Exogenous interleukin-10 attenuates hyperoxia-induced acute lung injury in mice.

NEW FINDINGS: What is the central question of this study? It is not known whether treatment with interleukin-10 (IL-10) attenuates hyperoxia-induced acute lung injury in mice. What is the main finding and its importance? Our results showed that exogenous IL-10 treatment alleviated hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. Lung injury caused by breathing air enriched with oxygen continues to be a major problem in clinical medicine. Here, we investigated the therapeutic role of interleukin-10 (IL-10) in hyperoxia-induced acute lung injury in mice. In the first experiment, mice were exposed to room air or 95% O2 and treated with IL-10 simultaneously. In the second experiment, wild-type mice and IL-10(-/-) mice were exposed to room air or 95% O2 . Exogenous IL-10 treatment attenuated hyperoxia-induced acute lung injury, evidenced by a reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, cell numbers and protein content in bronchoalveolar lavage fluid and cell death. Interleukin-10 treatment markedly prolonged the survival of mice during oxygen exposure. Interleukin-10 treatment reduced the activity of myeloperoxidase and mRNA levels of interleukin-6, tumour necrosis factor-α and macrophage inflammatory protein 2, suppressed nuclear factor-κB activation and decreased inducible nitric oxide synthnase expression and nitric oxide formation in lungs of mice exposed to hyperoxia. Interleukin-10 treatment suppressed activities of matrix metalloproteinase 2 and matrix metalloproteinase 9 and reduced lung permeability in mice during oxygen exposure. Furthermore, absence of IL-10 aggravated hyperoxia-induced acute lung injury and reduced the duration of survival of mice during oxygen exposure, which was attenuated by treatment with IL-10. In conclusion, our results show that exogenous IL-10 treatment alleviates hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. This suggests that IL-10 treatment may be a promising therapeutic strategy to reduce lung injury in patients exposed to hyperoxia.

Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells.

The bone protective effects of the hydrogen molecule (H2) have been demonstrated in several osteoporosis models while the underlying molecular mechanism has remained unclear. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. In this work, we evaluated the effects of incubation with H2 on receptor activator of NFκB ligand (RANKL)-induced osteoclast differentiation. We found that treatment with H2 prevented RANKL-induced osteoclast differentiation in RAW264.7 cells and BMMs. Treatment with H2 inhibits the ability to form resorption pits of BMMs stimulated by RANKL. Treatment with H2 reduced mRNA levels of osteoclast-specific markers including tartrate resistant acid phosphatase, calcitonin receptor, cathepsin K, metalloproteinase-9, carbonic anhydrase typeII, and vacuolar-type H(+)-ATPase. Treatment with H2 decreased intracellular reactive oxygen species (ROS) formation, suppressed NADPH oxidase activity, down-regulated Rac1 activity and Nox1 expression, reduced mitochondrial ROS formation, and enhanced nuclear factor E2-related factor 2 nuclear translocation and heme oxygenase-1 activity. In addition, treatment with H2 suppressed RANKL-induced expression of nuclear factor of activated T cells c1 and c-Fos. Furthermore, treatment with H2 suppressed NF-κB activation and reduced phosphorylation of p38, extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and protein kinases B (AKT) stimulated with RANKL. In conclusion, hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.

Treatment with exogenous hydrogen sulfide attenuates hyperoxia-induced acute lung injury in mice.

The aim of this work was to test the effect of treatment with hydrogen sulfide (H2S) on hyperoxia-induced acute lung injury in mice. Mice were exposed to room air or 95 % O2, and treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.56 mol/l NaHS). Treatment with H2S partly restored the reduced H2S levels in plasma and lungs of mice exposed to hyperoxia. Treatment with H2S attenuated hyperoxia-induced acute lung injury marked by reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, and cell numbers and protein content in bronchoalveolar lavage (BAL) and decreased apoptosis. Treatment with H2S markedly prolonged the survival of mice under oxygen exposure. Treatment with H2S abated hyperoxia-induced oxidative stress marked by reduced malondialdehyde and peroxynitrite formation, reduced NADPH oxidase activity, enhanced translocation of nuclear factor E2-related factor (Nrf2) into nucleus and increased activity of HO-1. Treatment with H2S decreased IL-1ß, MCP-1, and MIP-2, and increased IL-10 expression in lungs of mice exposed to hyperoxia. Treatment with H2S decreased NFκB activity and iNOS expression in lungs, and reduced NOx content in BAL of mice exposed to hyperoxia. Treatment with H2S reduced lung permeability and suppressed VEGF release and VEGFR2 expression in lungs of mice under oxygen exposure. Treatment with exogenous H2S attenuated hyperoxia-induced acute lung injury through abating oxidative stress, suppressing inflammation, and reducing lung permeability in mice.

How to enhance the ability of mesenchymal stem cells to alleviate intervertebral disc degeneration.

Intervertebral disc (ID) degeneration (IDD) is one of the main causes of chronic low back pain, and degenerative lesions are usually caused by an imbalance between catabolic and anabolic processes in the ID. The environment in which the ID is located is harsh, with almost no vascular distribution within the disc, and the nutrient supply relies mainly on the diffusion of oxygen and nutrients from the blood vessels located under the endplate. The stability of its internal environment also plays an important role in preventing IDD. The main feature of disc degeneration is a decrease in the number of cells. Mesenchymal stem cells have been used in the treatment of disc lesions due to their ability to differentiate into nucleus pulposus cells in a nonspecific anti-inflammatory manner. The main purpose is to promote their regeneration. The current aim of stem cell therapy is to replace the aged and metamorphosed cells in the ID and to increase the content of the extracellular matrix. The treatment of disc degeneration with stem cells has achieved good efficacy, and the current challenge is how to improve this efficacy. Here, we reviewed current treatments for disc degeneration and summarize studies on stem cell vesicles, enhancement of therapeutic effects when stem cells are mixed with related substances, and improvements in the efficacy of stem cell therapy by adjuvants under adverse conditions. We reviewed the new approaches and ideas for stem cell treatment of disc degeneration in order to contribute to the development of new therapeutic approaches to meet current challenges.

[Clinical analysis of arytenoid cartilage reposition with snake mouth forceps for the arytenoid cartilage dislocation].

OBJECTIVES: To investigate the clinical effect of the arytenoid cartilage reposition using snake mouth reduction forceps under general anesthesia. METHODS: Data of twenty-six cases accepted arytenoid cartilage reposition under intravenous general anesthesia were analyzed, nineteen cases accepted laryngeal CT scan and cricoarytenoid joint reconstruction, all patients underwent endolaryngeal muscle electromyography examination. According to the position of cartilage dislocation prompted by laryngoscope and CT, the arytenoid cartilage was repositoned under the visual laryngoscope using special snake mouth reduction forceps. If bilateral arytenoid cartilage were still asymmetrically at the end of the surgery, patients needed repeated reposition 1 to 2 times 1 week after operation. The efficacy was evaluated 4 weeks later. RESULTS: All patients had a hoarse and breathing voice preoperative. Under laryngoscope, there were different degrees of vocal cord movement disorders accompanied by incomplete glottis closure, 22 cases happened in left side and 4 in right side. The arytenoid cartilage was dislocated anteromedially in 25 cases and posterolaterally in 1 case. CT showed that 15 cases of arytenoid cartilage were tilted anteromedially; the interval of the cricoarytenoid joint was widened. In axial CT images, there were no direct signs of the arytenoid cartilage dislocation in the 4 cases, but the abnormal position was seen in the reconstruction images. The laryngeal electromyography indicated that 7 cases were abnormal, duration of motor unit potential were visible and the raising potential were mixed. There were 4 patients with normal voice in the first day after surgery, and 19 cases underwent twice and 3 cases underwent three times surgery. Vioce became normal in 4 weeks. Swallowing pain and bucking were all disappeared. Vocal cords movement were recovered to normal level in 25 cases. In 1 case with neck strangulation, the vocal cord movement was slightly worse than health side, but significantly better than that before operation. CONCLUSIONS: The arytenoid cartilage reposition using snake mouth reduction forceps under general anesthesia was an effective method for the treatment of the cricoary-tenoid joint dislocation.

[Relationship between inferior turbinate outfracture and the improvement of nasal ventilatory function].

OBJECTIVE: To discuss the relationship between structural change in nasal cavity and the change of nasal ventilatory function after outfracture of the inferior turbinate. METHODS: The inferior turbinate outfracture surgery was performed on 50 chronic hypertrophic rhinitis patients who suffered inferior turbinate hypertrophy according to endoscopy and CT scan. Preoperative and postoperative nasal endoscopy was carried out on all patients, by which the distance from the inferior turbinate front mucous membrane to nasal septum (DTNS) was measured. In addition, CT was used to measure the minimal distance between the inside edges of the bilateral inferior turbinate soft tissue (MDTT) and the minimal distance between the bilateral inferior turbinate bones (MDTB) at the central layer of coronal sectional infundibulum; the minimal distance between the inferior turbinate at asial nasal limen (NLDT); inferior turbinate thickness (ITT). In this way, the change in the structure of nasal cavity was evaluated. Acoustic rhinometry and rhinomanometry were utilized to evaluate the ventilatory function of the nasal cavity objectively. Visual analogue scale (VAS) was applied to evaluate the severity of preoperative and postoperative nasal obstruction subjectively. The test data were used to perform match t-test; Spearman rank correlation was adopted to evaluate the relationship between patients' bilateral VAS and nasal inspiratory effective resistance (IER),nasal expiratory effective resistance (EER) and DTNS. The relationship between the total resistance of nasal inspiratory phase as well as the total resistance of nasal expiratory phase and MDTT and MDTB was analyzed. SPSS 20.0 software was used to analyze the data. RESULTS: The preoperative data showed that rightward DTNS was (0.12 ± 0.07) cm, leftward DTNS was (0.10 ± 0.07) cm and MDTT was (0.70 ± 0.13) cm, and postoperative data showed that rightward DTNS was (0.47 ± 0.27) cm, leftward DTNS was (0.43 ± 0.15) cm, and MDTT was (1.05 ± 0.15) cm. Significant differences existed in rightward DTNS, leftward DTNS and MDTT between pre-and post operative data (t values were -8.827, -8.590, -17.525, all P < 0.05). According to the preoperative and postoperative comparison, the difference in MDTB, NLDT, rightward ITT, leftward ITT, IER, EER, 0-5 cm nasal cavity volume (0-5 cm NCV), nasal minimal cross-sectional area (NMCA), rightward VAS and leftward VAS had statistical significance (t values were -23.562, -8.374, 8.693, 6.684, 12.021, 14.510, -6.074, -2.285, 14.042 and 9.925, respectively, all P < 0.05). Patients' bilateral VAS grades had a positive relationship with IER and EER (left side: r values were 0.541 and 0.660, respectively,right side: r values were 0.940 and 0.688, respectively, all P < 0.05). Additionally, patients' VAS had a negative relationship with DTNS (r value was -0.861, P < 0.05). Besides,the total resistance of nasal inspiratory phase had a negative relationship with both MDTT and MDTB (r values were -0.565 and -0.546,respectively, all P < 0.05). The total resistance of nasal expiratory phase had a negative relationship with both MDTT and MDTB (r values were -0.562 and -0.546, all P <0.05). CONCLUSION: The inferior turbinate outfracture surgery was an ideal surgical method by which nasal cavity could be broadened and nasal ventilatory function improved.