LncRNA DLEU1/microRNA-300/RAB22A axis regulates migration and invasion of breast cancer cells.

OBJECTIVE: To explore the possible role of deleted in lymphocytic leukemia 1 (DLEU1) in regulating the metastasis of breast cancer and its underlying mechanism. PATIENTS AND METHODS: The expression levels of DLEU1 in 60 cases of breast cancer tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Survival analysis and receiver operating characteristic (ROC) curves were introduced to analyze the correlation between DLEU1 expression and the clinical features of enrolled breast cancer patients. After altering expressions of DLEU1, RAB22A or microRNA-300 by plasmid transfection, the abilities of breast cancer cells to migrate and invade were evaluated by transwell assay. Western blot was conducted to detect protein level changes of epithelial-mesenchymal transition (EMT)-related genes regulated by DLEU1, RAB22A or microRNA-300. Dual-luciferase reporter gene assay was performed to detect the binding relation between microRNA-300 with DLEU1 and RAB22A. RESULTS: DLEU1 expression remains higher in breast cancer tissues than in normal adjacent tissues, and has a certain diagnostic value. The overall survival of breast cancer patients was negatively correlated with DLEU1 expression. Overexpression of DLEU1 or RAB22A, or microRNA-300 knockdown could enhance the migratory and invasive capacities, as well as increase EMT ofBT549 cells. On the contrary, knockdown of DLEU1 or RAB22A, or microRNA-300 overexpression in MCF-7 cells obtained the opposite trends of cellular behaviors. Dual-luciferase reporter gene assay confirmed that DLEU1 and RAB22A could bind to microRNA-300. Further verification showed that RAB22A expression was positively regulated by DLEU1, but negatively regulated by microRNA-300. Finally, we found that DLEU1 overexpression could reverse the inhibitory effects of microRNA-300 on proliferation, migration, and EMT of breast cancer cells. CONCLUSIONS: DLEU1 is highly expressed in breast cancer, which promotes migration, invasion, and EMT of breast cancer cells by targeting microRNA-300 to mediate RAB22A.

[Application research on carotid arterial shunting during simultaneous coronary artery bypass grafting and carotid endarterectomy].

Objective: The optimal operative strategy in patients with asymptomatic severe carotid artery stenosis undergoing coronary artery bypass grafting (CABG) is unknown. We sought to investigate the safety of carotid arterial shunting during simultaneous CABG and carotid endarterectomy (CEA). Methods: The clinical data of patients undergoing synchronous combined CEA and CABG in the First Hospital of China Medical University between March 2017 and July 2019 was retrospectively studied. Patients with asymptomatic severe carotid artery stenosis ≥70% according to NASCET (North American Symptomatic Carotid Endarterectomy Trial) were required CABG surgery. During conventional CEA, carotid arterial shunting was used in all cases. Results: Ten patients were recruited. The average clamping time of carotid artery was 5 minutes. The average follow-up time was 10 months. We did not observe stroke, cerebral hyper perfusion syndrome, death and carotid restenosis. Conclusions: Carotid arterial shunting during synchronous combined CEA and CABG was helpful for obtaining good curative effect.

Long noncoding RNA LINC00473 indicates a poor prognosis of breast cancer and accelerates tumor carcinogenesis by competing endogenous sponging miR-497.

OBJECTIVE: Long noncoding RNA LINC00473 (LINC00473) has been reported to be involved in the progression of several tumors. Our present study was conducted to study the potential roles and mechanism of long noncoding RNA LINC00473 (LINC00473) on cells proliferation, migration, invasion, and apoptosis of breast cancer (BC). PATIENTS AND METHODS: RT-PCR was applied for the analysis of LINC00473 in BC cell lines and tissues samples. The correlations between the LINC00473 levels and clinicopathological parameters were investigated. Kaplan-Meier methods and Cox proportional hazards regression models were explored to reveal potential associations of LINC00473 levels with overall survival of BC patients. The effect of LINC00473 on tumor behavior was evaluated by colony formation, Cell Counting Kit-8, EdU assays, flow-cytometric analysis, wound healing assays and transwell assays. Interactions between LINC00473 and miR-497 were determined using a luciferase reporter assay and RT-PCR assays. RESULTS: Upregulation of the expression of LINC00473 was found in BC samples and cell lines, in comparison with non-tumor breast tissues and human breast epithelial cells. High expression of LINC00473 was correlated with lymph node metastasis, clinical stage, and poorer outcome in BC patients. Multivariate logistic regression assays further showed LINC00473 as an independent prognostic factor in BC. Lost-of-function assays revealed that knockdown of LINC00473 resulted in the suppression of tumor cell proliferation, promotion of cells apoptosis, inhibition of cells metastasis. Bioinformatics analysis and luciferase reporter assays revealed LINC00473 bonds to miR-497. Further RT-PCR revealed that knockdown of LINC00473 suppressed the expressions of miR-497 in BC cells. CONCLUSIONS: Our data revealed that LINC00473 acted as a tumor promoter in BC and LINC00473/miR-497 axis may be a novel therapeutic strategy for this tumor.

Increased expression of miR-1179 inhibits breast cancer cell metastasis by modulating Notch signaling pathway and correlates with favorable prognosis.

OBJECTIVE: MicroRNAs (miRNAs) play a key role in the regulation of gene expression. In this study, we aimed to identify the clinical values of miR-1179 and to investigate the potential molecular mechanisms in breast cancer (BC). MATERIALS AND METHODS: RT-PCR was used to detect the expression levels of miR-1179 in both BC tissues and cell lines. We analyzed the association between the miR-1179 levels and clinicopathological factors and patient prognosis. The proliferation ability of miR-1179 on BC cells was assessed by MTT and colony formation assay. The role of miR-1179 in BC cells migration and invasion was measured by transwell assays. Western blot analysis was used to quantify the expression of the molecular biomarkers of the Notch signaling pathway. RESULTS: Our results showed that miR-1179 expression was frequently downregulated in BC tissues and cell lines. Clinicopathologic analysis revealed that low miR-1179 expression is correlated with lymph node metastasis, advanced clinical stage and shorter overall survival. Multivariable Cox proportional hazards regression analysis suggested that increased miR-1179 expression was an independent prognostic factor of overall survival in BC patients. Gain-of-function assay indicated that the overexpression of miR-1179 significantly suppressed BC cells proliferation, migration and invasion. Mechanistically, miR-1179 up-regulation inhibited the expression of Notch 1, Notch 4 and Hes1, indicating that miR-1179 could suppress the activation of the Notch signaling pathway. CONCLUSIONS: We showed that miR-1179 was a tumor suppressor that may serve as a novel potential prognostic biomarker or molecular therapeutic target for BC.

miRNA-223 suppresses FOXO1 and functions as a potential tumor marker in breast cancer.

Breast cancer is the most commonly diagnosed cancer in women and a leading cause of cancer mortality. MicroRNAs (miRNAs) have been found to play a key role in proliferation, metastasis and invasion of cancer. In previous study, we found that miRNA-223 was significant expression inexosome derived from peripheral blood serum of breast cancer patients than in samples from control subjects, Therefor,the role ofmiRNA-223willbe researched in MCF-7 breast cancer cells.In this study, to explore the role of miRNA-223in influencing cell proliferation, metastasis and invasion of breast cancer, TargetScan tools (http://www.targetscan.org/vert_71/) was used to scan target genes of miRNA-223, and thenmiRNA expression, real time PCR, Western blotting andluciferase report assay were used to test regulates relationship of miRNA-223and its targets,cell viability and BrdU analysiswere used to test cell proliferation of MCF-7 breast cancer cells after expression miRNA-223inhibitor. Scanning targets of miRNA-223found FOXO1 was listed in targets content, and luciferase reporter assay was used to assess and confirm the binding sequence of 3'untranslated region between FOXO1 and miRNA-223. Results showedthat miRNA-223inhibitorexpression increased protein expression level of FOXO1 in MCF-7 breast cancer cells,meanwhile, cell viability and BrdU analysis showed MCF-7 breast cancer cells were suppressed proliferation after up-regulation of FOXO1.In conclusion, we demonstrated that the miRNA-223can maintain cell proliferation of breast cancer cell through targeting FOXO 1, these results provide a new insight in tumor marker and potential therapeutic targets for breast cancer.

Theophylline: a review of population pharmacokinetic analyses.

WHAT IS KNOWN AND OBJECTIVE: Numerous population pharmacokinetic studies of theophylline have been conducted in paediatric and adult patients. The purpose of this review was to summarize the published studies concerning population pharmacokinetics of theophylline in patients of different ages and discuss factors that might cause the large variability in the pharmacokinetics of theophylline. METHODS: A literature search was conducted in PubMed using the following keywords: 'theophylline', 'population pharmacokinetic(s)' and 'nonlinear mixed effect model'. Additionally, the relevant references listed in the retrieved articles were manually reviewed. All of the studies that reported the population pharmacokinetics of theophylline in humans were included in this review. However, articles were excluded if they were not written in English. RESULTS AND DISCUSSION: Sixteen articles were included in this review. Among them, 11 were conducted on paediatric patients, and five were conducted on adults. A one-compartment model with first-order elimination was employed in most of the included articles. A nonlinear mixed effect modelling approach (NONMEM) was the most commonly used software to develop a population pharmacokinetic model. Body weight and age (post-conceptional age and post-natal age) were the most important factors associated with the clearance (CL) of theophylline in paediatric patients. Body weight (ideal body weight and lean body mass), age and smoking status were most frequently used to estimate the CL of theophylline in adults. The median (range) estimate values of CL for paediatric and adult patients were 0·062 (0·0056-0·0949) L/h/kg and 0·053 (0·0493-0·0517) L/h/kg, respectively. The median values of the interindividual variability of CL were 33·5% in adults and 25·8% in paediatric patients. The mean values of the residual variability were 21% in paediatric patients and 14·3% in adults. WHAT IS NEW AND CONCLUSION: This review concludes that body weight and age were the most important factors associated with the clearance of theophylline in paediatric patients. Body weight, age and smoking were most frequently used to estimate the clearance of theophylline in adults. Future studies are warranted to detect the influence of new factors, such as cytochrome P450 (CYP) 1A2 gene polymorphisms, on the pharmacokinetics of theophylline because some pharmacokinetic variability was not fully explained.

In situ TEM observation of buffering the anode volume change by using NiTi alloy during electrochemical lithiation/delithiation.

A novel Ti3Sn/NiTi shape memory alloy anode with a sandwich structure was fabricated by arc melting. In order to characterize in situ the Ti3Sn/NiTi anode microstructure changes and phase transformations during cycling, a nanoscale lithium battery was set up inside a transmission electron microscope, which consists of Li metal as the cathode, the native Li2O layer on the surface of Li metal as the solid electrolyte, and the Ti3Sn/NiTi as the anode. Only the Ti3Sn intermetallic compound experienced the electrochemical reaction, while the NiTi alloy (inactive with Li(+)) was applied for buffering the Ti3Sn volume change during cycling. An obvious reaction front of Ti3Sn migrated from one end to the other during lithiation, which can also return after delithiation. It provides direct evidence that the NiTi alloy can effectively accommodate the anode volume change during electrochemical lithiation and delithiation.

[Clinical features of acute myocardial infarction in the young and middle-aged patients: analysis of 68 cases of coronary artery angiography].

OBJECTIVE: This study was to evaluate the clinical features of acute myocardial infarction (AMI) in young and middle-aged patients. METHODS: Eighty-seven patients were classified into two groups according to the age. Among them, 61 patients were 60 years old and above, 26 patients below 50 year old. Selective coronary artery angiography was performed on 68 cases and a scoring method which reflects the extent of narrowing of coronary artery was also used. RESULTS: The older group had more risk factors than the young group. The angina pectoris in the young group was less than the older group. The incidence of acute heart failure in the young group was higher than the older group. The mortality of both two groups had no significant differences. CONCLUSION: The high risk of AMI in the young and middle-aged patients should be paid more attention in the clinic.

[Effect of low molecular weight heparin on unstable angina].

OBJECTIVE: To evaluate the effect of low molecular weight heparin (LMWH) and verus urokinase (UK) on unstable angina (UA). METHODS: Sixty seven patients with UA were divided in two groups by a single blind, controlled, randomized method: LMWH (anti-thrombi) group and UK (thromblytic therapy) group. Total ischemia load in 24 hours ambulatory ECG, mortality and cases of acute myocardial infarction (AMI) in 30 days were employed to compare the effect and safety between two groups. RESULTS: There was no significant difference in decreasing attacks of angina pectoris and total ischemia load between two groups. The UK group had two cases of AMI and five cases of complications of bleeding (two cases of epistaxis, two cases of bleeding gums, one case of hematochezia). CONCLUSION: Antithrombin therapy is prior to thromblitic therapy, treatment of LMWH is safer than that of low dose UK in UA.

[Studies on the chemical constituents of Curcuma kwangsiensis].

A new sesquiterpene lactone named gweicurculactone, along with beta-sitosterol, germacrone, daucosterin and palmitic acid, was isolated from Curcuma kwangsiensis. Its structure has been confirmed by means of spectral and X-ray diffraction analysis.