Alterations in bile acids as metabolic signatures in the patients with human adenovirus type 7 infection.

Objectives: The changes in metabolism by human adenovirus (HAdV) infection was unclear. The potential mechanism of HAdV-7 causing acute respiratory tract infection was explored. Methods: Totally 35 patients with HAdV-7 infection, 32 asymptomatic cases with HAdV-7 and 14 healthy controls were enrolled from an outbreak of HAdV-7 in the army. The serum samples were analyzed by untargeted and targeted metabolomics. The effects of differential metabolites were verified on HAdV-7 replication in an A549 cell line. Results: The untargeted metabolomics analysis revealed more significant changes in the classes of sphingolipids, polyketides, glycerolipids, fatty acyls, and carboxylic acids and their derivatives in the patients with HAdV-7 than in healthy controls. Two key metabolic pathways of secondary and primary bile acid biosynthesis were noted from pathway enrichment analysis. Targeted metabolomics analysis showed that the levels of unconjugated bile acids in the patients were significantly lower, while the levels of glyco- and tauro- conjugated bile acids in patients and asymptomatic cases were higher than those in the healthy controls. The profiles of cytokines and peripheral lymphocyte subsets obviously varied at different levels of bile acids, with significant differences after HAdV-7 infection. A cell verification test demonstrated that the replication of HAdV-7 significantly reduced when GCDCA and TCA were added. Conclusion: Bile acids inhibited HAdV-7 replication in vitro. Alterations in bile acids was metabolic signatures of HAdV-7 infected subjects, and our results suggested bile acids might play protective roles against HAdV-7 infection.

Thiazolidinedione: A Privileged Scaffold for the Development of Anticancer Agents.

Thiazolidinedione, an important heterocyclic ring system, is a pharmacophore and a privileged scaffold in medicinal chemistry. Researchers have shown its potential application as a backbone for inhibitors, as it is involved in anticancer development strategies, cancer progression and metastasis. In this paper, the anticancer activities of thiazolidinedione derivatives were reviewed for the first time with respect to different substituents and their positions. This work may imitate a stirring wheel to guide further advanced development of new anticancer molecules with high efficacy.

Modification, Antitumor Activity, and Targeted PPARγ Study of 18ß-Glycyrrhetinic Acid, an Important Active Ingredient of Licorice.

Licorice is a traditional Chinese medicine, which is often used as sweetener and cosmetic ingredients in food and pharmaceutical industries. Among them, glycyrrhetic acid is one of the most important agents. Studies have shown that glycyrrhetic acid exhibited antitumor activities as PPARγ agonist. However, the limited number of PPARγ glycyrrhetinic agonists and their high toxicity greatly limit the design based on the structure. Therefore, clarifying the binding mode between PPARγ and small molecules, we focused on the introduction of a natural active piperazine skeleton in the position of glycyrrhetinic acid C-3. According to the Combination Principle and the Structure-Based Drug Design, 19 glycyrrhetic acid derivatives were designed and synthesized as potential PPARγ agonists. Compounds 4c and 4q were screened as high-efficiency and low-toxicity lead compounds.

RETRACTED: Function of the PLZF gene in early development and self-renewal of T cells in mice.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).. This article has been retracted at the request of < the Editor in Chief. The Editor in Chief has been made aware of numerous problems with this paper regarding authorship, poor or insufficient supervision of researchers and the unauthorized use of data acquired from a lab visit by one of the authors.

Identification of nitroimidazole-oxime derivatives targeting the polo-box domain of polo-like kinase 1.

Recent progress in the development of small molecular skeleton-derived polo-like kinase (PLK1) catalytic domain (KD) inhibitors has led to the synthesis of multiple ligands with high binding affinity. However, few systematic analyses have been conducted to identify key PLK1-PBD domain and characterize their interactions with potent PLK1 inhibitors. Therefore, we designed a series of PLK1-PBD inhibitors with an in silico scaffold modification strategy. A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. The biological profile of 4v suggests that this compound may be developed as a potential anticancer agent.

Evaluation of tumor growth in vivo in a rat model of liver metastasis, using a newly devised index obtained by positron emission tomography with [18F] FDG.

BACKGROUND/PURPOSE: [(18)F] fluorodeoxyglucose-positron emission tomography (FDG-PET) is regarded as a unique imaging modality, because the images reflect tumor activity. This characteristic of PET encouraged us to use it to develop a novel method of quantitatively measuring liver metastasis viability. METHODS: F344 rats were injected with rat colon adenocarcinoma cells (RCN-9 cell line) via the portal vein, and some of them were treated with 5-fluorouracil (5-FU). Tumor growth and tumor activity were measured by PET. We used a tumor viability index (TVI) to evaluate changes in tumor activity and to quantitatively evaluate tumor proliferation activity, instead of using the standardized uptake value (SUV) of the tumor tissue. The TVI was compared with the number of tumor nodules and the proliferating cell nuclear antigen (PCNA) index 28 days after RCN-9 cell inoculation. RESULTS: [(18)F] FDG uptake by the liver tumors was measured by PET, and the TVI was found to increase as the tumor nodules increased in number and size. The TVI values in the experimental model represented the viability of tumors suppressed by chemotherapy, and the values were significantly correlated with the number of nodules and the PCNA index. CONCLUSIONS: The TVI was concluded to be superior to the SUV, the commonly used indicator, for evaluating tumor growth, especially that of multiple, small tumors.

Tumor viability evaluation by positron emission tomography with [18F]FDG in the liver metastasis rat model.

We prepared a liver metastatic tumor model by injection of rat colon adenocarcinoma cells to Fischer F344 rats through portal vein, and applied positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) ([18F]FDG-PET) to this model. At an early stage of the model, multiple small tumor nodules appeared in the inferior lobes of the livers, and extended later into the superior lobes. To evaluate the tumor growth and tumor viability at the early stage, we proposed a new concept, tumor viability index (TVI), instead of the standardized uptake value (SUV) of the [18F]FDG uptake. The TVI was defined by subtracting the signal based on the normal liver from the total signal in the whole liver including tumor nodules: (whole liver SUV-normal liver SUV) x ml of whole liver region of interest (ROI). For the signal of the whole liver, ROIs were placed on six slices covering the whole liver, and the ROI of normal liver region was located in the superior lobe of the liver. The average TVI values increased with tumor growth and significantly correlated with the numbers of tumor nodules. The new concept may be useful for evaluating the tumor viability non-invasively and quantitatively by [18F]FDG-PET.