, respectively. Fluorescence microscopy, using 4',6­diamidino­2­phenylindole as a staining agent, was performed in order to detect the morphological changes of the MiapaCa­2 cancer cells and the presence of apoptotic bodies following treatment with the extract. The results of the present study demonstrated that the polyphenol­rich extract from S. chinensis induced potent cytotoxicity in the MCF­7 human breast cancer cells, A549 human lung cancer cells, HCT­116 and COLO 205 human colon cancer cells, and MiapaCa­2 human PC cells. The Colo 205 and MCF­7 cancer cell lines were the most susceptible to treatment with the extract, which exhibited increased rate of growth inhibition. Fluorescence microscopy revealed characteristic morphological features of apoptosis and detected the appearance of apoptotic bodies following treatment with the extract in the PC cells. Flow cytometric analysis demonstrated that the extract induced G0/G1 cell cycle arrest in a dose­dependent manner. In addition, treatment with the extract induced a significant and concentration-dependent reduction in the ΛΨm of the PC cells.

The medicinal potential of natural products for the development of anti- influenza agents.

Influenza neuraminidase (NA) is an important target for designing anti-influenza drugs. By now, three inhibitors, zanamivir, oseltamivir and peramivir have been approved. However, in recent years, the potential threat of influenza pandemics and constant emergence of new drug-resistant influenza virus strains have weaken the defensive role of the current anti-influenza drugs. From another point of view, in this review we focused on some novel NA inhibitors which were mainly derived from natural products that had a variety of structural scaffolds, such as flavonoids, xanthones and diarylheptanoids. Besides interfering the function of NA, some of these compounds also can potently inhibit the replication of influenza virus. It is hoped that these compounds could be the source of leads and provide a guide for discovering new potent anti-influenza virus agents.