Int J Med Sci
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Randomized Controlled Trial
In vivo application of Granulocyte-Macrophage Colony-stimulating Factor enhances postoperative qualitative monocytic function.
Granulocyte macrophage colony-stimulating factor (GM-CSF) can be used as a potent stimulator for immune suppressed patients as defined by a decrease of human leukocyte antigen-D related expression on monocytes (mHLA-DR) after surgery. However, the exact role of GM-CSF on monocytic and T cell function is unclear. ⋯ Postoperative application of GM-CSF significantly enhanced qualitative monocytic function by increased mHLA-DR and TNF-α release after LPS stimulation and apparently enhanced Th17/Treg ratio. Clinical trial registered with www.controlled-trials.com (ISRCTN27114642) 05 December 2008.
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Objectives: 4E-BP1 is a family member of eIF4E binding proteins (4E-BPs) which act as the suppressors of cap-dependent translation of RNA via competitively associating with cap-bound eIF4E. RNA translation regulation is an important manner to control the cellular responses to a series of stress conditions such as ionizing radiation (IR)-induced DNA damage response and cell cycle controlling. This study aimed to determine the mechanism of 4E-BP1 stabilization and its potential downstream target(s) in the response to IR. ⋯ Both PI3K and DNA-PKcs kinase inhibitors significantly decreased the protein level of 4E-BP1, which was associated with the accelerated degradation mediated by ubiquitination-proteasome pathway. Conclusion: PI3K kinase activity is necessary for maintaining 4E-BP1 stability. Our results also suggest 4E-BP1 a novel biological role of regulating cell cycle G2 checkpoint in responding to IR stress in association with controlling CHK2 phosphorylation.
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Comparative Study
Association of Maternal Serum 25-hydroxyvitamin D Concentrations in Second Trimester with Delivery Mode in A Chinese Population.
Objective: To determine the maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations in a Chinese population and investigate its associations with subsequent delivery mode by studying 1924 unrelated pregnant women. Methods: The serum 25(OH)D concentrations was measured by euzymelinked immunosorbent assay (ELISA). Simultaneously, maternal information and subsequent delivery mode were collected. ⋯ Only in the subgroup of the women without abnormal pregnancy history, higher 25(OH)D (> 75.0 nmol/L) concentrations could significantly decrease the risk of caesarean section. Conclusion: Vitamin D deficiency is a quite serious problem in Chinese pregnant women. There is no evidence that the maternal serum 25(OH)D concentrations is associated with increased risk of caesarean section.
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Background: Proton pump inhibitor (PPI) use was reportedly associated with an excess of adverse cardiovascular (CV) events, thus making their systemic effects relevant to public health. PPIs reduce gastric acid secretion, causing increased gastrin release. Gastrin stimulates β-cell neogenesis and enhances insulin release, exerting an incretin-like effect. ⋯ The results were substantially unchanged after adjustment for different characteristics of subjects with and without PPIs. Conclusions: PPI use does not appear associated with altered glycaemia in subjects with CV disease. Unchanged glucose tolerance despite PPI usage may result from simultaneous activation of pathways that counteract the putative PPI-induced incretin-like effect.
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Background: Currently, sorafenib is the only systemic chemotherapy drug for advanced stage Hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicate that sorafenib alone has only moderate antitumor efficacy, and could not inhibit disease metastasis and progression. KU-55933 is a specific ATM inhibitor, which has pro-apoptotic effect on tumor cells. ⋯ The combination treatment with sorafenib and KU-55933 resulted in a strong synergistic effect in vitro. Conclusion: Our results demonstrate that sorafenib combined with KU-55933 treatment does effectively inhibit proliferation of HCC cell lines synergistically. These data suggests that KU-55933 may be a promising chemosensitizer to sorafenib in the treatment of HCC.