Interaction between long noncoding RNA and microRNA in lung inflammatory diseases.

BACKGROUND: Non-coding RNAs (ncRNAs) are a group of RNAs that cannot synthesize proteins, but are critical in gene expression regulation. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), the two major family members, are intimately involved in controlling immune response, cell proliferation, apoptosis, differentiation and polarization, and cytokine secretion. Their interactions significantly influence lung inflammatory diseases and could be potential therapeutic targets. OBJECTIVES: The review aims to elucidate the role of ncRNAs, especially the interactions between lncRNA and miRNA in lung diseases, including acute and chronic lung inflammatory diseases, as well as lung cancer. And provide novel insights into disease mechanisms and potential therapeutic methods. METHODS: We conducted a comprehensive review of the latest studies on lncRNA and miRNA in lung inflammatory diseases. Our research involved searching through electronic databases like PubMed, Web of Science, and Scopus. RESULTS: We explain the fundamental characteristics and functions of miRNA and lncRNA, their potential interaction mechanisms, and summarize the newly explorations on the role of lncRNA and miRNA interactions in lung inflammatory diseases. CONCLUSIONS: Numerous lncRNAs and miRNAs have been found to partipicate in all stages of lung inflammatory diseases. While ncRNA-based therapies have been validated and developed, there remain challenges in developing more stable and effective drugs for clinical use.

The Role and Mechanism of Metformin in Inflammatory Diseases.

Metformin is a classical drug used to treat type 2 diabetes. With the development of research on metformin, it has been found that metformin also has several advantages aside from its hypoglycemic effect, such as anti-inflammatory, anti-aging, anti-cancer, improving intestinal flora, and other effects. The prevention of inflammation is critical because chronic inflammation is associated with numerous diseases of considerable public health. Therefore, there has been growing interest in the role of metformin in treating various inflammatory conditions. However, the precise anti-inflammatory mechanisms of metformin were inconsistent in the reported studies. Thus, this review aims to summarize various currently known possible mechanisms of metformin involved in inflammatory diseases and provide references for the clinical application of metformin.

Metformin Improves Burn Wound Healing by Modulating Microenvironmental Fibroblasts and Macrophages.

Metformin, a biguanide, exerts different functions through various signaling pathways. In order to investigate the function and mechanism of metformin in burn wounds, we established burn rat models, subcutaneously injected metformin to treat the wounds, and observed the morphologies and the expression of collagen I, collagen III, fibronectin, and pro-inflammatory markers. In vitro experiments were performed to investigate the effects of metformin on the proliferation, migration, and collagen I synthesis of the mouse embryonic fibroblast (NIH 3T3) cell line and on the proliferation, apoptosis, and immune response of the mouse mononuclear macrophage (RAW 264.7) cell line. Finally, we studied the regulatory effects of metformin on a co-culture of RAW 264.7/NIH 3T3 cells. We found that 100 mM of metformin reduced dermal thickness, collagen I deposition, and mRNA expression of IL1ß and CCL2 in rat burn wounds. In vitro experiments revealed that metformin inhibited the proliferation of NIH 3T3 and RAW 264.7 cells. Metformin attenuated NIH 3T3 cell migration via the AMPK/mTOR pathway and attenuated collagen I synthesis through the TGFß1/Smad3 pathway. Metformin inhibited the apoptosis of RAW 264.7 cells induced by 10 µg/mL LPS. Metformin downregulated the mRNA expression of IL1ß and CCL2 in RAW 264.7 cells under 1 µg/mL LPS induction by inhibiting NF-κB p65 phosphorylation. In a RAW 264.7/NIH 3T3 co-culture, metformin attenuated collagen I synthesis in NIH 3T3 cells by inhibiting RAW 264.7 paracrine secretion of TGF-ß1. This provides new evidence related to the development of metformin for potentially improving burn wound healing.

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.

Banana Peel-Derived Dendrite-Shaped Au Nanomaterials with Dual Inhibition Toward Tumor Growth and Migration.

PURPOSE: In order to prepare functional Au nanoparticles with low toxicity and high antitumor properties, we have used fruit waste (banana peel) to synthesize a new dendrite-shaped gold nanoparticle and used it for the treatment of tumors. METHODS: Dendrite-shaped gold nanoparticle (Au-dendrite) was synthesized through a facile hydrothermal process. The banana peel was used as both the reducing agent and the protective agent for reducing chloroauric acid to obtain Au-dendrite. The safety assessment of the Au-dendrite was conducted by H&E staining of the mouse's eyelid skin and CCK-8 assay. The antitumor effects were evaluated through in vitro tumor cytotoxicity experiments and in vivo treatment of animal tumors. RESULTS: In this work, a new type of gold nanomaterial (Au-dendrite) was synthesized by using a common agricultural waste (banana peel) through a facile hydrothermal process without any extra chemical reducing agent or protective agent. Subsequent experiments showed that, compared with some classical Au nanomaterials, the as-synthesized gold nanocomposites have superior biocompatibility and impressive characteristics of dual inhibition toward tumor growth and migration. CONCLUSION: We successfully synthesized a dendrite-shaped gold nanocomposite which was derived from a common agricultural waste (banana peel). A facile and environmentally friendly synthetic process was proposed accordingly without regular chemical additives. The as-prepared Au-dendrite nanocomposites not only had better biocompatibility than some classical gold nanoparticles but also exhibited unique advantages in tumor inhibition.

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 .

"The return of ceramic implants": Rose stem inspired dual layered modification of ceramic scaffolds with improved mechanical and anti-infective properties.

Nowadays, traditional ceramics for bone implants have considerably replaced by metal based biomedical materials, attributing to the friability of ceramics. However, ceramic implants possess excellent biocompatibility and longtime abrasion resistance. They should be more desirable for long-term uses of implants in case their fragility had been overcome. In the present work, inspired from natural rose, a dual-layer-modified ceramic scaffold was constructed by coating a superplastic layer of isocyanate (ISO) resin and a nano Zinc Oxide (nano-ZnO) layer on the ceramic scaffold. The ISO resin modification layer with 1 mm thickness, improved the mechanical properties of ceramic implants 2-3 times, and protect the ceramic implants from broken even drop from 1 m high. Moreover, such dual layered modification exhibited broad spectrum antibacterial behavior. In vivo biocompatible studies demonstrated that there was no obvious noticeable tissue damage in all major organs of mice after the implant surgeries.

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 myocardial ischemia and hypoxia and apoptosis of cardiomyocytes in dogs with smoke inhalation injury].

OBJECTIVE: To compare the effects of high frequency oscillatory ventilation (HFOV) combined with incremental positive end-expiratory pressure (IP) and those of pure HFOV on myocardial ischemia and hypoxia and apoptosis of cardiomyocytes in dogs with smoke inhalation injury. METHODS: Twelve healthy male dogs were divided into group HFOV and group HFOV+IP according to the random number table, with 6 dogs in each group. After being treated with conventional mechanical ventilation, dogs in both groups were inflicted with severe smoke inhalation injury, and then they received corresponding ventilation for 8 hours respectively. After treatment, the blood samples were collected from heart to determine the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase 1 (LDH1) in plasma. The dogs were sacrificed later. Myocardium was obtained for determination of content of TNF-α per gram myocardium by ELISA, apoptotic rate of cardiomyocytes by flow cytometer, degree of hypoxia with HE staining, and qualitative and quantitative expression of actin (denoted as integral absorbance value) with streptavidin-biotin-peroxidase staining. Data were processed with t test. The relationship between the content of TNF-α per gram myocardium and the apoptotic rate of cardiomyocytes was assessed by Spearman linear correlation analysis. RESULTS: (1) After treatment for 8 h, the values of activity of CK-MB and LDH1 in plasma of dogs in group HFOV+IP were respectively (734 ± 70) and (182 ± 15) U/L, which were both lower than those in group HFOV [(831 ± 79) and (203 ± 16) U/L, with t values respectively 2.25 and 2.35, P values below 0.05]. (2) Compared with that in group HFOV [(0.060 ± 0.018) µg], the content of TNF-α per gram myocardium of dogs in group HFOV+IP after treatment for 8 h was decreased significantly [(0.040 ± 0.011) µg, t=2.32, P<0.05]. (3) Compared with that in group HFOV [(33.4 ± 2.2)%], the apoptotic rate of cardiomyocytes of dogs in group HFOV+IP after treatment for 8 h was significantly decreased [(28.2 ± 3.4)%, t=3.15, P<0.05]. There was a positive correlation between the content of TNF-α per gram myocardium and the apoptotic rate of cardiomyocytes (r=0.677, P<0.05). (4) HE staining showed that myocardial fibers of dogs in both groups were arranged in wave shape in different degrees, indicating there was myocardial hypoxia in different degrees. Compared with that of group HFOV, the degree of hypoxia in group HFOV+IP was slighter. (5) The results of immunohistochemical staining showed that there was less loss of actin in myocardial fibers of dogs in group HFOV+IP than in group HFOV. The expression level of actin in myocardium of dogs in group HFOV+IP after treatment for 8 h (194.7 ± 3.1) was obviously higher than that in group HFOV (172.9 ± 2.6, t=13.20, P<0.01). CONCLUSIONS: Compared with pure HFOV, HFOV combined with IP can alleviate the inflammatory reaction in myocardium of dogs, reduce the apoptosis of cardiomyocytes, and ameliorate the myocardial damage due to ischemia and hypoxia.

[Effects of two kinds of lung recruitment maneuvers on the correlated indexes of dogs with severe smoke inhalation injury].

OBJECTIVE: To observe and compare the effects of two kinds of lung recruitment maneuvers, namely sustained inflation (SI) and incremental positive end-expiratory pressure (PEEP) (IP) on oxygenation, respiratory mechanics, and hemodynamics of dogs with severe smoke inhalation injury. METHODS: After being treated with conventional mechanical ventilation, 12 dogs were inflicted with severe smoke inhalation injury. They were divided into group SI and group IP according to the random number table, with 6 dogs in each group. Dogs in group SI were subjected to continuous positive airway pressure ventilation, with inspiratory pressure of 25 cmH2O (1 cmH2o = 0. 098 kPa), and it was sustained for 20 s. PEEP level in group IP was gradually increased by 5 cmH2O every 5 min up to 25 cmH2O, and then it was decreased by 5 cmH2O every 5 min until reaching 2-3 cmH2O. Then the previous ventilation mode was resumed in both groups for 8 hours. Blood gas analysis (pH value, PaO2, and PaCO2), oxygenation index (OI), respiratory mechanics parameters [peak inspiratory pressure (PIP), mean airway pressure, and dynamic lung compliance], and hemodynamic parameters [heart rate, mean arterial pressure (MAP), pulmonary arterial pressure (PAP), and cardiac output (CO)] were recorded or calculated before injury, immediately after injury, and at post ventilation hour (PVH) 2, 4, 6, 8. Data were processed with analysis of variance of repeated measurement and LSD-t test. RESULTS: (1) At PVH 6 and 8, pH values of dogs in group SI were significantly lower than those in group IP (with t values respectively 2. 431 and 2. 261, P values below 0.05); PaO2 levels in group SI [(87 ± 24), (78 ± 14) mmHg, 1 mmHg =0. 133 kPa] were lower than those in group IP [ (114 ± 18) , (111 ± 17) mmHg, with t values respectively 2. 249 and 3.671, P <0.05 or P <0.01]; OI values in group SI were significantly higher than those in group IP (with t values respectively 2.363 and 5.010, P <0.05 or P <0.01). No significant differences were observed in PaCO2 level within each group or between the two groups (with t values from 0. 119 to 1. 042, P values above 0.05). Compared with those observed immediately after injury, the pH values were significantly lowered (except for dogs in group IP at PVH 6 and 8, with t values from 2.292 to 3.222, P <0.05 or P <0.01), PaO2 levels were significantly elevated (with t values from 4. 443 to 6.315, P <0.05 or P <0.01), and OI values were significantly lowered (with t values from 2.773 to 9.789, P <0.05 orP <0.01) in both groups at all the treatment time points. (2) The PIP level at each time point showed no significant differences between two groups (with t values from 0. 399 to 1. 167, P values above 0. 05). At PVH 4 and 8, the mean airway .pressure values of dogs in group SI were significantly higher than those in group IP (with t values respectively 1.926 and 1. 190, P values below 0.05). At PVH 4, 6, and 8, the dynamic lung compliance levels of dogs in group SI [(9.5 ± 1.9), (12.8 ± 2. 1), (13. 1 ± 1.8) mL/cmH2O] were significantly lower than those in group IP [(11.6 ± 1.2), (15.4 ± 1.8), (14.9 ± 0.8) mL/cmH2O], with t values respectively 2. 289, 2. 303, 2. 238, P values below 0.05. Compared with those observed immediately after injury, PIP and the mean airway pressure values of dogs in two groups were significantly lowered at each treatment time point (with t values from 2. 271 to 7. 436, P <0. 05 or P < 0.01); the dynamic lung compliance levels were significantly elevated in both groups at PVH 6 and 8 (with t values from 2. 207 to 4. 195, P < 0.05 or P <0.01). (3) Heart rate, MAP, and PAP levels at each time point between two groups showed no significant differences (with t values from 0. 001 to 1. 170, P values above 0. 05). At PVH 4, 6, and 8, CO levels in group IP [(0. 6 + 0. 3), (0. 6 + 0. 4), (0. 5 + 0. 7) L/min] were significantly lower than those in group SI [(1.5 0.7), (1.8 + 1.1), (1.6 +0.9) L/min], with t values respectively 3. 028, 2.511, 2.363, P values below 0.05. Compared with that observed immediately after injury, CO level in group IP was significantly lowered at PVH 4, 6, or 8 (with t values respectively 2. 363, 2. 302, 2. 254, P values below 0. 05). CONCLUSIONS: Both lung recruitment maneuvers can effectively improve oxygenation and lung compliance of dogs with severe smoke inhalation injury. IP is more effective in improving lung compliance, while SI shows less impact on the hemodynamic parameters.

[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.