Knockdown of RTEL1 Alleviates Chronic Obstructive Pulmonary Disease by Modulating M1, M2 Macrophage Polarization and Inflammation.

Chronic obstructive pulmonary disease (COPD) is a common chronic disease characterized by airflow obstruction, which seriously threatens people's health. The COPD mouse model was established with cigarette smoke induction. Hematoxylin-eosin staining and Masson staining were carried out to observe the pathological changes of lung tissues in COPD mice. RTEL1 was silenced in COPD mice, and immunohistochemistry was used to detect RTEL1, ki67 and Caspase-3 expression. The role of RTEL1 in inflammation were evaluated by ELISA, and the impacts of RTEL1 on M1 and M2 macrophage markers (iNOS and CD206) were evaluated by qPCR and western blotting. In COPD model, there was an increase in the number of inflammatory cells, with slightly disorganized cell arrangement, unclear hierarchy, condensed and solidified nuclei, while knockdown of RTEL1 improved the inflammatory infiltration. Moreover, knockdown of RTEL1 reduced ki67-positive cells and increased Caspase-3 positive cells in COPD group. The increased inflammatory factors (IL-1ß, MMP-9, TNF-α, IL-4, IL-6, and IL-23) in COPD were suppressed by knockdown of RTEL1, while iNOS was raised and CD206 was inhibited. In conclusion, knockdown of RTEL1 promoted M1 and inhibited M2 macrophage polarization and inflammation to alleviate COPD.

Analysis of abnormal expression of signaling pathways in PQ-induced acute lung injury in SD rats based on RNA-seq technology.

Background: Paraquat (PQ) plays an important role in agricultural production due to its highly effective herbicidal effect. However, it has led to multiple organ failure in those who have been poisoned, with damage most notable in the lungs and ultimately leading to death. Because of little research has been performed at the genetic level, and therefore, the specific genetic changes caused by PQ exposure are unclear.Methods: Paraquat poisoning model was constructed in Sprague Dawley (SD) rats, and SD rats were randomly divided into Control group, paraquat (PQ) poisoning group and Anthrahydroquinone-2,6-disulfonate (AH2QDS) treatment group. Then, the data was screened and quality controlled, compared with reference genes, optimized gene structure, enriched at the gene expression level, and finally, signal pathways with significantly different gene enrichment were screened.Results: This review reports on lung tissues from paraquat-intoxicated Sprague Dawley (SD) rats that were subjected to RNA-seq, the differentially expressed genes were mainly enriched in PI3K-AKT, cGMP-PKG, MAPK, Focal adhesion and other signaling pathways.Conclusion: The signaling pathways enriched with these differentially expressed genes are summarized, and the important mechanisms mediated through these pathways in acute lung injury during paraquat poisoning are outlined to identify important targets for AH2QDS treatment of acute lung injury due to paraquat exposure, information that will be used to support a subsequent in-depth study on the mechanism of PQ action.

Prognostic value of hemodynamic indices in patients with sepsis after fluid resuscitation.

BACKGROUND: Sepsis usually causes hemodynamic abnormalities. Hemodynamic index is one of the factors to identify the severity of sepsis and an important parameter to guide the procedure of fluid resuscitation. The present study investigated whether the assessment of hemodynamic indices can predict the outcomes of septic patients undergoing resuscitation therapy. AIM: To evaluate the prognostic value of hemodynamic indices in patients with sepsis after fluid resuscitation. METHODS: A retrospective study was conducted in 120 patients with sepsis at Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University between October 2016 and October 2019. All patients were treated with sodium chloride combined with dextran glucose injection for fluid resuscitation. Patients' hemodynamic parameters were monitored, including heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), mean arterial pressure (MAP), central venous pressure (CVP), and central venous oxygen saturation. The prognostic value of hemodynamic indices was determined based on the prognosis status. RESULTS: During fluid resuscitation, 86 patients developed septic shock and 34 did not. Ninety-nine patients survived and 21 patients died at 28 d after the treatment. Heart rate, CI, mean arterial pressure, SVRI, and CVP were higher in patients with septic shock and patients who died from septic shock than in non-shock patients and patients who survived, and central venous oxygen saturation was lower in patients with shock and patients who died than in non-shock patients and the survivors (P < 0.05). When prognosis was considered as a dependent variable and hemodynamic parameters was considered as independent variables, the results of a logistic regression analysis showed that CI, SVRI, and CVP were independent risk factors for septic shock, and CI was an independent risk factor for 28-d mortality (P < 0.05). CONCLUSION: Hemodynamic indices can be used to evaluate the prognosis of septic patients after fluid resuscitation.

LncRNA PRNCR1 rs1456315 and CCAT2 rs6983267 Polymorphisms on 8q24 Associated with Lung Cancer.

BACKGROUND: Long noncoding RNA single nucleotide polymorphisms (lncRNA-SNPs) PCAT1 rs710886, PRNCR1 rs1456315 and CCAT2 rs6983267 on 8q24 region present generalizability in the susceptibility to multiple cancers, however, the influence of rs710886, rs1456315 and rs6983267 on lung cancer has not been assessed. The aim of this study was to investigate associations between three lncRNA-SNPs and lung cancer. METHODS: A case-control study was performed on 438 patients with lung cancer and 456 healthy controls in the Han population from southern China. The collected samples were genotyped by the TaqMan genotyping, and the association with clinical characteristics, including age, gender, drinking status, smoking status, pathological types and clinical stages were analyzed. And the SNP function prediction was based on lncRNASNP2, RNAfold and GTEx. RESULTS: The rs1456315 T allele increased the risk of lung cancer [OR=1.95, 95% CI (1.58-2.43), P=0.003] compared to the rs1456315 C allele, and rs1456315 significantly increased the risk of lung cancer in the dominant model [OR=1.86, 95% CI (1.16-3.00), P=0.002]. The rs6983267 G allele, compared with the T allele, increased the risk of lung cancer [OR=1.29, 95% CI (1.07-1.57), P=0.007], and rs6983267 was identified as a risk factor for lung cancer [OR=1.28, 95% CI (1.06-1.55), P=0.003] in the additive model. Both rs1456315 and rs6983267 demonstrated significance after adjusting for the smoking status, drinking status and age. The structure prediction found rs6983267 and rs1456315 influence the secondary structure of its lncRNA. The results from lncRNASNP2 indicated that rs6983267 and rs1456315 change gain/loss target of miRNAs. CONCLUSION: PRNCR1 rs1456315 and CCAT2 rs6983267 on 8q24 region are significantly associated with lung cancer in the Han population of southern China and alter the potential biological function in bioinformatic analysis, and the results further extended generalism of the susceptibility of cancer-associated lncRNA-SNPs to lung cancer and underlying mechanism involved in lung cancer.

Association of Ephrin receptor A3 gene polymorphism with susceptibility to chronic severe hepatitis B.

AIM: Previous research has suggested that Ephrin receptor A3 (EphA3) plays signaling roles in the processes of inflammation by regulating lymphocyte migration and proliferation. In this study, we investigated whether the EphA3 gene polymorphism was associated with disease progression of chronic hepatitis B virus (HBV) infection. METHODS: The EphA3 variant rs9310117 was genotyped in 1245 unrelated Han Chinese HBV carriers including 800 cases and 445 controls. χ(2) test was used to examine the difference in allele frequencies and genotype distributions between groups. The association between the polymorphism and disease progression of HBV infection was conducted by unconditional logistic regression analysis. RESULTS: Statistical analysis revealed that the genetic variant was significantly associated with the occurrence of chronic severe hepatitis B (CSHB). We observed that subjects bearing at least one T allele (C/T or T/T genotype) had a decreased susceptibility to chronic severe hepatitis B compared with those bearing C/C genotype (P = 0.003, odds ratio = 0.560; 95% confidence interval, 0.381-0.824, recessive model). Genotype C/T had also been confirmed to protect subjects from suffering chronic severe hepatitis B (P = 0.001, odds ratio = 0.498; 95% confidence interval, 0.330-0.752, additive model). CONCLUSION: Our results suggest that the genetic alteration at EphA3 locus plays a role in the occurrence of chronic severe hepatitis B.

Association of a TANK gene polymorphism with outcomes of hepatitis B virus infection in a Chinese Han population.

The host genetic compound plays a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. The tumor necrosis factor receptor-associated factor family member-associated nuclear factor-κB (NF-κB) activator (TANK) takes part in the tumor necrosis factor-α (TNF-α)-mediated NF-κB signaling pathway and the interferon (IFN)-induction pathways that have relevance to HBV-related liver disease. In this report, we explored whether the intronic polymorphism rs3820998 of the TANK gene was associated with outcomes of HBV infection by binary logistic regression analysis. A total of 1305 unrelated Han Chinese patients recruited from Wuhan, including 180 acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients, 331 HBV-related liver cirrhosis (LC) patients, 308 HBV-related hepatocellular carcinoma (HCC) patients, and 486 asymptomatic HBV carriers (AsC) were genotyped using the TaqMan probe method. Logistic analysis revealed that the single-nucleotide polymorphism (SNP) rs3820998 was significantly associated with susceptibility to ACLF-HBV (dominant model, OR 0.643, 95% CI 0.428,0.964, p=0.033; additive model, OR 0.640, 95% CI 0.414,0.990, p=0.045), and LC (recessive model, OR 0.398, 95% CI 0.164,0.966, p=0.042; additive model, OR 0.379, 95% CI 0.155,0.928, p=0.034). These results indicate that the G > T variant is a protective factor in the development of ACLF-HBV and LC, and that the SNP rs3820998 in the TANK gene may play a role in mediating susceptibility to ACLF-HBV and LC in a Chinese Han population.

[Insertion of TC motif into hepatitis B virus core protein c/e1 site does not affect the expression of S and e antigen].

OBJECTIVE: To investigate whether insertion of TC motif into hepatitis B virus (HBV) core protein c/e1 site affects the expression of S and e antigen. METHODS: Different oligonucleotides encoding TC motif were inserted into the c/e1 site of the core gene of a 1.3 copy wild-type HBV genome vector. HepG2 cells were divided into several groups of cells to transiently transfect with the wild-type and mutant HBV vectors, respectively. In each group, the expression level of core protein inside cells was detected by western blotting, and the levels of S and e antigen in culture medium were analyzed by ELISA assay. RESULTS: Western blotting showed that these TC-tagged core proteins were expressed at similar level of wild-type one. ELISA assay indicated that the level of S and e antigen in culture medium of different groups were not significantly different. CONCLUSION: Insertion of TC motif into HBV core protein c/e1 site does not interference with the expression of viral protein encoded by HBV genome.