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B7-H3 is a cell surface molecule in the immunoglobulin superfamily that has been shown to perform both immunological and non-immunological functions. It has also been found that vascular endothelial growth factor (VEGF) is an important molecule in the modulation of endothelial cell behavior. In this study, we analyzed the serum expression of B7-H3 in 113 rheumatoid arthritis and systemic lupus erythematous patients using the ELISA and found a positive correlation between B7-H3 and VEGF. Next, we investigated the involvement of B7-H3 in angiogenesis using human umbilical vein endothelial cells (HUVECs) with transient knockdown of B7-H3 and an in vivo Matrigel model. Data from the in vitro experiments showed that B7-H3 increased cell proliferation, migration, and tube formation, and correlated with the expression of VEGF. Furthermore, B7-H3 affected the formation of functional vascular networks in Matrigel plugs, which were dissected from mice injected with different HUVECs. Our data suggest that B7-H3 promotes angiogenesis through the enhancement of VEGF secretion. This is the first study proposing a significant role for B7-H3 in the promotion of angiogenesis and may provide further understanding of this gene's biological function.

Peng-Da Guo,1,* Zhong-Wen Sun,1,* Hui-Jun Lai,2 Jie Yang,1 Ping-Ping Wu,1 Yun-Di Guo,1 Jing Sun1 1Institute of Medical Technology, Suzhou Vocational Health College, Suzhou, Jiangsu 215009, China; 2Department of Ultrasound, Suzhou Traditional Chinese Medicine, Suzhou, Jiangsu 215007, China*These authors contributed equally to this workBackground: (PD-L2), a ligand of programmed cell death protein 1 (PD-1), is an inhibitory receptor of T cells and activated B cells. Many studies have focused on PD-L1, another ligand of PD-1, and the prognostic significance of PD-L1 has been reported in many tumors. However, the expression of PD-L2 in relation to clinical outcomes has not been fully investigated in cancer patients.Patients and methods: In this study, we investigated the expression of PD-L2 via immunohistochemistry (IHC) in the pathological specimens of 348 patients treated for colorectal cancer (CRC).Results: Strong PD-L2 expression was found in the cancer tissues from 41% of the CRC patients who also had a high TNM stage and carcinoembryonic antigen (CEA) concentration. We also carried out functional studies in vitro, which showed that PD-L2 did not influence the growth of the CRC cell line HCT116, but increased cell invasion.Conclusion: Collectively, these findings suggest that PD-L2 may be a potential therapeutic target for CRC.Keywords: PD-L2, colorectal cancer, migration, therapeutic target

The order of authors' affiliations in the published version of this article was not consistent with the order in the submitted manuscript due to typesetting.

Both membrane-bound and soluble forms of costimulatory molecules play important roles in immune-regulatory networks. B7-H3, a member of the B7 family, has been found with aberrant expression in tumors and infectious disease. However, the significance of sB7-H3 expression in systemic lupus erythematosus (SLE) has not been investigated. Using the peripheral blood of 78 SLE patients, we established a comprehensive database containing clinical data and relevant laboratory tests. We found that sB7-H3 expression in SLE patients was significantly lower compared with the healthy individuals. In addition, sB7-H3 levels in the patients were positively correlated with the disease activity as indicated by SLE disease activity index score, rashes, fever, and inflammatory cytokines. Moreover, sB7-H3 was associated with the counts of red blood cells and hemoglobin. Our findings suggest that sB7-H3 might counteract the aberrant immune response and potentially serve as a monitoring indicator of disease progression and therapeutic target in SLE treatment.

Nonalcoholic fatty liver disease (NAFLD), one of chronic liver diseases, seems to be rising as the obesity epidemic continues. In this study, 54 novel (thio)barbituric acid derivatives have been synthesized and evaluated for pharmacological activity. 7h exhibited potent glucose-lowering effects on insulin-resistant HepG2 cells and regulated adiponectin and leptin expression in 3T3-L1 adipocytes. Oral administration of 7h at 25 mg kg(-1) day(-1) for 4 weeks improved the progression of high fat diet-induced NAFLD by reducing the weight of body, liver, and fat, as well as modulating serum levels of fasting glucose, insulin, triglycerides, LDL-c, ALT, adiponectin and hepatic contents of triglycerides, total cholesterol. HE stainings revealed that 7h blocked fat deposition in liver and the increase of adipocyte number and size in adipose tissues from NAFLD. Furthermore, treatment with 7h alleviated the obese clinical symptoms, recovered serum biomarkers to appropriate ranges, and improved glucose tolerance by OGTT and IGTT in DIO mice.

A series of 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin congeners were synthesized by employing click chemistry and further evaluated for their antitumor activity by MTT assay. Among them, six congeners (10, 11, 12, 13, 22, and 24) exhibited approximately 100-fold more potent inhibitory activity against four tumor cell lines (HepG2, MKN-45, NCI-H1993, and B16) than etoposide as positive control. Docking studies on binding in the ATPase domain of topoisomerase II revealed perfect docking of four congeners in the active site. Furthermore, the podophyllotoxin congeners 10, 11, 12, and 13 induced cell cycle arrest of HepG2 cells at the G(2) /M phase in a concentration-dependent manner, assessed by flow cytometric analysis, highlighting that they exert their antitumor activity via HepG2 cell apoptosis.

In this paper, a combined high performance counter-current chromatography (HPCCC) and preparative high-performance liquid chromatography (HPLC) method was employed for rapid separation and enrichment of bioactive constituents from a water extract of Gentiana macrophylla Pall. With a two phase solvent system composed of ethyl acetate-n-butanol-water-acetic acid (2: 3: 5: 0.6, v/v), the water extract of G. macrophylla Pall was fractionated into six fractions with three targets isolated and four others highly concentrated, which were then further purified by preparative-HPLC. As a result, 37 mg deglucoserrulatoside, 22.4 mg loganic acid, 3.9 mg isoorientin, 22.4 mg swertiamarin, 52.3 mg gentiopicroside, 27.5 mg sweroside, and 7.9 mg macrophylloside D with the purity of 95.3%, 90.2%, 98%, 98%, 99.2%, 98.8%, and 98.4%, respectively, were isolated from the water extract of Gentiana macrophylla Pall. The structures were confirmed by UV spectra, MS, as well as NMR measurements.

Recycling counter-current chromatography (CCC) together with step-gradient CCC and medium-pressure liquid chromatography (MPLC) was employed to separate nine anthraquinone compounds from Cassia obtusifolia L. in this study. The results showed that recycling CCC is a powerful tool for compounds that are difficult to separate with common elution mode. CCC was the better option for crude material while MPLC had advantage for the final tuning. The combination of recycling CCC and MPLC could simplify the method exploring process in the separation process. The structures of these compounds were identified according to their mass spectra, by (1)H-NMR and compared with standard compounds.

Honokiol, a natural molecule isolated from Magnolia officinalis Rehd. et Wils., is widely known as an antitumor agent. In present work, an analysis of in vivo biotransformation and metabolites of honokiol has been performed by a combined method based on stable isotope cluster technique with honokiol-[ 13 C 6 ]-labeled and ultra-high performance liquid chromatography/quadrupole-time-of-flight-mass spectrometry (UHPLC/Q-TOF-MS). The metabolites could be easily identified by the determination of a chromatographically co-eluted pair of isotopomers (MS doublet peaks) with similar peak intensities and mass difference corresponding to that between isotope-labeled and non-isotope-labeled honokiol. A total of eighteen metabolites were detected and tentatively identified, fourteen of which were reported for the first time. The results indicated that the main metabolic pathways of honokiol in rats were hydroxylation, methylation, sulfation and glucuronidation. This study provided the first essential information on biotransformation and metabolites of honokiol in rats, which was very useful for further pharmacological and clinical studies of honokiol as a potent drug candidate.

A general approach based on stable isotope labeling and UPLC/Q-TOF-MS analysis of in vivo novel metabolites of honokiol has been developed in our study. In this method, urine samples were collected after intravenous administration of mixture of regular and [(13)C6]-labeled honokiol at 1:1 ratio to healthy rats. The metabolites could be easily recognized by the determination of a chromatographically co-eluted pair of isotopomers (MS doublet peaks) with similar peak intensities and mass difference corresponding to that between isotope-labeled and non-isotope-labeled honokiol. A total of 51 metabolites were detected, 37 of which were tentatively identified based on mass accuracy (

The aim of this study is to investigate the cytotoxic and apoptotic effects of constituents from the seeds of Millettia pachycarpa Benth. Fourteen compounds (1–14) including one novel chalcone (10) were isolated as active principles from Chinese herbal medicine M. pachycarpa Benth. Their structures were identified by using spectroscopic methods. All isolates were then evaluated for their cytotoxic effects against several cancer cell lines (HepG2, C26, LL2 and B16) with cisplatin as a positive control. And their apoptosis-inducing effects were tested against HeLa-C3 cells with taxol as a positive control. Both studies showed that compounds 1, 2, 7 and 10 demonstrated significant cytotoxic and apoptotic effects against cancer cells. Moreover, in the apoptosis assay the novel chalcone (10) showed strong apoptosis inducing effects at a concentration of 2 μM within 36 h. It was found to be the most potent apoptotic inducer of the compounds isolated from M. pachycarpa Benth.

Recycling counter-current chromatography (CCC) together with step-gradient CCC and medium-pressure liquid chromatography (MPLC) was employed to separate nine anthraquinone compounds from Cassia obtusifolia L. in this study. The results showed that recycling CCC is a powerful tool for compounds that are difficult to separate with common elution mode. CCC was the better option for crude material while MPLC had advantage for the final tuning. The combination of recycling CCC and MPLC could simplify the method exploring process in the separation process. The structures of these compounds were identified according to their mass spectra, by (1)H-NMR and compared with standard compounds.