Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway.

Cardiovascular diseases remain the leading cause of death, morbidity, and disability. Recently, it has been reported that gonadal hormones such as estradiol can act on membrane receptors and activate intracellular signaling mechanisms, thereby altering cellular function. This study aims to explore the function and molecular mechanism of estradiol on cardiac microvascular endothelial cells (CMVECs). Estradiol had low toxicity to CMVECs. Hypoxia/reoxygenation (H/R) stimulation inhibited the proliferation and migration of CMVECs, while estradiol significantly promoted proliferation and migration. Estradiol inhibited il-1, IL6, and TNF-α secretion levels after H/R stimulation. Meanwhile, estradiol inhibits oxidative stress and promotes angiogenesis. Further, estradiol upregulated the gene and protein levels of cyclin-dependent kinases 1 (CDK1) and CDK2 after H/R stimulation. When knocking down CDK1 and CDK2 of CMVECs, estradiol did not affect the protein expression of Cyclin E1 and Cyclin D1. Meanwhile, the regulatory effect of estradiol on oxidative stress, angiogenesis, and inflammatory response was significantly weakened or even disappeared. In conclusion, estradiol mediates oxidative stress and angiogenesis of myocardial microvascular endothelial cells by regulating the CDK/cyclin signaling pathway.

Retrospective Study of Clinical Features of COVID-19 in Inpatients and Their Association with Disease Severity.

BACKGROUND The aim of this study was to analyze the clinical features and laboratory indices of patients with coronavirus disease (COVID-19) and explore their association with the severity of the disease. MATERIAL AND METHODS A total of 61 patients with COVID-19 were divided into groups with common symptoms and with severe diseases, and clinical data were collected to analyze and compare the differences between them. RESULTS In patients with severe COVID-19, compared with the common group, lymphocyte count and albumin levels were lower, and aspartate aminotransferase (AST), blood urea, blood creatinine, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels, and prothrombin time (PT) were elevated (all P<0.05). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume-to-lymphocyte ratio (MPVLR), and C-reactive protein-to-albumin ratio (CAR) were significantly elevated in the severe group compared with the group with common symptoms; however, the lymphocyte-to-monocyte ratio (LMR) was significantly reduced (P<0.05). Univariate logistic regression showed that lower lymphocyte count, prolonged PT, elevated CRP and LDH levels, and elevated NLR, PLR, MPVLR, and CAR were risk factors for COVID-19 severity (P<0.05). Multivariate logistic regression showed that elevated CRP levels (odds ratio [OR], 0.028; 95% confidence interval [CI]: 0.002-0.526; P=0.017), prolonged PT (OR, 0.014; 95% CI: 0.001-0.341; P=0.09), and an MPVLR >8.9 (OR, 0.026; 95% CI: 0.002-0.349; P=0.006) were independent risk factors for COVID-19 severity. CONCLUSIONS Elevated CRP and prolonged PT, and an MPVLR >8.9 were independent risk factors for COVID-19 severity.

Mercury ion-DNA specificity triggers a distinctive photoluminescence depression in organic semiconductor probes guided with a thymine-rich oligonucleotide sequence.

DNA strands have been recently found to play a role in crystallizing organic semiconductors as a substitute for conventional surfactants. Such DNA-guided organic semiconductor particles possessed the recognition ability to complementary target DNAs, resulting in "enhanced luminescence" due to the lesser degree of non-radiative dissipation. Apart from this, in this study we developed selective recognition of mercury ions by utilizing DNA probes having ion-specific thymine-rich motifs. Strikingly, the specific ion-DNA interaction triggered rather distinctive "depressed luminescence" emitting from the particles. The mercury ions were found to be present both at the surface and the inner regions, which were discovered to relate to the drastic morphological distortion of the particles as evidenced by elemental, electron microscopy, and confocal fluorescence microscopy analyses. This novel phenomenon discovered would expand the technological values of organic semiconductors conjugated with oligonucleotides toward a wider range of target-specific applications.

Efficacy and safety of triple therapy versus dual antiplatelet therapy in patients with atrial fibrillation undergoing coronary stenting: A meta-analysis.

BACKGROUND: The optimal antithrombotic therapy for atrial fibrillation (AF) patients undergoing coronary stenting is unknown. The present meta-analysis sought to investigate the efficacy and safety of triple therapy (TT; warfarin, clopidogrel and aspirin) vs dual antiplatelet therapy (DAPT; clopidogrel plus aspirin) in those patients. METHODS: PubMed and Cochrane Library were searched for studies enrolling AF patients undergoing coronary stenting on TT and DAPT up to September 2016, and fourteen studies were included. Efficacy outcomes included ischemic stroke, stent thrombosis, major adverse cardiovascular event (MACE), all-cause mortality and myocardial infarction (MI); safety outcome was major bleeding. We conducted meta-analysis and used odds ratio (OR) with 95% confidence intervals (CI) to compare TT and DAPT. Meta-regression, sensitivity and subgroup analysis were taken to investigate the source of heterogeneity in the outcome of major bleeding. RESULTS: 14 eligible observational studies with 11,697 subjects were identified. Compared with DAPT, TT had decreased the risk of ischemic stroke [OR = 0.74, 95% CI (0.59, 0.93), P = 0.009] and stent thrombosis [OR = 0.40, 95% CI (0.18, 0.93), P = 0.033]. While, there was an increased risk of major bleeding [OR = 1.55, 95% CI (1.16, 2.09), P = 0.004] associated with TT. The risk of MACE, all-cause mortality and MI had no significant statistical difference between TT and DAPT. Furthermore, the results of univariate and multivariate meta-regression analysis implicated that there were no obvious correlations between certain baseline characteristics (age, gender, race, hypertension, study design) and risk of major bleeding. Also of major bleeding, the findings of sensitivity analysis were generally robust, and a prespecified subgroup analysis of race demonstrated that the source of heterogeneity might attribute to Asian studies mostly. CONCLUSIONS: TT reduced the risk of ischemic stroke and stent thrombosis with an acceptable major bleeding risk compared with DAPT, and TT was considered as a valid alternative in AF patients undergoing coronary stenting. Further prospective randomized trials are needed to ensure the reliability of these data and find the optimal therapeutic strategy in this setting of patients.

Circulating tumor cells as a potential biomarker in diagnosis of lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Accumulating evidences demonstrated that circulating tumor cells (CTCs) show significant high concentration in plasma of lung cancer patients compared to control cohorts, suggesting that CTCs may be a promising biomarker for lung cancer. The meta-analysis was used to evaluate potential diagnostic value of CTCs in diagnosing lung cancer. METHODS: Relevant literatures were searched in PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang Data. Summary estimates were used to evaluate CTCs as the diagnostic standard for lung cancer using Meta-DiSc and STATA 12.0 statistical software. RESULTS: This meta-analysis included five studies with a total of 460 lung cancer patients and 239 benign controls. The sensitivity and specificity (95% confidence interval [CI]) of CTCs was 75% (95% CI: 54%-88%) and 92% (95%CI: 82%-97%), respectively. In addition, the area under the summary ROC curve (AUC) was 0.93. CONCLUSION: CTCs is a novel potential biomarker in the diagnosis of lung cancer, and more prospective are needed in the future.

[Construction of retroviral vector carrying Twist gene and its induction of epithelial-mesenchymal transition in human mammary epithelial cells].

OBJECTIVE: To construct a retroviral vector carrying Twist gene and investigate its effect on human mammary MCF10A epithelial cells. METHODS: Myc-Twist was digested from pcDNA3/myc-Twist and subcloned into the retroviral vector pBABE-puro to construct a recombinant plasmid (pBABE-myc-Twist). The inserted Twist gene was confirmed by restriction enzyme digestion and DNA sequencing. The plasmid pBABE-myc-Twist and the packaging plasmid pAmpho were co-transfected into HEK293T cells for packaging of retrovirus. Meanwhile, the control plasmid pBABE-puro and the packaging plasmid were co-transfected into the other HEK293T cells as a control group. Human mammary MCF10A epithelial cells were infected with the retroviruses carrying Twist gene or the controls, and selected by puromycin. The expression of Twist in the MCF10A-Twist and MCF10A-Vector cells was determined by RT-PCR and Western blotting. The expressions of epithelial-mesenchymal transition (EMT) marker proteins induced by Twist in MCF10A cells were detected using immunofluorescence cytochemistry and Western blotting. Cell migration and invasion abilities were analyzed by Transwell(R); assay. RESULTS: The myc-tagged Twist gene was correctly inserted into the retroviral expression vector as a recombinant plasmid (pBABE-myc-Twist) as identified by restriction analysis and DNA sequencing. The Twist gene was efficiently delivered into human mammary MCF10A epithelial cells by the retrovirus, resulting in the stable expression of Twist mRNA and myc-tagged Twist protein as shown by RT-PCR and Western blotting, respectively. The expression of the epithelial biomarker E-cadherin was downregulated whereas, the mesenchymal marker vimentin upregulated in MCF10A-Twist cells as shown by immunofluorescence cytochemistry and Western blotting. Cell migration and invasion abilities were enhanced notably in MCF10A-Twist cells as compared with MCF10A-Vector control cells (P<0.01). CONCLUSION: Twist induces EMT of MCF10A cells and plays an important role in the promotion of cell migration and invasion.