Effects of Chinese traditional five-element music intervention on postoperative delirium and sleep quality in elderly patients after non-cardiac surgery: a randomized controlled trial.

BACKGROUND: Postoperative delirium (POD) is a common neurologic disorder among elderly patients after non-cardiac surgery, which leads to various negative outcomes. Sleep disorder is considered an important cause of POD. The objective of this study was to investigate whether the Chinese traditional five-element music intervention could reduce POD by improving sleep quality in elderly patients undergoing non-cardiac surgery. METHODS: A total of 132 patients aged 65 to 90 years who underwent non-cardiac surgery were randomized to two groups: the intervention (n = 60) and the control group (n = 63). Patients in the intervention group were subjected to the Chinese traditional five-element music intervention during the perioperative, while patients in the control group had no music intervention. POD was evaluated using the Confusion Assessment Method (CAM) in the first 5 days after surgery. The Richards‒Campbell Sleep Questionnaire (RCSQ) was used to assess subjective sleep quality. The levels of nocturnal melatonin and cortisol in saliva were measured on the preoperative and the first 2 postoperative days. RESULTS: The incidence of POD within 5 days was 27.0% in the control group and 11.7% in the intervention group. Preoperative PSQI and MMSE scores were associated with POD. The RCSQ scores on the first postoperative day were significantly decreased in the two groups compared to the preoperative day. Compared to the control group, the RCSQ scores showed a significant improvement in the intervention group on the first postoperative day. Compared to the control group, the level of saliva melatonin in the intervention group showed a significant increase on the first postoperative day. However, there was no statistical difference in cortisol levels between the two groups. CONCLUSIONS: Chinese traditional five-element music intervention decreased the incidence of POD in elderly patients who underwent noncardiac surgery via improving sleep quality, which may be associated with increased levels of melatonin.

Association between septic shock and tracheal injury score in intensive care unit patients with invasive ventilation: a prospective single-centre cohort study in China.

OBJECTIVES: There was no evidence regarding the relationship between septic shock and tracheal injury scores. Investigate whether septic shock was independently associated with tracheal injury scores in intensive care unit (ICU) patients with invasive ventilation. DESIGN: Prospective observational cohort study. SETTING: Our study was conducted in a Class III hospital in Hebei province, China. PARTICIPANTS: Patients over 18 years of age admitted to the ICU between 31 May 2020 and 3 May 2022 with a tracheal tube and expected to be on the tube for more than 24 hours. PRIMARY AND SECONDARY OUTCOME MEASURES: Tracheal injuries were evaluated by examining hyperaemia, ischaemia, ulcers and tracheal perforation by fiberoptic bronchoscope. Depending on the number of lesions, the lesions were further classified as moderate, severe or confluent. RESULTS: Among the 97 selected participants, the average age was 56.6±16.5 years, with approximately 64.9% being men. The results of adjusted linear regression showed that septic shock was associated with tracheal injury scores (ß: 2.99; 95% CI 0.70 to 5.29). Subgroup analysis revealed a stronger association with a duration of intubation ≥8 days (p=0.013). CONCLUSION: Patients with septic shock exhibit significantly higher tracheal injury scores compared with those without septic shock, suggesting that septic shock may serve as an independent risk factor for tracheal injury. TRIAL REGISTRATION NUMBER: ChiCTR2000037842, registered 03 September 2020. Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=57011&htm=4.

Correlation Between Blood Urea Nitrogen and Short- and Long-Term Glycemic Variability in Elderly Patients with Type 2 Diabetes Mellitus Who Were hospitalized:A Retrospective Study.

Objective: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and progressively impaired insulin secretion resulting in dynamic fluctuations in glucose levels.High blood urea nitrogen (BUN) levels have been linked to decreased insulin sensitivity, suppressed insulin synthesis and increased risk of incident diabetes mellitus in humans as well as insulin use in patients with T2DM.This study characterize the association between BUN levels and short-term and long-term glycemic variability(GV) in the elderly patients with T2DM who were hospitalized. Methods: A total of 927 elderly patients with T2DM were included in the study. The short-term GV was quantified using parameters such as standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), based on multi-point fingertip blood glucose monitoring. The long-term GV was quantified using parameters such as SD, CV, variation independent of the mean (VIM), and average successive variability (ARV), based on fasting blood glucose(FPG). The relationship between BUN levels and short-term and long-term GV in elderly T2DM who were hospitalized was explored using methods such as Spearman correlation coefficient, linear regression analysis, logistic regression analysis, and interaction tests. Results: In elderly patients with T2DM were hospitalized, there is a significant correlation between BUN levels and both short-term and long-term GV. BUN is negatively correlated with the GV parameter TIR (r=-0.12, P=0.000), and positively correlated with SD (r=0.12, P=0.000), CV (r=0.07, P=0.026), MAGE (r=0.11, P=0.001), FPG-SD (r=0.08, P=0.013), and FPG-CV (r=0.08, P=0.014).Furthermore, the association remains consistent across different age, gender, BMI, and haemoglobin A1c (HbA1c) subgroups (P interaction > 0.05). Conclusion: In elderly patients with T2DM were hospitalized, BUN levels were positively associated with GV.Therefore, monitoring BUN levels were beneficial in assessing the degree of GV.

Involvement of lncRNAs in the regulation of aerobic glycolysis in hepatocellular carcinoma: Main functions, regulatory mechanisms and potential therapeutic implications (Review).

Even under aerobic conditions, tumor cells can reprogram their metabolism to preferentially metabolize glucose into lactic acid. This abnormal metabolic pattern, known as the 'Warburg' effect or aerobic glycolysis, promotes cancer progression. Long non­coding RNAs (lncRNAs) are RNAs that are >200 nucleotides in length and do not have protein­coding capabilities. However, these RNAs play a key role in tumor development. There is increasing evidence to indicate that lncRNAs regulate glucose metabolism in tumor cells by affecting metabolic enzymes and some signaling pathways, thereby regulating the occurrence and progression of hepatocellular carcinoma (HCC). Therefore, it is crucial to understand which lncRNAs play a regulatory role in HCC glycolysis and to determine the related molecular mechanisms. The present review summarized and discussed the functions of lncRNAs, focusing on the regulatory mechanisms of lncRNAs in the process of glycolysis in HCC. In addition, the present review suggests the importance of lncRNAs as future therapeutic targets for antitumor cell metabolism.

Micronized acellular dermal matrix combined with platelet rich plasma in the treatment of atrophic acne scars: A self-controlled split face study.

BACKGROUND: Micronized acellular dermal matrix (mADM) can induce tissue regeneration and repair, and filling. OBJECTIVES: The efficacy and safety of (mADM) were evaluated in the treatment of atrophic acne scar. METHODS: In this single-blinded, self-controlled, split-face study, 16 patients (48 scar sites) were divided into treatment group (24 scar sites) and control group (24 scar sites). One side of the affected area was treated with mADM combined with platelet rich plasma (PRP) injection as the treatment group; the other side of the affected area was treated with PRP injection as the control group. The efficacy was evaluated by the Acne scar assessment scale (ASAS) and Acne Scar Weight Rating Scale (ECCA) 3 months after treatment. RESULTS: After 3-month treatment in 16 patients, the atrophic acne scars in both groups were all improved. The ASAS score and ECCA weight score in the treatment group was significantly lower than that in the control group (2.50 ± 0.51 vs. 3.62 ± 0.77 and 14.17 ± 10.18 vs. 31.88 ± 13.25; p < 0.001). LIMITATIONS: Short-term 3-month treatment period. Small sample size limits generalizability of results. CONCLUSION: The curative effect of mADM combined with PRP is significantly better than that of PRP alone.

Cohort profile: the China surgery and anesthesia cohort (CSAC).

The China Surgery and Anaesthesia Cohort (CSAC) study was launched in July 2020 and is an ongoing prospective cohort study recruiting patients aged 40-65 years who underwent elective surgeries with general anaesthesia across four medical centres in China. The general objective of the CSAC study is to improve our understanding of the complex interaction between environmental and genetic components as well as to determine their effects on a wide range of interested surgery/anaesthesia-related outcomes. To achieve this goal, we collected enriched phenotypic data, e.g., sociodemographic characteristics, lifestyle factors, perioperative neuropsychological changes, anaesthesia- and surgery-related complications, and medical conditions, at recruitment, as well as through both active (at 1, 3, 7 days and 1, 3, 6, 12 months after surgery) and passive (for more than 1 year after surgery) follow-up assessments. We also obtained omics data from blood samples. In addition, COVID-19-related information was collected from all participants since January 2023, immediately after COVID-19 restrictions were eased in China. As of July 18, 2023, 12,766 participants (mean age = 52.40 years, 57.93% were female) completed baseline data collection (response rate = 94.68%), among which approximately 70% donated blood and hair samples. The follow-up rates within 12 months after surgery were > 92%. Our initial analyses have demonstrated the incidence of and risk factors for chronic postsurgical pain (CPSP) and postoperative cognitive dysfunction (POCD) among middle-aged Chinese individuals, which may prompt further mechanistic exploration and facilitate the development of effective interventions for preventing those conditions. Additional studies, such as genome-wide association analyses for identifying the genetic determinants of CPSP and POCD, are ongoing, and their findings will be released in the future.

Esketamine Combined with Propofol TCI versus Propofol TCI for Deep Sedation during Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Prospective, Randomized, and Controlled Trial.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an invasive procedure that required deep sedation to suppress coughing and body movements. Deep sedation, on the other hand, has been shown to cause respiratory and circulatory depression, especially when the airway is shared with the endoscopist. Esketamine is a novel sedative and analgesic with little respiratory inhibition that appears to be an appropriate adjuvant in propofol sedation for EBUS-TBNA. We compared the efficacy and safety of esketamine combined with propofol target-controlled infusion (TCI) and propofol TCI for deep sedation in EBUS-TBNA. Methods: The study included 135 patients with ASA II-III undergoing EBUS-TBNA. They were randomly divided into two groups (group E and group P). Both groups received midazolam (0.01-0.03 mg/kg) and oxycodone (0.07-0.08 mg/kg). Then, patients in group E received 0.3 mg/kg esketamine, propofol TCI, and 0.2 mg·kg-1·h-1 esketamine for sedative maintenance. Patients in group P received only propofol TCI. The primary outcome was the dose of 1% lidocaine administrated by the endoscopist and the times of lidocaine sprays. Secondary outcome indicators were cough score, propofol dosage, patient satisfaction, endoscopist satisfaction, the incidence of sedation-related adverse effects and side effects, and recovery time. Results: Patients in group E were given significantly less lidocaine (4.36 ml/h (2.67-6.00) vs 6.00 ml/h (4.36-7.20), P < 0.001) and less spraying frequency (2.18 times/h (1.33-3.00) vs 3.00 times/h (2.18-3.60), P < 0.001) than group P. There was a statistically significant difference in cough score between the two groups (group E 2 (0-4) vs group P 3 (2-4), P=0.03). Also, mean arterial pressure (MAP) was higher in group E in the 30th min (T5, 84.10 ± 12.91 mmHg versus 79.04 ± 10.01 mmHg, P=0.012) and 40th min (T6, 87.72 ± 15.55 mmHg versus 82.14 ± 10.51 mmHg, P=0.026). There were no significant differences between the two groups in terms of sedation-related adverse events and side effects, recovery time, endoscopist satisfaction, and patient satisfaction. Conclusions: In patients with ASA II-III, esketamine as an adjuvant in combination with propofol TCI deep sedation for EBUS-TBNA can improve the sedation effect, reduce coughing reaction during the procedure, and obtain more stable blood pressure. No reduction in the occurrence of sedation-related side effects was observed. This trial is registered with ChiCTR2200061124.

Screening and identification of hub genes of scar physique via weighted gene co-expression network analysis.

Scar physique refers to the abnormal repair of skin injury in some people, which may easily lead to keloid or hypertrophic scar. However, the mechanism of scar physique is still unclear. GSE108110 was obtained from the gene expression omnibus database. Differently expression genes (DEGs) between normal skin tissue of non-scar physique individuals and normal skin tissue of scar physique individuals were screened by R package "limma". Weighted gene co-expression network analysis was performed to find highly relevant gene modules. Functional annotation of DEGs was made. Protein-protein interaction network was constructed, and the identification and analysis of hub DEGs were performed, including identification of hub DEGs associated with scar diseases, MiRNA of hub DEGs prediction, and functional annotation of miRNA. A total of 1389 up-regulate DEGs and 1672 down-regulate DEGs were screened. weighted gene co-expression network analysis analysis showed that the dendrogram and heatmap were used to quantify module similarity by correlation. The associations between clinic traits and the modules were identified based on the correlation between module and scar physique. Eight common hub genes were obtained. The comparative toxicogenomics database shows common hub genes associated with scar tissue. Gene ontology and Kyoto encyclopedia of genes and genomes analysis were significantly enriched in "fibroblast growth factor receptor signaling pathway", "epidermal growth factor receptor signaling pathway", "G1/S transition of mitotic cell cycle", protein polyubiquitination", and others. The 8 hub genes might be involved in the development of scarring and used as early diagnosis, prevention and treatment of scar physique.

Risk Factors Analysis of Phantom Limb Pain in Amputees with Malignant Tumors.

Purpose: Postamputation neuropathic pain is a common disease in patients with malignant tumor amputation, seriously affecting amputees' quality of life and mental health. The objective of this study was to identify independent risk factors for phantom limb pain in patients with tumor amputation and to construct a risk prediction model. Methods: Patients who underwent amputation due to malignant tumors from 2013 to 2023 were retrospectively analyzed and divided into phantom limb pain group and non-phantom limb pain group. To determine which preoperative factors would affect the occurrence of phantom limb pain, we searched for candidate factors by univariate analysis and used multivariate logistic regression analysis to identify independent factors and construct a predictive model. The receiver operating characteristic curve (ROC) was drawn to further evaluate the accuracy of the prediction model in evaluating the phantom limb pain after amputation of bone and soft tissue tumors. Results: Multivariate analysis showed that age (OR, 1.054; 95% CI, 1.027 to 1.080), preoperative pain (OR, 5.773; 95% CI, 2.362 to 14.104), number of surgeries (OR, 3.425; 95% CI, 1.505 to 7.795), amputation site (OR, 5.848; 95% CI, 1.837 to 18.620), amputation level (OR, 8.031; 95% CI, 2.491 to 25.888) were independent risk factors for phantom limb pain for bone and soft tissue tumors. The the area under the curve (AUC) of this model was 0.834. Conclusion: Risk factors for postoperative phantom limb pain were the site of amputation, proximal amputation, preoperative pain, multiple amputations, and older age. These factors will help surgeons to individualize and stratify phantom limb pain and help patients with risk counseling. In particular, an informed clinical decision targeting those modifiable factors can be considered when needed.

Multivisceral resection of nonfunctional pancreatic neuroendocrine neoplasm with nearby organ invasion: a case report.

Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare epithelial malignancies originating from pancreatic neuroendocrine cells, pathologically classified into well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (pNECs). Although they also fall under the category of pNENs, the almost entirely distinct biological characteristics and survival prognosis have caused debate among surgeons when it comes to the development of surgical intervention options, particularly for locally advanced G3 pNETs and pNECs. We present a case of 66-year-old male with nonfunctional G3 pNET, invasion of five nearby pancreatic organs and type II liver metastases. The patient achieved good outcomes after undergoing multivisceral resection and postoperative adjuvant chemotherapy. This finding helps surgeons better understand locally advanced pNENs, formulate treatment decisions systematically and confidently, and balance patient benefits and risks of surgery.

Insights on therapeutic potential of clemastine in neurological disorders.

Clemastine, a Food and Drug Administration (FDA)-approved compound, is recognized as a first-generation, widely available antihistamine that reduces histamine-induced symptoms. Evidence has confirmed that clemastine can transport across the blood-brain barrier and act on specific neurons and neuroglia to exert its protective effect. In this review, we summarize the beneficial effects of clemastine in various central nervous system (CNS) disorders, including neurodegenerative disease, neurodevelopmental deficits, brain injury, and psychiatric disorders. Additionally, we highlight key cellular links between clemastine and different CNS cells, in particular in oligodendrocyte progenitor cells (OPCs), oligodendrocytes (OLs), microglia, and neurons.

Eligibility for elective surgery in patients recovering from mild COVID-19: A propensity-matched analysis.

OBJECTIVE: To study the timing of surgery after a recent Omicron variant infection, to provide a reference for policymakers, clinicians, and patients. METHODS: This single-center propensity-matched analysis was designed and reported according to the EQUATOR-STROBE guidelines. Patients recovering from COVID-19 infection were divided into three groups based on the period from disappearance of respiratory symptoms to surgery: ≤7 days, 8-14 days, and >14 days groups. Outcome measures included postoperative respiratory complications, vascular thrombosis, myocardial infarction, ischemic stroke, and mortality. RESULTS: Between August 1 and December 31, 2022, 9023 surgical procedures were performed, of which 7490 surgeries met the inclusion criteria. Propensity matching resulted in a final cohort of 227 patients recovered from COVID-19 and 2043 SARS-CoV-2 negative patients. Compared with the SARS-CoV-2 negative group, the incidence of postoperative respiratory complications was significantly higher (15.91% vs. 6.71%, p = 0.028) only in the ≤7 days group. There were no statistically significant differences in the other 30-day outcomes between the SARS-CoV-2 negative and the three COVID-19 recovery groups. CONCLUSIONS: Patients who have recovered from mild COVID-19 may be eligible for elective surgery at least 7 days after recovery, since they do not have an increased risk of postoperative complications or mortality within 30 days.

LXA4 attenuates perioperative neurocognitive disorders by suppressing neuroinflammation and oxidative stress.

Perioperative neurocognitive disorder (PND) is a common complication that increases morbidity and mortality in elderly patients undergoing surgery. Abnormal microglia activation causes neuroinflammation and contributes to the development of PND. Growing evidence shows that lipoxin A4 (LXA4), a lipid mediator, possesses potent anti-inflammatory activities. In this study, we investigated whether LXA4 exerted a protective effect against surgery-induced neurocognitive deficits and explored the underlying mechanisms. Mice were subjected to laparotomy under sevoflurane anesthesia to establish an animal model of PND. LXA4 (15 µg/kg/d, ip) was administered three days prior surgery. We showed that LXA4 significantly alleviated surgery-induced cognitive impairments, attenuated neuroinflammation and microglial activation in hippocampus. In BV2 microglial cells treated with LPS (100 ng/mL), pre-application of LXA4 (100 nΜ) significantly inhibited M1 polarization and promoted M2 polarization, and decreased the levels of pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6) and increased the levels of anti-inflammatory cytokine (IL-10). LXA4 also mitigated LPS-regulated expression of HO-1, NOX2, and SOD1, elevated SOD activity, and attenuated ROS production. Furthermore, we revealed that LXA4 increased the expression of SIRT1 and decreased the protein level of acetylated NF-κB p65. SIRT1 inhibitor EX-527 abolished the anti-inflammatory and antioxidant response effects of LXA4 in BV2 microglial cells. Hence, LXA4 is a potential therapeutic agent for surgery-induced neuroinflammation, oxidative stress, and cognitive deficit, and the effect of LXA4 is probably mediated by the activation of the SIRT1/NF-κB signaling pathway in microglia.

Downregulated Acetyl-CoA Acyltransferase 2 Promoted the Progression of Hepatocellular Carcinoma and Participated in the Formation of Immunosuppressive Microenvironment.

Background: The aim of this study is to explore the role of acetyl-CoA acyltransferase 2 (ACAA2) in the progression of hepatocellular carcinoma (HCC). Methods: Bulk RNA data and single-cell RNA data were acquired from The Cancer Genome Atlas and Gene Expression Omnibus. Both in vitro and in vivo studies were used to determine the effect of ACAA2 on the progression of HCC, and RNA sequencing analysis was performed to explore the mechanism. Results: We found downregulation of ACAA2 was involved in the malignant progression of HCC. The patient with low ACAA2 level had an immunosuppressive microenvironment in the HCC and predicted to have a poor prognosis. Decreased ACAA2 facilitated HCC proliferation and metastasis by activating the nuclear factor-κB (NFκB) signaling pathway. And increased CXCL1 induced by NFκB signaling pathway might be responsible for low level of ACAA2 related immunosuppressive microenvironment. Furthermore, the expression of ACAA2 was also detected in immune cells. The expression of ACAA2 in CD4+TCF7+T, CD4+FOXP3+T, CD8+GZMK+T, and CD8+KLRD1+T cells was inversely correlated with the composition of CD8+PDCD1+T cells in HCC. This effect might be due to the CCL5-CCRs and HLA-E-KLRCs ligand-receptor networks. Conclusion: In a conclusion, downregulated ACAA2 promoted the progression of hepatocellular carcinoma and might be participated in the formation of immunosuppressive microenvironment. ACAA2 could be served as a favorable indicator for the prognosis of HCC and an ideal biomarker for immunotherapy.

Correlation Between Glycemic Variability and Diabetic Complications: A Narrative Review.

Diabetes mellitus is a metabolic disorder with a complex etiology in which glycemic dynamics are disturbed and the body is unable to maintain the process of glucose homeostasis through the pancreas. Persistent symptoms of high blood glucose or low blood glucose may lead to diabetic complications, such as neuropathy, nephropathy, retinopathy, and cardiovascular diseases. Glycemic variability which can represent the presence of excessive glycemic excursions is an indicator for evaluating glucose homoeostasis. Limiting glycemic variability has gradually become an emerging therapeutic target in improve diabetes metabolism and prevent associated complications. This article reviews the progress of research on the various quantifiable parameters of glycemic variability and their relationships with vascular lesions and mechanisms.

An impedance based microfluidic sensor for evaluation of individual red blood cell solute permeability.

-In this paper, we investigate a microfluidic based sensing device for cell membrane permeability measurements in real time with applications in rapid assessment of red blood cell (RBC) quality at the individual cell level. The microfluidic chip was designed with unique abilities to line up the RBCs in the centerline of the microchannel using positive dielectrophoresis (p-DEP) forces, rapid mixing of RBCs with various media (e.g. containing permeating or nonpermeating solutes) injected from different inlets to achieve high mixing efficiency. The chip detects the impedance values of the RBCs within 0.19 s from the start of mixing with other media, at ten electrodes along the length of the channel and enables time series measurements of volume change of individual cell caused by cell osmosis in anisosmotic fluids over a 0.8 s postmixing timespan. This technique enables estimating water permeability of individual cell accurately. Here we first present confirmation of a linear voltage-diameter relationship in polystyrene bead standards. Next, we show that under equilibrium conditions, the voltage-volume relationship in rat red blood cells (RBCs) is linear, corresponding to previously published Boyle van 't Hoff plots. Using rat cells as a model for human, we present the first measurement of water permeability in individual red blood cells and confirm that these data align with previously published population level values for human RBC. Finally, we present preliminary evidence for possible application of our device to identify individual RBCs infected with Plasmodium falciparum malaria parasites. Future developments using this device will address the use of whole blood with non-homogenous cell populations, a task currently performed by clinical Coulter counters.

Lipoxin A4 methyl ester attenuated ketamine-induced neurotoxicity in SH-SY5Y cells via regulating leptin pathway.

Ketamine, the widely used intravenous anesthetic, has been reported to cause neurotoxicity and disturbs normal neurogenesis. However, the efficacy of current treatment strategies targeting ketamine's neurotoxicity remains limited. Lipoxin A4 methyl ester (LXA4 ME) is relatively stable lipoxin analog, which serves an important role in protecting against early brain injury. The purpose of this study was to investigate the protective effect of LXA4 ME on ketamine-caused cytotoxicity in SH-SY5Y cells, as well as the underlying mechanisms. Cell viability, apoptosis and endoplasmic reticulum stress (ER stress) were detected by adopting experimental techniques including CCK-8 assay, flow cytometry, western blotting and transmission electron microscope. Furthermore, examining the expression of leptin and its receptor (LepRb), we also measured the levels of activation of the leptin signaling pathway. Our results showed that LXA4 ME intervention promoted the cell viability, inhibited cell apoptosis, and reduced the expression of ER stress related protein and morphological changes induced by ketamine. In addition, inhibition of leptin signaling pathway caused by ketamine could be reversed by LXA4 ME. However, as the specific inhibitor of leptin pathway, leptin antagonist triple mutant human recombinant (leptin tA) attenuated the cytoprotective effect of LXA4 ME against ketamine-induced neurotoxicity. In conclusion, our findings demonstrated LXA4 ME could exert a neuroprotective effect on ketamine-induced neuronal injury via activation of the leptin signaling pathway.

MAPK/AP-1 Signaling Pathway Is Involved in the Protection Mechanism of Bone Marrow Mesenchymal Stem Cells-Derived Exosomes against Ultraviolet-Induced Photoaging in Human Dermal Fibroblasts.

INTRODUCTION: The role of bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exo) in skin photoaging was explored in human dermal fibroblasts (HDFs). The underlying mechanism was further explored. METHODS: HDFs were exposed to UVB irradiation to establish the cell photodamage models. The cell viability and levels of oxidative stress-related factors were tested. ELISA was done to detect TNF-α, IL-6, and IL-1ß concentrations. Western blot was applied for protein examination. RESULTS: UVB treatment led to the inhibition of cell viability. But after BMSCs-exo addition, the inhibitory effect was returned in a dose manner. UVB exposure contributed to the increase of reactive oxygen species and LDH and the downregulation of superoxide dismutase. In addition, excessive secretion of TNF-α, IL-6, and IL-1ß was also detected in cells exposed to UVB. However, BMSCs-exo addition eliminated the effects of UVB on oxidative stress and inflammation in HDFs. BMSCs-exo inhibited matrix metalloproteinases MMP-1 and MMP-3 expression but promoted collagen I expression. UVB radiation activated the MAPK/AP-1 signaling, manifested as the increase of p-p38, c-Jun, and c-Fos protein levels, which were reversed by BMSCs-exo. As a p38 agonist, anisomycin counteracted the effect of BMSCs-exo on HDF's viability, oxidative stress, and inflammation. CONCLUSION: BMSCs-exo protected HDFs against UVB-induced inhibition of cell viability and the activation of cell oxidative stress and inflammation, which might be related to the inhibition of the MAPK/AP-1 signaling pathway.

Bone marrow mesenchymal stem cell-derived exosome miR-29b-3p alleviates UV irradiation-induced photoaging in skin fibroblast.

BACKGROUND: Mesenchymal stem cells-derived exosome (MSCs-exo) was identified to reduce photoaging. The purpose of this study was to investigate the potential role of microRNA (miR)-29b-3p derived from bone marrow MSCs-exo (BMSCs-exo) in photoaging. METHODS: Exosomes were isolated from BMSCs and verified by Western blot. A photoaging cell model was constructed by UVB irradiation of human dermal fibroblasts (HDFs). Quantitative real-time PCR (RT-qPCR) was performed to detect the mRNA levels of miR-29b-3p, collagen type I and matrix metalloproteinases (MMPs). CCK-8, Transwell and flow cytometry were applicated to examine cell viability, migration and apoptosis. Commercial kits are used to measure levels of oxidative stress indicators. Finally, a dual-luciferase reporter assay was applied to validate the target of miR-29b-3p. RESULTS: Extracted exosomes were positive for HSP70 and CD9. Survival of HDFs increased in an exosome concentration-dependent manner. UVB irradiation inhibited miR-29b-3p levels compared with controls, but BMSCs-exo treatment restored miR-29b-3p levels (p < .05). Additionally, BMSCs-exo-miR-29b-3p reversed the inhibition of HDFs migration and oxidative stress by UVB irradiation, as well as the promotion of apoptosis. However, this reversal was attenuated by the suppression of miR-29b-3p (p < .05). Furthermore, BMSCs-exo-miR-29b-3p also inhibited the degradation of collagen type I and the production of MMPs in photoaging, and they were also eliminated by the reduced miR-29b-3p. Finally, MMP-2 was the target gene of miR-29b-3p. CONCLUSION: Our study presented a novel role for BMSCs-exo-miR-29b-3p in improving skin photoaging function, and these findings may provide new insights into the targeted treatment of skin photoaging.