Hyperleptinemia is a common feature of obese women who have a higher risk of endometrial cancer than women with normal weights, and epidemiologic studies have suggested a correlation between obesity and endometrial carcinoma. Therefore, understanding of the molecular mechanism involved in leptin signaling transduction is important in endometrial cancer prevention and treatment. In this study, both isoforms of the leptin receptor (Ob-R), the long form (Ob-Rb) and short form (Ob-Ra), were detected as being expressed in six endometrial cancer cell lines with various differentiation status by western blotting, and Ob-Ra was found to be more abundant than Ob-Rb in these cells. Moreover, the expressions of both isoforms were inversely correlated with histoprognostic grading. We also showed that leptin stimulated cell proliferation

The treatment of bone defects has plagued clinicians. Exosomes, the naturally secreted nanovesicles by cells, exhibit great potential in bone defect regeneration to realize cell-free therapy. In this work, we successfully revealed that human umbilical cord mesenchymal stem cells-derived exosomes could effectively promote the proliferation, migration, and osteogenic differentiation of a murine calvariae preosteoblast cell line in vitro. Considering the long period of bone regeneration, to effectively exert the reparative effect of exosomes, we synthesized an injectable hydroxyapatite (HAP)-embedded in situ cross-linked hyaluronic acid-alginate (HA-ALG) hydrogel system to durably retain exosomes at the defect sites. Then, we combined the exosomes with the HAP-embedded in situ cross-linked HA-ALG hydrogel system to repair bone defects in rats in vivo. The results showed that the combination of exosomes and composite hydrogel could significantly enhance bone regeneration. Our experiment provides a new strategy for exosome-based therapy, which shows great potential in future tissue and organ repair.

Cancer cells exhibit the reprogrammed metabolism mainly via aerobic glycolysis, a phenomenon known historically as the Warburg effect; however, the underlying mechanisms remain largely unknown. In this study, we characterized the critical role of transcription factor Forkhead box protein M1 (FOXM1) in aerobic glycolysis of human epithelial ovarian cancer (EOC) and its molecular mechanisms. Our data showed that aberrant expression of FOXM1 significantly contributed to the reprogramming of glucose metabolism in EOC cells. Aerobic glycolysis and cell proliferation were down-regulated in EOC cells when FOXM1 gene expression was suppressed by RNA interference. Moreover, knockdown of FOXM1 in EOC cells significantly reduced glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. FOXM1 bound directly to the GLUT1 and HK2 promoter regions and regulated the promoter activities and the expression of the genes at the transcriptional level. This reveals a novel mechanism by which glucose metabolism is regulated by FOXM1. Importantly, we further demonstrated that the expression levels of FOXM1, GLUT1 and HK2 were significantly increased in human EOC tissues relative to normal ovarian tissues, and that FOXM1 expression was positively correlated with GLUT1 and HK2 expression. Taken together, our results show that FOXM1 promotes reprogramming of glucose metabolism in EOC cells via activation of GLUT1 and HK2 transcription, suggesting that FOXM1 may be an important target in aerobic glycolysis pathway for developing novel anticancer agents.

Increasing evidence shows that the long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) plays important roles in tumor progression. However, the function and the underlying mechanism of NEAT1 in osteosarcoma (OS) remain unclear. In the present study, we found that NEAT1 expression was significantly upregulated in OS tissues and cell lines. High NEAT1 expression was closely associated with advanced clinicopathologic features and poor overall survival of patients with OS. Using in vitro function assay, we found that NEAT1 could promote the proliferation, invasion, and epithelial‐mesenchymal transition (EMT) process of OS cells. NEAT1 could also promote OS cell growth in vivo. In addition, our studies showed that miR‐186‐5p was a downstream target of NEAT1 in OS. Functionally, miR‐186‐5p suppressed the proliferation, invasion, and EMT process of OS cells. Furthermore, our data revealed that HIF‐1α was a downstream target of miR‐186‐5p and that NEAT1 could exert its tumor oncogenic roles on OS cells via the miR‐186‐5p/HIF‐1α axis. Taking our results together, we elucidated that the NEAT1/miR‐186‐5p/HIF‐1α axis might be a therapeutic approach for the treatment of OS.

Growing evidences suggested that microRNAs (miRNAs) played important roles in the development of intervertebral disc degeneration (IDD). However, the expression level and function of miR-665 in IDD remain unknown. In this study, we showed that the expression level of miR-665 was upregulated in degenerative human NP samples. In addition, miR-665 expression level gradually increased with the exacerbation of disc degeneration grade. Moreover, miR-665 expression level was positively associated with the Pfirrmann grade. Ectopic expression of miR-665 promoted NP cell growth. Furthermore, miR-665 overexpression decreased aggrecan and Col II expression and ectopic expression of miR-665 increased MMP-3 and MMP-13 expression in NP cell. We identified growth differentiation factor 5 (GDF5) was a direct target gene of miR-665 in NP cell and enforced expression of miR-665 decreased GDF5 expression. Elevated expression of miR-665 enhanced NP cell proliferation and decreased aggrecan and Col II expression. In addition, ectopic expression of miR-665 increased MMP-3 and MMP-13 expression through inhibiting GDF5 expression in NP cells. These results suggested that dysregulated miR-665 expression might act an important role in the development of IDD.

Aberrant nucleus pulposus cell proliferation is implicated in the development of intervertebral disk degeneration (IDD). Recent studies have suggested that long noncoding RNAs (lncRNAs) can modulate cell proliferation in several pathological conditions. Here, we indicate that expression of SNHG1 was upregulated in IDD tissues compared with control tissues and that higher SNHG1 expression was associated with disk degeneration grade. In addition, we show that ectopic expression of SNHG1 promoted nucleus pulposus (NP) cell proliferation and increased the PCNA and cyclin D1 expression in NP cells. Ectopic expression of SNHG1 inhibited miR-326 expression in nucleus pulposus cells and promoted CCND1 expression, which is a direct target gene of SNHG1. Moreover, we demonstrate that expression of miR-326 was downregulated in IDD tissues compared with control tissues and that lower SNHG1 expression was associated with disk degeneration grade. Expression of miR-326 was negatively associated with SNHG1 expression in disk degeneration tissues. Overexpression of miR-326 inhibited NP cell growth and inhibited PCNA and cyclin D1 expression in NP cells. Furthermore, we show that overexpression of SNHG1 promoted nucleus pulposus cell proliferation through inhibiting miR-326 expression. These data shed novel light on the role of SNHG1 in the pathogenesis of IDD.

Background: Qing-Yi Decoction (QYD) is a classic precompounded prescription with satisfactory clinical efficacy on acute pancreatitis (AP). However, the chemical profile and overall molecular mechanism of QYD in treating AP have not been clarified.Methods: In the present study, a rapid, simple, sensitive and reliable ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS)-based chemical profile was first established. An integration strategy of network pharmacology analysis and molecular docking based identified ingredients was further performed to screen out the potential targets and pathways involved in the treatment of QYD on AP. Finally, SD rats with acute pancreatitis were constructed to verify the predicted results through a western blot experiment.Results: A total of 110 compounds, including flavonoids, phenolic acids, alkaloids, monoterpenes, iridoids, triterpenes, phenylethanoid glycosides, anthraquinones and other miscellaneous compounds were identified, respectively. Eleven important components, 47 key targets and 15 related pathways based on network pharmacology analysis were obtained. Molecular docking simulation indicated that ERK1/2, c-Fos and p65 might play an essential role in QYD against AP. Finally, the western blot experiments showed that QYD could up-regulate the expression level of ERK1/2 and c-Fos, while down-regulate the expression level of p65.Conclusion: This study predicted and validated that QYD may treat AP by inhibiting inflammation and promoting apoptosis, which provides directions for further experimental studies.

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