miR-126 promotes M1 to M2 macrophage phenotype switching via VEGFA and KLF4.

Background: Macrophage polarization and microRNA play crucial roles in the development of atherosclerosis (AS). The M1 macrophage phenotype contributes to the formation of plaques, while the M2 macrophage phenotype resolves inflammation and promotes tissue repair. MiR-126 has been found to play a role in regulating macrophage polarization in the context of AS. However, the exact mechanism of miR-126 requires further research. Methods: The foam cell model was established by stimulating THP-1 with oxidized low-density lipoprotein (ox-LDL). We transfected foam cells with miR-126 mimic and its negative control. The transfection of miR-126 was implemented by riboFECT CP transfection kit. The levels of miR-126 and M1/M2 associated genes in foam cells were quantified using reverse transcription-quantitative PCR (RT-qPCR). Additionally, the expressions of CD86+ and CD206+ cells in foam cells were determined by flow cytometry. Western blotting and RT-qPCR were used to determine the protein and mRNA levels of the vascular endothelial growth factor A (VEGFA) and the transcriptional regulator Krüppel-like factor 4 (KLF4), respectively. Additionally, we detected endothelial cell migration after co-culturing endothelial cells and macrophages. MG-132 was used to indirectly activate the expression of VEGFA, and the expression of KLF4 was also evaluated. Results: The activation of apoptosis and production of foam cells were boosted by the addition of ox-LDL. We transfected foam cells with miR-126 mimic and its negative control and observed that miR-126 greatly suppressed foam cell development and inhibited phagocytosis. Moreover, it caused pro-inflammatory M1 macrophages to switch to the anti-inflammatory M2 phenotype. This was reflected by the increase in anti-inflammatory gene expression and the decrease in pro-inflammatory gene expression. Additionally, miR-126 dramatically decreased the expressions of VEGFA and KLF4. The protein-protein interaction network analysis showed a significantly high correlation between miR-126, VEGFA, and KLF4. MiR-126 may also promote EC migration by activating macrophage PPAR γ expression and effectively suppressing macrophage inflammation. MG-132 indirectly activated the expression of VEGFA, and the expression of KLF4 also significantly increased, which indicates a direct or indirect relationship between VEGFA and KLF4. Conclusion: Our study shows that miR-126 can reverse ox-LDL-mediated phagocytosis and apoptosis in macrophages. Consequently, the potential role of miR-126 was manifested in regulating macrophage function and promoting vascular endothelial migration.

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease.

BACKGROUND: Five types of HIF-PHIs have been authorized for anemia treatment in CKD patients in China and Japan. These are enarodustat, roxadustat, daprodustat, vadadustat, and molidustat. How effectively they compare to ESAs about clinical results in CKD-DD patients is uncertain. This study examined the RCT evidence about the benefits and risks of HIF-PHIs and ESAs in dialysis CKD patients. METHODS: We conducted an extensive investigation and network meta-analysis of RCTs. In these RCTs, patients with CKD-DD received one of five different HIF-PHI or ESAs, a placebo, and no medical intervention. Outcomes included hemoglobin, iron parameters, and adverse events, and there were four weeks of follow-up at least. A frequentist framework for multivariate random effects meta-analyzed the results. The effect sizes of categorical variables were displayed as odds ratios. Mean differences were employed for computing continuous outcomes with common units; otherwise, standardized mean differences were applied. The Cochrane tool evaluated the bias risk in RCTs. RESULTS: 26 RCTs with 14945 patients were qualified for inclusion. Compared to the placebo, HIF-PHIs and ESAs dramatically boosted hemoglobin without affecting serum iron. Roxadustat performed better hemoglobin levels than ESAs (MD 0.32, 95% CI 0.10 to 0.53) and daprodustat (0.46, 0.09 to 0.84). Roxadustat (91.8%) was the top hemoglobin treatment among all medical interventions, as determined by the SUCRA ranking. However, roxadustat caused more thrombosis and hypertension than ESAs (1.61, 1.22 to 2.12) and vadadustat (1.36, 1.01 to 1.82). The lowest rates of hypertension and thrombosis were seen in molidustat (80.7%) and ESAs (88.5%). Compared with a placebo, ESAs and HIF-PHIs all affected TSAT levels. Except for molidustat, the other four HIF-PHIs impact different iron parameters. Regarding ferritin reduction, roxadustat (90.9%) and daprodustat (60.9%) came out on top. Enarodustat (80.9%) and roxadustat (74%) placed best and second in lowering hepcidin levels. The former two medicines for TIBC improvement were vadadustat (98.7%) and enarodustat (80.9%). CONCLUSION: The most effective treatment for hemoglobin correction is roxadustat. The superior efficacy of reducing hepcidin makes roxadustat and enarodustat appropriate for patients with inflammation. However, the increased risk of hypertension and thrombosis associated with roxadustat should be noted. In patients at risk for hypertension and thrombosis, molidustat and ESAs may be preferable options. When administering roxadustat and daprodustat, clinicians should check ferritin to assess iron storage. Lower TSAT in patients receiving HIF-PHIs and ESAs treatment suggests intravenous iron supplements are needed.

Research progress of omalizumab in the treatment of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering disease associated with anti-BP180 and anti-BP230 antibodies. The pathogenic action mechanism of immunoglobulin E (IgE) antibodies in BP has been studied since the 1970s, and IgE antibodies have gradually been confirmed as being important in BP; therefore, anti-IgE therapy may be a new option for the treatment of BP. Omalizumab, as an IgE monoclonal antibody, has been increasingly used clinically to treat BP in recent years. Here, we collected 35 papers investigating omalizumab for BP treatment in a total of 83 patients, and the vast majority of patients showed varying degrees of improvement after treatment, except for a small number of patients with poor clinical outcomes. The patients were then divided into three groups according to dosing frequency and number of doses. Statistical analysis indicated that dosing frequency had little effect on clinical efficacy. While the groups with different numbers of doses were evaluated, the results concluded that clinical efficacy was affected by the number of doses, but there was no positive correlation between the number of doses and clinical efficacy.

Development and validation of a prognostic nomogram for Takotsubo syndrome patients in the intensive care units: a retrospective cohort study.

Patients with Takotsubo syndrome (TTS) admitted to the intensive care unit (ICU) always confront a higher risk of in-hospital death than those hospitalized in the cardiology unit. The prognosis of the latter was analyzed by a large number of studies. However, there was no utility model to predict the risk of in-hospital death for patients with TTS in the ICU. This study aimed to establish a model predicting in-hospital death in patients with TTS admitted to ICU. We retrospectively included ICU patients with TTS from the MIMIC-IV database. The outcome of the nomogram was in-hospital death. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. The model was developed by multivariable logistic regression analysis. Calibration, decision curve analysis (DCA), and receiver operating characteristic (ROC) measured the performance of the nomogram on the accuracy, clinical utility, and discrimination, respectively. Eventually, 368 ICU patients with TTS were enrolled in this research. The in-hospital mortality was 13.04%. LASSO regression and multivariate logistic regression analysis verified risk factors significantly associated with in-hospital mortality. They were potassium, prothrombin time (PT), age, myocardial infarction, white cell count (WBC), hematocrit, anion gap, and sequential organ failure assessment (SOFA) score. This nomogram excellently discriminated against patients with a risk of in-hospital death. The area under curve (AUC) was 0.779 (95%CI: 0.732-0.826) in training set and 0.775 (95%CI: 0.711-0.839) in test set. The calibration plot and DCA showed good clinical benefits for this nomogram. We developed a nomogram that predicts the probability of in-hospital death for ICU patients with TTS. This nomogram was able to discriminate patients with a high risk of in-hospital death and performed clinical utility.

A nomogram to predict in­hospital mortality in post-cardiac arrest patients: a retrospective cohort study.

INTRODUCTION: Nomograms of prognosis in patients with a history of cardiac arrest (CA) have been established. However, there are some shortcomings and interferences in their clinical application. OBJECTIVES: Our study aimed at developing a utility nomogram to predict the risk of in­hospital death in post­CA patients. PATIENTS AND METHODS: We retrospectively extracted data from the MIMIC­IV database. The least absolute shrinkage and selection operator logistic regression and multivariable logistic regression were used to investigate independent risk factors. A nomogram defined as a prediction model was established for these independent risk factors. The model performance was measured by examining discrimination (area under the receiver operating characteristic curve [AUC]), calibration (calibration curve analysis), and utility (decision curve analysis [DCA]). RESULTS: A total of 1724 post­CA patients were enrolled in the study. Of those, 788 survived and 936 died. The incidence of in­hospital death was 54.3%. In this nomogram, the predictors included age, malignant cancer, bicarbonate, blood urea nitrogen, sodium, heart rate, respiratory rate, temperature, SPO2, norepinephrine prescription, and lactate level. The internally validated nomogram showed good discrimination (AUC 0.801; 95% CI, 0.775-0.835). The calibration curve analysis and DCA confirmed that this prediction model can be clinically useful. CONCLUSIONS: We established a risk prediction model based on the admission characteristics to accurately predict the clinical outcome in post­CA patients. The nomogram might help with the risk identification and individual clinical interventions.