Molecular modeling and biological effects of peptidomimetic inhibitors of TACE activity.

We investigated the molecular basis of specificity for the interaction between tumor necrosis factor-alpha converting enzyme (TACE) and peptidomimetic inhibitors. Four novel peptidomimetic TACE inhibitors (8a-d) were designed and synthesized by introducing a substituted sulfur group and a hydrophobic group to a novel matrix metalloprotease (MMP) inhibitor. Inhibition was determined by in vitro lipopolysaccharide (LPS) cytotoxicity tests in HL-60 cell lines and by measuring the expression of mTNF-alpha using FCM techniques and immunohistochemistry in vivo. We simulated the interaction of the inhibitors with the 3D structure of the TACE active site in the Brookhaven Protein Database (PDB). The four inhibitors (8a-d) inhibited activity by 9.1%, 54.5%, 27.3%, and 54.5%, respectively. 8b and 8d showed significant in vitro inhibition in cytotoxicity tests, which corresponded to the molecular docking results. 8d also showed inhibitory activity in vivo. We explored the interface between enzyme and substrate by combining bioinformatics with experimental observations to further the development of specific TACE inhibitors to reduce inflammatory responses.

[Comparison of Different Leaching Methods for Heavy Metals in Sludge Fly Ash and Comprehensive Toxicity Evaluation].

Fly ash from sludge incineration was separated into five different sizes (<1 µm, 1-2.5 µm, 2.5-10 µm, 10-50 µm, and > 50 µm) by high-precision air classification equipment. The leaching of heavy metals was contrastively studied using the HJT 299-2007-sulfuric acid/nitric acid method, HJ 557-2009-Horizontal Oscillation Method, toxicity characteristic leaching procedure (TCLP), and European standard protocol (EN 12457-3) for the different size fractions of the fly ash. Based on the leaching results, an evaluation method for the comprehensive toxicity of heavy metal leaching was established. The results show that the content of heavy metals and the amount of leaching from the fly ash decrease with the increase in fly ash particle size. The leaching of the heavy metals Zn and Cu in the < 1 µm particle size range of TCLP leaching method was the highest, at 107.34 mg·kg-1 and 318 mg·kg-1, respectively. The TCLP and sulfuric acid/nitric acid methods of heavy metal leaching were more effective than the EU (EN 12457-3) and horizontal oscillation methods. According to the value of OPTI, the OPTI value of < 10 µm fly ash was much larger than that of fly ash that was > 10 µm. This indicated that the fly ash of particle size < 10 µm was more toxic and more harmful.

Berberine relieves insulin resistance via the cholinergic anti-inflammatory pathway in HepG2 cells.

Berberine (BBR) is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus (T2DM) in China. The development of T2DM is often associated with insulin resistance and impaired glucose uptake in peripheral tissues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in HepG2 cells. Cellular glucose uptake, quantified by the 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-2-deoxy-D-glucose (2-NBDG), was inhibited by 21% after HepG2 cells were incubated with insulin (10(-6) mol/L) for 36 h. Meanwhile, the expression of alpha7 nicotinic acetylcholine receptor (α7nAChR) protein was reduced without the change of acetylcholinesterase (AChE) activity. The level of interleukin-6 (IL-6) in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-ß (IKκß) Ser181/IKKß and the expression of nuclear factor-kappa B (NF-κB) p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of α7nAChR protein and inhibited AChE activity. These changes were also accompanied with the decrease of the ratio of pIKKß Ser181/IKKß, NF-κB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in HepG2 cells. The mechanism may be related to the cholinergic anti-inflammatory pathway and the inhibition of AChE activity.

[Study on emission spectrum of some single element hollow cathode lamps].

In this paper, the emission spectra of 13 kinds of elements were determined on 19 single element hollow cathode lamps. The spectral overlap was discovered among emission lines of some elements and resonance lines or non-resonance lines of other elements. The reason for producing this phenomena was discussed initially. The viewpoint that these single element lamps can be used to the multielement determination and as the light sources of simultaneous multi-elements determining atomic absorption spectrophotometer was put forward.