Background & Aims: Although it is well established that fatty acids (FA) are indispensable for the proliferation and survival of cancer cells in hepatocellular carcinoma (HCC), inhibition of Fatty Acid Synthase (FASN) cannot completely repress HCC cell growth in culture. Thus, we hypothesized that uptake of exogenous FA by cancer cells might play an important role in the development and progression of HCC. Lipoprotein lipase (LPL) is the enzyme that catalyses the hydrolysis of triglycerides into free fatty acids (FFA) and increases the cellular uptake of FA. Methods: We used immunohistochemistry and quantitative reverse transcription real-time polymerase chain reaction to evaluate LPL expression in human and mouse HCC samples. Using lipoprotein-deficient medium as well as siRNAs against LPL and/or FASN, we investigated whether human HCC cells depend on both endogenous and exogenous fatty acids for survival in vitro. Results: We found that LPL is upregulated in mouse and human HCC samples. High expression of LPL in human HCC samples is associated with poor prognosis. In HCC cell lines, silencing of FASN or LPL or culturing the cells in lipoprotein-deficient medium significantly decreased cell proliferation. Importantly, when FASN suppression was coupled to concomitant LPL depletion, the growth restraint of cell lines was further augmented. Conclusions: The present study strongly suggests that both de novo synthetized and exogenous FA play a major role along hepatocarcinogenesis. Thus, combined suppression of LPL and FASN might be highly beneficial for the treatment of human HCC.
Mechanisms underlying beta(2)-adrenoreceptor (beta(2)AR) inverse agonist mediated bronchoprotectiveness remain unknown. We incubated ICI118,551, formoterol, budesonide, and formoterol plus budesonide, as well as ICI118,551 or pindolol plus formoterol, ICI118,551 plus forskolin, SQ22,536 or H89 plus formoterol in ASMCs to detect expressions of M3R, PLC beta(1) and IP3. The level of M3R in the presence of 10(-5) mmol/L ICI118,551 were significantly decreased at 12 h, 24 h and 48 h (P < 0.05), and at 24 h were significantly reduced in ICI118,551 with concentration of 10(-5) mmol/L, 10(-6) mmol/L, 10(-7) mmol/L, and 10(-8) mmol/L (P < 0.05). The level of IP3 in 10(-5) mmol/L ICI118,551 was significantly diminished at 24 h (P < 0.01), except for that at 1 h, neither was in the level of PLC beta(1). A concentration of 10(-5) mmol/L ICI118,551 at 24 h showed a significant reduction of M3R level compared to formoterol (P < 0.01), budesonide (P < 0.01), and formoterol + budesonide (P < 0.05), but significant reduction of PLC beta(1) and IP3 was only found between 10(-5) mmol/L ICI118,551 and formoterol at 24 h, but not in the comparison of budesonide or formoterol + budesonide. Pindolol and H89 could not inhibit the formoterol-induced expression of M3R (P > 0.05), but SQ22,536 significantly antagonized the formoterol-induced M3R expression (P < 0.05). In conclusions, beta(2)AR inverse agonist, ICI118,551, exerts similar bronchoprotective effects to corticosteroids via decreasing the expression of M3R and inhibiting the production of IP3.
Polypropylene (PP), as one of the most common prosthetic materials, has been widely used in intra-peritoneal repair. However, its adhesion to viscera has severely limited its application. Therefore it is critical to improve the PP surface with an anti-adhesion property. In this work, based on dopamine-inspired chemistry, virgin PP (V-PP) mesh was first pretreated with O-2 plasma, subsequently dipped in dopamine aqueous solution for 24 h, and then chitosan (CS) was grafted onto it. Finally the anti-adhesion mesh (O-PP/PDA/CS) was obtained. The formation procedure of a PDA/CS ad-layer was characterized by water contact angle measurements, ATR-FTIR, SEM, and XPS. The results show that a PDA/CS ad-layer could be coated on the PP surface efficiently. NIH/3T3 cells were first cultured on O-PP/PDA/CS meshes to evaluate the availability of anti-adhesion and biocompatibility in vitro, and then the efficacy of the PDA/CS-coating as a barrier for reducing postsurgical adhesions was evaluated using a rat abdominal wall defect model. Compared with the V-PP group, NIH/3T3 cells exhibited higher viability in the O-PP/PDA/CS groups as evaluated by the CCK-8 method. In addition, NIH/3T3 cells grow into round-shapes on the O-PP/PDA/CS surface. This indicates that the modification strategy can facilely lead to excellent properties of anti-adhesion. In vivo tests further indicate that O-PP/PDA/CS meshes were effective in reducing adhesion formation.
AIM: To assess the neuro-protective effect of bone marrow mesenchymal stem cells (BMSCs) on retinal ganglion cells (RGCs) following optic nerve crush in mice. METHODS: C56BL/6J mice were treated with intravitreal injection of PBS, BMSCs, BDNF-interference BMSCs (BIM), and GDNF-interference BMSCs (GIM) following optic nerve crush, respectively. The number of surviving RGCs was determined by whole-mount retinas and frozen sections, while certain mRNA or protein was detected by q-PCR or ELISA, respectively. RESULTS: The density (cell number/mm(2)) of RGCs was 410.77 +/- 56.70 in the retina 21d after optic nerve crush without any treatment, compared to 1351.39 195.97 in the normal control (P<0.05). RGCs in BMSCs treated eyes was 625.07 +/- 89.64/mm(2), significantly higher than that of no or PBS treatment (P<0.05). While RGCs was even less in the retina with intravitreal injection of BIM (354.07 +/- 39.77) and GIM (326.67 +/- 33.37) than that without treatment (P<0.05). BMSCs injection improved the internal BDNF expression in retinas. CONCLUSION: Optic nerve crush caused rust loss of RGCs and intravitreally transplanted BMSCs at some extent protected RGCs from death. The effect of BMSCs and level of BDNF in retinas are both related to BDNF and GDNF expression in BMSCs.
Breast cancer is the most common malignant disease in women, and metastasis formed at distant anatomic sites was the major cause of cancer-related mortality. Thus, a novel therapy target and progression biomarker for breast cancer metastasis was necessary. microRNA (miR)-376b has been demonstrated to regulate angiogenesis; however, its role in cancer metastasis remains elusive. In the present study, the expression of miR-376b in normal breast tissue, JC and 4T1 cells was determined by qPCR. Furthermore, in vitro and in vivo experiments were performed to determine the effect of miR-376b on breast cancer metastasis. The direct target of miR-376b was determined by the luciferase assay and western blotting. The results indicated that silencing of miR-376b by the miR-376-mimic significantly inhibited 4T1 cell migration and invasion in vitro. Lung metastasis was also evidently decreased after silencing of miR-376b in 4T1 cells. Moreover, the luciferase assay and western blotting identified that Hoxd10 is the direct target of miR-376b during the regulation of breast cancer metastasis. To the best of our knowledge, the present study was the first to demonstrate the promoting breast cancer metastasis role of miR-376b by directly targeting Hoxd10. Therefore, it would be a novel therapy target and prognostic biomarker for breast cancer.