Testosterone Levels in Adolescents and Young Men with Type 1 Diabetes and Their Association with Diabetic Nephropathy.

The association between serum testosterone levels and type 1 diabetes (T1D), especially in adolescents and young adults, has not been fully investigated. We aimed to compare testosterone levels between adolescents/young men with T1D and controls and to determine the factors affecting testosterone levels. We enrolled 47 men with T1D and 32 controls aged 15-29 years. We evaluated anthropometric measurements, lipid profiles, diabetic complications, and levels of serum luteinizing hormone, follicle-stimulating hormone, hemoglobin A1c, 24-h urine albumin, insulin autoantibody, and total serum testosterone. We assessed the correlation between serum testosterone levels and clinical characteristics. Total testosterone levels were higher in T1D patients than in controls (694.6 ± 182.2 vs. 554.1 ± 147.3 ng/dL, p = 0.001), and 24-h urine albumin level positively correlated with total testosterone levels (correlation coefficient 0.415, p = 0.004). T1D patients with nephropathy showed higher total testosterone levels than those without nephropathy (778.4 ± 198.9 vs. 655.4 ± 162.5 ng/dL, p = 0.029). However, diabetic nephropathy and testosterone levels were not significantly associated after adjusting for confounders (ß ± SE 77.5 ± 55.2, p = 0.169). Further longitudinal studies are imperative to confirm a causal relationship between testosterone levels and T1D.

Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells.

BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells. RESULTS: MTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co. Hinokitiol reduced DNA methyltransferase 1 (DNMT1) and ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression in HCT-116 cells. In addition, the expression of ten-eleven translocation protein 1 (TET1), a known DNA demethylation initiator, was increased by hinokitiol treatment. ELISA and FACS data showed that hinokitiol increased the 5-hydroxymethylcytosine (5hmC) level in the both colon cancer cells, but 5-methylcytosine (5mC) level was not changed. Furthermore, hinokitiol significantly restored mRNA expression of O6-methylguanine DNA methyltransferase (MGMT), carbohydrate sulfotransferase 10 (CHST10), and B-cell translocation gene 4 (BTG4) concomitant with reduction of methylation status in HCT-116 cells. CONCLUSIONS: These results indicate that hinokitiol may exert DNA demethylation by inhibiting the expression of DNMT1 and UHRF1 in colon cancer cells.

Spin-orbit torque in a bulk perpendicular magnetic anisotropy Pd/FePd/MgO system.

Spin-orbit torques, including the Rashba and spin Hall effects, have been widely observed and investigated in various systems. Since interesting spin-orbit torque (SOT) arises at the interface between heavy nonmagnetic metals and ferromagnetic metals, most studies have focused on the ultra-thin ferromagnetic layer with interface perpendicular magnetic anisotropy. Here, we measured the effective longitudinal and transverse fields of bulk perpendicular magnetic anisotropy Pd/FePd (1.54 to 2.43 nm)/MgO systems using harmonic methods with careful correction procedures. We found that in our range of thicknesses, the effective longitudinal and transverse fields are five to ten times larger than those reported in interface perpendicular magnetic anisotropy systems. The observed magnitude and thickness dependence of the effective fields suggest that the SOT do not have a purely interfacial origin in our samples.

Effects of cadmium on the expression of placental lactogens and Pit-1 genes in the rat placental trophoblast cells.

Cadmium is an endocrine disrupter (ED) with detrimental effects on mammalian reproduction. The placenta is a primary target for cadmium toxicity during pregnancy. Very little of this metal crosses the placenta to the fetus, and consequently it accumulates in high concentrations in the placenta. Cadmium affects on steroid synthesis and has estrogen- and androgen-like activities. In this study, we investigated the toxic effects of cadmium on placental trophoblast cells as well as the mRNA levels of placental lactogens (PLs), which are under the control of estrogen and play a pivotal role during pregnancy. Pregnant F344 Fisher rats were injected subcutaneously with 0, 0.2, and 2.0mg/kg BW/day of cadmium (CdCl(2)) dissolved in saline from days 11 to 19 of pregnancy and were sacrificed on day 20. The mRNA levels of the PL-Iv and -II genes and Pit-1alpha and beta isotype genes, the trans-acting factor of PLs, were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction, respectively. The frequency of the placental trophoblast cells was observed histochemically. Developmental data and apoptotic chromosomal DNA fragmentation of placental cells were also observed. The mRNA levels of PL-Iv and -II were reduced in a dose-dependent manner by cadmium. The mRNA levels of the Pit-1alpha and beta isotype genes were also reduced by cadmium. In the uterus-conjugated region of the placental junctional zone, the frequency rates of trophoblast cells were lower in the cadmium-treated groups than in the control group. High-dose cadmium exposure (2.0mg) induced not only the reduction of trophoblast cell frequency but also apoptotic chromosomal DNA fragmentation in the junctional zone of the placenta. Developmental metrics such as placental and fetal weights and a number of live fetuses, decreased, while a numbers of resorptions, dead fetuses, and post-implantation losses increased significantly (p<0.05) in the cadmium-treated groups compared to the control. These data suggested that cadmium inhibits the expression of PL genes and reduces the number of trophoblast cells in the rat placenta via an estrogen-like activity, leading to significant toxic effects on placental growth and physiological function in rats.