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Abstract: Omentin-1, a new adipokine released from adipose tissue, is associated with several key aspects of metabolic syndrome such as insulin sensitivity. However, it is not known whether omentin-1 affects cancer cell growth. In this study, we studied the influence of omentin-1 on two types of human hepatocellular carcinoma cells: HepG2 and HuH-7 cells. Cell viability assay showed that omentin-1 (1 and 2μg/ml) significantly inhibited the proliferation of HepG2 and HuH-7 cells. Both annexin+PI staining and TUNEL assay showed that omentin-1 induced apoptosis in these cells. Moreover, omentin-1 treatment upregulated protein levels of p53 and p21, a main transcriptional target of p53. Interestingly, omentin-1 did not affect p53 mRNA level. Further mechanism study showed that omentin-1 upregulated p53 protein level through decreasing p53 deacetylation and thereby increasing the stability of p53 protein. Using small interfering RNA (siRNA)-mediated knockdown, we found that Sirt1 deacetylase, but not histone deacetylase 1 (HDAC1), was required for the effect of omentin-1 on p53 deacetylation and cancer cell proliferation. In omentin-1 treated HepG2 cells, the bax/bcl-2 protein ratio was increased, while the caspase-3 signaling pathway was also activated. Omentin-1 triggered JNK signaling but not p38 and ERK1/2 signaling pathways. Collectively, our data suggests that the novel adipokine omentin-1 may contribute to the therapeutic strategy for hepatocellular carcinoma. [Copyright &y& Elsevier]

Background and Purpose: Zuojin capsule (ZJC), a classical prescription, is outstanding in improving the conditions of patients with gastrointestinal diseases and colorectal cancer (CRC). Although ZJC has multi-ingredient and multi-target characteristics, its pharmacological effect on colorectal cancer and the underlying mechanism remain unclear.Method: Here, the activity of ZJC against CRC was evaluated by the experiments with CRC cells and HCT-116 xenografted mice. The key genes of CRC were obtained from the cancer genome atlas (TCGA). The genes potentially targeted by ZJC were collected from traditional Chinese medicine systems pharmacology (TCMSP) database. The underlying pathways related to selected targets were analyzed through gene ontology (GO) and pathway enrichment analyses. Western blot (WB), cellular thermal shift assay (CETSA), molecular docking and quantitative real-time PCR (QRT-PCR) were carried out to confirm the validity of the targets.Results: In vitro and in vivo results indicated that ZJC may inhibit CRC cells and tumor growth. The network pharmacological analysis indicated that 22 compounds, 51 targets and 20 pathways were involved in the compound-target-pathway network. Our results confirmed that ZJC inhibited cycle progression, migration and induced apoptosis by targeting candidate genes (CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2, and MMP9). We found that ZJC could directly change the protein level by regulating the protein stability and transcriptional activity of the target.Conclusions: In summary, combined network pharmacology and biological experiments proved that the main ingredients of ZJC such as quercetin, (R)-Canadine, palmatine, rutaecarpine, evodiamine, beta-sitosterol and berberine can target CDKN1A, Bcl2, E2F1, PRKCB, MYC, CDK2 and MMP9 to combat colorectal cancer. The results of this study provide a basic theory for the clinical trials of Zuojin Capsules against colorectal cancer. [ABSTRACT FROM AUTHOR]

Abstract: The in situ reaction of AgClO4·6H2O with 5,6-dihydro-1,4-dithiin-2,3-dicarboxylic anhydride in the presence of lithium hydroxide afforded a photoluminescent three-dimensional (3-D) AgI coordination polymer, [Ag2(L)] ∞ ( 1 ), which exhibited an unusual trinodal 6-connected (412.63)2(49.66) topological net (L=5,6-dihydro-1,4-dithiin-2,3-dicarboxylate). Moreover, the luminescent/thermal properties of 1 have also been briefly investigated. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of the study was to identify expressions of Notch-1, microRNA-21 (miR-21), and phosphatase and tensin homolog (PTEN) in colorectal cancer (CRC), and to explore their relationship with clinical stages and metastatic status of CRC. Main methods: 102 CRC patients were enrolled and clinical data were analyzed. Expressions of Notch-1 and miR-21 in CRC and adjacent non-tumor tissues of these patients were measured by real time-PCR. Protein expressions of Notch-1 and PTEN of 12 paired tissues were determined by Western blot and immunohistochemistry. The correlations between gene expressions in different clinical stages as well as metastatic status were evaluated by linear regression. Key findings: Notch-1 was over-expressed in 86.27% (88/102) CRC tissues, particularly in advanced stages, while miR-21 expression was increased to 74.51% (76/102) in CRC tissues compared with matched adjacent non-tumor tissues. The expressions of Notch-1 and miR-21 were positively correlated with CRC development, especially in advanced-stages (r2 =0.3839, p<0.01). Expressions of PTEN were significantly down-regulated in CRC tissues and negatively correlated with expressions of Notch-1 (r2 =0.5207, p<0.01) and miR-21 (r2 =0.6996, p<0.01). Significance: These data indicate that the crosstalk between Notch-1 and miR-21 is involved in CRC development through degradation of PTEN. [Copyright &y& Elsevier]

Aim: To investigate whether losartan has protective effects in mice with chronic viral myocarditis induced by coxsackievirus B3 (CVB3). Main methods: Thirty two male Balb/c mice were intraperitoneally injected with CVB3 (10×TCID50) to induce chronic viral myocarditis (CVM). Losartan at 12.5mg/kg (n=16) or normal saline (n=16) were orally administered daily for 28days to these mice. Uninfected mice (n=6) were used as controls. On day 29, all mice underwent anesthesia and echocardiography prior to sacrifice. Serum IL-17, IL-4, IFN-γ and TNF-α levels were measured by enzyme-linked immunosorbent assay, and cardiac tissues were histologically examined after hematoxylin & eosin staining. In addition, the effect of losartan on the virus titers in primary cultured neonatal rat cardiomyocytes infected with CVB3 was measured on Hep-2 cells at 72h post infection. Key findings: Mice infected with CBV3 had significantly increased mortality, heart/body weight ratios, necrosis and inflammatory scores and decreased cardiac ejection fractions, compared with the controls (all P<0.05). Losartan significantly decreased mortality from 40.0% to 12.5%, heart/body weight ratios from 7.08±2.17 to 4.15±0.99, and necrosis and inflammatory scores from 3.33±0.50 to 2.50±0.65 (all P<0.05), and increased ejection fractions from 55.80±9.25 to 72.31±12.15 (P<0.05). Losartan significantly enhanced IL-4, and decreased IFN-γ, TNF-α and IL-17 (all P<0.05). In the in vitro experiment, losartan had no influence on virus titers. Significance: Losartan protects mice against CVB3-induced CVM, most likely through upregulating Th2 responses, and down-regulating Th1 and Th17 responses. [ABSTRACT FROM AUTHOR]

Abstract: The reaction of AgClO4 with 2-naphthol-5-carboxylic acid (HL) and hexamethylenetetramine (hmt) in the presence of 2,6-dimethylpyridine afforded a photoluminescent three-dimensional (3D) AgI polymer {[Ag6(L)(μ3-hmt)2(μ4-hmt)2(ClO4)](ClO4)4(H2O)}∞ (1), which exhibited an unusual (3,4)-connected (6·7·8)2(4·6·7)2(4·7·8)2(72·8)2(62·7·83)(62·72·8·10) topological network (L =2-naphthol-5-carboxylate). Moreover, the luminescent properties of 1 have been briefly investigated. [Copyright &y& Elsevier]

A series of flavonoids, chalcones and chalcone-like compounds were evaluated for inhibitory activity against Mycobacterium tuberculosis H37Rv. Among them, eight compounds exhibited >90% inhibition on the growth of the bacteria at a concentration of 12.5 μg/mL. Chalcones 1-(2-hydroxyphenyl)-3-(3-chlorophenyl)-2-propen-1-one (22) and 1-(2-hydroxyphenyl)-3-(3-iodophenyl)-2-propen-1-one (37) demonstrated 90 and 92% inhibition, respectively. Chalcone-like compounds (heterocyclic ring-substituted 2-propen-1-one) 1-(4-fluorophenyl)-3-(pyridin-3-yl)-2-propen-1-one (48), 1-(3-hydroxyphenyl)-3-(phenanthren-9-yl)-2-propen-1-one (49), 1-(pyridin-3-yl)-3-(phenanthen-9-yl)-2-propen-1-one (50) and 1-(furan-2-yl)-3-phenyl-2-propen-1-one (51) exhibited 98, 97, 96 and 96% inhibition, respectively. The actual minimum inhibitory concentrations (MIC), defined as the lowest concentration inhibiting 99% of the inoculum, for 22, 37, 48, 49, 50 and 51 were 20.3, 31.5, 48.3, >35.7, 6.8 and 19.2, respectively. A hydrophobic substituent on one aromatic ring, and a hydrogen-bonding group on the other aromatic ring resulted in increased anti-TB activity of the chalcones and chalcone-like compounds. Flavones and flavanones are more geometrically constrained than the corresponding chalcone analogues. The decreased activity of the flavones with respect to the chalcones may be due to the confinement of the terminal aromatic rings to the same plane. [Copyright &y& Elsevier]