MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptional regulate gene expression in a variety of cancers. Increasing evidences indicate that miR-30 expression is down-regulated in numerous human cancers including non-small cell lung cancer (NSCLC) which hypothesizes that miR-30 may play an important role in tumorigenesis. The aim of this study was to investigate the target gene of miR-30 and its roles in tumor growth of NSCLC. Luciferase reporter assays were employed to validate regulation of a putative target of miR-30. The effect of miR-30 on endogenous levels of this target were subsequently confirmed via Western blot (WB). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-30 in NSCLC specimens and adjacent non-tumor tissues. MTT assays were conducted to explore the impact of miR-30 overexpression on the proliferation of human NSCLC cells. Both miR-30b and miR-30c (miR-30b/c) were found having target site in same region of Rab18 mRNA. Luciferase assays using a reporter carrying a putative miR-30b/c target site in the coding DNA sequence (CDS) region of Rab18 revealed that miR-30b/c directly targeted Rab18. Overexpression of miR-30b/c led to down-regulation of Rab18 in A549 and H23 cells at protein levels but not mRNA levels. Down-regulation of miR-30b/c and up-regulation of Rab18 protein levels were detected in NSCLC specimens compared with adjacent non-tumor tissues. Overexpression of miR-30b/c suppressed NSCLC cells growth. Knockdown of Rab18 by siRNA significantly inhibited the proliferation of NSCLC cells. We demonstrated that miR-30b/c was down-regulated in NSCLC specimens compared with adjacent non-tumor tissues. miR-30b/c directly targeted and down-regulated Rab18 expression and inhibited NSCLC cells proliferation. These data indicated that miR-30b/c could serve as a tumor suppressor gene involved in NSCLC pathogenesis.
Decellularized extracellular matrix (dECM), a promising tissue engineering scaffold for cardiovascular applications, might exhibit enhanced durability when endowed with anticalcification and antithrombotic properties. Herein, we present a biomimetic bilayer hydrogel coating applied to acellular swim bladders (ASBs). First, we designed an endothelium-mimicking (HCT) hydrogel coating, comprising alternately assembled endothelial glycocalyx macromolecule hyaluronic acid, copper ions, and tannic acid. Subsequently, a hydrophilic methacrylated silk fibroin (SilMA) hydrogel was incorporated as the outer coating layer. Notably, the HCT hydrogel penetrated and anchored into the ASB matrix, forming an interpenetrating network that enhanced the biostability and mechanical properties of the ASB matrix. Additionally, the SilMA hydrogel enhanced the hydrophilicity and antifouling properties of the HCT coating. In vitro experiments and subcutaneous implantation further revealed that the bilayer hydrogel (H/S) coating exhibited excellent biocompatibility, hemocompatibility, antibacterial activity, and anticalcification properties. Furthermore, a blood circulation model and rabbit shunt assay confirmed the great anticoagulation properties of the H/S coating. Moreover, in an in vivo rat carotid aorta replacement model, the H/S coating effectively promoted endothelialization, enhanced vascular remodeling, prevented calcification and thrombosis, and ultimately improved ASB durability. Based on these findings, our endothelium-mimicking hydrophilic bilayer hydrogel coating holds great promise as a surface modification strategy for tissue engineering scaffolds.
1 January 2025 in American Journal of Translational Research
To evaluate the effects of 75% ethanol on the disinfection efficacy, biocompatibility, extracellular matrix (ECM) integrity, and mechanical properties of swim bladders from Hypophthalmichthys nobilis, a promising biomaterial for cardiovascular applications. Swim bladders were immersed in 75% ethanol for 30, 60, or 120 minutes, followed by phosphate-buffered saline (PBS) rinsing. Disinfection efficacy was assessed using bacterial cultures; cytotoxicity and blood compatibility were evaluated using CCK-8 assays and hemolysis tests. The decellularization efficiency, ECM integrity, and mechanical properties were analyzed through histological staining, DNA quantification, and uniaxial tensile test. 75% ethanol effectively disinfected the swim bladder with minimal cytotoxicity and good hemocompatibility. Histological staining demonstrated preservation of collagen fibers, elastin, and glycosaminoglycans (GAGs), indicating minimal impact on the ECM structure. The uniaxial tensile test revealed that ethanol immersion caused tissue dehydration and increased stiffness, but these effects were reversible after PBS rinsing, with mechanical properties returning to baseline. DNA content and tissue thickness normalized following PBS washing, suggesting that ethanol did not impair decellularization. 75% ethanol is an effective disinfectant for swim bladder biomaterials, preserving biocompatibility, ECM structure, and mechanical properties after rinsing. These findings support the use of swim bladder-derived scaffolds in cardiovascular tissue engineering applications.
Background: Acute type A aortic dissection (AADA) is a life-threatening cardiovascular disease, and improving perioperative mortality remains a significant challenge. The purpose of this study is to investigate the impact of preemptive intubation under adequate sedation and analgesia on the prognosis of AADA patients under the high rupture risk. Methods: The medical records of patients diagnosed with AADA and admitted to Changhai Hospital from January 2019 to January 2020 were retrospectively reviewed. Patients were divided into two groups based on whether they received preoperative preemptive intubation in the cardiac intensive care unit (ICU) before surgery. We used propensity score matching (PSM) analysis to conduct statistical analyses on the preoperative, intraoperative, and postoperative clinical data of the two groups. Results: A total of 134 patients were eventually included in the study. One patient (3.8%) in the pre-intubation group and 15 (13.9%) in the control group died of dissection rupture before surgery. After excluding patients with dissection rupture, there were 25 patients in the pre-intubation group and 93 patients in the non-intubation group. After PSM, there were 17 patients in the pre-intubation group and 68 patients in the non-intubation group. Baseline data analysis showed that the pre-intubation group had a higher Sequential Organ Failure Assessment (SOFA) score (10.2±3.9 vs. 8.0±4.7, P=0.036) and a higher proportion of patients with coronary artery disease (16.0% vs. 1.1%, P=0.007). The rate of massive pericardial effusion was also higher in the intubation group (28.0% vs. 10.8%, P=0.049), and preoperative oxygenation index was lower (273.2±97.3 vs. 322.1±100.9, P=0.032) compared to the control group. The results showed no significant differences in intraoperative and postoperative data for the two groups. Kaplan-Meier survival curves indicated a trend towards a more favorable prognosis for patients in the preemptive intubation group, but this difference was not significant either before or after PSM. Conclusions: Preemptive pre-intubation may benefit high-risk patients with factors such as hypoxia, massive pericardial effusion, and agitation, improving the more critically AADA patients’ perioperative outcomes.