MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibiting TGF-ß1 expression.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibiting TGF-ß1 expression, by S.-N. Yu, Y.-Y. Miao, B.T. Zhang, Y.-M. Dai, L. Liu, Z.-L. Gao, G.-F. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (3): 972-981-DOI: 10.26355/eurrev_201902_16984-PMID: 30779063" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16984.

Reconstruction of lymphatic vessels in the mouse tail after cupping therapy.

BACKGROUND: The aim of the study was to investigate the regulatory mechanism of local lymphatic reconstruction after cupping therapy in a mouse model. MATERIALS AND METHODS: The lymphatic reconstruction process in the mouse tail after cupping therapy as well as the expression levels of the vascular endothelial identification molecule CD34, prospero homeobox protein 1 (PROX1), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) were investigated for a duration of 4 days through immunohistochemistry experiments. RESULTS: On day 1 after cupping therapy, the CD34+ and LYVE-1+ cell densities were significantly increased, and the formed CD34+LYVE-1+ tubular structure started to express PROX1. This was followed by a decrease in both the CD34+ and LYVE-1+ stem cell densities to basal levels on the second day after cupping therapy. Both the CD34+ and LYVE-1+ cell densities subsequently increased again on the third day after cupping therapy. The increase in the LYVE-1+ density was accompanied by tubular structure formation, which is characteristic of lymphangiogenesis. In addition, the colocalisation of CD34+ and LYVE-1+ cells by immunohistochemistry suggests that the CD34+ stem cells differentiated into new lymphatic endothelial cells. CONCLUSIONS: Our findings indicate that the mechanism underlying the therapeutic effect of cupping therapy involves upregulation of vascular and lymphatic endothelial markers (CD34+, LYVE-1+, and CD34+LYVE-1+) in local tissues, which in turn promotes local new lymphatic vessel formation through the expression of PROX1.

MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibit-ing TGF-ß1 expression.

OBJECTIVE: MicroRNAs are endogenous, non-coding small RNAs that are capable of regulating biological and pathological processes. Previous studies have shown that microRNA-1269a serves as an oncogene. However, the role of microRNA-1269a in the pathogenesis of osteosarcoma (OS) has not been reported. The aim of this work was to investigate the expression characteristics of microRNA-1269a in OS and to further study its regulatory effects on the malignant progression of OS. PATIENTS AND METHODS: The expression of microRNA-1269a in 61 pairs of OS tissues and para-cancerous tissues was detected by quantitative Real Time-polymerase Chain Reaction (qRT-PCR). Chi-square test was used to analyze the relationship between microRNA-1269a expression and the characteristics of OS patients, including age, sex, clinical stage and distant metastasis. Subsequently, microRNA-1269a expression in OS cell lines was detected as well. After knockdown of microRNA-1269a by constructing relevant small interference RNA, biological performances of MG63 and U2OS cells were accessed by cell counting kit-8 (CCK-8), colony formation and transwell assay. Meanwhile, the protein expressions of key genes in the EMT/Smad pathway were detected by Western blot. Finally, si-TGF-ß1 (transforming growth factor-ß1) was transfected into OS cells, and cell migration and invasion were detected by transwell assay. RESULTS: MicroRNA-1269a was highly expressed in OS tissues compared with para-cancerous tissues. High expression of microRNA-1269a was positively correlated with young OS patients and high rate of distant metastasis, whereas was not correlated with age, sex and Enneking stage. Kaplan-Meier survival curves showed that high expression of microRNA-1269a was significantly associated with poor prognosis of OS. The knockdown of microRNA-1269a in MG63 and U2OS cells significantly inhibited cell proliferation, migration and invasion. Meanwhile, microRNA-1269a knockdown in OS cells markedly downregulated the expressions of TGF-ß1, p-Smad2, p-Smad3, N-cad, Vimentin and MMP9. Furthermore, TGF-ß1 knockdown remarkably decreased migratory and invasive abilities of OS cells. CONCLUSIONS: MicroRNA-1269a is highly expressed in OS, which is remarkably correlated with tumor stage, distant metastasis and poor prognosis of OS. In addition, microRNA-1269a promotes the malignant progression of OS by regulating TGF-ß1 expression.

A stress-induced cellular aging model with postnatal neural stem cells.

This corrects the article DOI: 10.1038/cddis.2014.82.

TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway.

We have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK-STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2-overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK-STAT signaling pathway.

A stress-induced cellular aging model with postnatal neural stem cells.

Aging refers to the physical and functional decline of the tissues over time that often leads to age-related degenerative diseases. Accumulating evidence implicates that the senescence of neural stem cells (NSCs) is of paramount importance to the aging of central neural system (CNS). However, exploration of the underlying molecular mechanisms has been hindered by the lack of proper aging models to allow the mechanistic examination within a reasonable time window. In the present study, we have utilized a hydroxyurea (HU) treatment protocol and effectively induced postnatal subventricle NSCs to undergo cellular senescence as determined by augmented senescence-associated-ß-galactosidase (SA-ß-gal) staining, decreased proliferation and differentiation capacity, increased G0/G1 cell cycle arrest, elevated reactive oxygen species (ROS) level and diminished apoptosis. These phenotypic changes were accompanied by a significant increase in p16, p21 and p53 expression, as well as a decreased expression of key proteins in various DNA repair pathways such as xrcc2, xrcc3 and ku70. Further proteomic analysis suggests that multiple pathways are involved in the HU-induced NSC senescence, including genes related to DNA damage and repair, mitochondrial dysfunction and the increase of ROS level. Intriguingly, compensatory mechanisms may have also been initiated to interfere with apoptotic signaling pathways and to minimize the cell death by downregulating Bcl2-associated X protein (BAX) expression. Taken together, we have successfully established a cellular model that will be of broad utilities to the molecular exploration of NSC senescence and aging.

Interferon-ß gene-modified human bone marrow mesenchymal stem cells attenuate hepatocellular carcinoma through inhibiting AKT/FOXO3a pathway.

OBJECTIVE: This study aims to investigate the using of bone marrow mesenchymal stem cells (BMSCs) genetically engineered to produce interferon-ß (IFN-ß) as a gene delivery system to treat hepatocellular carcinoma (HCC) in vitro and in vivo. METHODS: To measure the effects on tumour cell growth in vitro, IFN-ß-producing BMSCs (BMSC/IFN-ß) were co-cultured with the HCC cell line HepG2 and Huh7. Enzyme-linked immunosorbent assay (ELISA) was used to detect the IFN-ß secretion in the BMSC culture condition medium (CM). The effect of BMSC/IFN-ß on HCC cells proliferation was examined both in vitro and in vivo by using MTT, colony formation assay, BrdU staining, cell cycle analysis, and xenografted NOD/SCID mouse tumour model. To examine the impact of BMSC/IFN-ß on the AKT/FOXO3a signalling, RT-PCR and western blotting were performed. RESULTS: The BMSC/IFN-ß cells can stably secrete high levels of IFN-ß. Both MTT and colony forming assay showed that HCC cells had a lower growth rate when cultured in BMSC/IFN-ß-CM as compared with that in BMSC/vector-CM or DMEM culture group. Co-culture with BMSC/IFN-ß-CM dramatically decreased the percentages of cells with incorporated BrdUrd. In BMSC/IFN-ß-CM-treated HCC cells, the proportion of G1-phase cells increased but it decreased in the S phase of the cell. The BMSC/IFN-ß inhibited HCC growth in NOD/SCID mice and proved the survival period of these mice. Compared with the control group, p21 and p27 expression of hepatoma cells increased, whereas cyclin D1 and phosphorylation of Rb expression decreased when co-cultured with BMSC/IFN-ß-CM. It was associated with suppression of Akt activity and enhanced transcriptional activity of FOXO3a. CONCLUSION: The IFN-ß gene-modified BMSCs can effectively inhibit the proliferation of HCC cells in vitro and in vivo through inhibiting AKT/FOXO3a pathway. These results indicate that BMSC/IFN-ß are a powerful anticancer cytotherapeutic tool for HCC.

The PPI network and cluster ONE analysis to explain the mechanism of bladder cancer.

BACKGROUND: Bladder cancer is a common cancer worldwide whose incidence continues to increase. It is estimated that there are 261,000 cases of bladder cancer resulting in 115,000 deaths worldwide. AIM: Although some studies can be initiated using small local tissue collections, high quality collection of fresh tissues from new clinical trials will be crucial for proper evaluation of associations with clinical outcome. For superficial bladder cancer, identification of tumors that will progress has long been perceived as a potential application of genetic studies. MATERIALS AND METHODS: In our study, we constructed the Protein-Protein Interactions (PPI) network using the Cytoscape and detected some network modeling clusters. In addition, we enriched GO categories among these genes in the first cluster and detected a pathway i.e. Spliceosome (hsa03040). Most Gene Ontology (GO) categories and Spliceosome were closely to RNA splicing and cellular macromolecular complex (CMC) assembly, which indicates that the mutation of RNA splicing and CMC assembly maybe important factors causing bladder cancer. RESULTS: In our study, these clusters of GO:0034622, GO:0006397 and GO:0034621 in bladder cancer belong to cellular macromolecular complex assembly, which may play an important role in the occurrence of cancer cells. CONCLUSIONS: It is a great significance for the detection and treatment of bladder cancer to understand the mechanism of RNA splicing and CMC assembly.

There were no differences in serum HBV DNA level between HBeAg-positive and HBeAg-negative chronic hepatitis B with same liver histological necroinflammation grade but differences among grades 1, 2, 3 and 4 apportioned by the same hepatic parenchyma cell volume.

Hepatitis B virus (HBV) DNA levels and liver histological necroinflammation grades are correlated with the antiviral efficacy. It is necessary to clarify the relationship between HBV replication levels apportioned by the same hepatic parenchyma cell volume and severity of liver histological necroinflammation grades in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B. The serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume were compared between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4, respectively. There were no differences in the serum HBV DNA levels between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4. However, there were differences in the serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume among liver histological necroinflammation grades 1, 2, 3 and 4 in both HBeAg-positive and HBeAg-negative chronic hepatitis B, respectively. There were no differences in HBV DNA levels with the same liver histological necroinflammation grade activated by HBV wild-type and variant strains. After the differences in hepatic parenchyma cell volume for HBV replication of the same liver histological necroinflammation grade accompanied by different hepatic fibrosis stages were adjusted, the serum HBV DNA level apportioned by the same hepatic parenchyma cell volume was correlated with the severity of liver histological necroinflammation grade.