BMP6 and BMP4 expression in patients with cancer-related anemia and its relationship with hepcidin and s-HJV.

In the present study, we investigated BMP6 and BMP4 expression in patients with cancer-related anemia (CRA) as well as its relationship with hepcidin and s-HJV. The avidin-biotin system enzyme-linked immunosorbent assay was used to test serum levels of BMP6, BMP4, s-HJV, and hepcidin in 53 cancer patients with anemia and 52 control cancer patients without anemia. Serum levels of BMP6 and hepcidin in the anemia group were 434.53 ± 212.11 ng/mL and 5.68 ± 3.89 µg/L, respectively. In the non-anemia cancer group, serum BMP6 and hepcidin levels were 334.37 ± 171.32 ng/mL and 4.60 ± 2.28 µg/L, which were significantly lower than the levels for the CRA group (P < 0.05). In addition, the serum level of s-HJV was 0.69 ± 0.28 ng/mL in the CRA group, which was significantly lower compared to that for the non-anemia group (1.07 ± 1.00 ng/mL, P < 0.01). There were no significant differences in BMP4 expression between the two groups. BMP6 was negatively correlated with s-HJV and Hb (r = -0.2536 and -0.2949, P < 0.01), but was not correlated with hepcidin. Similarly, BMP4 expression was not correlated with Hb, s-HJV, or hepcidin. Our study shows that patients with CRA had high expression of BMP6 and hepcidin and low expression of s-HJV. BMP6 was found to be negatively correlated with s-HJV; both regulate hepcidin expression and play important roles in the development of anemia.

Distribution of LIM domain kinase 1 in the olfactory bulb, cerebral cortex, hippocampus, and cerebellum of the App/PS+/- mice.

LIM domain kinase 1 (LIMK1), an actin-binding kinase, can phosphorylate and inactivate its substrates, and can regulate long-term memory and synaptic plasticity. Both ß-amyloid precursor protein (App) and presenilin (PS) are functional degeneration factors during early neuronal development, and are considered as potential factors that contribute to the development of Alzheimer's disease (AD). However, hardly any information is available about the distribution and expression of LIMK1. Thus, using the App and PS deficient mice, the role of LIMK1 was demonstrated in the absence of App and PS. Our results showed that LIMK1 was present in the nerve fiber layer and external plexiform layer of the olfactory bulb, as well as in the mitral cells and Purkinje cells of the cerebellum in App and PS deficient mice. Additionally, LIMK1 was concentrated in the granule cell layer of the olfactory bulb and cerebellum and LIMK1 positive cells were located in the CA1 region of the hippocampus. Our study indicates that there is a connection between LIMK1 and AD in the mouse model of AD. This might explain neurological problems such as cerebellar ataxia, impaired long-term memory, and impaired synaptic plasticity observed in AD.

Knockdown expression of Apc11 leads to cell-cycle distribution reduction in G2/M phase.

Anaphase-promoting complex/cyclosome (APC/C) is a key E3 ubiquitin ligase in cell division, which catalyses ubiquitination of cell-cycle regulators. Studying this complex could reveal important information regarding its application in cancer research and therapy. In this study, 4 synthesized small interfering RNAs (siRNAs) were transfected into HEK293T cells to suppress messenger RNA (mRNA) of Apc11; 2 of these reduced the amount of Apc11 mRNA by over 50%. Further experiments showed that rather than causing apoptosis, siRNA transfection led to cell-cycle distributions characterized by less time spent in G2/M phase and more time spent in G1 phase. This phenomenon was specifically induced by Apc11 silencing, as co-transfection of siRNA and an Apc11 plasmid could reverse this distribution bias. Our results suggested that siRNA targeted against Apc11 could hamper entry into G2/M phase. Current efforts are focused on elucidating the function and utility of the APC complex for clinical applications.