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1.
J Biol Regul Homeost Agents ; 34(3): 775-783, 2020.
Article in English | MEDLINE | ID: mdl-32627519

ABSTRACT

To investigate the role of microRNA-206 (miRNA-206) in the malignant progression of osteosarcoma and the underlying mechanism, expression pattern of miRNA-206 in osteosarcoma tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between miRNA-206 level and prognosis of osteosarcoma patients was analyzed. Regulatory effects of miRNA-206 on the proliferation and metastasis of U2OS and MG63 cells were evaluated by cell counting kit-8 (CCK-8), Transwell and wound healing assay. Through dual-luciferase reporter gene assay, the target gene of miRNA-206 was verified. A series of rescue experiments were conducted to explore the role of miRNA-206/Notch3 in regulating the malignant progression of osteosarcoma. MiRNA-206 was downregulated in osteosarcoma tissues and cell lines, and its level was correlated to poor prognosis and distant metastasis of osteosarcoma patients. Overexpression of miRNA-206 attenuated the proliferative and metastatic abilities of osteosarcoma cells, and miRNA-206 knockdown obtained the opposite trends. Notch3 was verified to be the target gene of miRNA-206, which was upregulated in osteosarcoma and accelerated osteosarcoma cells to proliferate and metastasize. Finally, rescue experiments showed that Notch3 overexpression partially reversed the regulatory effects of miRNA-206 on cellular behaviors of osteosarcoma cells. MiRNA-206 is downregulated in osteosarcoma. Overexpression of miRNA-206 accelerates osteosarcoma cells to proliferate and metastasize by targeting Notch3, thus accelerating the malignant progression of osteosarcoma.


Subject(s)
Bone Neoplasms , MicroRNAs/genetics , Osteosarcoma , Bone Neoplasms/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation/genetics , Humans , Osteosarcoma/genetics , Receptor, Notch3
2.
Eur Rev Med Pharmacol Sci ; 24(11): 5895-5904, 2020 06.
Article in English | MEDLINE | ID: mdl-32572902

ABSTRACT

OBJECTIVE: The anti-inflammatory effect of Sirtuin 1 (Sirt1) during intervertebral disc degeneration (IDD) has been widely confirmed. Monocyte chemoattractant protein-1 (MCP-1) activation is the initiating inflammatory response associated with the IDD. However, whether Sirt1 suppresses MCP-1 in the intervertebral disc is unclear. PATIENTS AND METHODS: The MCP-1 and Sirt1 protein expression in the degenerated and non-degenerated NP tissues were compared by immunohistochemistry (IHC). We induced nucleus pulposus (NP) cell degeneration by IL-1ß and mediated cellular Sirt1 expression through the Sirt1 activator resveratrol (Res) or inhibitor Nicotinamide (Nico). In addition, the inhibitors of MCP-1 and Activator protein 1 (AP-1) were also used in cell culture. The function of NP cells was determined by the type II collagen and Cell Counting Kit-8 (CCK-8) assay. We assessed the Sirt1 and MCP-1 expression by the Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR). The AP-1 activity was valued by the phosphorylation of its components c-Fos, and c-Jun. RESULTS: Both in vivo and in vitro experimental results indicated that MCP-1 was upregulated in the degenerated condition, which was opposite to Sirt1 expression. Res suppressed AP-1, the phosphorylation of c-Fos/c-Jun, and the MCP-1 expression. On the contrary, Sirt1 downregulation by Nico aggravated the phosphorylation of c-Fos/c-Jun and MCP-1 expression. However, the MCP-1 suppression did not affect the Sirt1 and AP-1 levels. The destruction of AP-1 activation also inhibited MCP-1 expression but not Sirt1. The upregulation of Sirt1 and suppression of MCP-1 improved the type II collagen expression and cell viability, which was injured by IL-1ß. CONCLUSIONS: Sirt1 suppresses the MCP-1 production in the degenerated NP cells by suppressing the phosphorylation of the AP-1 subunits c-Fos and c-Jun.


Subject(s)
Chemokine CCL2/biosynthesis , Intervertebral Disc Degeneration/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Sirtuin 1/metabolism , Cell Line , Cell Survival , Chemokine CCL2/genetics , Humans , Interleukin-1beta/metabolism , Intervertebral Disc Degeneration/pathology , Phosphorylation , Sirtuin 1/genetics
4.
Br J Radiol ; 83(989): 411-8, 2010 May.
Article in English | MEDLINE | ID: mdl-19723766

ABSTRACT

The aim of this study was to evaluate the imaging features of hepatic angiomyolipoma (AML) on contrast-enhanced ultrasound (CEUS). The imaging features of 12 pathologically proven hepatic AML lesions in 10 patients who had undergone baseline ultrasound (BUS) and CEUS examinations were evaluated retrospectively. The enhancement extent, pattern and dynamic change, along with the enhancement process, on CEUS were analysed. The diagnostic results of BUS and CEUS before pathological examination were also recorded. The results showed that 75% (9/12) of the AML lesions exhibited mixed echogenicity on BUS and most showed remarkable hyperechogenicity in combination with a hypoechoic or anechoic portion. Arterial flow signals were detected in 75% (9/12) of the lesions on colour Doppler imaging. On CEUS, 66.7% (n = 8) of the 12 lesions exhibited hyperenhancement in the arterial phase, slight hyperenhancement (n = 2) or isoenhancement (n = 6) in the portal phase, and slight hyperenhancement (n = 1) or isoenhancement (n = 7) in the late phase. Three (25%) lesions exhibited hyperenhancement in the arterial phase and hypoenhancement in both portal and late phases. One (8.3%) lesion exhibited hypoenhancement throughout the CEUS process. Before pathological examination with BUS, only 3 (25%) lesions were correctly diagnosed as hepatic AML. Conversely, on CEUS, correct diagnoses were made for 66.8% (8/12) of hepatic AMLs. Therefore, arterial hyperenhancement and subsequent sustained enhancement on CEUS were found in the majority of hepatic AMLs. The combination of BUS and CEUS leads to the correct diagnosis in the majority of hepatic AMLs, and is higher than the success rate achieved by BUS alone.


Subject(s)
Angiomyolipoma/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Adult , Contrast Media , Female , Humans , Image Enhancement , Male , Middle Aged , Renal Circulation , Retrospective Studies , Ultrasonography, Doppler, Color/methods
5.
Br J Radiol ; 81(971): 881-9, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18941048

ABSTRACT

The aim of this study was to compare the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). 40 pathologically proven ICC lesions in 40 patients were evaluated retrospectively with both CEUS and CECT. The enhancement level and pattern in the dynamic phases on both CEUS and CECT were analysed. The diagnostic results of CEUS and CECT before pathological examination were also recorded. During arterial phases, the number of lesions that appeared as (i) peripheral irregular rim-like hyperenhancement, (ii) diffuse heterogeneous hyperenhancement, (iii) diffuse homogeneous hyperenhancement and (iv) diffuse heterogeneous hypoenhancement were 19 (47.5%), 9 (22.5%), 5 (12.5%) and 7 (17.5%), respectively, on CEUS, and 22 (55.0%), 3 (7.5%), 2 (5.0%) and 13 (32.5%), respectively, on CECT (p = 0.125). In the portal phase, the number of lesions showing hyperenhancement and hypoenhancement were 1 (2.5%) and 39 (97.5%), respectively, on CEUS, and 15 (37.5%) and 25 (62.5%) on CECT (p = 0.0001). CEUS made a correct diagnosis in 32 (80.0%) lesions before pathological examination; CECT made a correct diagnosis in 27 (67.5%) lesions (p = 0.18). In conclusion, the enhancement patterns of ICC on CEUS were consistent with those on CECT in the arterial phase, whereas in the portal phase ICC faded out more obviously on CEUS than on CECT. CEUS had the same accuracy as CECT in diagnosing ICCs, and so can be used as a new modality for the characterization of ICC.


Subject(s)
Bile Duct Neoplasms , Bile Ducts, Intrahepatic , Cholangiocarcinoma , Contrast Media , Adult , Aged , Bile Duct Neoplasms/diagnostic imaging , Bile Ducts, Intrahepatic/diagnostic imaging , Cholangiocarcinoma/diagnostic imaging , Female , Hemodynamics/physiology , Humans , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed/methods , Tomography, X-Ray Computed/standards , Treatment Outcome , Ultrasonography/methods , Ultrasonography/standards
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