BMSC-derived exosomes alleviate smoke inhalation lung injury through blockade of the HMGB1/NF-κB pathway.

AIMS: To investigate the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomes in smoke inhalation lung injury. MAIN METHODS: In this study, we initially isolated exosomes from BMSCs and identified them by western blot and transmission electron microscopy. BMSC-derived exosomes were then used to treat in vitro and in vivo models of smoke inhalation lung injury. Pathologic alterations in lung tissue, the levels of inflammatory factors and apoptosis-related factors, and the expression of HMGB1 and NF-κB were determined to evaluate the therapeutic effect of BMSC-derived exosomes. KEY FINDINGS: We found that BMSC-derived exosomes could alleviate the injury caused by smoke inhalation. Smoke inhalation increased the levels of inflammatory factors and apoptosis-related factors and the expression of HMGB1 and NF-κB, and these increases were reversed by BMSC-derived exosomes. HMGB1 overexpression abrogated the exosome-induced decreases in inflammatory factors, apoptosis-related factors and NF-κB. SIGNIFICANCE: Collectively, these results indicate that BMSC-derived exosomes can effectively alleviate smoke inhalation lung injury by inhibiting the HMGB1/NF-κB pathway, suggesting that exosome, a noncellular therapy, is a potential therapeutic strategy for inhalation lung injury.

Stem cell derived exosomes-based therapy for acute lung injury and acute respiratory distress syndrome: A novel therapeutic strategy.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common critical disease which can be caused by multiple pathological factors in clinic. However, feasible and effective treatment strategies of ALI/ARDS are limited. At present, the beneficial effect of stem cells (SCs)-based therapeutic strategies for ALI/ARDS can be attributed to paracrine. Exosomes, as a paracrine product, are regarded as a critical regulatory mediator. Furthermore, substantial evidence has indicated that exosomes from SCs can transmit bioactive components including genetic material and protein to the recipient cells and provide a protective effect. The protective role is played through a series of process including inflammation modulation, the reconstruction of alveolar epithelium and endothelium, and pulmonary fibrosis prevention. Therefore, SCs derived exosomes have the potential to be used for therapeutic strategies for ALI/ARDS. In this review, we discuss the present understanding of SCs derived exosomes related to ALI/ARDS and provide insights for developing a cell-free strategy for treating ALI/ARDS.

A case report of a woman after childbirth with a dehisced abdominal wound as well as fat liquefaction and large skin necrosis.

Recently high-frequency electric knife and abdominal binder are widely used in the abdominal operation in China. Nevertheless, with the high occurrence of the abdominal wound, we think that whether both these operations could be used or not. Here, we report the case of a 40-year-old female patient where negative pressure wound therapy (NPWT) was applied to her dehisced abdominal wound as well as fat liquefaction and large skin necrosis with pleasing results. The patient with high fever was referred to our department from her earlier hospital for 6 days after cesarean delivery. During the surgery, her earlier doctor used a high-frequency electric knife for convenient-using, and after the operation, the patient immediately used an abdominal binder for good shape. However, the abdominal surgical incision was opened at postoperative day 3, with fat liquefaction releasing large fatty acids along both abdominal sides with penetration under the abdominal binder. After admitted at postoperative day 6 with aggravating wound, surgery was considered because of no reduction in the size of the wound. A series of vacuum sealing drainage (VSD) or vacuum-assisted closure (VAC) as well as others, were operated. In the admitted 25th day, the wound was completely closed. NPWT is a practical and effective therapy for the treatment of numerous refractory and intractable wounds. Therefore, we suggest that the high-frequency electric knife and an abdominal binder should be avoided using an abdominal operation. This case is the first report of the use of NPWT over a dehisced abdominal wound with fat liquefaction and large skin necrosis on a postpartum patient in China.

Efficacy and Safety of Intralesional Triamcinolone Versus Combination of Triamcinolone with 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Systematic Review and Meta-analysis.

BACKGROUND: Although keloids and hypertrophic scars are common benign hyperproliferative growths of dermal fibroblasts, the clinical problems including physical and psychological problems are significant and impairing, with few proven treatments. Intralesional triamcinolone acetonide (TAC) and combination of TAC with 5-fluorouracil (5-FU) are widely used to treat keloids and hypertrophic scars, but their efficacy and safety remain controversial. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, and CNKI for relevant trials. RESULTS: The mean scar height and the erythema score in the TAC + 5-FU group were lower than those in the TAC group after treatment (P < 0.05). The effectiveness based on observer assessment after treatment in the TAC + 5-FU group was superior than that in the TAC group (P < 0.05); further, the subgroup analysis showed the TAC + 5-FU group was also superior than the TAC group in the treatment of hypertrophic scars (P = 0.01), and there were no significant differences in the treatment of keloid (P = 0.12). The effectiveness based on patient self-assessment after treatment in the TAC + 5-FU group was also superior than the TAC group (P < 0.05). The overall complication rate in the TAC + 5-FU group was lower than the TAC group (P < 0.05). CONCLUSIONS: Combination of TAC with 5-FU is more effective and safer than TAC alone therapy in the treatment of keloids and hypertrophic scars. Data on keloids alone or hypertrophic scars alone are, however, limited. A better understanding of effective after intralesional combination of TAC with 5-FU in the treatment of keloids alone or hypertrophic scars alone is imperative. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model.

The aim of the present study was to determine the effects of early anticoagulation treatment on severe burns complicated by inhalation injury in a rabbit model. Under anesthetization, an electrical burns instrument (100˚C) was used to scald the backs of rabbits for 15 sec, which established a 30% III severe burns model. Treatment of the rabbits with early anticoagulation effectively improved the severe burns complicated by inhalation injury­induced lung injury, reduced PaO2, PaCO2 and SPO2 levels, suppressed the expression of tumor necrosis factor­α, interleukin (IL)­1ß and IL­6, and increased the activity of IL­10. In addition, it was found that early anticoagulation treatment effectively suppressed the activities of caspase­3 and caspase­9, upregulated the protein expression of vascular endothelial growth factor (VEGF) and decreased the protein expression of protease­activated receptor 1 (PAR1) in the severe burns model. It was concluded that early anticoagulation treatment affected the severe burns complicated by inhalation injury in a rabbit model through the upregulation of VEGF and downregulation of PAR1 signaling pathways. Thus, early anticoagulation is a potential therapeutic option for severe burns complicated by inhalation injury.

[Effects of high frequency oscillatory ventilation combined with incremental positive end-expiratory pressure on respiratory and circulatory functions of dogs with inhalation injury].

OBJECTIVE: To study the effects of high frequency oscillatory ventilation (HFOV) combined with incremental positive end-expiratory pressure (IP) on respiratory and circulatory functions, and lung histopathology of dogs with smoke inhalation injury. METHODS: After being treated with conventional mechanical ventilation, 12 dogs were inflicted with severe smoke inhalation injury and divided into group HFOV and group HFOV+IP according to the random number table, with 6 dogs in each group. Then they received corresponding ventilation for 8 hours respectively. Blood gas analysis results (pH value, PaO2 and PaCO2 levels) and hemodynamic parameters [heart rate, mean arterial pressure (MAP), pulmonary arterial pressure (PAP), central venous pressure (CVP), cardiac output (CO)] were recorded before injury, immediately after injury, and at post ventilation hour (PVH) 2, 4, 6, and 8. The dogs of two groups were sacrificed at PVH 8. A healthy dog without any treatment and a dog with smoke inhalation injury but no subsequent treatment were sacrificed in addition. Lung tissues of all dogs were obtained for histopathological observation. Lung injury score examination was conducted in both groups. Data were processed with rank sum test, analysis of variance of repeated measurement, and LSD- t test. RESULTS: (1) The PaO2 levels in both groups were significantly decreased immediately after injury, compared with those before injury (with t values respectively 4.960, 5.310, P values all below 0.01). The PaO2 levels in both groups from PVH 2 to PVH 8 were significantly increased, compared with those observed immediately after injury (with t values from 4.930 to 6.050, P values all below 0.01). At PVH 2, 4, and 8, PaO2 levels in group HFOV+IP were significantly higher than those in group HFOV (with t values from 3.775 to 5.774, P values all below 0.01); no statistically significant differences were observed in pH value and PaCO2 level at each time point between two groups (with t values from 0.002 to 0.997, P values all above 0.05). (2) There were no statistically significant differences in MAP, PAP, and CVP within two groups at each time point (with F values from 1.316 to 4.959, P values all above 0.05). In group HFOV, heart rate from PVH 2 to PVH 8 was significantly lower than that observed immediately after injury (with t values from 3.780 to 8.970, P values all below 0.01). In group HFOV+IP, CO at PVH 4, 6, and 8 was significantly lower than that observed immediately after injury (with t values from 3.990 to 11.200, P values all below 0.01). There were no statistically significant differences in MAP, PAP, and CVP between two groups at the same time point (with t values from 0.089 to 2.123, P values all above 0.05). At PVH 4, 6, and 8, heart rate in group HFOV+IP was higher than that in group HFOV (with t values from 2.931 to 7.229, P < 0.05 or P < 0.01), while CO was lower (with t values from 4.297 to 11.206, P values all below 0.01). (3) Compared with those of the healthy dog, inflammatory cell infiltration and bleeding in the lung were observed in alveolar space in both group HFOV and group HFOV+IP, while the degree was less serious than that of the dog with smoke inhalation injury only. Compared with those of group HFOV, inflammatory cell infiltration in group HFOV+IP was less significant, the alveolar structure was relatively intact, and no thickening of alveolar walls was observed. The lung injury score in group HFOV [(3.27 ± 0.24) points] was higher than that of group HFOV+IP [(2.79 ± 0.31) points, t = 27, P < 0.05]. CONCLUSIONS: HFOV combined with IP can improve gas exchange and alleviate pulmonary injury without any adverse effect on blood gas analysis or hemodynamic parameters. Therefore, it may be considered as an appropriate mode of ventilation for the treatment of smoke inhalation injury.