Human placenta-derived mesenchymal stem cell administration protects against acute lung injury in a mouse model.

This study aims to investigate the effect of placenta-derived mesenchymal stem cells (PMSCs) administration on tissue repair following acute lung injury (ALI). PMSCs were transplanted intravenously to a mouse model of lipopolysaccharide-induced ALI. The therapeutic effects were determined by evaluating several indicators, including pathology; the wet/dry ratio of the lungs; blood gas analysis; the total protein content, cell numbers, and the activity of myeloperoxidase (MPO) in bronchial alveolar lavage fluid (BALF); and the levels of anti-inflammatory and proinflammatory cytokines in serum and BALF. To investigate the underlying mechanism, PMSC-derived exosomes were used for ALI treatment. Administration of PMSCs improved the degree of lung injury, reduced inflammation, increased the expression levels of anti-inflammatory cytokines, and protected lung function. As expected, the effects of PMSC-derived exosomes in the ALI model were similar to those of PMSCs, both in terms of improved lung function and reduced inflammation. These findings suggest that PMSCs have ameliorating effects on ALI that are potentially mediated via their secreted exosomes.

Effects of Sepsis Serum on the Fate of Adipose Tissue-Derived Stem Cells.

BACKGROUND: Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem cell, have been used extensively in clinical trials for the treatment of multiple conditions, including sepsis. However, increasing evidence indicates that ADSCs vanish from tissues within days of administration. Consequently, it would be desirable to establish the mechanisms underlying the fate of ADSCs following transplantation. METHODS: In this study, sepsis serum from mouse models was used to mimic microenvironmental effects. Healthy donor-derived human ADSCs were cultured in vitro in the presence of mouse serum from normal or lipopolysaccharide (LPS)-induced sepsis models for the purposes of discriminant analysis. The effects of sepsis serum on ADSC surface markers and cell differentiation were analyzed by flow cytometry, and the proliferation of ADSCs was assessed using a Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was applied to assess the degree of ADSC differentiation. The effects of sepsis serum on the cytokine release and migration of ADSCs were determined based on ELISA and Transwell assays, respectively, and ADSC senescence was assessed by ß-galactosidase staining and western blotting. Furthermore, we performed metabolic profiling to determine the rates of extracellular acidification and oxidative phosphorylation and the production of adenosine triphosphate and reactive oxygen species. RESULTS: We found that sepsis serum enhanced the cytokine and growth factor secretion and migratory capacities of ADSCs. Moreover, the metabolic pattern of these cells was reprogrammed to a more activated oxidative phosphorylation stage, leading to an increase in osteoblastic differentiation capacity and reductions in adipogenesis and chondrogenesis. CONCLUSIONS: Our findings in this study reveal that a septic microenvironment can regulate the fate of ADSCs.

Effects of dexmedetomidine on postoperative sleep quality: a systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVES: To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances. METHODS: An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis. RESULTS: Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes. CONCLUSIONS: Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials.

The Clinical Application of Ultra-Fast-Track Cardiac Anesthesia in Right-Thoracoscopic Minimally Invasive Cardiac Surgery: A Retrospective Observational Study.

OBJECTIVES: The purpose of this study was to investigate the effect of ultra-fast-track cardiac anesthesia (UFTCA) on rapid postoperative recovery in patients undergoing right-thoracoscopic minimally invasive cardiac surgery. DESIGN: A retrospective observational study. SETTING: A single large teaching hospital. PARTICIPANTS: A total of 153 patients who underwent right-thoracoscopic minimally invasive cardiac surgery between January 2021 and August 2021 were enrolled. The inclusion criteria were American Society of Anesthesiologists grade I to III, New York Heart Association (NYHA) cardiac function class I to III, and age ≥18 years. The exclusion criteria were NYHA class IV, local anesthetic allergy, severe pulmonary hypertension (pulmonary arterial systolic pressure, PASP >70 mmHg), age ≤18 years or ≥80 years old, emergency surgery, and patients with incomplete or missing data. INTERVENTIONS: Finally, a total of 122 patients were included and grouped by different anesthesia strategies. Sixty patients received serratus anterior plane block-assisted ultra-fast- track cardiac anesthesia (UFTCA group), and 62 patients received conventional general anesthesia (CGA group). The primary outcomes were lengths of hospital stay and postoperative intensive care unit (ICU) stay. The secondary outcomes were postoperative pain scores, opioids use, postoperative chest tube drainage, and complications. MEASUREMENTS AND MAIN RESULTS: The intraoperative dosages of sufentanil and remifentanil in the UFTCA group were significantly lower than those in the CGA group (66.25 ± 1.03 µg v 283.31 ± 11.36 µg, p < 0.001; and 1.94 ± 0.38 mg v 2.14 ± 0.99 mg, p < 0.001, respectively). The incidence of postoperative rescue analgesia in the UFTCA group was significantly lower than that in the CGA group (10 patients [16.67%] v 30 patients [48.38%], p < 0.001). In the postoperative ICU, there were fewer patients with pain score Numeric Rating Scale ≥3 in the UFTCA group than that in the CGA group (10 patients [16.67%] v 29 patients [46.78%], p < 0.001). The postoperative extubation time in the UFTCA group was shorter than that in the CGA group (0.3 hours [range, 0.25-0.4 hours] v 13.84 hours [range, 10.25-18.36 hours], p < 0.001). Lengths of ICU stay and hospital stay in the UFTCA group were shorter than those in the CGA group (27.73 ± 16.54 hours v 61.69 ± 32.48 hours, p < 0.001; and 8 days [range, 7-9] v 9 days [range, 8-12], p < 0.001, respectively). Compared with the CGA group, the patients in the UFTCA group had less chest tube drainage within 24 hours after surgery (197.67 ± 13.05 mL v 318.23 ± 160.10 mL, p < 0.001). There were no significant differences in in-hospital mortality, postoperative bleeding, or secondary surgery between the 2 groups. The incidences of postoperative nausea, vomiting, or atelectasis were comparable between the 2 groups. CONCLUSIONS: Serratus anterior plane block-assisted ultra-fast-track cardiac anesthesia can promote rapid postoperative recovery in patients with right-thoracoscopic minimally invasive cardiac surgery. This anesthesia regimen is clinically safe and feasible.

Retraction Notice to: lncRNA MALAT1 Accelerates Wound Healing of Diabetic Mice Transfused with Modified Autologous Blood via the HIF-1α Signaling Pathway.

[This retracts the article DOI: 10.1016/j.omtn.2019.05.020.].

To Research the Effects of Storage Time on Autotransfusion based on Erythrocyte Oxygen-Carrying Capacity and Oxidative Damage Characteristics.

Autotransfusion refers to a blood transfusion method in which the blood or blood components of the patient are collected under certain conditions, returned to himself when the patient needs surgery or emergency after a series of storing and processing. Although autotransfusion can avoid blood-borne diseases and adverse reactions related to allogeneic blood transfusion, a series of structural and functional changes of erythrocytes will occur during extension of storage time, thus affecting the efficacy of clinical blood transfusion. Our research was aimed to explore the change of erythrocyte oxygen-carrying capacity in different storage time, such as effective oxygen uptake (Q), P50, 2,3-DPG, Na+-K+-ATPase, to detect membrane potential, the change of Ca2+, and reactive oxygen species (ROS) change of erythrocytes. At the same time, Western blot was used to detect the expression of Mitofusin 1 (Mfn1) and Mitofusin 2 (Mfn2) proteins on the cytomembrane, from the perspective of oxidative stress to explore the function change of erythrocytes after different storage time. This study is expected to provide experimental data for further clarifying the functional status of erythrocytes with different preservation time in patients with autotransfusion, achieving accurate infusion of erythrocytes and improving the therapeutic effect of autologous blood transfusion, which has important clinical application value.

To study the effect of oxygen carrying capacity on expressed changes of erythrocyte membrane protein in different storage times.

Erythrocyte membrane is crucial to maintain the stability of erythrocyte structure. The membrane protein on the surface of erythrocyte membrane enables erythrocyte to have plasticity and pass through the microcirculation without being blocked or destroyed. Decreased deformability of erythrocyte membrane protein will lead to a series of pathological and physiological changes such as tissue and organ ischemia and hypoxia. Therefore, this research collected 30 cases of healthy blood donors, and explored erythrocyte stored at different times relating indicators including effective oxygen uptake (Q), P50, 2,3-DPG, Na+-k+-ATP. Erythrocyte morphology was observed by electron microscopy. Western blot and immunofluorescence assay were used to detect membrane protein EPB41, S1P, GLTP, SPPL2A expression changes of erythrocyte. To explore the effective carry oxygen capacity of erythrocyte at different storage time resulting in the expression change of erythrocyte surface membrane protein.

Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF-1α pathway by improving the blood preservation solution.

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1ß, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.

lncRNA MALAT1 Accelerates Wound Healing of Diabetic Mice Transfused with Modified Autologous Blood via the HIF-1α Signaling Pathway.

Impaired wound healing is a debilitating complication of diabetes. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized to be differentially expressed in various diseases. However, its underlying mechanism in diabetes has not been fully understood. Notably, we aim to examine the expression of MALAT1 in diabetic mice and its role in wound healing involving the hypoxia-inducible factor-1α (HIF-1α) signaling pathway with a modified autologous blood preservative solution reported. A mouse model of diabetes was established. MALAT1 was identified to promote the activation of the HIF-1α signaling pathway and to be enriched in autologous blood through modified preservation, which might facilitate the improvement of physiological function of blood cells. Through gain- or loss-of-function approaches, viability of fibroblasts cultured in high glucose, wound healing of mice, and collagen expression in wound areas were enhanced by MALAT1 and HIF-1α. Taken together, the present study demonstrated that the physiological status of mouse blood was effectively improved by modified autologous blood preservation, which exhibited upregulated MALAT1, thereby accelerating the fibroblast activation and wound healing in diabetic mice via the activation of the HIF-1α signaling pathway. The upregulation of MALAT1 activating the HIF-1α signaling pathway provides a novel insight into drug targets against diabetes.

Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1α signaling pathway.

BACKGROUND: Impaired wound healing frequently occurs in diabetes mellitus (DM) and is implicated in impaired angiogenesis. Long non-coding RNA (lncRNA) H19 has been reported as being reduced in DM and played a critical role in inducing angiogenesis. Thus, we hypothesized that H19 may affect impaired wound healing in streptozotocin (STZ)-induced diabetic mice transfused with autologous blood preserved in standard preservative fluid or modified preservative fluid. METHODS: Fibroblasts in injured skin were isolated and cultured in vitro. After location of H19 in fibroblasts using fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), Co immunoprecipitation (COIP) and dual luciferase reporter gene assay were used to verify the binding of H19 to HIF-1α. RESULTS: The modified preservative fluid preserved autologous blood increased the H19 expression in fibroblasts, and maintained better oxygen-carrying and oxygen release capacities as well as coagulation function. Furthermore, H19 promoted HIF-1α histone H3K4me3 methylation and increased HIF-1α expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1α signaling pathway in fibroblasts and enhanced wound healing in diabetic mice. CONCLUSIONS: Taken together, H19 accelerated fibroblast activation by recruiting EZH2-mediated histone methylation and modulating the HIF-1α signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice.