Endocytosis of peroxiredoxin 1 links sterile inflammation to immunoparalysis in pediatric patients following cardiopulmonary bypass.

After cardiopulmonary bypass (CPB), the occurrence of systemic inflammatory response is often accompanied by a persistent compensatory anti-inflammatory response syndrome that can lead to a compromised immune competence termed immunoparalysis, rendering the patients susceptible to infections which is a leading complication following cardiac surgery. However, the underlying mechanisms of CPB-elicited immunoparalysis remain obscure. In this study we showed that peroxiredoxin 1 (Prdx1), a putative cytosolic antioxidant, was released immediately after CPB in a cohort of pediatric patients receiving congenital cardiac surgery. This increased Prdx1 was correlated to a reduced human leukocyte antigen-DR expression and an elevated interleukin-10 (IL-10) production, as well as a hypo-responsiveness of macrophages to endotoxin and a higher incidence of nosocomial infection. We demonstrated that substitution of Ser83 for Cys83 prevented Prdx1 from oligomerization and subsequent binding and internalization to macrophages. These effects mitigated Prdx1-induced IL-10 induction and endotoxin tolerance. Furthermore, after engagement with toll-like receptor (TLR) 4, clathrin-dependent endocytosis is crucial for Prdx1 to elicit IL-10 production in phagocytes. Congruently, inhibition of Prdx1/TLR4 endocytosis in phagocytes reversed the Prdx1/IL-10-mediated hypo-responsiveness to endotoxin. Our findings unveiled the possible mechanisms by which Prdx1 undertakes to cause immunoparalysis, and targeting endocytosis of Prdx1 could be a novel therapeutic approach for postoperative infections associated with CPB.

Influential factors for visit time for tracheobronchial foreign bodies in pediatrics.

PURPOSE: This study aims to investigate the inflential factors for visit time for tracheobronchial foreign bodies in pediatrics, and to shorten the time of diagnosis and reduce complications. METHODS: A questionnaire survey was designed and conducted among the caretakers of children with tracheobronchial foreign bodies, and the related inflential factors for visit time were analyzed. RESULTS: The visit time for tracheobronchial foreign body was correlated with the age of the child, the type of foreign body, the educational level of the caretaker, a history of foreign body aspiration were provided, an examination was performed during the visit, the anti-inflammatory and anti-allergic treatment, and transfer to a higher level hospital. Age, history of foreign body aspiration were provided, and anti-inflammatory and anti-allergic treatment were the independent inflential factors for the time of diagnosis (P < 0.05). CONCLUSION: The visit time for tracheobronchial foreign bodies was affected by many factors. It is necessary to strengthen the publicity scope and intensity on health education for tracheobronchial foreign bodies in community doctors and parents, to shorten the time of diagnosis and reduce complications.

Perioperative plasma mitochondrial DNA dynamics and correlation with inflammation during infantile cardiopulmonary bypass.

OBJECTIVE: Numerous studies in animals and humans have demonstrated that inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 play a role in cardiopulmonary bypass (CPB), which might affect surgical outcomes. Plasma mitochondrial DNA (mtDNA), a recently discovered pro-inflammatory agent, is released by cells upon insult. This study aimed to detect changes in plasma mtDNA levels at different time points after infantile CPB and explore its potential association with inflammatory mediators. METHODS: In the present study, we analyzed the perioperative plasma mtDNA and inflammatory cytokine levels of 48 infants undergoing ventricular septal defect closure. Blood samples were collected before aortic cross-clamping (T1), at the end of CPB (T2), and 6h (T3), 12h (T4), and 24h (T5) post-CPB. Reverse transcription-polymerase chain reaction and specific enzyme-linked immunosorbent assay were used to quantify the plasma mtDNA and inflammatory cytokines, respectively. Bivariate correlation analysis was used to determine the correlations between plasma mtDNA and inflammatory cytokines. RESULTS: Plasma mtDNA levels increased at T2 and peaked at T3. Significant positive correlations were found between peak plasma mtDNA (at T3) and several inflammatory biomarkers, including IL-6 (at T3) (r=0.62, P<0.001), IL-8 (at T2) (r=0.53, P<0.001), and TNF-α (at T3) (r=0.61, P<0.001). CONCLUSION: Here we report that mtDNA may participate in a systemic inflammatory response to CPB.

Berberine targets epidermal growth factor receptor signaling to suppress prostate cancer proliferation in vitro.

Berberine is a well­known component of the Chinese herbal medicine Huanglian (Coptis chinensis), and is capable of inhibiting the proliferation of multiple cancer cell lines. However, information available regarding the effect of berberine on prostate cancer cell growth is limited. In the present study, LnCaP and PC­3 human prostate cancer cell lines were selected as in vitro models in order to assess the efficacy of berberine as an anticancer agent. A cell proliferation assay demonstrated that berberine inhibited cell growth in a dose­and time­dependent manner. Further investigation revealed berberine significantly accumulated inside cells that were in the G1 phase of the cell cycle and enhanced apoptosis. Western blot analysis demonstrated that berberine inhibited the expression of prostate­specific antigen and the activation of epidermal growth factor receptor (EGFR), and it attenuated EGFR activation following EGF treatment in vitro. In conclusion, the results indicate that berberine inhibits the proliferation of prostate cancer cells through apoptosis and/or cell cycle arrest by inactivation of the EGFR signaling pathway.

Identification of a keratinase-producing bacterial strain and enzymatic study for its improvement on shrink resistance and tensile strength of wool- and polyester-blended fabric.

A wool-degrading bacterium was isolated from decomposition wool fabrics in China. The strain, named 3096-4, showed excellent capability of removing cuticle layer of wool fibers, as demonstrated by removing cuticle layer completely within 48 h. According to the phenotypic characteristics and 16S rRNA profile, the isolate was classified as Pseudomonas. Bacteria growth and keratinase activity of the isolate were determined during cultivation on raw wool at different temperatures, initial pH, and rotation speed using orthogonal matrix method. Maximum growth and keratinase activity of the bacterium were observed under the condition including 30 °C, initial pH 7.6, and rotational speeds 160 rpm. The keratinase-containing crude enzyme prepared from 3096-4 was evaluated in the treatment of wool fabrics. The optimal condition of our enzymatic improvement of shrink resistance was the combination of 30 °C, initial pH 7.6, and rotation speeds 160 rpm. After the optimized treatment, the wool fabrics felting shrink was 4.1% at 6 h, and textile strength was not lost.