Preparation and evaluation of chitosan-polyvinyl alcohol/polyhexamethylene guanidine hydrochloride antibacterial dressing to accelerate wound healing for infectious skin repair.

BACKGROUND: Wound infections, especially multidrug-resistant (MDR) bacterial infections, are a major challenge in clinical medicine. METHODS: In this study, a new type of antibacterial sponge was prepared from a solution containing a chitosan-polyvinyl alcohol (CTS-PVA) emulsion with added polyhexamethylene guanidine hydrochloride (PHMG) in a homogeneous medium using lyophilization technology. The antibacterial ability of and CTS-PVA/PHMG sponge against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Acinetobacter baumannii in vitro. The structure and physical properties were characterized. The sponge dressing was tested in a Pseudomonas aeruginosa-infected full-thickness mouse skin wound defect model. The effects were evaluated by wound area measurement and histological analysis. RESULTS: The CTS-PVA/PHMG sponge showed broad-spectrum antibacterial ability, including for MDR bacterial stains from clinical sources, while maintaining excellent physicochemical properties, including a high swelling degree and good moisture retention capability. Scanning electron microscopy images displayed the surface morphology of the CTS-PVA/PHMG sponge dressing. The detection of the wound healing rate and histological analysis supported that the new dressing can alleviate the inflammation and accelerate the healing speed of infected wounds and in vivo. CONCLUSIONS: CTS-PVA/PHMG sponge shows broad-spectrum antibacterial activity, which can provide a new pathway for clinical prevention and treatment of superbug-infected wounds.

Down-Regulation of miR-301a-3p Reduces Burn-Induced Vascular Endothelial Apoptosis by potentiating hMSC-Secreted IGF-1 and PI3K/Akt/FOXO3a Pathway.

Vascular endothelium dysfunction plays a pivotal role in the initiation and progression of multiple organ dysfunction. The mesenchymal stem cell (MSC) maintains vascular endothelial barrier survival via secreting bioactive factors. However, the mechanism of human umbilical cord MSC (hMSC) in protecting endothelial survival remains unclear. Here, we found IGF-1 secreted by hMSC suppressed severe burn-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and alleviated the dysfunction of vascular endothelial barrier and multiple organs in severely burned rats. Severe burn repressed miR-301a-3p expression, which directly regulated IGF-1 synthesis and secretion in hMSC. Down-regulation of miR-301a-3p decreased HUVECs apoptosis, stabilized endothelial barrier permeability, and subsequently protected against multiple organ dysfunction in vivo. Additionally, miR-301a-3p negatively regulated PI3K/Akt/FOXO3 signaling through IGF-1. Taken together, our study highlights the protective function of IGF-1 against the dysfunction of multiple organs negatively regulated by miR-301a-3p, which may provide the theoretical foundation for further clinical application of hMSC.

Electroacupuncture Improves the Survival Rate and Organ Function in a Rat Model of Hemorrhagic Shock.

Electroacupuncture (EA) at ST36 can improve the survival rate in rats after hemorrhagic shock (HS). The current study investigated rats with 60% blood loss. 144 rats were divided into four groups: hemorrhage without fluid resuscitation (HS), EA after hemorrhage without fluid resuscitation (EA), hemorrhage with delayed resuscitation (DFR), and EA after hemorrhage with delayed resuscitation (EA + DFR). The survival rate and biological parameters 0, 3, 12, and 24 h after HS were investigated. The 24 h survival rate of EA + DFR was significantly higher than that of DFR. 12 h after hemorrhage, the level of mean arterial blood pressure of EA + DFR was significantly higher than that of DFR, and the levels of renal blood flow, intestinal mucosal blood flow, and hepatic blood flow of EA + DFR were also significantly higher than those of DFR. Three hours after hemorrhage, the levels of lactate, PaCO2, alanine aminotransferase, and creatinine of groups receiving EA were significantly lower than those of non-EA groups, and the levels of pH, PaO2, and diamine oxidase of groups receiving EA were significantly higher. EA at ST36 can improve the 24 h survival rate and produce the experimental antishock effects on tissue perfusion and organ protection from fatal HS.

MIR-190B Alleviates Cell Autophagy and Burn-Induced Skeletal Muscle Wasting via Modulating PHLPP1/Akt/FoxO3A Signaling Pathway.

INTRODUCTION: Cell autophagy is an important material recycling process and is involved in regulating many vital activities under both physiological and pathological conditions. However, the mechanism of autophagy regulating burn-induced skeletal muscle wasting still needs to be elucidated. METHODS: The rat burn model with 30% total body surface area and L6 cell line were used in this study. An immunofluorescence assay was used to detect autophagic levels. MicroRNA array and real-time PCR were employed to measure miR-190b levels, and its influence on PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) protein translation was estimated using luciferase reporter assay. The expression levels of autophagy-related proteins were analyzed by Western blot. Skeletal muscle wasting was evaluated by the ratio of tibias anterior muscle weight to body weight. RESULTS: Our study demonstrates that burn injury promotes expression of the autophagy-related proteins light chain 3 (LC3) and Beclin-1, suppresses expression of Akt and Forkhead box O (FoxO) 3a protein phosphorylation, and increases PHLPP1 protein level which is required for Akt dephosphorylation. miR-190b, the regulator of PHLPP1 protein translation, also significantly decreases after burn injury. Ectopic expression of miR-190b in L6 myoblast cell downregulates PHLPP1 protein expression, elevates Akt and FoxO3a phosphorylation, and subsequently reduces cell autophagy. Finally, suppressing autophagy with 3-methyladenine represses the protein expression of LC3 and Beclin-1 and mitigates burn-induced skeletal muscle wasting. CONCLUSION: Burn injury induced skeletal muscle cell autophagy and subsequently resulted in skeletal muscle wasting via regulating miR-190b/PHLPP1/Akt/FoxO3a signaling pathway.