Mortality trends of liver cancer among patients with type 2 diabetes at the global and national level.

BACKGROUND: Primary liver cancer (PLC) is a commonly diagnosed malignancy, especially in developing countries. Diabetes is one of the well-determined risk factors for PLC. We aimed to describe the temporal trends of PLC mortality among diabetic patients. METHODS: We retrieved the PLC mortality data among diabetic patients from the Global Burden of Disease (GBD) study 2017 online database. Estimated average percentage change (EAPC) was used to quantify the PLC age-standardized mortality rate (ASMR) trends, by sex and country, between 1990 and 2017. RESULTS: Globally, the number of PLC related deaths increased from 3732.1 in 1990 to 9506.4 in 2017, with the ASMR increased from 0.09/100,000 to 0.12/100,000 (EAPC = 0.98, 95% CI 0.82, 1.14) among diabetic patients. Both the ASMR of PLC and its temporal trend were highly heterogeneous across the world. Between 1990 and 2017, a total of 135, 19, and 41 countries or territories experienced a significant increase, remained stable, and experienced a significant decrease in PLC ASMR, respectively. The greatest increase was mainly detected in developed countries, such as the USA, the UK, and Australia. By contrast, the most pronounced decrease was majorly found in developing regions. CONCLUSIONS: In diabetic patients, the PLC mortality was significantly increased at the global level and in approximately 70% of countries or territories over the last three decades. The increasing trend indicated that diabetes is an increasingly important risk factor for PLC and suggested that more tailored prevention strategies are needed for each country.

Cetuximab enhances the efficiency of irinotecan through simultaneously inhibiting the MAPK signaling and ABCG2 in colorectal cancer cells.

BACKGROUND: The present study sought to investigate the combined effects of cetuximab and irinotecan on colorectal cancer cells as well as the mechanisms underlying their anti-cancer effects. MATERIAL AND METHODS: High performance liquid chromatography, Hoechst staining assay, and western blotting analysis were used to detect intracellular drug concentrations, cell apoptosis, and protein expression in the presence of cetuximab, irinotecan, and the combination of both. RESULTS: Cetuximab was found to increase intracellular concentrations of irinotecan as well as cytotoxicity by inhibiting the epidermal growth factor receptor and, by extension, the downstream RAS-RAF-MEK-ERK signaling pathway. Cetuximab therefore induced apoptosis and improved the effect of irinotecan in colorectal cancer cells. It was also shown that cetuximab inhibited the drug efflux activity of ABCG2. In combination with irinotecan, cetuximab can both significantly induce cell apoptosis by inhibiting the RAS-RAF-MEK-ERK signaling pathway and improve the effects of irinotecan by decreasing drug efflux through the inhibition of ABCG2. CONCLUSION: These features contribute to its anti-cancer potential.

H19 contributes to poor clinical features in NSCLC patients and leads to enhanced invasion in A549 cells through regulating miRNA-203-mediated epithelial-mesenchymal transition.

Recent studies have demonstrated that the overexpression of H19 may contribute towards development of tumorigenesis in various types of cancer. To investigate the role of H19 in the development of non-small cell lung cancer (NSCLC), 76 NSCLC tissues samples and their adjacent normal tissue samples were collected. Expression level of H19, and its association with clinicopathological features and overall survival was analyzed. It was found that compared with normal adjacent tissues, H19 expression was elevated in NSCLC tissues along with a decreased miR-203 expression level. It was also found that patients who were in advanced clinical stages had a higher H19 and a lower miR-203 expression compared to normal tissues. The overall survival time of patients with higher H19 expression was shorter compared with the lower H19 expression group. Upregulation of A549 enhanced cell proliferation and promoted invasion. Overexpression of H19 stimulated the epithelial-mesenchymal transition (EMT) process in lung cancer cells and demonstrated typical morphological characteristics of EMT. The level of mesenchymal marker protein, such as Vimentin and SNAI1 increased; while CDH1 protein level decreased. Also, H19 negatively regulated miR-203. Inhibition of H19 attenuated miR-203 induced EMT process. Upregulation of H19 contributes to poor clinical features in patients with NSCLC, induces occurrence of EMT, promotes proliferation and stimulates cell invasion in NSCLC cell line through regulating miRNA-203 mediated EMT.

Extended and contorted conformations of alkanediammonium ions in symmetrical α,α',δ,δ'-tetramethylcucurbit[6]uril cavity.

Binding interactions between symmetrical α,α',δ,δ'-tetramethylcucurbit[6]uril (TMeQ[6]) and a series of alkyldiammonium ions in aqueous solution and in the solid state were investigated by (1)H NMR spectroscopy, MALDI-TOF mass spectrometry, X-ray crystallography, and isothermal titration calorimetry (ITC). Their (1)H NMR spectra reveal that the actual binding behaviors vary depending upon the alkyl chain length. Their single-crystal X-ray diffraction analyses indicate the guest 1,2-ethanediammonium is located outside of the TMeQ[6] portal, while the other four alkyldiammonium guests can be accommodated in the TMeQ[6] cavity, forming 1:1 inclusion complexes. Most importantly, the long-chain alkyldiammoniums (1,8-octanediammonium and 1,10-decanediammonium) take a contorted conformation when bound within the TMeQ[6] cavity. Additionally, ITC experiments show that the complexation of the alkyldiammonium guests with TMeQ[6] is mainly enthalpy driven, which benefits from ion-dipole interactions.

Structure of supramolecular assemblies formed by alpha,delta-tetramethylcucurbit[6]uril and 4-nitrophenol.

A host-guest assembly, [(C(40)H(44)N(24)O(12)).(C(6)H(5)NO(3))(8).13(H(2)O)] (1), based on a partial substituted cucurbituril, alpha,delta-tetramethylcucurbit[6]uril (TMeQ[6]), and 4-nitrophenol was synthesized and structurally characterized by single-crystal X-ray diffraction. A combination of hydrogen-bonding between the latticed water molecule and the hydroxyl group of 4-nitrophenol, the hydroxyl group of 4-nitrophenol and the carbonyl groups lining the portals in additon, the C-H...pi interactions between the 4-nitrophenol molecules could be the driving forces of formation such an exclusion host-guest assembly.

4-[3-(4-Nitro-phen-oxy)prop-oxy]aniline.

The mol-ecules of the title compound, C(15)H(16)N(2)O(4), are linked via N-H⋯O hydrogen bonds, forming undulating one-dimensional chains. Adjacent chains are linked by weak C-H⋯π inter-actions, forming a three-dimensional network.