Retraction Notice to: lncRNA UCA1 Promotes Gefitinib Resistance as a ceRNA to Target FOSL2 by Sponging miR-143 in Non-small Cell Lung Cancer.

[This retracts the article DOI: 10.1016/j.omtn.2019.10.047.].

MicroRNA miR-495 regulates the development of Hepatocellular Carcinoma by targeting C1q/tumor necrosis factor-related protein-3 (CTRP3).

Hepatocellular carcinoma (HCC) represents a type of lethal cancer in the world and its treatment options produce limited and unsatisfactory effectiveness. MicroRNAs (miRNAs) that play critical roles in tumorigenesis have shown promising clinical therapeutic potential. Here, we reported that miRNA-495 (miR-495) plays important roles in inhibiting HCC cell growth via its regulation of cell-cycle progression as well as senescence. MiR-495 showed low levels in human HCC tissues and cells. Overexpressing miR-495 in HCC cells caused strong cell growth inhibition, which results from cell-cycle arrest and senescence. CTRP3 functioned as a possible target of miR-495 in HCC cells by bioinformatics prediction and biological assay. By inhibiting the expression of CTRP3 with siRNA, HCC cells also showed similar growth inhibition as miR-495 overexpression. The re-expression of CTRP3 in HCC cells with high-level miR-495 abolished miR-495 and caused cell growth inhibition. These results strongly suggested that CTRP3 was the functional target that weakened the effects of miR-495 in HCC cells. The in vivo experiment demonstrated miR-495 overexpression had great therapeutic effects on HCC in xenograft. Above all, this research revealed that miR-495 is essential in suppressing HCC growth, and its application serves as a promising strategy for HCC treatment.

Rapid Recovery in COVID-19 Patients with Chronic Hepatitis B Virus Infection Treated with Tenofovir Disoproxil Fumarate.

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide. We report here two cases of chronic hepatitis B patients with acute respiratory syndrome coronavirus 2 infection treated with tenofovir disoproxil fumarate who demonstrated a favorable outcome. This report adds some evidence that concurrent HBV infection may not worsen COVID-19 infection and tenofovir disoproxil fumarate treatment may have partial positive effect on COVID-19 rapid recovery.

HBV induces liver fibrosis via the TGF-ß1/miR-21-5p pathway.

MicroRNA (miR)-21-5p is a newly discovered factor that mediates TGF-ß1 signaling. The present study was designed to investigate the role of TGF-ß1/miR-21-5p in hepatitis B virus (HBV)-induced liver fibrosis. HBV-infected sodium taurocholate co-transporting polypeptide (NTCP)-transfected Huh7.5.1 cells were co-cultured with LX2 cells to simulate HBV infection in the present study. A total of 29 patients with chronic HBV infection were enrolled. Cells were transfected with miR-21-5p mimic or inhibitor with or without TGF-ß1 stimulation. The demographic, biochemical and virological data from the 29 patients were analyzed and liver tissues were collected. miR-21-5p levels and the mRNA and protein expression of α-smooth muscle actin (SMA), collagen type 1 α 1 (CoL1A1), tissue inhibitor of metalloproteinase (TIMP)-1 and Smad from liver cells or tissues were detected by quantitative PCR analysis and western blotting, respectively. Cell viability was observed, and the liver fibrosis score was evaluated. The association between miR-21-5p and liver fibrosis was evaluated by correlation analysis. HBV infection upregulated TGF-ß1/miR-21-5p mRNA expression in NTCP-Huh7.5.1 cells compared with mock infection (P<0.05). TGF-ß1 incubation significantly increased miR-21-5p levels, as well as the mRNA and protein expression of α-SMA, CoL1A1 and TIMP-1, and reduced Smad7 expression in LX2 cells compared with the normal group, and these effects were counteracted by miR-21-5p inhibitor (P<0.05). miR-21-5p overexpression also contributed to TGF-ß1-induced α-SMA, CoL1A1 and TIMP-1 expression in LX2 cells (P<0.05). Co-culture with HBV-infected NTCP-Huh7.5.1 cells upregulated TGF-ß1/miR-21-5p activity and CoL1A1 expression in LX2 cells compared with normal control, which were significantly reduced by miR-21-5p inhibitor (P<0.05). miR-21-5p levels were significantly correlated with the liver fibrosis score (r=0.888; P<0.05). These data demonstrated that HBV induced liver fibrosis via the TGF-ß1/miR-21-5p pathway and suggested that miR-21-5p may be an effective anti-fibrosis target.

Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.

BACKGROUND: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. METHODS: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. FINDINGS: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0·6 (0·6-0·8)] but increases in neutrophil counts [4·7 (3·6-5·8)] than 27 mild cases [1.1 (0·8-1·4); 2·0 (1·5-2·9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0·93) and neutrophil-to-CD8+ T cell ratio (N8R) (AUC =0·94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19. INTERPRETATION: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases. FUNDING: The National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.

lncRNA UCA1 Promotes Gefitinib Resistance as a ceRNA to Target FOSL2 by Sponging miR-143 in Non-small Cell Lung Cancer.

Exosomes could mediate cell-cell crosstalk in cancer progression by transferring long noncoding RNAs (lncRNAs). The aim of this study is to explore the roles of the exosomal lncRNA urothelial carcinoma-associated 1 (UCA1) on gefitinib resistance in non-small cell lung cancer (NSCLC). First, we detected the expression of UCA1 in gefitinib-resistant and gefitinib-sensitive NSCLC by quantitative real-time PCR; the expression occurred in tissues, cell lines, and exosomes. Cell phenotypes and animal experiments were performed to determine the effects of UCA1 and exosomal UCA1. Furthermore, bioinformatics online programs and luciferase reporter assay were used to validate the association of UCA1 and miR-143 in NSCLC cells. We observed that UCA1 was increased in both gefitinib-resistant NSCLC cells and their secreted exosomes. In vitro and in vivo experiments demonstrated that UCA1 knockdown impaired cell proliferation and promoted the gefitinib-induced cell apoptosis. Then we demonstrated that repressed UCA1 promoted the miR-143 expression, and miR-143 could bind to the predicted binding site of UCA1. We then dissected the effect of miR-143 on gefitinib resistance in NSCLC and proved the suppressive role of miR-143. Furthermore, we found that miR-143 displayed its role via modulating the FOSL2 expression. In summary, our findings indicate that exosomal UCA1 may serve as a promising therapeutic target for the treatment of epidermal growth factor receptor-positive (EGFR+) NSCLC patients.

Vascular protective potential of the total flavanol glycosides from Abacopteris penangiana via modulating nuclear transcription factor-κB signaling pathway and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: "Sanxuelian", the rhizome of Abacopteris penangiana (AP), is traditionally used in Chinese medicine for the treatment of blood circulation stasis, hemorheology barriers, edema and inflammation for patients of metabolic syndrome. This study was to investigate the protective effect of the total flavanol glycosides from AP (FAP) on diabetic vascular impairments by measuring the extents of oxidative stress and inflammatory response in mice. MATERIALS AND METHODS: The experimental aortic pathology in diabetic mice was induced by fed on high-fat diet and injected with streptozotocin. The activities of FAP on attenuating aortas injuries, hypoglycemic, hypolipidemic, inhibiting oxidative stress and anti-inflammation were investigated. Additionally, the aortic expressions of nuclear transcription factor-κB (NFκB) were determined by western blot and immunohistochemistry analysis. Furthermore, the effects of FAP on human umbilical vein endothelia cells (HUVECs) were studied. RESULTS: In animal study, the results showed that FAP enhanced the activities of antioxidant enzymes and attenuated the levels of proinflammatory cytokines. The plasma lipid profiles and glucose level in FAP treated groups were significantly decreased along with the vascular impairments were alleviated. Moreover, the aortic expression of NFκB was decreased. In cellular experiment, FAP could inhibit the apoptosis of HUVECs induced by H(2)O(2). CONCLUSIONS: The results indicated that FAP had hypolipidemic, hypoglycemic and vascular protective activities and represented a potential herb for the treatment of aortic pathology involved with metabolic syndrome.

Pokeweed antiviral protein down-regulates Wnt/ß-catenin signalling to attenuate liver fibrogenesis in vitro and in vivo.

BACKGROUND AND AIM: Pokeweed antiviral protein (PAP) has been regarded as a strong negative regulator of Wnt/ß-catenin signalling, which promotes tissue fibrogenesis. Whether PAP inhibits hepatic fibrosis remains unknown. Here, the inhibitory effects of PAP on hepatic fibrosis induced by CCl4 in rats were monitored. METHODS: Plasmid pXF3H-PAP was transduced into liver in vivo and hepatic stellate cell (HSC-T6) in vitro. Changes in liver pathology were examined by haematoxylin and eosin (H&E) and Masson's trichrome staining. Hepatic function and the levels of hyaluronic acid (HA) and laminin (LN) in serum and hydroxyproline (Hyp) in liver were measured. We also observed the expressions and distribution of α-SMA, TIMP-1, smad3 and ß-catenin in HSCs and liver, together with the viability of HSC-T6 cells. RESULTS: PAP obviously attenuated the histological changes, decreased the content of Hyp in liver and improved liver function in rats (P<0.05). PAP significantly reduced the expressions and distribution of α-SMA and ß-catenin in vivo (0.0125 ± 0.002 vs. 0.0374 ± 0.003, 0.0135 ± 0.003 vs. 0.0382 ± 0.004; P<0.05, respectively) and in vitro as well as the cell viability (P<0.05). CONCLUSIONS: Our results revealed that PAP attenuated liver fibrogenesis through down-regulating the Wnt/ß-catenin pathway. It provides us an alternative new strategy for the treatment of hepatic fibrosis.