Association between pre-ICU statin use and ARDS mortality in the MIMIC-IV database: a cohort study.

Background: Acute respiratory distress syndrome (ARDS) is a severe condition associated with high morbidity, mortality, and healthcare costs. Despite extensive research, treatment options for ARDS are suboptimal. Methods: This study encompassed patients diagnosed with ARDS from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Pre-intensive care unit (ICU) statin use was assessed as the exposure variable. Kaplan-Meier survival analysis was conducted to evaluate mortality at 30 and 90 days. Adjusted multivariable Cox models were utilized to estimate hazard ratios. Subgroup analyses and propensity score-matching (PSM) were undertaken for further validation. Results: Our study comprised 10,042 participants diagnosed with ARDS, with an average age of 61.8 ± 15.3 years. Kaplan-Meier survival analysis demonstrated a significantly lower prevalence of mortality at 30 and 90 days in individuals who used statins before ICU admission. Adjusted multivariable Cox models consistently showed a significant decrease in mortality prevalence associated with pre-ICU statin use. After accounting for confounding factors, patients who used statins before ICU admission experienced a 39% reduction in 30-day mortality and 38% reduction in 90-day mortality. We found a significant decrease in ICU stay (0.84 days) for those who used statins before ICU admission. These results were supported by subgroup analyses and PSM. Conclusion: This large cohort study provides evidence supporting the association between pre-ICU statin use, reduced risk of death, and shorter ICU stay in patients with ARDS, thereby suggesting the potential benefits of statin use in critically ill patients.

Alpha-Lipoic Acid Protects Against Doxorubicin-Induced Cardiotoxicity by Regulating Pyruvate Dehydrogenase Kinase 4.

As a widely used anti-tumor anthracycline, the accumulation of Doxorubicin (DOX) in body causes irreparable cardiomyocyte damage and therefore is limited in clinical application. Strategies to prevent from DOX-associated cardiotoxicity are urgent for patients who undergo DOX-based chemotherapy. Since oxidative stress injury being the major reason for myocardial toxicity of DOX, here we demonstrated that, Alpha-lipoic acid (ALA), which is a reductive agent, plays a cardioprotective role in attenuating DOX-induced cardiotoxicity by inhibiting pyruvate dehydrogenase kinase 4 (PDK4) expression. In vivo, the beneficial effect of ALA was evidenced by increased survival rate, mechanical contraction, and oxidative phosphorylation, while decreased reactive oxidative species (ROS) and apoptosis. In vitro, PDK4 overexpression remarkably increased DOX-induced apoptosis and ROS production in H9C2 cells. Notably, the protective effect of ALA was abrogated by PDK4 overexpression. We further used PDK4 knockout mice to identify the role of PDK4 in DOX-induced cardiotoxicity. Results elicited that PDK4 deficiency showed a consistent effect in protecting DOX cardiotoxicity as ALA treatment, which was evidenced by restored redox homeostasis and mitochondrial metabolism, finally inhibited myocardial injury. In conclusion, the cardioprotective role of ALA against DOX cardiotoxicity was dependent on PDK4-mediated regulation of oxidative stress and mitochondria metabolism.

Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia-reperfusion injury via upregulation of splenic regulatory T cells.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25+Foxp3+ regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor ß1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen.

Increased Th17 and Th22 Cell Percentages Predict Acute Lung Injury in Patients with Sepsis.

PURPOSE: This study was conducted to investigate the percentages of Th22 and Th17 cells in the peripheral blood of septic patients with and without acute lung injury (ALI) and their clinical significance. METHODS: A total of 479 patients were divided into non-ALI and ALI groups. The percentages of Th22 and Th17 cells and the levels of interleukin 22 (IL-22), 6 (IL-6), and 17 (IL-17) were determined. Receiver operating characteristic curve analysis was performed to assess the diagnostic value of Th22 and Th17 cells to predict sepsis-induced ALI. RESULTS: The lung injury prediction score (LIPS), IL-6, IL-17, and IL-22 levels and the percentages of Th17 and Th22 cells were significantly higher in the ALI group (P < 0.05). They were significant factors affecting sepsis-induced ALI (P < 0.05). Multivariate logistic regression analysis showed that the LIPS (OR = 1.130), IL-17 (OR = 1.982), IL-22 (OR = 2.612) and the percentages of Th17 (OR = 2.211) and Th22 (OR = 3.230) cells were independent risk factors for ALI. The area under the curve of Th22 cells was 0.844 to predict ALI with a cutoff value of 6.81%. The sensitivity and specificity for early diagnosis of sepsis-induced ALI by the Th22 cell percentage were 78.72% and 89.13%, respectively. CONCLUSIONS: Th22 and Th17 cells in peripheral blood are significantly increased in septic patients with ALI and they may be used as biomarkers for early diagnosis of sepsis-induced ALI.

Plasma osteopontin acts as a prognostic marker in acute intracerebral hemorrhage patients.

BACKGROUND: Osteopontin (OPN), a matricellular protein, is greatly generated from brain tissues after acute brain injury. We determine the relationship between plasma OPN concentrations and outcome after acute intracerebral hemorrhage (ICH) in a clinical setting. METHODS: In this prospective, observational study enrolling 162 ICH patients and 162 healthy controls, hemorrhagic severity was assessed using National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volumes, a poor outcome was defined as modified Rankin Scale >2 at poststroke 90 days, and early neurologic deterioration (END) was defined as an increase of ≥4 points in the NIHSS score or death at 24 h from symptoms onset. RESULTS: Plasma OPN concentrations were significantly higher in patients than in controls (median value, 1287.6 vs. 405.7 pmol/l; P < 0.001). OPN concentrations were strongly correlated with admission NIHSS scores (r value = 0.520) and hematoma volumes (r value = 0.468). Areas under receiver operating characteristic curve for poor outcome and END were 0.811 and 0.753 respectively. Plasma OPN emerged as an independent predictor of functional outcome and END, with odds ratio values of 3.897 and 6.004 respectively. CONCLUSIONS: Plasma OPN could serve as a useful prognostic biomarker in ICH.

Association between dietary fiber and endometrial cancer: a meta-analysis.

To explore a potential relationship between dietary fiber consumption and risk of endometrial cancer (EC), eligible studies published up to 30 June 2018 were retrieved via computer searches and manual review of references. Random-effects models were used to calculate summary relative risk (RR) estimates based on contrasting high- and low-fiber intake values. Sensitivity analysis was conducted, and heterogeneity among study results was explored through stratified analyses by study design, geographic region, Newcastle-Ottawa Scale (NOS) score, impact factor, and adjustment for several confounders (age, body mass index, smoking, energy intake, and education). We extracted data from 16 studies (involving 6,563 cases). There was a significant association between dietary fiber intake and EC (RR = 0.86, 95% confidence interval [CI]: 0.78, 0.93). In stratified analysis, this trend was more pronounced in the case-control studies, and in studies conducted in the Americas and Asia. The relationship was further confirmed after adjusting for education level (RR = 0.74; 95% CI: 0.60, 0.88) and age (RR = 0.70; 95% CI: 0.57, 0.83), and NOS scores of 6 (RR = 0.81; 95% CI: 0.67, 0.95) and 7 (RR = 0.75; 95% CI: 0.62, 0.88). In conclusion, our meta-analysis revealed an inverse association between dietary fiber consumption and EC risk. Further efforts should be made to confirm these findings.

Effect of bovine lactoferrin as a novel therapeutic agent in a rat model of sepsis-induced acute lung injury.

Sepsis is a serious clinical condition resulting from severe infection. High rates of mortality and tissue damage have been reported in intensive care unit (ICU) patients with sepsis. Bovine lactoferrin (BLF) is a well-known 80-kDa glycoprotein in the transferrin family that inhibits sepsis in low-birth-weight neonates. The present study investigated the protective effects of BLF in a rat model of sepsis-induced acute lung injury (ALI). The wet/dry ratio, lipid peroxidation, antioxidant markers, total protein, total cell count, inflammatory markers and myeloperoxidase (MPO) levels were assessed. Histopathological analysis was also carried out. BLF treatment reduced the wet/dry ratio of lung tissue by 30.7% and 61.3%, and lipid peroxidation by 22.3% and 67%, at concentrations of 100 and 200 mg/kg, respectively. Superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (Gpx) and catalase were increased by more than 50% under treatment with 200 mg/kg BLF. Inflammatory markers, neutrophils, lymphocytes and total cell count were reduced by more than 50% under treatment with 200 mg/kg BLF. BLF treatment significantly reduced MPO activity, by 28.2% and 74.3%, at concentrations of 100 and 200 mg/kg, respectively. Neutrophilic infiltration and edema were observed in control rats. However, BLF treatment restored intestinal microvilli to the normal range and reduced inflammatory cell invasion. Collectively, these results suggest that BLF is an effective therapeutic agent against sepsis-induced ALI.

miR-26a prevents neural stem cells from apoptosis via ß-catenin signaling pathway in cardiac arrest-induced brain damage.

Neural stem cells (NSCs) transplantation is one of the most promising strategies for the treatment of CA-induced brain damage. The transplanted NSCs could differentiate into new neuron and replace the damaged one. However, the poor survival of NSCs in severe hypoxic condition is the limiting step to make the best use of this kind of therapy. In the present study, we investigated whether the overexpression of miR-26a improves the survival of NSCs in hypoxic environment in vitro and in vivo. In vitro hypoxia injury model is established in NSCs by CoCl2 treatment, and in vivo cardiac arrest (CA) model is established in Sprague-Dawley (SD) rats. Quantitative real-time polymerase chain reaction is used to detect the mRNA level and Western blot is used to examine the protein level of indicated genes. TUNEL staining and flow cytometry are applied to evaluate apoptosis. Dual-luciferase reporter assay is utilized to analyze the target gene of miR-26a. The expression of miR-26a is reduced in both in vitro and in vivo hypoxic model. MiR-26a directly targets 3'-UTR of glycogen synthase kinase 3ß (GSK-3ß), resulting in increased ß-catenin expression and decreased apoptosis of NSCs. Overexpression of miR-26a in transplanted NSCs improves the survival of NSCs and neurological function in CA rats. MiR-26a prevents NSCs from apoptosis by activating ß-catenin signaling pathway in CA-induced brain damage model. Modulating miR-26a expression could be a potential strategy to attenuate brain damage induced by CA.