Pulmonary surfactant is the complex mixture of lipid and protein that covers the alveolar surface. Pulmonary surfactant deficiency is one of the main causes of neonatal respiratory distress. Recent studies showed that miRNA plays an important role in lung development, but research into miR-431 regulation of pulmonary surfactant are sparse. In this study, we explored the regulatory role of miR-431-5p in the expression of pulmonary surfactant and identified its potential target gene, Smad4. The bioinformatics tool TargetScan was used to predict the targets of miR-431. The expression of miR-431-5p was achieved via transfection of miR-431-5p mimics, an miR-431-5p inhibitor and corresponding negative control. The level of miR-431-5p was determined using quantitative real-time PCR. The CCK8 assay was conducted to confirm cell growth 12 h after transfection with miR-431-5p mimics, inhibitor or NC. Smad4 and surfactant-associated proteins in A549 were analyzed using western blot and quantitative real-time PCR. Smad4 was validated as a target of miR-431 in A549 cells. Overexpression of miR-431 accelerated A549 proliferation and inhibited A549 apoptosis. The mRNA and protein levels for the surfactant proteins (SP-A, SP-B, SP-C and SP-D) were found to be differentially expressed in A549 cells over- or under-expressing miR-431-5p. Our results show that miR-431-5p is critical for pulmonary surfactant expression and that its regulation is closely related to the TGF-β/Smad4 pathway. These results will help us to study the pathophysiological mechanism of lung developmental diseases.

Data from The Cancer Genome Atlas (TCGA) indicate that the expression levels of 14‐3‐3ζ and beclin 1 (a key molecule involved in cellular autophagy) are up‐regulated and positively correlated with each other (R = .5, P < .05) in HCC tissues. Chemoresistance developed in hepatoma cancer cells is associated with autophagy initiation. This study aimed to explore 14‐3‐3ζ’s role in regulating autophagy in HCC cells, with a focus on beclin 1. The co‐localization of 14‐3‐3ζ and beclin 1 was detectable in primary HCC tissues. To simulate in vivo tumour microenvironment (hypoxia), CSQT‐2 and HCC‐LM3 cells were exposed to 2% oxygen for 24 hours. The protein levels of 14‐3‐3ζ and phospho‐beclin 1^S295 peaked at 12 hours following hypoxia. Meanwhile, the strongest autophagy flux occurred: LC3II was increased, and p62 was decreased significantly. By sequencing the coding area of BECN 1 gene of CSQT‐2 and HCC‐LM3 cells, we found that the predicted translational products of BECN 1 gene contained RLPS²⁹⁵VP (R, arginine; L, leucine; P, proline; S, serine; V, valine), a classic 14‐3‐3ζ binding motif. CO‐IP results confirmed that 14‐3‐3ζ bound to beclin 1, and this connection was markedly weakened when S²⁹⁵ was mutated into A²⁹⁵ (alanine). Further, 14‐3‐3ζ overexpression prevented phospho‐beclin 1^S295 from degradation and enhanced its binding to VPS34, whilst its knockdown accelerated the degradation. Additionally, 14‐3‐3ζ enhanced the chemoresistance of HCC cells to cis‐diammined dichloridoplatium by activating autophagy. Our work reveals that 14‐3‐3ζ binds to and stabilizes phospho‐beclin 1^S295 and induces autophagy in HCC cells to resist chemotherapy.

Background: Large-scale population studies showed that the SNP rs1764391 of Connexin37 gene also known as Cx37 gene may play a pivotal role in the occurrence and development of acute myocardial infarction (AMI). Published results, however, are highly controversial. Objective: This study aimed to examine the association between SNP rs1764391 of Cx37 and diseasesusceptibility, several risk factors, and gene-environment interactions of AMI in Guangxi Han Chinese population. Methods: In this study, 344 healthy controls and 344 AMI patients of Han Chinese population were enrolled. The TaqMan assay was implemented to identify genotypes of Cx37 and allele frequencies of SNP rs1764391 in both the AMI and control groups. Results: Significant differences were detected in TT genotype frequencies of SNP rs1764391 between the AMI and control groups (P < 0.05). In the context of gender stratification, the result was also statistically different in women (P < 0.05). Each variable such as age, BMI, diabetes, high blood pressure, smoking and TC was a risk factor and correlated significantly (P < 0.05) with the development of AMI. HDL-C correlated negatively with the risk of AMI (P < 0.001). BMI, smoking or alcohol consumed interacts significantly (P < 0.017) with the presence of the SNP rs1764391 CC genotype. Conclusions: Evidences were presented that Cx37 rs1764391 variation may contribute to the risk for AMI, especially in women and this genetic variant may prove to be a potential biomarker for AMI risk stratification and may prove to be a useful target for therapeutic intervention to further improve prognosis in high-risk patients.

We investigated the clinical significance of mechanical ventilation on ischemic-reperfusion injury caused by lung chest trauma as well as vascular endothelial growth factor (VEGF) expression levels in peripheral blood. Sixty‑eight patients with severe chest trauma complicated with acute respiratory distress syndrome that were treated at our Tianjin Hospital from September 2013 to July 2016 were recruited. These patients were randomly and evenly divided into two groups, the research group and the control group. Thirty‑four age and gender matched healthy people were selected as the normal group. Routine treatment was given to both the research and control groups, but mechanical ventilation was used in the research group. We detected pulmonary vascular resistance (PVR) and alveolar-arterial oxygen difference (AaDO2) for patients in both groups before treatment, and after treatment for 1, 3, 6 and 12 h. We also tested PMN, superoxide dismutase (SOD), malondialdehyde (MDA), NO and Ang II value 30 min before and after treatment. We used the ELISA‑test to detect VEGF expression levels in peripheral blood, followed by a statistical analysis. PVR levels of different time points in the research group were significantly lower than control group after treatment. The AaDO2 value of the control group is much smaller than research group (P<0.5) after treatment for 1, 3 or 6 h. PMN count difference and MDA level in the research group is significantly lower than the control group after treatment for 30 min, but SOD and NO levels are much higher. Ang II levels of the research group in left atrial blood is significantly lower than control group (P<0.05). By comparing the hospitalization times, we found that patients in the research group have a shorter duration in hospital than the control group; differences are statistically significant (P<0.05). Additionally, compared to control group, research group VEGF expression levels in peripheral blood are significantly lower (P<0.05). Therefore, mechanical ventilation can reduce the high VEGF expression levels in serum caused by ischemic‑reperfusion and can be used for clinical application.

: Background: The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) on the coronavirus disease 2019 (COVID-19) remains controversial from clinic evidence. Objectives: The objectives of this study were to report the major characteristics and clinical outcomes of COVID-19 patients treated with ACEIs and ARBs and compare the different effects of the two drugs for outcomes of COVID-19 patients. Methods: This is a retrospective, two-center case series of 198 consecutive COVID-19 patients with a history of hypertension. Results: Among 198 patients, 58 (29.3%) and 16 (8.1%) were on ARB and ACEI, respectively. Patients who were on ARB or ACEI/ARB had a significantly lower rate of severe illness and acute respiratory distress syndrome (ARDS) when compared with patients treated with ACEI alone or not receiving RAAS blocker ( P < 0.05). The Kaplan-Meier survival curve showed that patients with ARB in their antihypertensive regimen had a trend toward a higher survival rate when compared with individuals without ARB (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.07-1.02; P = 0.054). The occurrence rates of severe illness, ARDS, and death were similar in the two groups regardless of receiving ACEI. The Cox regression analyses showed a better survival in the ARB group than the ACEI group (adjusted hazard ratio, 0.03; 95% CI, 0.00-0.58; P = 0.02). Conclusions: Our data may provide that some evidence of using ARB, but not ACEI, was associated with a reduced rate of severe illness and ARDS, indicating their potential protective impact in COVID-19. Further large sample sizes and multiethnic populations are warranted to confirm our findings.