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@#Ferroptosis is a newly discovered method of programmed cell death. Current studies have shown that activation of ferroptosis-related pathways can inhibit the growth and proliferation of tumor cells and reverse their drug resistance. Oral cancer is a common malignant tumor with a high recurrence rate and high drug resistance. Inducing ferroptosis is a potential treatment strategy. There are still many uncertainties in the application of ferroptosis in the treatment of oral cancer, which need to be further explored. This article systematically introduces the mechanism of ferroptosis and its recent progress in oral cancer treatment to provide new mechanisms and methods for the clinical treatment of oral cancer. Current research shows that the mechanism of ferroptosis is mainly related to amino acid metabolism, Fe2+ metabolism, and lipid metabolism. Ferroptosis in oral cancer cells can reverse drug resistance in cancer cells and improve the activity of immune cells. New drugs, such as curcumin analogs and triptolide, can induce ferroptosis in oral cancer, and the development of nanomaterials has improved the utilization rate of drugs. Inhibiting the expression of the ferroptosis-related factors SLC7A11, NF-E2-related factor 2 (Nrf2), and ferritin heavy chain 1 (FTH1) can promote ferroptosis in oral cancer cells. It is a potential target for the clinical treatment of oral cancer, but its translation into clinical practice still needs further research.
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Abstract This study aimed to investigate the cardioprotection of rosuvastatin pre-conditioning (R-Pre) in a rat model of myocardial ischemia / reperfusion (I/R). Male SD rats were assigned into three groups: sham group, I/R group and R-Pre group. Rats in I/R group and R-Pre group received ischemia for 30 min and reperfusion for 2 h. In R-Pre group, rats received intragastrical administration with rosuvastatin at 5 mg/kg once daily for 1 week. After 2-h reperfusion, the cardiac function was detected by ultrasonography; the blood was collected for biochemical analysis; the heart was collected for the TUNEL staining and immunohistochemistry for Bcl-2 and Bax. Our results showed rosuvastatin pre-conditioning for 1 week could significantly reduce the infarct ratio and improve the cardiac function after myocardial I/R injury, in which attenuation of oxidative stress and cell apoptosis played an important role. Our study provides evidence on the cardioprotection of rosuvastatin pre-conditioning and highlight the use of rosuvastatin before cardiopulmonary bypass.
Subject(s)
Animals , Rats , Myocardial Reperfusion , Ischemia/therapy , Cardiotonic Agents/administration & dosage , Apoptosis , Oxidative Stress , Models, Animal , Rosuvastatin Calcium/administration & dosageABSTRACT
@# Objective: To observe the expression of miR-488-5p in cervical cancer tissues and to explore its effect on the proliferation and migration of cervical cancer C33Acells. Methods: 12 pairs of cervical cancer tissues and corresponding paracancer tissues from patients, who underwent total hysterectomy at the Luoyang Central Hospital of Zhengzhou University from March 2017 to September 2017, were collected for this study; and the expression of miR-488-5p was detected by fluorescence quantitative and real-time polymerase chain reaction (qRT-PCR). Lipofectamine 3000 was used to transfect miR-488-5p (experiment group) and miR-NC (control group) into cervical cancer C33Acells. Cell cycle distribution was detected by Flow cytometry. Cell proliferation was assessed by CCK8 assay and Transwell assay was used to detect cell migration. Bioinformatics software was used to predict the possible target genes of miR-488-5p, and luciferase activity assay was used to verify the binding of miR-488-5p to target genes. The expressions of tumor endothelial marker 8 (TEM8) and downstream EGFR signaling pathway related proteins in two groups were detected by qRT-PCR and Western blotting. Results: The relative expression level of miR-488-5p in cervical cancer tissues (1.33±0.20) was significantly lower than that in paracancer tissues (3.68±0.45) (P<0.01). The relative expression level of miR-488-5p in the experimental group (25.23±3.11) was significantly higher than that in the control group (1.02±0.10) (P<0.01). The percentage of C33A cells at G0/G1 phase in experimental group (53.39±2.48)% was significantly higher than that in control group (39.57±1.21)% (P<0.01). When the culture time extended to 96 h and 120 h, the proliferation ability of C33Acells in experimental group was significantly lower than that in control group (P<0.05), and the number of migrated cells in the experimental group (117.90±18.86) was significantly less than that in the control group (295.10±19.33) (P <0.01). Luciferase activity assay confirmed that miR-488-5p could directly bind with TEM8 and inhibit its expression (P<0.01). The relative expression of TEM8 mRNAin experimental group (0.42±0.06) was significantly lower than that in control group (1.00 ± 0.06) (P<0.01).After transfection with miR-488-5p for 48h, the protein expressions of TEM8, p-EGFR, p-ERK and pAKT were significantly lower than those in control group (P <0.01). Conclusion: The expression of miR-488-5p in cervical cancer tissues was decreased. Over-expression of miR-488-5p could inhibit the cell cycle progression of cervical cancer cells and reduce the proliferation and migration of cervical cancer cells. The mechanism may be related to the interference of TEM8 gene expression.
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During the development of B and T lymphocytes, Ig and TCR variable region genes are assembled from germline V, D, and J gene segments by a site-specific recombination reaction known as V(D)J recombination. The process of somatic V(D)J recombination, mediated by the recombination-activating gene (RAG) products, is the most significant characteristic of adaptive immunity in jawed vertebrates. Flounder (Paralichthys olivaceus) RAG1 and RAG2 were isolated by Genome Walker and RT-PCR, and their expression patterns were analysed by RT-PCR and in situ hybridization on sections. RAG1 spans over 7.0 kb, containing 4 exons and 3 introns, and the full-length ORF is 3207 bp, encoding a peptide of 1068 amino acids. The first exon lies in the 5′-UTR, which is an alternative exon. RAG2 full-length ORF is 1062 bp, encodes a peptide of 533 amino acids, and lacks introns in the coding region. In 6-monthold flounders, the expression of RAG1 and RAG2 was essentially restricted to the pronephros (head kidney) and mesonephros (truck kidney). Additionally, both of them were mainly expressed in the thymus. These results revealed that the thymus and kidney most likely serve as the primary lymphoid tissues in the flounder.
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<p><b>OBJECTIVES</b>To compare the effects of losartan, enalapril and their combination in the prevention of left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in the rat.</p><p><b>METHODS</b>AMI model was induced in female SD rats by ligating left coronary artery. Forty-eight hours after the procedure, 83 surviving rats were randomized into one of the following 4 groups : 1) AMI control group (n = 19), 2) losartan group (n = 22, 3 mg x kg(-1) x d(-1)), 3) enalapril group (n = 20, 1 mg x kg(-1) x d(-1)), 4) losartan-enalapril combinative group (n = 22, 3 and 1 mg x kg(-1) x d(-1) respectively). 5) Sham-operated group (n = 10) and 6) normal rats group (n = 10) were selected randomly to serve as non-infarction controls. Losartan and enalapril were delivered by direct gastric gavage. After 4 weeks of medical therapy, hemodynamic studies were performed in each group, then the rat hearts were fixed with 10% formalin and pathologic analysis on them was performed. Complete experimental data was obtained in 56 rats, comprising 1) AMI controls (n = 11), 2) losartan group (n = 10), 3) enalapril group (n = 10), 4) the combination of losartan and enalapril group (n = 11), 5) sham-operated group (n = 6) and 6) normal controls (n = 8).</p><p><b>RESULTS</b>There were no significant differences among the 4 AMI groups in MI size (41.7% to approximately 43.4%, all P > 0.05). Compared with sham group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), long and short axis length (L and D), as well as LV absolute and relative weight (LVAW and LVRW) in AMI group were all significantly increased (P < 0.05 to approximately 0.001); whereas the maximum left ventricular pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were significantly reduced (all P < 0.001), indicating LVRM occurred and LV systolic and diastolic function impaired after AMI. Compared with AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased (P < 0.05 to approximately 0.001); while +/- dp/dt/LVSP were significantly enhanced in all 3 treatment groups (P < 0.05 to approximately 0.001) except -dp/dt/LVSP in losartan group (P > 0.05). There were no significant differences in the above indices among the 3 treatment groups (all P > 0.05).</p><p><b>CONCLUSION</b>Both losartan and enalapril can prevent from LVRM after AMI in the rat and improve LV function with equivalent effects. There seems no additive effect when the 2 drugs are used in combination.</p>