M2 Microglia-Derived Exosomes Protect Against Glutamate-Induced HT22 Cell Injury via Exosomal miR-124-3p.

As one of the most serious complications of sepsis, sepsis-associated encephalopathy has not been effectively treated or prevented. Exosomes, as a new therapeutic method, play a protective role in neurodegenerative diseases, stroke and traumatic brain injury in recent years. The purpose of this study was to investigate the role of exosomes in glutamate (Glu)-induced neuronal injury, and to explore its mechanism, providing new ideas for the treatment of sepsis-associated encephalopathy. The neuron damage model induced by Glu was established, and its metabolomics was analyzed and identified. BV2 cells were induced to differentiate into M1 and M2 subtypes. After the exosomes from both M1-BV2 cells and M2-BV2 cells were collected, exosome morphological identification was performed by transmission electron microscopy and exosome-specific markers were also detected. These exosomes were then cocultured with HT22 cells. CCK-8 method and LDH kit were used to detect cell viability and toxicity. Cell apoptosis, mitochondrial membrane potential and ROS content were respectively detected by flow cytometry, JC-1 assay and DCFH-DA assay. MiR-124-3p expression level was detected by qRT-PCR and Western blot. Bioinformatics analysis and luciferase reporter assay predicted and verified the relationship between miR-124-3p and ROCK1 or ROCK2. Through metabolomics, 81 different metabolites were found, including fructose, GABA, 2, 4-diaminobutyric acid, etc. The enrichment analysis of differential metabolites showed that they were mainly enriched in glutathione metabolism, glycine and serine metabolism, and urea cycle. M2 microglia-derived exosomes could reduce the apoptosis, decrease the accumulation of ROS, restore the mitochondrial membrane potential and the anti-oxidative stress ability in HT22 cells induced by Glu. It was also found that the protective effect of miR-124-3p mimic on neurons was comparable to that of M2-EXOs. Additionally, M2-EXOs might carry miR-124-3p to target ROCK1 and ROCK2 in neurons, affecting ROCK/PTEN/AKT/mTOR signaling pathway, and then reducing Glu-induced neuronal apoptosis. M2 microglia-derived exosomes may protect HT22 cells against Glu-induced injury by transferring miR-124-3p into HT22 cells, with ROCK being a target gene for miR-124-3p.

[Research progress of exosomes in the diagnosis and treatment of sepsis].

Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.

Circ_0110251 overexpression alleviates IL-1ß-induced chondrocyte apoptosis and extracellular matrix degradation by regulating miR-3189-3p/SPRY1 axis in osteoarthritis.

BACKGROUND: Mounting evidence indicates that circular RNAs (circRNAs) are involved in the progression of human diseases, including osteoarthritis (OA). In this study, we focussed on the functions and potential mechanism of circ_0110251 in OA. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circ_0110251, collagen type XI alpha 1 chain (COL11A1), microRNA-3189-3p (miR-3189-3p) and sprouty receptor tyrosine kinase signalling antagonist 1 (SPRY1). The cyclisation analysis of circ_0110251 was analysed by RNase R and Actinomycin D assays. Flow cytometry analysis was conducted to analyse cell apoptosis. Western blot assay was used to measure the levels of extracellular matrix degradation (ECM)-associated markers and SPRY1. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were performed to analyse the relationships among circ_0110251, miR-3189-3p and SPRY1. RESULTS: Circ_0110251 was downregulated in OA cartilage tissues and IL-1ß-induced chondrocytes. IL-1ß promoted the apoptosis and ECM degradation in chondrocytes, while circ_0110251 overexpression relieved the effects. Circ_0110251 functioned as the sponge for miR-3189-3p and miR-3189-3p overexpression reversed the effect of circ_0110251 on IL-1ß-induced chondrocyte damage. Additionally, SPRY1 served as the target gene of miR-3189-3p. MiR-3189-3p inhibition ameliorated IL-1ß-induced chondrocyte apoptosis and ECM degradation, while SPRY1 silencing rescued the impacts. CONCLUSION: Circ_0110251 protected chondrocytes from IL-1ß-induced apoptosis and ECM degradation in OA via sponging miR-3189-3p and elevating SPRY1.

Meta-Analysis Treatment Hyperphosphatemia Chronic Renal Failure Based on Nano Lanthanum Hydroxide.

In this study, our aim is to investigate the effect of lanthanum carbonate in chronic treatment renal failure complicated with hyperphosphatemia. Using methods with lanthanum carbonate, hyperphosphatemia, placebos, calcium carbonate, end-stage renal disease as keywords, we searched the Chinese Journal Full-text Database, Chinese sci-tech journal database, Wanfang Data knowledge service platform, web of science, PubMed, and other databases for literature quality; meta analysis was carried out after a subsequent evaluation. The meta analysis results showed a significant difference in the control of the blood phosphorus level between weighted mean difference WMD = -0.60, 95% CI: -0.75~-0.45, lanthanum carbonate and placebo; WMD = -0.01, 95% CI: -0.07~-0.05; the lanthanum carbonate and placebo had no significant difference in the control of the blood calcium levels after treatment; WMD = -29.75, 95% CI: -39.22 for the control of blood PIH level after treatment, indicating that the difference between lanthanum carbonate and placebo in the control of the parathyroid hormone (PTH) level was statistically significant. WMD=0.41, 95% CI: -0.48~0.34; the difference between the lanthanum carbonate and calcium carbonate in the control of the blood phosphorus level was statistically significant; WMD = 0.19, 95% CI: -0.25~0.13, lanthanum carbonate and calcium carbonate were statistically significant in blood control calcium level; WMD = 174.66, 95% CI: -150.86~150.46, lanthanum carbonate and calcium carbonate were statistically significant in the control of blood PIH level; the difference was statistically significant. Conclusion: Lanthanum carbonate can significantly reduce blood phosphorus and PIH complicated hyperphosphatemia, and has no significant effect on blood calcium, which is superior to calcium carbonate in effectiveness.