ABSTRACT Platelets can protect from lipopolysaccharide-induced septic shock by inhibiting inflammation, but it is unknown whether platelets have an anti-atherosclerotic effect. The aim of this study was to investigate the effect of platelet transfusion on atherosclerosis (AS) in a mouse model of AS. Apolipoprotein E deficiency (ApoE−/−) mice were fed with a high-fat diet (HFD) for 8 weeks to establish a mouse model of AS. Mice weekly underwent bi-weekly injection with or without platelets during AS induction (HFD+platelet). Hematoxylin–eosin (H&E), Oil Red O, and Sudan IV stainings were used to assess pathological and morphological changes in the aortic tissue. Lipid levels, and liver and kidney function were examined using an automatic biochemical analyzer. Immune histochemical assays were used to detect the infiltration and distribution of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, and monocyte chemotactic protein-1 (MCP-1) in the aortic arch. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to examine the expression levels of TNF-α, IL-1β, IL-6, and MCP-1 in the aorta or the peripheral blood, respectively. Compared with the HFD group, AS pathological lesions from the aortic arch in the HFD+platelet group were significantly smaller and alterations in the lipid metabolism were also less pronounced. Furthermore, TNF-α, IL-1β, IL-6, and MCP-1 levels were all significantly reduced in mice that received platelet injection. Platelets transfusion can effectively ameliorate lipid metabolism, suppress the inflammatory response in the vascular wall, and inhibit the development of AS in mice.

ABSTRACT There are two main types of growth hormone (GH) in the circulatory system. One is 22 kD-GH, which is the predominant isoform in the circulating system, 90% GH is present as a 22 kD protein, and 10% of GH is present as a 20 kD protein. Amino acid sequences are identical between 20 kD-GH and 22 kD-GH protein, except that 20 kD-GH lacks 15 amino acid residues 32 to 46. Studies have shown that GH has many important biological effects on mesenchymal stem cells (MSCs). However, so far, the cellular characteristics of the two types of GH have not been studied in BM-MSCs. Furthermore, the biological activity of 20 kD-GH has not been explored in BM-MSCs. For this, in the current work, BM-MSCs were used as in vitro cell model. We have carried out the current research using a series of experimental techniques (such as Western-blot and indirect immunofluorescence). Firstly, we explored the cell behavior of two types of GH in the Bm-MSC model and found that they showed different biological characteristics; Secondly, we investigated the biological characteristics of 20 kD-GH and 22 kD-GH, and results showed that 22 kD-GH and 20 kD-GH exhibited different signaling profiles; Thirdly, we found that the 20 kD-GH and 22 kD-GH Gexhibited different regulatory effects on the osteogenic differentiation of BM-MSCs. The current research lays a solid foundation for further studies on the regulatory effects of GH on MSCs.

ABSTRACT Obesity is associated with elevated levels of free fatty acids (FFAs). Excessive saturated fatty acids (SFAs) exhibit significant deleterious cytotoxic effects in many types of cells. However, the effects of palmitic acid (PA), the most common circulating SFA, on cell cycle progression in neuronal cells have not been well-examined. The aim of this study was to examine whether PA affects the proliferation and cell cycle progression in mouse neuroblastoma Neuro-2a (N2a) cells. Our studies found that 200 µM PA significantly decreased DNA synthesis and mitotic index in N2a cells as early as 4 h following treatment. 24 h treatment with 200 µM PA significantly decreased the percentage of diploid (2 N) cells while dramatically increasing the percentage of tetraploid (4 N) cells as compared to the BSA control. Moreover, our studies found that 24 h treatment with 200 µM PA increased the percentage of binucleate cells as compared to the BSA control. Our studies also found that unsaturated fatty acids (UFAs), including linoleic acid, oleic acid, α-linolenic acid, and docosahexaenoic acid, were able to abolish PA-induced decrease of 2 N cells, increase of 4 N cells, and accumulation of binucleate cells. Taken together, these results suggest that PA may affect multiple aspects of the cell cycle progression in N2a cells, including decreased DNA synthesis, G2/M arrest, and cytokinetic failure, which could be abolished by UFAs. Abbreviations: 4-PBA, 4-Phenylbutyric Acid; ALA, α-linolenic acid; BrdU, 5-bromo-2’-deoxyuridine; DAPI, 4′,6-diamidino-2-phenylindole; ER, endoplasmic reticulum; FFA, free fatty acids; FITC, fluorescein isothiocyanate; LA, linoleic acid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; N2a, Neuro-2a; NAC, N-acetyl cysteine; OA, oleic acid; PA, palmitic acid; pHH3, Phosphorylation of histone H3; PI, propidium iodide; SFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; UFA, unsaturated fatty acids

ABSTRACT Long non-coding RNA long intergenic non-protein coding RNA 01315 (LncRNA LINC01315) has been found to be implicated in various cancers, but its role and functions in colorectal cancer (CRC) remain to be addressed. Data on LINC01315 expression in CRC were gathered using bioinformatics analysis, and cancer stem cells (CSCs) were sorted by aldehyde dehydrogenase (ALDH) assay and flow cytometry. Migration, invasion, and stemness of CSCs isolated from CRC cells after transfection were determined by scratch, Transwell, and sphere-formation assays, respectively. Tumor xenograft model was constructed. Target genes and potential-binding sites were predicted using online databases and further confirmed via dual-luciferase reporter assay. Relative factors expressions were determined via quantitative real-time polymerase-chain reaction and Western blot as needed. LINC01315 was high-expressed in CRC and ALDH+ cells. LINC01315 silencing suppressed the migration, invasion, and sphere formation of CRC cells and tumor growth, and downregulated expressions of CSC molecules (ALDH, cluster of difference 44 (CD44), Prominin, and sex determining region Y-box 2 (SOX2)), Zinc Finger E-Box Binding Homeobox 1 (ZEB1) and Vimentin but upregulated E-Cadherin expression. MiR-484 could competitively bind with LINC01315, and LINC01315 silencing promoted miR-484 expression. The level of Delta Like Non-Canonical Notch Ligand 1 (DLK1), the target gene of miR-484, was enhanced by overexpressed LINC01315 yet was suppressed by LINC01315 silencing. Also, DLK1 silencing reversed the effects of downregulated miR-484 on migration, invasion, sphere formation, and CSC molecules expressions in CRC cells. LINC01315 silencing modulated CSC properties and epithelial-to-mesenchymal transition via miR-484/DLK1 axis.

ABSTRACT Cell cycle is an important and complex biological system. A lot of efforts have been put in understanding cell cycle arrest for its vital role in clinical therapies. The cell-cycle-arrest outcomes upon stimulation are complicated. The response could be stringent or relaxed, and graded or quantized. A model fully addressing various cell-cycle-arrest outcomes is to be developed. Here, we developed a mathematical model of cell cycle control incorporating distinct characteristics of various cell-cycle-arrest outcomes. The model can simulate two typical properties of cell cycle arrest, quantized and graded. We also characterized the inheritable quiescence and refractory state, which were crucial in long-term response of the population. Then, we monitored cells respond to multiple stimulations, and the results indicated that cells responded to stimulations with small interval did not induce significantly sustained cell cycle arrest as the existence of refractory state. Our work will benefit fundamental research and make efforts to predicting outcomes of clinical therapeutics.

ABSTRACT Long non-coding RNA tumor protein 53 target gene 1 (TP53TG1) has been unraveled to exert regulatory effects on cancer progression, while the regulatory function of TP53TG1 on cervical cancer (CC) via regulating microRNA (miR)-33a-5p/Forkhead box K2 (FOXK2) axis remains rarely explored. This study aims to unearth the regulatory mechanism of TP53TG1/miR-33a-5p/FOXK2 axis in CC. The CC clinical samples were collected, and CC cells were cultured. TP53TG1, miR-33a-5p and FOXK2 levels were examined in CC tissues and cells. The CC cells were transfected with high- or low-expressed TP53TG1, FOXK2 or miR-33a-5p to determine the changes of CC cell biological activities and the status of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. The tumorigenesis in nude mice was conducted. The relationship among TP53TG1, miR-33a-5p and FOXK2 was validated. TP53TG1 and FOXK2 expression levels were increased and miR-33a-5p expression level was reduced in CC cells and tissues. The silenced TP53TG1 or FOXK2, or elevated miR-33a-5p decelerated the CC cell development and restrained the activation of PI3K/AKT/mTOR signaling pathway. The depleted FOXK2 or elevated miR-33a-5p reversed the effects of decreased TP53TG1 on CC cell progression. TP53TG1 sponged miR-33a-5p, which targeted FOXK2. The experiment in vivo validated the outcomes of the experiment in vitro. TP53TG1 accelerates the CC development via regulating miR-33a-5p to target FOXK2 with the involvement of PI3K/AKT/mTOR signaling pathway. This study provides novel theory basis and distinct therapeutic targets for CC treatment.

ABSTRACT Nasopharyngeal carcinoma (NPC) has a low five-year survival rate, and its pathogenesis remains unclear. There is an urgent need to improve our understanding of the genetic regulation of NPC tumorigenesis and development. The role of miR-26a-5p in NPC growth regulation and the expression of its target, PTGS2, was analyzed. Quantitative Real-time PCR assay was used to detect miR-26a-5p and PTGS2 expression in human NPC tissues and cell lines. The RNA pull-down dual-luciferase reporter assay was used to determine the association between miR-26a-5p and PTGS2. The effects of miR-26a-5p and PTGS2 on NPC cell viability, proliferation, migration, and invasion were measured by CCK-8, BrdU, and Transwell assays. miR-26a-5p expression in NPC tissues and cell lines was significantly decreased. The overexpression of miR-26a-5p inhibited the viability, proliferation, migration, and invasion of NPC cells. miR-26a-5p bound to the 3-ʹuntranslated region of PTGS2, thus reducing PTGS2 protein levels. miR-26a-5p inhibited NPC development by reducing the expression of its target PTGS2.

ABSTRACT Drug resistance is a significant challenge in the present treatment regimens of renal cell carcinoma (RCC). Our previous study confirmed that nc886 functions as an oncogene in RCC. Nevertheless, the role and underlying mechanism of nc886 in RCC drug resistance are unclear. In the present study, Sunitinib and Everolimus treatment, respectively, downregulated nc886 expression in a dose-dependent manner in all four renal cancer cell lines. Nc886 overexpression in 786-O cells and ACHN cells significantly reduced the sensitivity of cancer cells to both Sunitinib and Everolimus treatment, respectively, by promoting cell viability and inhibiting cell apoptosis, whereas nc886 silencing increased cancer cell sensitivity. In renal cancer cell line with the highest drug-resistance, 786-O cells, Sunitinib, or Everolimus treatment enhanced the cellular EMT and was further enhanced by nc886 overexpression while attenuated by nc886 silencing. In 786-O cells, nc886 overexpression significantly promoted EMT, ROCK2 phosphorylation, and β-catenin nucleus translocation under Sunitinib or Everolimus treatment. Moreover, ROCK2 silencing significantly reversed the effects of nc886 overexpression on EMT, ROCK2 phosphorylation, and β-catenin nucleus translocation, as well as drug-resistant renal cancer cell viability and apoptosis. In conclusion, it was demonstrated that nc886 promotes renal cancer cell proliferation, migration, and invasion, as demonstrated previously. nc886 also promotes renal cancer cell drug-resistance to Sunitinib or Everolimus by promoting EMT through Rock2 phosphorylation-mediated nuclear translocation of β-catenin.

ABSTRACT Osteoarthritis is a degenerative joint disease and a leading cause of adult disability. Our previous study has reported that mesenchymal stem cell-derived exosomes (MSC-Exo) mediated long non-coding RNA KLF3-AS1 improves osteoarthritis. This study aims to investigate the molecular mechanism of KLF3-AS1 in osteoarthritis. Chondrocytes were treated with IL-1β to induce chondrocyte injury, followed by MSC-Exo treatment. We found that MSC-Exo enhanced KLF3-AS1 expression in IL-1β-treated chondrocytes. IL-1β treatment reduced cell viability and enhanced apoptosis in chondrocytes. MSC-Exo-mediated KLF3-AS1 promoted cell viability and repressed apoptosis of IL-1β-treated chondrocytes. Rapamycin (autophagy activator) promoted cell viability and suppressed apoptosis of chondrocytes by activating autophagy. Moreover, KLF3-AS1 interacted with YBX1 in chondrocytes. MSC-Exo-mediated KLF3-AS1 activated PI3K/Akt/mTOR signaling pathway, which was abrogated by YBX1 silencing. MSC-Exo-mediated KLF3-AS1 repressed autophagy and apoptosis of chondrocytes by activating PI3K/Akt/mTOR signaling pathway. In conclusion, our data demonstrate that MSC-Exo-mediated KLF3-AS1 inhibits autophagy and apoptosis of IL-1β-treated chondrocyte through PI3K/Akt/mTOR signaling pathway. KLF3-AS1 activates PI3K/Akt/mTOR signaling pathway by targeting YBX1 to improve the progression of osteoarthritis. Thus, this work suggests that MSC-Exo-mediated KLF3-AS1 may be a potential therapeutic target for osteoarthritis.

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Gang Wang, Lecheng Zhang, Chao Yan and Yuelei Zhang. Upregulation of microRNA-576-5p protects from steroid-induced avascular necrosis of the femoral head by suppressing ANXA2. Cell Cycle. 2022;21(1):49-62. doi: 10.1080/15384101.2021.1988377 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.