NEAT1 Confers Radioresistance to Hepatocellular Carcinoma Cells by Inducing PINK1/Parkin-Mediated Mitophagy.

A long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) variant 1 (NEAT1v1), confers radioresistance to hepatocellular carcinoma (HCC) cells by inducing autophagy via γ-aminobutyric acid A receptor-associated protein (GABARAP). Radiation induces oxidative stress to damage cellular components and organelles, but it remains unclear how NEAT1v1 protects HCC cells from radiation-induced oxidative stress via autophagy. To address this, we precisely investigated NEAT1v1-induced autophagy in irradiated HCC cell lines.

Confers Radioresistance to Hepatocellular Carcinoma Cells by Inducing Autophagy through GABARAP.

A long noncoding RNA (lncRNA), () (), is involved in the maintenance of cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). CSCs are suggested to play important roles in therapeutic resistance. Therefore, we investigated whether is involved in the sensitivity to radiation therapy in HCC.

Case of lipoatrophic diabetes induced by juvenile dermatomyositis.

Lipodystrophy is a rare condition that is often accompanied by one or more metabolic diseases. Here, we report a case of lipoatrophic diabetes induced by juvenile dermatomyositis. Although pioglitazone was not effective for lowering blood glucose levels, our observation suggested that it improved liver function slightly.

Dried Saliva Spot (DSS) as a Convenient and Reliable Sampling for Bioanalysis: An Application for the Diagnosis of Diabetes Mellitus.

This paper proposes the dried saliva spot (DSS) as a convenient sampling technique for bioanalysis. The analytical method with the DSS was used for the determination of D,L-lactic acid (D,L-LA) and the D/L ratio of diabetic patients and prediabetic persons for the simple screening of the disease. The D,L-LA in the DSS was labeled with a chiral reagent (DMT-3(S)-Apy) for carboxylic acids and determined by UPLC-ESI-MS/MS.

Profiling of chiral and achiral carboxylic acid metabolomics: synthesis and evaluation of triazine-type chiral derivatization reagents for carboxylic acids by LC-ESI-MS/MS and the application to saliva of healthy volunteers and diabetic patients.

Novel triazine-type chiral derivatization reagents, i.e., (S)-1-(4,6-dimethoxy-1,3,5-triazin-2-yl)pyrrolidin-3-amine (DMT-3(S)-Apy) and (S)-4,6-dimethoxy-N-(pyrrolidin-3-yl)-1,3,5-triazin-2-amine (DMT-1(S)-Apy), were developed for the highly sensitive and selective detection of chiral carboxylic acids by UPLC-MS/MS analysis.

Determination of acetone in saliva by reversed-phase liquid chromatography with fluorescence detection and the monitoring of diabetes mellitus patients with ketoacidosis.

Background: In diabetes mellitus (DM) patients with ketoacidosis, ketone bodies, i.e., acetone, acetoacetic acid (AA) and β-hydroxybutyric acid (HA), are increased in the blood and urine.

Roles of MED1 in quiescence of hair follicle stem cells and maintenance of normal hair cycling.

MED1 (mediator complex subunit 1) is expressed by human epidermal keratinocytes and functions as a coactivator of several transcription factors. To elucidate the role of MED1 in keratinocytes, we established keratinocyte-specific Med1-null (Med1(epi-/-)) mice using the K5Cre/LoxP system. Development of the epidermis and appendages of Med1(epi-/-) mice were macroscopically and microscopically normal until the second catagen of the hair cycle.

Simultaneous determination of DL-lactic acid and DL-3-hydroxybutyric acid enantiomers in saliva of diabetes mellitus patients by high-throughput LC-ESI-MS/MS.

A simultaneous determination method for the enantiomers of chiral carboxylic acids by the combination of ultraperformance liquid chromatography and mass spectrometry (UPLC-MS/MS) has been developed. (S)(+)-1-(2-Pyrrolidinylmethyl)-pyrrolidine (S-PMP) was used as the derivatization reagent for the high-throughput determination of biological chiral carboxylic acids, i.e.

Utility of organotypic raphe slice cultures to investigate the effects of sustained exposure to selective 5-HT reuptake inhibitors on 5-HT release.

Background And Purpose: Selective 5-hydroxytryptamine (5-HT, serotonin) reuptake inhibitors (SSRIs) are widely used antidepressants and their therapeutic effect requires several weeks of drug administration. The delayed onset of SSRI efficacy is due to the slow neuroadaptive changes of the 5-hydroxytryptaminergic (5-HTergic) system. In this study, we examined the acute and chronic effects of SSRIs on the 5-HTergic system using rat raphe slice cultures.

Augmentation of serotonin release by sustained exposure to MDMA and methamphetamine in rat organotypic mesencephalic slice cultures containing raphe serotonergic neurons.

Several lines of evidence suggest the involvement of the raphe-serotonergic neurons in addiction to psychostimulants and some recreational drugs. In this study, we established rat organotypic mesencephalic slice cultures containing the raphe nuclei and examined the effects of sustained exposure to 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH). Immunostaining for tryptophan hydroxylase (TPH) studies revealed that serotonergic neurons were abundant in the slice cultures.

Isoproterenol-induced hypertrophied rat hearts: does short-term treatment correspond to long-term treatment?

In consideration of clinical implications, it is often complained that short-term experimental diseased heart models do not mimic long-term diseased hearts that are often clinically encountered. The aim of the present study was (i) to compare the left ventricular function between rat cardiac hypertrophy models treated with isoproterenol for 3 days (Iso 3d) and 7 days (Iso 7d) by pressure-volume measurements with a catheter method, and (ii) to follow up the left ventricular function in the same model treated with Iso up to 16 weeks with a less-invasive echocardiography. An infusion of either Iso (1.

Effects of a novel histone deacetylase inhibitor, N-(2-aminophenyl) benzamide, on a reversible hypertrophy induced by isoproterenol in in situ rat hearts.

The aim of the present study was performed to determine whether a novel histone deacetylase (HDAC) inhibitor, N-(2-aminophenyl)-4-{[benzyl(2-hydroxyethyl)amino]methyl} benzamide (K-183), prevents a reversible cardiac hypertrophy induced by isoproterenol and improves left ventricular (LV) dysfunction in rats. Either isoproterenol or vehicle was infused for 3 days by osmotic minipump. One hour prior to the implantation of isoproterenol, K-183 or trichostatin A (TSA) was injected twice a day for 3 days.

Positive inotropic effect of nicorandil in adult rats in situ.

Purpose: Although the cardiac protective and negative inotropic effects of nicorandil via opening the sarcolemmal or mitochondrial K(ATP) channel and NO-like action are well known, positive inotropic effects of nicorandil in normal hearts have not been reported. The aim of the current study was to investigate how nicorandil affects left ventricular (LV) function of in situ adult rat hearts through the entire cardiovascular system.

Methods: We performed simultaneous and continuous measurements of LV pressure (P) by a catheter-tip micromanometer and LV volume (V) using a conductance catheter.

A brief regional ischemic-reperfusion enhances propofol-induced depression in left ventricular function of in situ rat hearts.

Background: Propofol is short-acting intravenous general anesthetics that reduces cardiovascular hemodynamics. The effects of propofol on intrinsic myocardial contractility, however, remain debatable. The aim of the current study was to test the hypothesis that inhibitory effects of propofol on left ventricular (LV) contractility and mechanical work capability of in situ ejecting rat hearts are attenuated after a brief regional ischemia and reperfusion.

Reversible effects of isoproterenol-induced hypertrophy on in situ left ventricular function in rat hearts.

The aim of the present study was to evaluate specifically left ventricular (LV) function in rat hearts as they transition from the normal to hypertrophic state and back to normal. Either isoproterenol (1.2 and 2.

O2 consumption of mechanically unloaded contractions of mouse left ventricular myocardial slices.

Left ventricular (LV) myocardial slices were isolated from murine hearts (300 microm thick) and were stimulated at 1 Hz without external load. Mean myocardial slice O(2) consumption (MVo(2)) per minute (mMVo(2)) without stimulation was 0.97 +/- 0.

Postextrasystolic contractility normally decays in alternans in canine in situ heart.

We have reported that the postextrasystolic (PES) potentiation of left ventricular (LV) contractility usually decays in alternans at heart rates above 80-100 beats/min in the canine excised, cross-circulated heart. We examined whether the PES contractility would also decay in alternans even in the canine in situ heart presumably more physiological than the excised heart. In anesthetized, ventilated, and open-chest mongrel dogs, we measured LV pressure and volume with a micromanometer and a conductance catheter cannulated into the LV and obtained LV end-systolic maximum elastance (E(max)) as the reasonably load-independent contractility index.

Aziridination of Activated Imines with Monocarbonyl Iodonium Ylides Generated from (Z)-(2-Acetoxyvinyl)iodonium Salts via Ester Exchange: Stereoselective Synthesis of 2-Acylaziridines.

Monocarbonyl iodonium ylides, generated in situ from (Z)-(2-acetoxyvinyl)iodonium salts via an ester exchange reaction with EtOLi, undergo alkylidene transfer reactions to activated imines yielding 2-acylaziridines in good yields. The stereochemical outcome of this aziridination was shown to be dependent on both the activating groups of the imines and the reaction solvents: that is, the aziridination of N-(2,4,6-trimethylbenzenesulfonyl)imines in THF affords cis-aziridines as a major product while that of N-benzoylimines in THF-DMSO or THF gives the trans isomer stereoselectively.

Nucleophilic Vinylic Substitutions of (Z)-(beta-Haloalkenyl)phenyliodonium Salts with Sodium Benzenesulfinate: First Evidence of a Michael Addition of Nucleophiles to Alkenyliodonium Salts at the C(beta) Atom.

Evidence for a Michael addition of a nucleophile to alkenyl(phenyl)iodonium salts at the C(beta) atom is reported here for the first time. Nucleophilic vinylic substitutions of (Z)-(beta-chloroalkenyl)- 2b and (Z)-(beta-bromoalkenyl)iodonium tetrafluoroborates 3b with sodium benzenesulfinate in THF afforded stereoselectively (Z)-1,2-bis(benzenesulfonyl)alkene 5b with retention of configuration. Intermediate formation of (Z)-(beta-(benzenesulfonyl)alkenyl)iodonium salt 9b in these reactions was established by (1)H NMR experiments in CDCl(3).

alpha-Vinylation of 1,3-Dicarbonyl Compounds with Alkenyl(aryl)iodonium Tetrafluoroborates: Effects of Substituents on the Aromatic Ring and of Radical Inhibitors.

Direct alpha-vinylations of enolate anions derived from 1,3-dicarbonyl compounds with 4-tert-butyl-1-cyclohexenyl(aryl)iodonium 2 and 1-cyclopentenyl(aryl)iodonium tetrafluoroborates 3 are reported. Frequently, alpha-phenylations compete with the vinylations in the reaction of 1,3-dicarbonyl compounds with alkenyl(phenyl)iodonium salts 2a and 3a. Use of alkenyl(p-methoxyphenyl)iodonium salts 2b and 3b, however, leads to selective alpha-vinylation at the expense of the competing arylation of 1,3-dicarbonyl compounds.