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The aim of the present study was to observe the dynamic changes of the growth arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of curcumin pretreatment. A total of 60 rats were randomly divided into the normal group (N), the sham operation group (S), the dimethyl sulfoxide control group (D) and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72 h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of GADD153 and caspase-12 in the brain tissue were detected and compared among the groups by immunohistochemistry, immunofluorescence double staining and western blotting. The expression levels of GADD153 and caspase-12 were increased at T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in group D, while GADD153 was increased until T3 in group D. Compared with group D, the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the pathological process of CIRI. Curcumin may decrease the expression levels of the above two factors, thus exhibiting protective effects against CIRI in rats.

Parkinson disease (PD) is one of the most frequent neurodegenerative disorders. The aim of this study was to identify blood biomarkers capable to discriminate PD patients with different progression rates. Differentially expressed genes (DEGs) were acquired by comparing the expression profiles of PD patients with rapid and slow progression rates, using an expression dataset from Gene Expression Omnibus (GEO) under accession code of GSE80599. Altered biological processes and pathways were revealed by functional annotation. Potential biomarkers of PD were identified by protein-protein interaction (PPI) network analysis. Critical transcription factors (TFs) and miRNAs regulating DEGs were predicted by TF analysis and miRNA analysis. A total of 225 DEGs were identified between PD patients with rapid and slow progression profiles. These genes were significantly enriched in biological processes and pathways related to fatty acid metabolism. Among these DEGs, ZFAND4, SRMS, UBL4B, PVALB, DIRAS1, PDP2, LRCH1, and MYL4 were potential progression rate associated biomarkers of PD. Additionally, these DEGs may be regulated by miRNAs of the miR-30 family and TFs STAT1 and GRHL3. Our results may contribute to our understanding of the molecular mechanisms underlying different PD progression profiles.

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Objective. This study is aimed at exploring the regulatory mechanism of 73HOXC-AS1 overexpression plasmid-activated Wntβ-catenin classic signaling pathway and eukaryotic initiation factor 4A (eIF4AIII) expression increased by lentivirus-eIF4AIII-RNAi (44682-1) (LV-eIF4AIII-RNAi (44682-1)). Methods. Focusing on the occurrence and progression of gastric cancer, the human gastric cancer cell line BGC823 (University Experimental Center) was taken as the research object and was transfected after subculture. According to the different ways of transfection, the cells were divided into the P1 group (LV-eIF4AIII-RNAi (44682-1) overexpressed plasmid), the P2 group (pcDNA-HOXC-AS1 overexpressed plasmid), the P3 group (LV-eIF4AIII-RNAi (44682-1) + pcDNA-HOXC-AS1), and the P4 group (no transfection, control group). Cell proliferation was detected by CCK-8 (Cell Counting Kit-8) assay, Western blotting was adopted to detect Wnt3a and P-GSK3β proteins, Transwell assay was adopted to detect the ability of cell migration and invasion, and cell cycle and apoptosis were detected by flow cytometry. Results. The results show that the protein expression levels of Wnt3a and P-GSK3β (glycogen synthase kinase-3β) in the P1 and P4 groups were lower than those in the P2 and P3 groups ( P < 0.05 ). The cell activity and clone number of BGC823 in the P3 group were higher than those in the P1, P2, and P4 groups ( P < 0.05 ). The apoptosis rate of BGC823 cells in the P3 group was significantly higher than those in the P1, P2, and P4 groups ( P < 0.05 ). The proportion of BGC823 cells in the P3 group at the S phase was significantly higher than those in the P1, P2, and P4 groups, while the proportion in the G2 phase was significantly lower than those in the P1, P2, and P4 groups ( P < 0.05 ). The number of migrating and invading BGC823 cells in the P3 group was significantly higher than those in the P1, P2, and P4 groups, while the number of migrating BGC823 cells in the P4 group was significantly lower than those in the P1 and P2 groups ( P < 0.05 ). Conclusion. The 73HOXC-AS1 overexpression plasmid-activated Wntβ-catenin classic signaling pathway and eIF4AIII expression increased by LV-eIF4AIII-RNAi (44682-1) could act together on BGC823 cells to improve cell proliferation activity, migration, and invasion; inhibit cell apoptosis; and prevent cells from entering the S phase.

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Heterocycles with tetrahydroisoquinolines moiety are important biologically, and α‐aminophosphonates derivatives have unusual features in agrochemicals and medicines. In this paper, we combined these two parts to afford α‐aminophosphonates tetrahydroisoquinolines. A highly facile, one step direct carbon‐phosphor bond formation and N‐alkylation of tetrahydroisoquinolines was developed. It is a three‐component reaction of Nitrogen‐unprotected tetrahydroisoquinolines, aldehydes and trialkyl phosphites, which provides C1‐phosphonylated and N‐alkylation of THIQs (Tetrahydroisoquinolines) with moderate to high yields. The mild reaction conditions were investigated to give a broad range of substrates. Under the optimized reaction condition at reaction temperature 120 oC, after heating 8 h the desired final product was given in 90% yield, which is a satisfied reaction result. The different substituted benzaldehydes and THIQs were investigated in detail and proved to be broad. The proposed mechanism was also showed.

Since its emergence in the mid 90's, the in vivo bioluminescent imaging (BLI) technology has been widely accepted by academia and pharmaceutical industry for research and pre-clinical drug development. The non-invasiveness and high sensitivity nature of BLI enables tumor lesions to be detectable far before they are palpable, allowing longitudinal tracking of tumors from their early development stages. BLI is particularly advantageous for monitoring systemic and orthotopic tumors that are not accessible by caliper measurement. Current preclinical evaluation of anti-cancer agents relies heavily on subcutaneous xenograft models. However, ectopically developed tumors in the subcutaneous tissue differ drastically in tumor stromata in aspects of cell contents and drug permeability, thus will often poorly predict pharmacological efficacy of the test agents. The notion that orthotopic models can better recapitulate the clinical tumor development and metastasis, thus better predict the clinical outcome of the anticancer drugs has gradually gained acceptance. Towards the development of better mouse models for pre-clinical drug development, we have established over twenty imaging based orthotopic tumor cell lines, including U87MG and AM38 brain tumors, HCT116, LoVo and SW620 colorectal cancers, A549 lung cancer, MSTO-211H mesothelioma, Raji and Namalwa lymphoma, MiaPaca-3 and Panc-1 pancreatic cancer, HepG2 liver cancer, and DU145 prostatic cancer. These tumor cells are extremely bright in luminescence emission, ranging from 1085 to 6397 photons/second/cell, thus allowing very sensitive detection in orthotopic tissues even with a few hundred cells. The tumorigenicity of the luciferase labeled cells has been validated in the pertinent orthotopic models. Evaluation of the responsiveness of some of the models to standard therapeutic agents has been conducted. In the U87MG orthotopic glioma model, we observed tumor regression in mice treated with temozolomide in a 5 mg/kg, po, q2d x 5 regimen. Current study of the orthotopic MSTO-211H mesothelioma model in response to standard clinical treatment drugs, such as pemetrexed, carboplatin and paclitaxel is in progress. It is expected that these imaging based orthotopic models will improve the pre-clinical pharmacological evaluation of anti-cancer agents and therefore better bridge the preclinical to clinical translation. Citation Format: Ning Zhang, Wei Wang, Dan Meng, Jinjin Pan, Jing Jin, Yanxia Fan, Wenhao Jin, Shuo Zhang, Ze Chen, Xueqin Yang, Hongjun Wang. Establishment of imaging-based orthotopic tumor models for pharmacological evaluation of anticancer agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 105. doi:10.1158/1538-7445.AM2014-105