Recent progress on the roles of DAMP and NET in organ ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon, secondary to multiple pathological processes, such as organ transplantation, acute kidney injury and myocardial infarction. IRI may significantly aggravate the severity of diseases and increase the fatality of patients. Aseptic inflammation is one of the critical mechanisms of IRI. Damage-associated molecular pattern (DAMP) is a pivotal substance, which mediates aseptic inflammation. After released into extracellular space, it could effectively activate the immune system, and initiate and maintain the inflammatory responses by binding with pattern recognition receptor (PRR). Neutrophil extracellular trap (NET) is a DNA-based network structure released by neutrophils during the process of inflammatory responses, which contains histones and multiple granular proteins. Recent studies have demonstrated that DAMP and NET may aggravate IRI via aseptic inflammation. In this article, relevant studies of DAMP, NET and their relationship in IRI were reviewed, which was of great significance for understanding the pathophysiological mechanism of IRI and studying the corresponding prevention and treatment strategies.

Diagnosis and treatment experience of granulomatous cheilitis: case report and literature review / 口腔疾病防治

Objective@#To investigate the etiology, diagnosis and treatment of granulomatous cheilitis（GC）.@*Methods@# For a patient with recurrent granulomatous cheilitis for more than 1 year in whom no medical treatment was used, only systemic treatment of the teeth was performed, and its efficacy was observed. We also reviewed the relevant literature. @*Results@#The vermilion of the right lower lip of the patient was obviously swollen and soft. There was rebound and no pitting edema with palpation. A large dark red rash with local desquamation was observed on the skin over the right mandible. There were residual roots in tooth 35, 46, and 47, a porcelain bridge on 11-24, deep caries in 15, 16, 26, and 36, and many calculi in the whole mouth, and the gingival margin was obviously congested and swollen. Histopathological examination showed many lymphocytes infiltrated the superficial dermis, and granulation tissue, plasma cells and eosinophils infiltrated locally. The diagnosis was as follows: ① GC; ② 35, 46, and 47 residual roots; ③ 15, 16, 26, and 36 deep caries; ④ gingivitis. The treatment included extraction of 35, 46, and 47 residual roots, periodontal basic treatment, and fillings for 15, 16, 26, and 36. No drugs were administered except for 3 days after tooth extraction. After 5 weeks of treatment, the swelling of the lower lip and the skin rash completely disappeared. There was no recurrence in the follow-up observation at six months. Through a literature review and analysis, we found that GC may be related to various factors such as immunity, infection, and genetics. Local oral infections may be closely related to the incidence of GC.@*Conclusion @#Resolution of local oral infections is effective for the treatment of granulomatous cheilitis, and local oral infections may be closely related to the onset of granulomatous cheilitis. In the treatment of granulomatous cheilitis, attention should be paid to the systematic examination of the oral condition, and the treatment of suspected lesions in the oral cavity should begin in the early stages of treatment.

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m

Background Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol.L−1 (S. aureus) and 10.10 μmol.L−1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.(AU)

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m

Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 mol.L1 (S. aureus) and 10.10 mol.L1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 g of LyeTx I-K-HYNIC; 250 g of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

Clinical research of external application of sihuang-honey for aseptic inflammation after total knee arthroplasty / 国际中医中药杂志

ObjectiveTo observe the clinical efficacy of external application of sihuang-honey for aseptic inflammation after total knee arthroplasty.Methods 30 cases of total knee arthroplasty patients were recruited into two groups,of 15 cases in each group.The treatment group was treated with sihuang-honey (made of rhubarb,scutellaria,phellodendron,coptis according to the same proportion of powder with honey ),which was placed on a sterile plastic sheet,0.5 cm thickness.The sheet was applied on the knee of the highest skin temperature for 6 hours,removed it for 2 hours interval,and reapplied on it,for altogether 24 hours before changing another sheet.The control group were treated by continued covering ice on the knee every day,with the ice completely surrounded the knee.Both groups were treated for 2 weeks.Clinical efficacy was observed before the treatment,and 3 d,7 d,14 d after the treatment.ResultsAfter the treatment,compared with the control group,the treatment group was effective in terms of VAS score (4.12± 1.08) points in 3d,(3.34±0.61)points in the first 7 days; skin temperature (37.56±0.40) ℃,activity (98.56±3.24) ° in 3d,and the difference was statistically significant (P＜0.05).The degree of swelling in 3 d (5.80±2.00) ％,7 d (9.33±2.55)％,14 d (12.13 ± 2.70)％ in the treatment group were better than the control group (P＜0.05); The rate of pain relief of treatment group was 93.33％ and satisfaction was 66.67％,although better than 86.67％ and 46.67％ of the control group,the difference was not statistically significant (x2 were 1.33,3.04,P＞0.05).Conclusion Sihuang-honey was effective for the treatment of aseptic inflammation after the surgery of total knee arthroplasty.