Paraquat (PQ) is one of the most frequently used pesticides in worldwide. In most countries, PQ is used without restrictions. To investigate the effect of PQ on myogenesis, cultures of C2C12, a useful model to study differentiation of myoblasts into myotubes, were exposed to various concentrations of PQ. Myotube formation did not occur in the presence of 50 µM PQ. Although cell death was not observed at this concentration, growth inhibition was evident in the growth medium. Production of myosin heavy chain, a myogenesis marker protein, decreased dose dependently with the concentration of PQ, which was added to the C2C12 cell culture during differentiation. Inhibition of myogenesis by PQ was not reversed by the addition of ascorbic acid. These results show that PQ is a strong inhibitor of muscle differentiation in vitro.
Our aim was to evaluate the antitumor activities of tocopherol (Toc) and tocotrienol (T3) derivatives. At first, we examined the effect of these vitamin E homologues on the proliferation of rat normal hepatocyte RLN-10 and hepatoma dRLh-84 cells and found that especially T3 inhibited cell proliferation in dRLh-84 cells. Then, we examined the effect of vitamin E homologues on apoptosis induction and found that T3 induced DNA fragmentation and stimulated a rise of caspase-3 activity. In addition, T3 stimulated a rise in caspase-8 activity, while a caspase-8 inhibitor suppressed apoptosis induction by T3. We also examined the incorporation of vitamin E homologues into dRLh-84 cells. T3 was incorporated more quickly compared to Toc. These results indicated that T3 induces apoptosis in dRLh-84 cells and that caspase-8 is involved in this apoptosis induction. The difference in terms of apoptosis induction by vitamin E homologues seems to be related to their different rates of cellular incorporation.
Logistic regression is a widely used method in several fields. When applying logistic regression to imbalanced data, for which majority classes dominate over minority classes, all class labels are estimated as `majority class.' In this article, we use an F-measure optimization method to improve the performance of logistic regression applied to imbalanced data. While many F-measure optimization methods adopt a ratio of the estimators to approximate the F-measure, the ratio of the estimators tends to have more bias than when the ratio is directly approximated. Therefore, we employ an approximate F-measure for estimating the relative density ratio. In addition, we define a relative F-measure and approximate the relative F-measure. We show an algorithm for a logistic regression weighted approximated relative to the F-measure. The experimental results using real world data demonstrated that our proposed method is an efficient algorithm to improve the performance of logistic regression applied to imbalanced data.
Type 2 diabetes (T2DM) is associated with cardiovascular death, including sudden cardiac death due to arrhythmias. Patients with an implantable cardioverter-defibrillator (ICD) are also at high risk of developing a clinically significant ventricular arrhythmia. It has been reported that sodium–glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular deaths; however, the physiological mechanisms of this remain unclear. It is, however, well known that SGLT2 inhibitors increase blood ketone bodies, which have been suggested to have sympatho-suppressive effects. Empagliflozin (EMPA) is an SGLT2 inhibitor. The current clinical trial titled "Placebo-controlled, double-blind study of empagliflozin (EMPA) and implantable cardioverter-defibrillator (EMPA-ICD) in patients with type 2 diabetes (T2DM)" was designed to investigate the antiarrhythmic effects of EMPA. The EMPA-ICD study is a prospective, multicenter, placebo-controlled, double-blind, randomized, investigator-initiated clinical trial currently in progress. A total of 210 patients with T2DM (hemoglobin A1c 6.5–10.0%) will be randomized (1:1) to receive once-daily placebo or EMPA, 10 mg, for 24 weeks. The primary endpoint is the number of clinically significant ventricular arrhythmias for 24 weeks before and 24 weeks after study drug administration, as documented by the ICD. The secondary endpoints of the study are the change from baseline concentrations in blood ketone and catecholamine 24 weeks after drug treatment. The EMPA-ICD study is the first clinical trial to assess the effect of an SGLT2 inhibitor on clinically significant ventricular arrhythmias in patients with T2DM and an ICD. Unique trial number, jRCTs031180120 ( https://jrct.niph.go.jp/latest-detail/jRCTs031180120 ).
Eight-month-old male Sprague Dawley rats were fed diets containing α-tocopherol (Toc) or tocotrienol (T3) mixture (composed of 20.5% α-Toc, 21.4% α-T3, 36.5% γ-T3 and other analogs) at the 0.1 or 0.5% level for 3 weeks to examine their dietary effects on lipid metabolism and immune indices. Feeding of α-Toc and T3 significantly de-creased liver phosphatidylcholine peroxide and serum phospholipid levels. In the regulation of immunoglobulin level, significant increase in serum IgA level was observed in the rats fed α-Toc or T3, but the effect on immunoglobulin productivity from spleen and mesenteric lymph node (MLN) was not as marked. Feeding of α-Toc and T3 significantly decreased LTB4-releasing activity of peritoneal exudate cells without decreasing arachidonic acid level. The suppression of LTB4 release was more marked in the rats fed 0.1% α-Toc or T3 than in these fed them at the 0.5% level. When animals were killed after 10 h of fasting, T3 was detected only in MLN and epidydimal adipose tissue. These results suggest that T3 modulates lipid metabolism and immune functions as well as α-Toc, and that MLN and adipose tissue are the main target tissues of T3.
