Escherichia coli GutM4 produces 2, 5-diketopiperazines and inhibits human pathogens in vitro

Background: It has been a very common practice to use probiotics or their metabolites as alternative antimicrobial strategies for the treatment and prevention of infections as rampant and indiscriminate use of antibiotics causes the development of antibiotic-resistant pathogens. The objective of this study was to select a potential antimicrobial probiotic strain of Escherichia coli from the human gastrointestinal tract and investigate the production of diketopiperazines that contribute to the antimicrobial activity. Results: E. coli GutM4 was isolated from the feces of a healthy adult. E. coli GutM4 showed significant antagonistic activity against 10 indicator pathogens, and this activity was no less than that of the reference strain E. coli Nissle 1917 against eight of the indicator pathogens. Moreover, E. coli GutM4 produced antagonistic substances containing trypsin-targeted peptide bonds because the inhibitory effects of E. coli GutM4 supernatant significantly decreased upon treatment with trypsin. Consistent with the antagonistic activity and peptide compounds of E. coli GutM4, 14 2,5-diketopiperazines were isolated from the fermented broth of E. coli GutM4, including 12 cyclo(Pro-Phe), 3 cyclo(Pro-Tyr), and 5 cyclo(4-hydroxyl-Pro-Leu), which are reported to have antipathogenic activity. Conclusion: E. coli GutM4 produces 2,5-diketopiperazines that are partly involved in antagonistic action against human pathogens in vitro.

Effect of propranolol gel on plasma VEGF, bFGF and MMP-9 in proliferating infantile hemangiomas of superficial type / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of topical propranolol gel on the levels of plasma vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF) and matrix metalloproteinases-9 (MMP-9) in proliferating infantile hemangiomas (IHs) of superficial type.</p><p><b>METHODS</b>33 consecutive children with superficial IHs were observed pre-treatment, 1 and 3 months after application of topical propranolol gel for the levels of plasma VEGF, MMP-9 and bFGF by enzyme-linked immunosorbent assay (ELISA) in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants. The clinical efficacy in IHs was evaluated by Achauer system. Differences of plasma results between the healthy group and the IHs group pre-treatment were analyzed using Mann-Whitney U-test. Paired sample comparisons of any two time points of pre-treatment, 1 month and 3 months after treatment in IHs were evaluated by Wilcoxon signed-rank test.</p><p><b>RESULTS</b>The clinical efficiency of topical propranolol gel at 1, 3 months after application were 45.45%, 81.82% respectively. The levels of plasma VEGF and MMP-9 in patients pre- treatment were higher than those in healthy infants [(362.16 ± 27.29) pg/ml vs (85.63 ± 8.14) pg/ml, (1376.41 ± 42.15) pg/ml vs (687.27 ± 44.1) pg/ml, P < 0.05], but the level of bFGF did not show significant difference [(176.03 ± 13.60 ) pg/ml vs (235.94 ± 35.43 ) pg/ml, P > 0. 05 ]. The concentrations of VEGF and bFGF at 1, 3 months after treatment decreased obviously [(271.51 ± 18.59) pg/ml vs (362.16 ± 27.29 ) pg/ml, (135.85 ± 12.66) pg/ml vs (176.03 ± 13.60) pg/ml], 1 month after treatment vs pre-treatment, P < 0.05; (240.80 ± 19.89) pg/ml vs (362.16 ± 27.29) pg/ml, (107.31 ± 5.82) pg/ml vs (176.03 ± 13.60) pg/ml, 3 month after treatment vs pre-treatment, P < 0.05, whereas the levels of plasma MMP-9 declined slightly [(1321.18 ± 48.74) pg/ml vs (1376.41 ± 42.15 ) pg/ml, (1468.68 ± 32.78) pg/ml vs (1376.41 ± 42 2.15 ) pg/ml, P > 0.05 ].</p><p><b>CONCLUSIONS</b>Propranolol gel may suppress the proliferation of superficial infantile bemangiomas by reducing VEGF and bFGF.</p>

Effects of topical propranolol hydrochloride gel for treatment of infantile hemangioma in nude mice / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the effect and safety of topical propranolol hydrochloride gel for treatment of infantile hemangioma. METHODS Thirty nude mice (BALA/c, nu/nu) were divided into three groups, experimental group, control group and normal group. Human hemangioma endothelial cells cultured in vitro were injected subcutaneously in experimental group and control group to establish infantile hemangioma model. Topical propranolol hydrochloride gel was applied on the surface of the hemangioman in experimental group and normal group. Tumor volumn change and the skin situations (edema, erythema, ulceration) were observed at different periods. 45 days after cell injection, the mice were killed and plasma concentration was detected in the experimental group and the control group by high performance liquid chromatography with evaporative light scattering detector, and tumors were subjected to histopathologic examination and immunohistochemistry for CD31 and CD34. The correlation between volumes and plasma concentration was statistically analyzed with SPSS 13.0 paired samples t test with α = 0.05 as statistical standard.</p><p><b>RESULTS</b>At 45 days, the volume of the tumor in control group was (366.57 ± 17.08) mm³, which has a significant difference as compared to the experimental group (13.36 ± 2.09) mm³ (P < 0.05); and the plasma concentration was (16.83 ± 1.53) ng/ml in experimental group, and (18.42 ± 2.21) ng/ ml in normal group (P > 0.05 ). Topical propranolol hydrochloride gel (3%) has no irritation to nude mice's skin.</p><p><b>CONCLUSIONS</b>Topical application of 3% propranolol hydrochloride gel is effective and safe for the treatment of infantile hemangioma.</p>