Antibacterial Activity of Squaric Amide Derivative SA2 against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA)-caused infection is difficult to treat because of its resistance to commonly used antibiotic, and poses a significant threat to public health. To develop new anti-bacterial agents to combat MRSA-induced infections, we synthesized novel squaric amide derivatives and evaluated their anti-bacterial activity by determining the minimum inhibitory concentration (MIC). Additionally, inhibitory activity of squaric amide 2 (SA2) was measured using the growth curve assay, time-kill assay, and an MRSA-induced skin infection animal model. A scanning electron microscope and transmission electron microscope were utilized to observe the effect of SA2 on the morphologies of MRSA. Transcriptome analysis and real-time PCR were used to test the possible anti-bacterial mechanism of SA2. The results showed that SA2 exerted bactericidal activity against a number of MRSA strains with an MIC at 4-8 µg/mL. It also inhibited the bacterial growth curve of MRSA strains in a dose-dependent manner, and reduced the colony formation unit in 4× MIC within 4-8 h. The infective lesion size and the bacterial number in the MRSA-induced infection tissue of mice were reduced significantly within 7 days after SA2 treatment. Moreover, SA2 disrupted the bacterial membrane and alanine dehydrogenase-dependent NAD+/NADH homeostasis. Our data indicates that SA2 is a possible lead compound for the development of new anti-bacterial agents against MRSA infection.

High levels of HB-EGF and interleukin-18 are associated with a high risk of in-stent restenosis.

OBJECTIVE: To explore the clinical significance of heparin-binding epidermal growth factor-like growth factor (HB-EGF), interleukin-18 (IL-18), and interleukin-10 (IL-10) in restenosis after percutaneous coronary intervention (PCI). METHODS: A total of 198 patients with acute coronary syndrome underwent coronary drug-eluting stent implantation and were divided into the restenosis group and non-restenosis group on the basis of second coronary angiography. Biological parameters and HB-EGF, IL-18, and IL-10 levels were measured. Patients in the restenosis group were further divided into 3 subgroups according to Gensini score: group A (Gensini score of <20), group B (Gensini score of ≥20 but <40), and group C (Gensini score of ≥40). RESULTS: Compared with the non-restenosis group, HB-EGF and IL-18 levels were significantly higher but serum IL-10 levels were significantly lower in the restenosis group. Furthermore, HB-EGF levels increased with the Gensini score among the 3 subgroups. Spearman's correlation analysis showed that HB-EGF levels were associated with IL-18 levels and the number of diseased vessels. Multivariate logistic regression analysis showed that diabetes, HB-EGF, and IL-18 were risk factors for restenosis [odds ratio with 95% confidence interval: 3.902 (1.188-4.415), 2.185 (1.103-4.014), and 2.079 (1.208-4.027), respectively]. CONCLUSION: The present study has demonstrated that HB-EGF may be used to evaluate the severity of restenosis and coronary artery lesion and that inflammatory responses may be involved in the process of restenosis.

Toxicity of ethanedinitrile to Anoplophora glabripennis (Coleoptera: Cerambycidae) larvae.

The mortality of naked Anoplophora glabripennis Motschulsky (Coleoptera: Cerambycidae) larvae exposed to ethanedinitrile (cyanogen; C2N2) varied with temperature, time of exposure, and dose of ethanedinitrile. The concentration x time (Ct) product of ethanedinitrile over a range of temperatures (4.4, 10.1, 15.6, and 20.1 degrees C) decreased with increasing temperature, for both 3- and 6-h exposures. The Ct products varied with time of exposure at different temperatures. The variations in mortality at different temperatures are described with a slope ratio (Y = [slope]6h/ [slope]3h). At different temperatures, the concentration of ethanedinitrile and the duration of exposure play different roles in killing A. glabripennis larvae. These results suggest the control of A. glabripennis larvae within wood is achievable.