Background/Aims: Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. Methods: Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). Results: Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. Conclusions: Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin-ferroportin signaling.
Background
Cyclin-dependent kinase-like 1 (CDKL1) is a member of the cell division control protein 2-related serine–threonine protein kinase family. It is known to occur in various malignant tumors, but its role in neuroblastoma (NB) remains unclear.
Methods
We constructed a CDKL1-silenced NB cell strain (SH-SY5Y) and used real-time PCR and western blotting to confirm the silencing. Functional analyses were performed using the MTT, colony-formation, FACS, wound-healing and transwell invasion assays.
Results
The expression of CDKL1 was significantly upregulated in NB tissue as compared to the adjacent normal tissue. CDKL1 knockdown significantly suppressed cell viability and colony formation ability. It also induced cell cycle G0/G1 phase arrest and apoptosis, and suppressed the migration and invasion ability of SH-SY5Y cells. CDKL1 knockdown decreased the CDK4, cyclin D1 and vimentin expression levels, and increased the caspase-3, PARP and E-cadherin expression levels in SH-SY5Y cells.
Conclusions
Our findings suggest that CDKL1 plays an important role in NB cell proliferation, migration and invasion. It might serve as a potential target for NB therapy.
These results indicate that insulin at even physiological concentration attenuates suppressive efficacies of several immunosuppressive drugs against mitogen-activated proliferation of human PBMCs, possibly via insulin receptors. Insulin used in dialysis patients accompanying diabetes mellitus is suggested to attenuate efficacies of immunosuppressive drugs after renal transplantation.
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