[Effect of Staphylococcal Nuclease and Tudor Domain Containing 1/SLC7A11 on the Occurrence and Development of Osteosarcoma by Inhibiting Ferroptosis].

Objective To investigate the effect of staphylococcal nuclease and tudor domain containing 1(SND1) on the biological function of osteosarcoma cells and decipher the mechanism of SND1 in regulating ferroptosis in osteosarcoma cells via SLC7A11. Methods Human osteoblasts hFOB1.19 and osteosarcoma cell lines Saos-2,U2OS,HOS,and 143B were cultured,in which the expression level of SND1 was determined.Small interfering RNA was employed to knock down the expression of SND1(si-SND1) in the osteosarcoma cell line HOS and 143B.The CCK8 assay kit,colony formation assay,and Transwell assay were employed to examine the effect of SND1 expression on the biological function of osteosarcoma cells.Furthermore,we altered the expression of SND1 and SLC7A11 in osteosarcoma cells to investigate the effect of SND1 on osteosarcoma ferroptosis via SLC7A11. Results The mRNA and protein levels of SND1 in Saos-2,U2OS,HOS,and 143B cells were higher than those in hFOB1.19 cells(all P<0.01).Compared with the control group,transfection with si-SND1 down-regulated the expression level of SND1 in HOS and 143B cells(all P<0.01),decreased the viability of HOS and 143B cells,reduced the number of colony formation,and inhibited cell invasion and migration(all P<0.001).The ferroptosis inducer Erastin promoted the apoptosis of HOS and 143B cells,while the ferroptosis inhibitor Ferrostatin-1 improved the viability of HOS and 143B cells(all P<0.001).After SND-1 knockdown,Erastin reduced the viability of HOS and 143B cells,while Ferrostatin-1 restored the cell viability(all P<0.001).After treatment with Erastin in the si-SND1 group,the levels of iron and malondialdehyde were elevated,and the level of glutathione was lowered(all P<0.001).The results of in vivo experiments showed that SND1 knockdown inhibited the mass of the transplanted tumor in 143B tumor-bearing nude mice(P<0.001).Knocking down the expression of SND1 resulted in down-regulated SLC7A11 expression(all P<0.001) and increased ferroptosis in HOS and 143B cells(P<0.001,P=0.020). Conclusions SND1 presents up-regulated expression in osteosarcoma cells.It may inhibit ferroptosis by up-regulating the expression of SLC7A11,thereby improving the viability of osteosarcoma cells.

Single-cell RNA sequencing reveals distinct gene expression patterns in glucose metabolism of human preimplantation embryos.

Precise regulation of glucose metabolism-related genes is essential for early embryonic development. Although previous research has yielded detailed information on the biochemical processes, little is yet known of the dynamic gene expression profiles in glucose metabolism of preimplantation embryos at a single-cell resolution. In the present study, we performed integrated analysis of single-cell RNA sequencing (scRNA-seq) data of human preimplantation embryos that had been cultured in sequential medium. Different cells in the same embryo have similar gene expression patterns in glucose metabolism. During the switch from the cleavage to morula stage, the expression of glycolysis-related genes, such as glucose transporter genes (solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) and solute carrier family 2 (facilitated glucose transporter), member 3 (SLC2A3) and genes encoding hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase, is increased. The genes involved in the pentose phosphate pathway are highly expressed at the cleavage stage, generating the reducing power to balance oxidative stress derived from biosynthesis. Expression of the genes involved in the biosynthesis of glycerophospholipids is increased after the morula stage. Nevertheless, the expression of tricarboxylic acid-related genes remains relatively unchanged during the preimplantation stages. In conclusion, we discovered that the gene expression profiles are dynamic according to glucose utilisation in the embryos at different stages, which contributes to our understanding of regulatory mechanisms of glucose metabolism-related genes in human preimplantation embryos.

Transcriptomic and proteomic profiling of the anterior cingulate cortex in neuropathic pain model rats.

Background: Neuropathic pain (NP) takes a heavy toll on individual life quality, yet gaps in its molecular characterization persist and effective therapy is lacking. This study aimed to provide comprehensive knowledge by combining transcriptomic and proteomic data of molecular correlates of NP in the anterior cingulate cortex (ACC), a cortical hub responsible for affective pain processing. Methods: The NP model was established by spared nerve injury (SNI) in Sprague-Dawley rats. RNA sequencing and proteomic data from the ACC tissue isolated from sham and SNI rats 2 weeks after surgery were integrated to compare their gene and protein expression profiles. Bioinformatic analyses were performed to figure out the functions and signaling pathways of the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) enriched in. Results: Transcriptomic analysis identified a total of 788 DEGs (with 49 genes upregulated) after SNI surgery, while proteomic analysis found 222 DEPs (with 89 proteins upregulated). While Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the DEGs suggested that most of the altered genes were involved in synaptic transmission and plasticity, bioinformatics analysis of the DEPs revealed novel critical pathways associated with autophagy, mitophagy, and peroxisome. Notably, we noticed functionally important NP-related changes in the protein that occurred in the absence of corresponding changes at the level of transcription. Venn diagram analysis of the transcriptomic and proteomic data identified 10 overlapping targets, among which only three genes (XK-related protein 4, NIPA-like domain-containing 3, and homeodomain-interacting protein kinase 3) showed concordance in the directions of change and strong correlations between mRNA and protein levels. Conclusion: The present study identified novel pathways in the ACC in addition to confirming previously reported mechanisms for NP etiology, and provided novel mechanistic insights for future research on NP treatment. These findings also imply that mRNA profiling alone fails to provide a complete landscape of molecular pain in the ACC. Therefore, explorations of changes at the level of protein are necessary to understand NP processes that are not transcriptionally modulated.

LncRNA A2M-AS1 lessens the injury of cardiomyocytes caused by hypoxia and reoxygenation via regulating IL1R2.

BACKGROUND: Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear. OBJECTIVE: To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism. METHODS: Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Human neonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively. RESULTS: The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1. CONCLUSION: This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.

Clinical efficacy of ticagrelor in patients undergoing emergency intervention for acute myocardial infarction and its impact on platelet aggregation rate.

OBJECTIVE: This study aims to investigate the clinical efficacy of ticagrelor in patients who underwent emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and its impact on platelet aggregation rate. METHODS: A total of 257 AMI patients who underwent emergency PCI in our hospital were included in the present study. These patients were randomly divided into two groups: ticagrelor group (n = 129), patients took 180 mg of ticagrelor (qd) before the intervention, and subsequently took 90 mg of ticagrelor (bid) for maintenance; clopidogrel group (n = 128), patients took 300 mg of clopidogrel (qd) before PCI, and subsequently took 75 mg of clopidogrel (qd) for maintenance. Patients in both groups took 100 mg of aspirin. The major adverse cardiovascular events (MACE) within one year, changes in LVEF and LVEDD, platelet aggregation rate and drug safety before PCI and at one week and 30 days after PCI were observed in these two groups. RESULTS: The differences in baseline data between these two groups were not statistically significant. Within one year after the intervention, in the ticagrelor group, the total incidence of MACE was lower (P < 0.05), LVEF and LVEDD was improved (P < 0.05), and the decrease in platelet aggregation rate after the intervention was more significant (P < 0.05). Furthermore, the incidence of bleeding events was higher in the ticagrelor group than in the clopidogrel group (P < 0.05). CONCLUSIONS: Compared with clopidogrel, ticagrelor decreases the incidence of adverse cardiovascular events in AMI patients who underwent emergency PCI, does better in improving the fluctuation level of LVEF and LVEDD, and strongly inhibits platelet aggregation. Some patients encountered adverse drug events, but drug withdrawal or medication change did not occur.

[Health risk assessment of soil heavy metals in residential communities built on brownfields].

Nine residential communities which were built on different brownfields in a city of Henan Province were chosen to investigate the health risks of heavy metals (As, Hg, Cd, and Pb) in surface soils. Concentrations of soil heavy metals were measured according to the methods described in the national standard. Based on the health risk models recommended by the U. S. Environmental Protection Agency (US EPA), non-carcinogenic and carcinogenic health risks of soil heavy metals were assessed. The results showed that compared with the original brownfields, the heavy metal concentrations in soils and their health risks in residential communities built on brownfields were significantly improved, and the concentrations and health risks of soil heavy metals in these communities were all higher than those in non-brownfield residential communities. The HQ and HI values of soil heavy metals in all the residential communities were lower than 1, which indicated that there was no non-carcinogenic risk in these communities. Meanwhile, the values of CR and TCR were slightly higher than the standard suggested by the US EPA, indicating that slight carcinogenic risks in the communities, but these values were lower than the lenient standard proposed by some experts. The HI value of the four metals for children was exactly seven times higher than that for adults. The contribution rate of HQ(As) to HI was about 75%, CR(AS) to TCR was about 80%, and therefore arsenic was the crucial factor for carcinogenic and non-carcinogenic risk in the residential communities of the city.