No abstract

Background: Numerous studies have examined the association between heavy metal contamination (including arsenic [As] [Pb], and zinc [Zn]) and lung cancer. However, data from previous studies on pathological cell types are limited, particularly regarding exposure to low-dose soil heavy metal contamination. The purpose of this study was to explore the association between soil heavy metal contamination and lung cancer incidence by specific cell type in Taiwan. Methods: We conducted an ecological study and calculated the annual averages of eight soil heavy metals (i.e., As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) by using data from the Taiwan Environmental Protection Administration from1982 to 1986. The age-standardized incidence rates of lung cancer according to two major pathological types (adenocarcinoma [AC] and squamous cell carcinoma [SCC]) were obtained from the National Cancer Registry Program conducted in Taiwan from 2001 to 2005. A geographical information system was used to plot the maps of soil heavy metal concentration and lung cancer incidence rates. Poisson regression models were used to obtain the adjusted relative ratios (RR) and 95% confidence intervals (CI) for the lung cancer incidence associated with soil heavy metals.

There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.

We examined the amount of gelatinases (matrix metalloproteinase-2 and -9 [MMP-2 and MMP-9] in a series of chondral, meniscal, and synovial cultures of early osteoarthritis (OA) after treatment with or without catabolic cytokines. These included interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and pharmacological agents, including plasmin/serine proteinase antagonist aprotinin, protein synthesis inhibitor cycloheximide, and protein kinase C (PKC) inhibitors staurosporine, H7, and Gö6976 for investigation of their effects on MMP-2 and -9 production in OA. Gelatin zymography revealed that IL-alpha, TNF-alpha, and LPS could elevate MMP-2 secretion in all tissue cultures and also increase MMP-9 production in all synovial and some meniscal cultures. In contrast, aprotinin, cycloheximide, staurosporine, H7, and Gö6976 could suppress MMP-2 secretion in all tissue cultures and also decrease MMP-9 production in all synovial and some meniscal cultures. Our data indicate that catabolic cytokines and LPS may promote tissue destruction and disintegration of extracellular matrix in early OA. Agents that target on the PKC pathway, plasmin/serine proteinase or protein synthesis for MMP-2 and -9 in early OA may inhibit the production of MMPs. These findings might contribute to the design of more efficacious therapies.