Exosomes from human induced pluripotent stem cells derived mesenchymal stem cells improved myocardial injury caused by severe acute pancreatitis through activating Akt/Nrf2/HO-1 axis.

Human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) have been believed to be a promising alternative for the stem cell transplantation therapy. The exosomes (Exo) from iMSCs play an important role in several kinds of life activities. The role of exosomes from iMSCs in severe acute pancreatitis (SAP) induced myocardial injury (MI) has not been investigated. The Exo were isolated from iMSCs through differential centrifugation method. The SAP rat model was established with 5% sodium taurocholate injection into the distal end of the bilepancreatic duct. RT-PCR and western blotting were used to measure related gene expression. Masson trichrome and Sirius Red stainings were used to evaluate MI injury. Cardiac function was detected through cardiac ultrasound.Exo promoted cell viability through activating Akt/nuclear factor E2 related factors 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway in vitro. Exo improved MI induced by SAP through activating Akt/Nrf2/HO-1 signaling pathway. Exo improved cardiac function, and suppressed oxidative status in the SAP model. Exo increased the expression of von Willebrand Factor (vWF) and vascular endothelial growth factor (VEGF) through activating Nrf2/HO-1 signaling pathway. Our data indicated that the Exo from iMSCs could improve MI caused by SAP through activating Nrf2/HO-1 axis. These findings firstly unfold the potential application of Exo from iMSCs in treating MI induced by SAP.Abbreviations: LVEF: Left ventricular ejection fraction; LVFS: left ventricular fractional shorten; LVDd: left ventricular end-diastolic diameter; LVDs: left ventricular end-systolic diameter; MI: Myocardial infarction; MSCs: Mesenchymal stem cells; iPSCs: Human-induced pluripotent stem cells; SAP: Severe acute pancreatitis; iMSCs: iPSCs derived VEGF: MSCs; vascular endothelial growth factor; Nrf2: Nuclear factor erythroid 2-related factor; RT-PCR: Real-time polymerase chain reaction; HE: Hematoxylin-eosin; MODS: Multiple organ dysfunction syndrome; PI3K: Phosphatidylinositol 3-kinase; SOD: Superoxide dismutase; FBS: Fetal bovine serum; ECL: Enhanced chemiluminescence; IHC: Immunohistochemistry.

[Clinical study on intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia caused by multidrug-resistant Gram-negative bacteria].

OBJECTIVE: To investigate the efficacy of intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia caused by multidrug-resistant Gram-negative (G-) bacteria. METHODS: A observational study was conducted. The clinical data of 45 patients with pneumonia due to multidrug-resistant G- bacteria admitted to intensive care unit of Fujian Medical University Union Hospital from January to October in 2020 were analyzed. According to the different use methods of polymyxin B, 25 patients who received single intravenous drip (the first dose was 2.0 mg/kg, then 1.25 mg/kg, once every 12 hours) from January to April in 2020 were enrolled in the routine group, and 20 patients who received intravenous drip combined with aerosol inhalation (25 mg once every 12 hours, sputum in the airway was sucked and then sprayed aerosol) from May to October in 2020 were enrolled in the combination group. After the treatment course of polymyxin B, the total bacterial clearance rate, total clinical efficiency rate, recovery time of body temperature, time of bacterial clearance and the change of serum procalcitonin (PCT) level before and after treatment were compared between the two groups. Moreover, the incidence of adverse reactions during treatment in the two groups was observed. RESULTS: The results of sputum culture in the routine group were Acinetobacter baumannii in 13 patients, Klebsiella pneumoniae in 5 patients, Pseudomonas aeruginosa in 6 patients, Enterobacter cloacae in 1 patient; the sputum culture results of the combination group showed that there were 5 patients of Acinetobacter baumannii, 9 Klebsiella pneumoniae and 6 Pseudomonas aeruginosa. There was no significant difference in the results of sputum culture between the two groups (P > 0.05). The total bacterial clearance rate and the total clinical efficiency rate of the combination group were significantly higher than those in the routine group (total bacterial clearance rate: 70.0% vs. 40.0%, total clinical efficiency rate: 75.0% vs. 40.0%, both P < 0.05). The recovery time of body temperature and the time of bacterial clearance of the combination group were significantly shorter than those in the routine group [recovery time of body temperature (days): 6.0±3.9 vs. 10.2±7.3, time of bacterial clearance (days): 6.1±5.2 vs. 11.5±6.8, both P < 0.05]. No significant difference was found in serum PCT level before treatment between the two group. There was no significant difference in serum PCT level before and after treatment in the routine group [µg/L: 0.85 (0.44, 2.87) vs. 1.43 (0.76, 5.30), P > 0.05]. The serum PCT level after treatment in the combination group was significantly lower than that before treatment [µg/L: 0.27 (0.10, 0.70) vs. 0.91 (0.32, 3.53), P < 0.05], and it was significantly lower than that in the routine group [µg/L: 0.27 (0.10, 0.70) vs. 0.85 (0.44, 2.87), P < 0.01]. The incidence of renal toxicity of polymyxin B between the combination group and the routine group was not significantly different (5.0% vs. 4.0%, P > 0.05). CONCLUSIONS: The efficacy of intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia due to multidrug-resistant G- bacteria is better than that of intravenous drip of polymyxin B only. The aerosolized polymyxin B will not increase the risk of renal injury.

MicroRNA-127-5p attenuates severe pneumonia via tumor necrosis factor receptor-associated factor 1.

Pneumonia is a persistent and pervasive disease, the effects of which can be severe. MicroRNA (miR)-127-5p has been utilized as a novel biomarker for the diagnosis of severe pneumonia. The present study aimed to investigate the function of miR-127-5p during severe pneumonia. An in vitro model of severe pneumonia in Ana-1 murine macrophages was established using lipopolysaccharide (LPS). Subsequently, reverse transcription-quantitative PCR and ELISA were performed to detect the mRNA and protein expression levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. Western blotting was also performed to measure the activity of AKT and NF-κB. The results indicated that compared with the control group, LPS treatment increased TNF receptor-associated factor 1 (TRAF1) expression levels and reduced miR-127-5p expression levels. Furthermore, the results revealed that the 3'-untranslated region of TRAF1 was targeted by miR-127-5p. miR-127-5p mimic reduced LPS-induced increases in IL-1ß, IL-6 and TNF-α expression by targeting TRAF1, which was potentially mediated by inactivation of the AKT and NF-κB signaling pathways. Collectively, the results demonstrated that miR-127-5p may attenuate severe pneumonia by reducing LPS-induced inflammatory cytokine production, and inactivating the AKT and NF-κB signaling pathways by targeting TRAF1.

Morusin alleviates mycoplasma pneumonia via the inhibition of Wnt/ß-catenin and NF-κB signaling.

Morusin has been traditionally used for the treatment of Mycoplasma pneumoniae pneumonia (MPP), but the underlying mechanism remains elusive. The present study aimed to explore the mechanism by which morusin achieves efficacy on mycoplasma pneumonia. Mycoplasma pneumonia model was established in BALB/c mouse and the effects of morusin were evaluated in the model. Compared with the model group, DNA amount of M. pneumoniae decreased by 24.6 ± 3.14% and 47.6 ± 6.78% in low morusin (20 mg/kg) and high morusin (50 mg/kg) groups, respectively (P<0.05). Moreover, morusin treatment led to decreased levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor α and increased level of anti-inflammatory IL-10 in mice lung tissue. Furthermore, morusin treatment inhibited the activation of Wnt/ß-catenin and NF-κB pathways in mice lung tissue. Taken together, our results suggest that morusin relieves mycoplasma pneumonia via the inhibition of the activation of Wnt/ß-catenin and NF-κB pathways, and is a potential natural agent for the treatment of mycoplasma pneumonia.

Electrically bioactive coating on Ti with bi-layered SnO2-TiO2 hetero-structure for improving osteointegration.

The potential for the use of electric stimulation to control cell behavior on a surface has been well documented. In terms of orthopaedic applications, there is a need to develop bioactive surfaces with a built-in electric field for clinically relevant materials, such as load-bearing titanium (Ti). In this work, a bi-layered SnO2-TiO2 coating is fabricated via microarc oxidation and subsequent hydrothermal treatment to adjust the surface electrical properties for improving bioactivity. An oxidized titanium interlayer on Ti substrate allows the growth of SnO2 nanorods with different morphologies, which leads to a built-in n-n heterojunction of SnO2 and TiO2 on the Ti surface with varied surface electrical properties. The crystallization of the TiO2 interlayer facilitates the growth of SnO2 nanorods, showing excellent hydrophilicity and good apatite-inducing ability due to the formation of a heterojunction. The results suggest that the bi-layered SnO2-TiO2 coating with electrically stimulated bioactivity could provide a novel way to enhance osteointegration on the Ti surface.

Enhanced Osseointegration of Hierarchically Structured Ti Implant with Electrically Bioactive SnO2-TiO2 Bilayered Surface.

The poor osseointegration of Ti implant significantly compromise its application in load-bearing bone repair and replacement. Electrically bioactive coating inspirited from heterojunction on Ti implant can benefit osseointegration but cannot avoid the stress shielding effect between bone and implant. To resolve this conflict, hierarchically structured Ti implant with electrically bioactive SnO2-TiO2 bilayered surface has been developed to enhance osseointegration. Benefiting from the electric cue offered by the built-in electrical field of SnO2-TiO2 heterojunction and the topographic cue provided by the hierarchical surface structure to bone regeneration, the osteoblastic function of basic multicellular units around the implant is significantly improved. Because the individual TiO2 or SnO2 coating with uniform surface exhibits no electrical bioactivity, the effects of electric and topographic cues to osseointegration have been decoupled via the analysis of in vivo performance for the placed Ti implant with different surfaces. The developed Ti implant shows significantly improved osseointegration with excellent bone-implant contact, improved mineralization of extracellular matrix, and increased push-out force. These results suggest that the synergistic strategy of combing electrical bioactivity with hierarchical surface structure provides a new platform for developing advanced endosseous implants.