Improved hemocompatibility by modifying acellular blood vessels with bivalirudin and its biocompatibility evaluation.

The incidence rate of cardiovascular diseases is increasing year by year. The demand for coronary artery bypass grafting has been very large. Acellular blood vessels have potential clinical application because of their natural vascular basis, but their biocompatibility and anticoagulant energy need to be improved. We decellularized the abdominal aorta of SD rats, and then modified with bivalirudin via polydopamine. The mechanical properties, blood compatibility, cytocompatibility, immune response, and anticoagulant properties were evaluated, and then the bivalirudin-modified acellular blood vessels were implanted into rats for remodeling evaluation in vivo. The results we got show that the bivalirudin-modified acellular blood vessels showed good cytocompatibility and blood compatibility, and its anti-inflammatory trend was dominant in the immune response. After 3 months of transplantation, the bivalirudin-modified acellular blood vessels did not easily form thrombus. It was not easy to form calcification and could make the host cells grow better. Through vascular stimulation and immunofluorescence test, we found that vascular smooth muscle cells and endothelial cells proliferated well in the bivalirudin group. Bivalirudin-modified acellular blood vessels provided new idea for small diameter tissue engineering blood vessels, and may become a potential clinical substitute for small-diameter vascular grafts.

The Effect of Atrial Septal Defect in the Treatment of ARDS with Left Ventricular Dysfunction Simulating Severe COVID-19.

OBJECTIVE: To explore the effect of atrial septal defect (ASD) and venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the treatment of ARDS combined with left ventricular dysfunction (LVD) to find a new effective method for treating severe COVID-19 patients. MATERIALS AND METHODS: Five large animal ARDS models of sheep were established by intravenous injection of Lipopolysaccharide. ASD was made under general anesthesia and VA-ECMO was simulated by extracorporeal circulation machine. The oxygenation of peripheral blood, systemic circulation, and cardiac function were observed under conditions of closed and opened ASD, and the significance of ASD shunt in improving cardiopulmonary function was evaluated. RESULTS: With ASD closed, the atrial shunts disappeared, the peripheral artery pressure of oxygen(PaO2): 141.2±21.4mmHg, the oxygenation index (PaO2/FiO2): 353.0±53.5, the mean blood pressure (MAP): 49.3±13.5 mmHg, the heart was full; with ASD opened, the left-to-right shunt was observed, PaO2: 169.3±18.9mmHg, PaO2/FiO2: 423.3±47.3, MAP: 68.2±16.1 mmHg, the range of cardiac motion significantly increased, heart beat was powerful, and systemic circulation significantly improved. Statistical analysis showed that there were significant differences between opened and closed ASD (P < .01). CONCLUSION: ASD plus VA-ECMO is an effective method for the treatment of ARDS combined with LVD, which is the main cause of death in severe COVID-19 patients. However, further clinical validation is needed.

MiR-433-3p Inhibits Proliferation and Invasion of Esophageal Squamous Cell Carcinoma by Targeting GRB2.

BACKGROUND/AIMS: MicroRNAs (miRNAs) are non-coding single stranded RNAs of 17-25 nucleotides in size, and their altered expression has been observed in various cancers. Previous studies have confirmed that miR-433-3p has effects on cancer cell proliferation, invasion, and migration, and its expression also correlates with sensitivity to chemotherapy. However, to date, there have been no studies on the biological functions of miR-433-3p in esophageal squamous cell carcinoma (ESCC). METHODS: The Cell Counting Kit-8, transwell, and matrigel assays were used to test the effects of miR-433-3p and its predicted target, growth factor receptor-bound protein 2 (GRB2), on the proliferation, migration, and invasion of Eca109 and KYSE30 cells, two types of esophageal cancer cell lines. The miR-433-3p binding site in the 3' untranslated region (UTR) region of GRB2 was predicted and verified using miRNA target site prediction software and structuring correct mutant examination. Western blotting and fluorescent quantitative PCR (FQ-PCR) techniques were employed to evaluate GRB2 expression. The inhibitory effects of miR-433-3p on tumor growth were investigated using a tumor xenograft model. RESULTS: The binding site of miR-433-3p was identified in the 3'UTR region of GRB2. Western blotting and FQ-PCR showed that miR-433-3p inhibited the mRNA and protein expression of GRB2. Overexpression of GRB2 inhibited tumorigenesis in nude mice. MiR-433-3p overexpression inhibited the proliferation, migration, and invasion of ESCC cells by suppressing GRB2 gene expression. CONCLUSIONS: Our findings suggest that targeting miR-433-3p may have therapeutic benefits in ESCC.

Associations between polymorphisms in IL-12A, IL-12B, IL-12Rß1, IL-27 gene and serum levels of IL-12p40, IL-27p28 with esophageal cancer.

PURPOSE: The aim of this study was to investigate whether IL-12A, IL-12B, IL-12Rß1, and IL-27 gene polymorphisms and serum levels of IL-12, IL-27 are associated with esophageal cancer. METHODS: We genotyped IL-12A gene rs568408, IL-12B gene rs3212227, IL-12Rß1 gene 378 C/G, IL-27 gene rs153109, rs17855750, and rs181206 polymorphisms in a case-control study of 426 esophageal cancer patients and 432 health controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Both serum IL-12p40 and IL-27p28 levels were significantly higher in controls than those in patients (P < 0.01). Rs568408 AG/AA, rs3212227 CC/AC, and IL-12Rß1 378 GG/GC genotypes were associated with significantly increased risk of esophageal cancer (rs568408: χ(2) = 5.704, P = 0.017; rs3212227: χ(2) = 7.689, P = 0.006; IL-12Rß1 378C/G: χ(2) = 5.206, P = 0.023). Moreover, rs3212227 CC/AC and 378 GG/GC genotypes were observed significantly associated with decreased serum IL-12p40 level in patients compare to other genotypes (rs3212227: t = 2.129, P = 0.034; IL-12Rß1 378 C/G: t = 2.178, P = 0.030). Furthermore, frequency of rs3212227 CC/AC genotypes was significantly higher in patients with poor differentiation than those with AA genotype (χ(2) = 4.314, P = 0.035). CONCLUSION: Our data suggest that the impaired production of IL-12p40 and IL-27p28 behaves as risk factors for esophageal cancer occurrence. IL-12B gene rs3212227 CC/AC and IL-12Rß1 gene 378 GG/GC genotypes, which associated with decreased IL-12p40 level, may contribute to esophageal cancer susceptibility.