C3H/HeNSlc mouse with low phospholipid transfer protein expression showed dyslipidemia.

High serum levels of triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of coronary heart disease in humans. Herein, we first reported that the C3H/HeNSlc (C3H-S) mouse, a C3H/HeN-derived substrain, is a novel model for dyslipidemia. C3H-S showed hypertriglyceridemia and low total cholesterol (TC), HDL-C, and phospholipid (PL) concentrations. To identify the gene locus causing dyslipidemia in C3H-S, we performed genetic analysis. In F2 intercrosses between C3H-S mice and strains with normal serum lipids, the locus associated with serum lipids was identified as 163-168 Mb on chromosome 2. The phospholipid transfer protein (Pltp) gene was a candidate gene within this locus. Pltp expression and serum PLTP activity were markedly lower in C3H-S mice. Pltp expression was negatively correlated with serum TG and positively correlated with serum TC and HDL-C in F2 mice. Genome sequencing analysis revealed that an endogenous retrovirus (ERV) sequence called intracisternal A particle was inserted into intron 12 of Pltp in C3H-S. These results suggest that ERV insertion within Pltp causes aberrant splicing, leading to reduced Pltp expression in C3H-S. This study demonstrated the contribution of C3H-S to our understanding of the relationship between TG, TC, and PL metabolism via PLTP.

Investigation of appropriate needle length considering skin thickness with the real injection posture for insulin injections in diabetic patients.

BACKGROUND: Insulin treatment is widely used not only for type 1 but also for type 2 diabetes patients. Insulin must be injected into the subcutaneous tissue to be effective. The needle length has been shortened for safety and efficiency. However, whether patients use an appropriate needle length is unclear. METHODS: Skin thickness was measured by ultrasound with patients in their usual posture during injection. Furthermore, the effect of the intervention in which the needle length was changed was investigated. RESULTS: Thirty-eight percent of the patients had fluid leakage and injected the needle intradermally. The average skin thickness was 3.3 mm while sitting, which was greater than that in a previous report including measurements taken while lying down. Consequently, the skin thickness was > 4 mm in 9.5% of the patients who used 4-mm needles. Cases of leakage and intradermal injection decreased when the needle length was changed. CONCLUSIONS: This study identified that the needle length should be considered in patients with thick skin or a lower body mass index due to possibility of intradermal injection.

Anti-tumor effects of mAb against L-type amino acid transporter 1 (LAT1) bound to human and monkey LAT1 with dual avidity modes.

L-Type amino acid transporter 1 (LAT1) disulfide linked to CD98 heavy chain (hc) is highly expressed in most cancer cells, but weakly expressed in normal cells. In the present study, we developed novel anti-LAT1 mAbs and showed internalization activity, inhibitory effects of amino acid uptake and cell growth and antibody-dependent cellular cytotoxicity, as well as in vivo antitumor effects in athymic mice. Furthermore, we examined the reactivity of mAbs with LAT1 of Macaca fascicularis to evaluate possible side-effects of antihuman LAT1 mAbs in clinical trials. Antihuman LAT1 mAbs reacted with ACHN human and MK.P3 macaca kidney-derived cells, and this reactivity was significantly decreased by siRNAs against LAT1. Macaca LAT1 cDNA was cloned from MK.P3, and only two amino acid differences between human and macaca LAT1 were seen. RH7777 rat hepatoma and HEK293 human embryonic kidney cells expressing macaca LAT1 were established as stable transfectants, and antihuman LAT1 mAbs were equivalently reactive against transfectants expressing human or macaca LAT1. Dual (high and low) avidity modes were detected in transfectants expressing macaca LAT1, MK.P3, ACHN and HCT116 human colon cancer cells, and KA values were increased by anti-CD98hc mAb, suggesting anti-LAT1 mAbs detect an epitope on LAT1-CD98hc complexes on the cell surface. Based on these results, LAT1 may be a promising anticancer target and Macaca fascicularis can be used in preclinical studies with antihuman LAT1 mAbs.

Memorized chiral arrangement of gemini surfactant assemblies in nanometric hybrid organic-silica helices.

Hybrid nanohelices were obtained from silicification of self-assemblies of gemini surfactants with tartrate counterions. The chiral arrangement of these non-chiral gemini surfactants was preserved in the silica matrix even after the counterion exchange for a non-chiral bromide, and was capable of inducing the chiral organisation of a non-chiral dye, methyl orange.