Sepsis-induced myocardial dysfunction (SIMD) is a fatal disease with no specific treatment worldwide to this day. As a biological product, platelet-rich plasma (PRP) has attracted much attention due to its diverse and potential biological effects. However, its role in lipopolysaccharide (LPS)-induced cardiac injury has not been fully investigated. This study aimed to explore the mechanism of PRP in SIMD. PRP (30 µL) was injectedin situinto the heart, and LPS (10 mg/kg) was injected intraperitoneally into mice. Neonatal rat cardiomyocytes were treated with LPS (1 μg/ml) for 24 h. The results showed that, compared with the LPS group, PRP significantly decreased the levels of Lactate dehydrogenase (LDH) and Creatine Kinase MB (CK-MB), and improved cardiac function. In addition, PRP markedly decreased the Malonic dialdehyde (MDA) content, and increased the Superoxide dismutase (SOD) activity and Glutathione (GSH) level, demonstrating that PRP alleviated LPS-induced oxidative stress. The Western blot and qPCR results showed that LPS-induced ferroptosis and inflammation effectsin vivoandin vitrowere ameliorated after PRP treatment. Moreover, PRP can alleviate erastin-induced ferroptosis and improve cell viability. Mechanistically, p-AKT and p-mTOR expressions were down-regulated after treatment with LPS, while PRP pretreatment could reverse this effect. In summary, our study demonstrated that PRP could play a unique role in reducing LPS-induced cardiac injury through regulation of AKT/mTOR signaling pathways. These findings provide a new therapeutic direction for treating SIMD.

To evaluate the relationship between red blood cell distribution width (RDW) and carotid intima-media thickness (CIMT) in metabolic syndrome (MetS) patients. In this study, we analyzed 803 patients with MetS who underwent carotid ultrasonography examination at Henan Province Hospital of Traditional Chinese Medicine from October 2014 to September 2015. Demographic data were collected using a questionnaire. An automatic biochemistry analyzer measured RDW. Pearson correlation coefficient, multivariate linear and logistic regression was used to evaluate the correlation between RDW and CIMT. Compared with control group, case group had higher RDW level (P < 0.001) and CIMT (P < 0.001). CIMT was positively related to RDW (r = 0.436, P < 0.001). Logistic regression indicated that RDW was a predictor of CIMT ≥ 1 mm. Compared with the first quartile, people with third and fourth quartile level gave obvious higher risk of carotid artery atherosclerotic trend (OR = 1.41, 95% CI:1.01–197; OR = 2.10, 95% CI: 1.30–3.40). Using a cutoff point of 13.9%, RDW predicts elevated CIMT with a sensitivity of 62.1% and a specificity of 70.3%. High RDW is related to the increased CIMT in MetS patients, which highlights the role of RDW in the progression of elevated CIMT in MetS patients.

Neutrophils are the most important component of the innate immune system. Mechanistic understanding of the mechanism underlying neutrophil differentiation remains elusive. Using genome-wide RNA-seq, we identified genes whose expression is dramatically up-regulated during neutrophil differentiation. Among them is nucleotide-binding leucine-rich repeat and pyrindomain-containing receptor 12 (NLRP12), which plays a role in immune inflammatory responses. Genetic ablation of NLRP12 suppresses NF-κB inducing kinase (NIK) stabilization, RelB nuclear translocation and neutrophil differentiation in vitro. At a mechanistic level, NLRP12 inhibits the activity of mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK1/2), relieves ERK1/2 suppression of NIK protein levels. Thus, NLRP12 enhances noncanonical NF-κB signaling through inhibition of ERK1/2 signaling, thereby promoting neutrophil differentiation.

The immune system plays a significant role in controlling systemic metabolism. Innate-like T (ILT) cells in particular, such as mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells and γδ T cell receptor expressing cells, have been reported to promote metabolic homeostasis. However, these different ILT cell subsets have, to date, been generally studied in isolation. Here we conducted a pilot study assessing the phenotype and function of circulating MAIT, iNKT, and Vδ2⁺ T cells in a small cohort of 10 people with obesity and type 2 diabetes (T2D), 10 people with obesity but no diabetes, and 12 healthy individuals. We conducted phenotypic analysis by flow cytometry ex vivo, and then functional analysis after in vitro stimulation using either PMA/ionomycin or synthetic agonists, or precursors thereof, for each of the cell-types; use of the latter may provide important knowledge for the development of novel therapeutics aimed at activating human ILT cells. The results of our pilot study, conducted on circulating cells, show clear dysfunction of all three ILT cell subsets in obese and obese T2D patients, as compared to healthy controls. Importantly, while both iNKT and Vδ2⁺ T cell dysfunctions were characterized by diminished IL-2 and interferon-γ production, the distinct dysfunctional state of MAIT cells was instead defined by skewed subset composition, heightened sensitivity to T cell receptor engagement and unchanged production of all measured cytokines.

We conducted comprehensive analyses to assess the diagnostic ability of miRNA-451 in cancers. A systematic online search was conducted in PubMed, Web of Science, China’s national knowledge infrastructure, and VIP databases from inception to July 31, 2017. The bivariate random effect model was used for calculating sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under cure (AUC). The whole pooled sensitivity and specificity were 0.85 (0.77–0.90) and 0.85 (0.78–0.90) with their 95% confidence interval (95%CI), respectively. The pooled AUC was 0.91 (95%CI: 0.89–0.94). Positive likelihood ratio was 5.57 (95%CI: 3.74–8.31), negative likelihood ratio was 0.18 (95%CI: 0.11–0.28), and diagnostic odds ratio was 31.33 (95%CI: 15.19–64.61). Among Asian population, the sensitivity and specificity were 0.85 (95%CI: 0.77–0.91) and 0.86 (95%CI: 0.78–0.91), respectively. The positive likelihood ratio and negative likelihood ratio were 5.87 (95%CI: 3.78–9.12) and 0.17 (95%CI: 0.11–0.28). The diagnostic odds ratio and AUC were 34.31 (15.51–75.91) and 0.92 (0.89–0.94). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and AUC for digestive system cancer were 0.83, 0.88, 6.87, 0.20, 35.13, and 0.92, respectively. The other cancers were 0.87, 0.81, 4.55, 0.16, 28.51, and 0.90, respectively. For sample source, the results still remain consistent. Our results indicated miRNA-451 has a moderate diagnostic ability for cancers, and could be a potential early screening biomarker, and considered as an adjuvant diagnostic index when being combined with other clinical examinations.