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BACKGROUND: Through experimental research on the biological function of GATA6-AS1, it was confirmed that GATA6-AS1 can inhibit the proliferation, invasion, and migration of gastric cancer cells, suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer. Further experiments confirmed that the overexpression of fat mass and obesity-associated protein (FTO) inhibited the expression of GATA6-AS1, thereby promoting the occurrence and development of gastric cancer. AIM: To investigate the effects of GATA6-AS1 on the proliferation, invasion and migration of gastric cancer cells and its mechanism of action. METHODS: We used bioinformatics methods to analyze the Cancer Genome Atlas (https://portal.gdc.cancer.gov/. The Cancer Genome Atlas) and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue. We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation, migration and invasion, and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer. Next, we used a database (http://starbase.sysu.edu.cn/starbase2/) to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1. Furthermore, RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme. These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer. RESULTS: Low expression levels of GATA6-AS1 were detected in gastric cancer. We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells. GATA6-AS1 had strong binding ability with the m6A demethylase FTO, which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1. Following transfection with siRNA to knock down the expression of FTO, the expression levels of GATA6-AS1 were up-regulated. Finally, the proliferation, migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression. CONCLUSION: During the occurrence and development of gastric cancer, the overexpression of FTO may inhibit the expression of GATA6-AS1, thus promoting the proliferation and metastasis of gastric cancer.
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Background: Transforaminal endoscopic lumbar discectomy (TELD) has been widely used for lumbar disc herniation. However, in some challenging cases such as very highly migrated disc herniation (VHMDH), traditional TELD is difficult to access the pathology. Methods: From January 2016 to December 2019, 63 patients with single-level VHMDH underwent TELD using targeted puncture and foraminotomy techniques were included. All patients were followed up for 26.5 months on average (range, 24-48 months). Operative time, length of hospital stay, visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab criteria and surgical complications were evaluated. Results: The operative time was 40-120 min (56.8 on average). The length of hospitalization was 2.5 days (range, 2-4 d). VAS score decreased significantly from 5.5 ± 1.3 preoperatively to 1.9 ± 1.30 (p < 0.001) 1 day postoperatively, and to 0.9 ± 0.8 (p < 0.001) at the final follow-up. ODI score improved significantly from 23.5 ± 3.2 preoperatively to 13.4 ± 3.0 (p < 0.001) 1 day postoperatively; and 3.1 ± 1.2 (p < 0.001) at the final follow-up. According to the modified MacNab criteria, 40 patients (63.5%) showed excellent results, 20 patients (31.7%) were rated as good, 2 patients (3.2%) were rated as fine, and 1 patient (1.6%) was rated as bad at the final follow-up. No residual fragments, nerve root or cauda equina injury was shown in this series. One recurrent case was resolved by open surgery. Conclusions: With modified targeted puncture and foraminotomy techniques, VHMDH can be accessed safely and effectively, and satisfactory clinical outcomes can be obtained for these patients.
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Background: The clinical benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for preventing and treating cardiovascular events remains controversial. We aimed to study the effect of SGLT2 inhibitors on cardiovascular outcomes and safety events, giving particular attention to the benefits in subgroups of patients with different diseases. Method: Randomized controlled trials (RCTs) reporting cardiovascular outcomes following the administration of SGLT2 inhibitors and placebo were included in this study. Cardiovascular outcomes included all-cause death, major adverse cardiovascular events (MACEs), cardiovascular (CV) death, myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF). We also focused on the cardiovascular benefits of SGLT2 inhibitor application in subgroups of patients with different diseases, including type 2 diabetes (T2D), heart failure (HF), high risk of atherosclerotic cardiovascular disease (ACD), diagnosed ACD, and chronic kidney disease (CKD). Safety events associated with SGLT2 inhibitors, including acute kidney injury (AKI), diabetic ketoacidosis (DKA), hypoglycemia, urinary tract infection, thromboembolic event, bone fracture, volume depletion, and amputation, were also reported. Results: This meta-analysis included 15 RCTs with 78,212 participants. SGLT2 inhibitors reduced the risk of all-cause death (RR 0.89; 95% CI: 0.85-0.94; I2 = 32%; p < 0.01), CV death (RR 0.87; 95% CI: 0.82-0.93; I2 = 11%; p < 0.01), MACEs (RR 0.89; 95% CI: 0.84-0.94; I2 = 46%; p < 0.01), HHF (RR 0.70; 95% CI: 0.66-0.74; I2 = 0%; p < 0.01), and AKI (RR 0.81; 95% CI: 0.73-0.90; I2 = 0%; p < 0.01) but increased the risk of DKA (RR 2.56; 95% CI: 1.72-3.80; I2 = 0%; p < 0.01). However, no apparent benefit in MI and stroke was observed between the SGLT2 inhibitor and control groups. SGLT2 inhibitors reduced the risk of all-cause death, MACEs, CV death, and HHF in diabetic patients; reduced the risk of all-cause death, MACEs, CV death, MI, and HHF in primary prevention; reduced the risk of all-cause death, CV death, and HHF in patients with ACD and HF; and reduced the risk of MACEs, CV death, and HHF in patients with CKD. Conclusion: SGLT2 inhibitors have a positive effect in reducing the risk of all-cause death, CV death, MACE, HHF, and AKI and increasing the risk of DKA. The application of SGLT2 inhibitors in the primary prevention of ACD also has certain clinical benefits in reducing MI. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022306490].
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An iron-catalyzed asymmetric intramolecular cyclopropanation was realized in high yields and excellent enantioselectivity (up to 97%â ee) by using the iron complexes of chiral spiro-bisoxazoline ligands as catalysts. The superiority of iron catalysts exhibited in this reaction demonstrated the potential abilities of this sustainable metal in asymmetric carbenoid transformation reactions.
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Endoglin (CD105, END) is upregulated in proliferating endothelial cells, suggesting potential therapeutic properties. However, it is not clear whether endoglin mediates an enhanced proliferative rate or may be upregulated as part of a negative feedback loop. To gain insights into context-dependent and cell type-dependent regulatory effects of endoglin, we studied its role properties in human ovarian carcinoma-derived endothelial cells (ODMECs). We isolated and cultured primary ODMECs from epithelial ovarian carcinoma tissue. ODMECs had higher expression of endoglin and VEGFR-2, and also exhibited enhanced spontaneous formation of vessel-like structures in vitro. Transfection of siRNA targeting endoglin in ODMECs cells resulted in the reduction of the proliferation and tube formation. These results indicate that a subset of ODMECs display abnormal angiogenic properties and this phenotype was blocked by decreasing endoglin levels, suggesting endoglin is essential for stimulating angiogenesis, and targeting it may be an attractive approach to anti-angiogenesis therapy for ovarian carcinoma.
