Ferroptosis, a newly identified form of regulated cell death, is characterized by overwhelming iron-dependent accumulation of lethal lipid reactive oxygen species (ROS). Preventing cellular iron overload by reducing iron uptake and increasing iron storage may contribute to inhibit ferroptosis. Mitochondrial ferritin (FtMt) is an iron-storage protein that is located in the mitochondria, which has a significant role in modulating cellular iron metabolism. Recent studies showed that FtMt played inhibitory effects on oxidative stress-dependent neuronal cell damage. However, the potential role of FtMt in the progress of ferroptosis in neuronal cells has not been studied. To explore this, we established ferroptosis models of cell and drosophila by erastin treatment. We found that overexpression of FtMt in neuroblastoma SH-SY5Y cells significantly inhibited erastin-induced ferroptosis, which very likely was achieved by regulation of iron homeostasis. Upon erastin treatment, significant increases of cellular labile iron pool (LIP) and cytosolic ROS were observed in wild-type SH-SY5Y cells, but not in the FtMt-overexpressed cells. Consistent with that, the alterations of iron-related proteins in FtMt-overexpressed cells were different from that of the control cells. We further investigated the role of FtMt in erastin-induced ferroptosis in transgenic drosophila. We found that the wild-type drosophilas fed an erastin-containing diet didn't survive more than 3 weeks. In contrast, the FtMt overexpressing drosophilas fed the same diet were survival very well. These results indicated that FtMt played a protective role in erastin-induced ferroptosis.

At present, no single indicator could be used as a golden index to estimate aging process. The biological age (BA), which combines several important biomarkers with mathematical modeling, has been proposed for >50 years as an aging estimation method to replace chronological age (CA). The common methods used for BA estimation include the multiple linear regression (MLR), the principal component analysis (PCA), the Hochschild’s method, and the Klemera and Doubal’s method (KDM). The fundamental differences in these four methods are the roles of CA and the selection criteria of aging biomarkers. In MLR and PCA, CA is treated as the selection criterion and an independent index. The Hochschild’s method and KDM share a similar concept, making CA an independent variable. Previous studies have either simply constructed the BA model by one or compared the four methods together. However, reviews have yet to illustrate and compare the four methods systematically. Since the BA model is a potential estimation of aging for clinical use, such as predicting onset and prognosis of diseases, improving the elderly’s living qualities, and realizing successful aging, here we summarize previous BA studies, illustrate the basic statistical steps, and thoroughly discuss the comparisons among the four common BA estimation methods.

Acute kidney injury (AKI) is a serious complication in the intensive care unit (ICU), which may increase the mortality of critically ill patients. The red blood cell distribution width (RDW) has proved useful as a predictor of short-term prognosis in critically ill patients with AKI. However, it remains unknown whether RDW has a prognostic value of long-term all-cause mortality in these patients. The data of 18279 critically ill patients with AKI at first-time hospital admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The tertiles of the RDW values were used to divide subjects into three groups, namely RDW < 13.6% for the low RDW group, 13.6% ≤ RDW < 15.2% for the middle RDW group and RDW ≥ 15.2% for the high RDW group. Demographic data, mortality, 4-year survival time and severity scale scores were compared among groups. The Kaplan-Meier analysis and the Cox regression analysis were performed to assess the impact of RDW on all-cause mortality in AKI patients. The receiver operating characteristic (ROC) curve analysis was done to evaluate the prognostic value of RDW on the long-term outcome of critically ill patients with AKI. The median age of the enrolled subjects was 65.6 years. AKI patients with a higher RDW value had significantly shorter survival time and higher death rate. By the Kaplan-Meier analysis, patients in the higher RDW group presented significantly shorter survival time and higher death rate. The Cox regression model indicated RDW as an independent risk factor of all-cause mortality of AKI patients (HR 1.219, 95% CI, 1.211 to 1.228). By the ROC analysis, RDW appeared more efficient in predicting long-term prognosis as compared with conventional severity scales. The AUC of RDW (95% CI, 0.712 to 0.725) was significantly higher than other severity scale scores. In conclusion, RDW is positively correlated to survival time of 4-year follow-up in critically ill patients with AKI, and RDW is an independent prognostic factor of longterm outcomes of these patients. Acute kidney injury (AKI) is one of the most common complications in critically ill patients, which results in poor prognosis and high risk of death 1. Approximately 57% of patients in the intensive care unit (ICU) were complicated with AKI, and up to 27% died consequently during hospitalization 2. When AKI occurs concomitantly with other severe organ dysfunctions like myocardial infarction or sepsis, the mortality rate is further increased to 45% to 60% 3 .

Background/Aims: Accumulating evidence has highlighted the importance of long non-coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology. Among others, actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been associated with non-small cell lung cancer (NSCLC). However, it remains unclear how AFAP1-AS1 participates in the development and progression of NSCLC. Methods: The peripheral blood samples were collected from patients with NSCLC. White blood cell subsets were classified and levels of interleukin (IL)-10, IL-12 and IFN-γ in serum were measured. We then identified its target gene of AFAP1-AS1 via bioinformatics methods. NSCLC cell line with the highest expression of AFAP1-AS1, i.e. H1975 was selected for in vitro experiments. A series of inhibitor, vector and siRNA were employed to validate the regulatory mechanisms of AFAP1-AS1 in the development and progression of NSCLC. Cell proliferation was detected by MTT assay and EdU staining. Cell migration and invasion, and cell cycle and apoptosis were measured by transwell assay and flow cytometry, respectively. Results: A high expression of AFAP1-AS1 was identified in NSCLC, alongside with a reduced level of IL-12 and increased levels of IL-10 and interferon (IFN)-γ. Aberrant expressions of AFAP1-AS1 were associated with pathological grade, TNM staging and metastatic potential of NSCLC. AFAP1-AS1 could activate interferon regulatory factor (IRF)7, the retinoid-inducible protein (RIG)-I-like receptor signaling pathway and Bcl-2 in vitro. Over-expression of AFAP1-AS1 promoted NSCLC cell proliferation, invasion and migration while inhibiting cell apoptosis. Conclusion: lncRNA AFAP1-AS1 promotes migration and invasion of non-small cell lung cancer via up-regulating IRF7 and the RIG-I-like receptor signaling pathway.

Background/Aims: Dysbiosis of the intestinal microbiota may accelerate the progression of chronic kidney disease (CKD) by increasing the levels of urea toxins. In recent years, probiotics have been recognized to maintain the physiological balance of the intestinal microbiota. In this study, we aim to assess the therapeutic effects of probiotics on CKD patients with and without dialysis via meta-analysis. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) by searching the databases of Pubmed, EMBASE and Cochrane Library (No. CRD42018093080). Studies on probiotics for treatment of CKD adults lasting for at least 4 weeks were selected. The primary outcomes were the levels of urea toxins, and the second outcomes were the levels of interleukin (IL)-6, C-reactive protein (CRP) and hemoglobin (Hb). The risk of bias was assessed by Cochrane Collaboration’ tool, and the quality of evidence was appraised with the Grading of Recommendation Assessment. Means and standard deviations were analyzed by random effects analysis. Stratified analysis was done and sensitivity analysis was performed when appropriate. Results: Totally, eight studies with 261 patients at CKD stage 3 to 5 with and without dialysis were included. We found a decrease of p-cresyl sulfate (PCS) of 3 studies with 125 subjects (P = 0.01, SMD -0.57, 95% CI, -0.99 to -0.14, I² = 25%) and an increase of IL-6 in 3 studies with 134 subjects (P = 0.03, 95% CI, SMD 0.37, 0.03 to 0.72, I² = 0%) in the probiotics groups. Analysis of serum creatinine (P = 0.47), blood urine nitrogen (P = 0.73), CRP (P = 0.55) and Hb (P = 0.49) yielded insignificant difference. Conclusion: Limited number of studies and small sample size are limitations of our study. Probiotics supplementation may reduce the levels of PCS and elevate the levels of IL-6 whereby protecting the intestinal epithelial barrier of patients with CKD.