Tissue-scale tensional homeostasis in skin regulates structure and physiological function.

Tensional homeostasis is crucial for organ and tissue development, including the establishment of morphological and functional properties. Skin plays essential roles in waterproofing, cushioning and protecting deeper tissues by forming internal tension-distribution patterns, which involves aligning various cells, appendages and extracellular matrices (ECMs). The balance of traction force is thought to contribute to the formation of strong and pliable physical structures that maintain their integrity and flexibility.

The effects of health education on health science teachers' intention to recommend adolescent HPV vaccine for female students in Japan.

The Japanese government suspended proactive recommendation of human papillomavirus (HPV) vaccination due to several reports of adverse events related to it in 2013. After that, the immunization rate of HPV vaccine quickly declined in Japan. Health science teachers (HSTs) are qualified and licensed teachers in charge of health care and health education for students in Japanese schools.

Descemet membrane endothelial keratoplasty using ophthalmic viscoelastic devices for eyes with laser iridotomy-induced corneal endothelial decompensation: Analysis of 11 eyes.

Graft insertion into the anterior chamber is one of the most important procedures for successful Descemet membrane endothelial keratoplasty (DMEK). Especially in eyes with fragile zonular fibers and a shallow anterior chamber, smooth graft insertion tends to become more difficult. Ophthalmic viscoelastic devices (OVDs) can usually help to retain the space in the anterior chamber and to improve the safety of manipulations during various ophthalmic surgeries.

Chandelier Illumination for Descemet Membrane Endothelial Keratoplasty.

Purpose: To describe a simple technique that uses posterior chandelier illumination during Descemet membrane endothelial keratoplasty in cases of severe bullous keratopathy (BK).

Methods: Five eyes of 4 patients with advanced BK undergoing Descemet membrane endothelial keratoplasty were retrospectively analyzed. The pupil of the host eye was not treated with mydriatic or miotic agents.

HUHS1015 Suppresses Colonic Cancer Growth by Inducing Necrosis and Apoptosis in Association with Mitochondrial Damage.

Background: The newly-synthesized naftopidil analog HUHS1015 suppresses tumor growth and induces apoptosis of cells from a variety of cancer types. The present study was conduced to assess the effect of HUHS1015 on human colonic cancer cells and to clarify the underlying mechanism.

Results: HUHS1015 reduced cell viability of Caco-2 and CW2 human colonic cancer cell lines in a concentration (0.

Phosphatidylinositol Derivatives Induce Gastric Cancer Cell Apoptosis by Accumulating AIF and AMID in the Nucleus.

Background: The present study investigated the mechanism underlying the apoptosis of MKN28 human gastric cancer cells induced by the phosphatidylinositol (PI) derivative 1,2-O-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidyl-D-1-inositol (diDCP-LA-D-PI) and its enantiomer diDCP-LA-L-PI.

Materials And Methods: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, enzymatic caspase assay, real-time reverse transcription-polymerase chain reaction (RT-PCR), and western blotting were carried-out.

Results: Both diDCP-LA-D-PI and diDCP-LA-L-PI induced caspase-independent apoptosis of MKN28 cells, with the potential for diDCP-LA-L-PI being much greater than that of diDCP-LA-D-PI.

Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway.

1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX).

Amyloid-β peptide increases cell surface localization of α7 ACh receptor to protect neurons from amyloid β-induced damage.

Amyloid-β peptide 1-42 (Aβ1-42) reduced PC-12 cell viability in a concentration (1-10 μM)- and treatment time (48-72 h)-dependent manner. Nicotine prevented Aβ1-42-induced PC-12 cell death, but conversely, the α7 ACh receptor antagonist α-bungarotoxin enhanced Aβ1-42-induced cell toxicity. Extracellularly applied Aβ1-42 significantly increased cell surface localization of α7 ACh receptor in PC-12 cells as compared with that for non-treated control cells.

Anticancer effect of adenosine on gastric cancer via diverse signaling pathways.

Extracellular adenosine induces apoptosis in a variety of cancer cells via intrinsic and extrinsic pathways. In the former pathway, adenosine uptake into cells triggers apoptosis, and in the latter pathway, adenosine receptors mediate apoptosis. Extracellular adenosine also induces apoptosis of gastric cancer cells.

Adipose-derived stem cell-conditioned medium ameliorates antidepression-related behaviors in the mouse model of Alzheimer's disease.

The present study investigated the effect of adipose-derived stem cell-conditioned medium (ASC-CM) on behavioral disorders in 5xFAD transgenic mice, a model of Alzheimer's disease (AD). The immobility time in the tail suspension and forced swim tests for 5xFAD mice was shorter than that for wild-type mice. Intravenous injection with ASC-CM restored the shortened immobility time for 5xFAD mice to the normal levels or to an extent, being still persistent 4 weeks after injection.

Combination of PKCε Activation and PTP1B Inhibition Effectively Suppresses Aβ-Induced GSK-3β Activation and Tau Phosphorylation.

Glycogen synthase kinase-3β (GSK-3β) is a key element to phosphorylate tau and form neurofibrillary tangles (NFTs) found in tauopathies including Alzheimer's disease (AD). A current topic for AD therapy is focused upon how to prevent tau phosphorylation. In the present study, PKCε activated Akt and inactivated GSK-3β by directly interacting with each protein.

DCP-LA Activates Cytosolic PKCε by Interacting with the Phosphatidylserine Binding/Associating Sites Arg50 and Ile89 in the C2-Like Domain.

Background/aims: The linoleic acid derivative DCP-LA selectively and directly activates PKCε. The present study aimed at understanding the mechanism of DCP-LA-induced PKCε activation.

Methods: Point mutation in the C2-like domain on PKCε was carried out, and each kinase activity was monitored in PC-12 cells using a föerster resonance energy transfer (FRET) probe with cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) at the N- and C-terminal ends of PKCε, respectively, or in the cell-free systems using a reversed phase high-performance liquid chromatography (HPLC).

Rac1 and ROCK are implicated in the cell surface delivery of GLUT4 under the control of the insulin signal mimetic diDCP-LA-PE.

The phosphatidylethanolamine derivative 1,2-O-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE) promoted GLUT4 translocation to the cell surface in differentiated 3T3-L1-GLUT4myc adipocytes through a pathway along a phosphatidylinositol 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt axis, that mimics insulin signaling. Moreover, diDCP-LA-PE-induced GLUT4 translocation was suppressed by inhibitors of the Rho GTPase Rac1 and Rho-associated coiled-coil-containing protein kinase (ROCK) or knocking-down Rac1 and ROCK1. The results of the present study show that Rac1 and ROCK are critical for regulation of GLUT4 trafficking by diDCP-LA-PE as well as insulin.

Phosphatidylinositol Induces Caspase-Independent Apoptosis of Malignant Pleural Mesothelioma Cells by Accumulating AIF in the Nucleus.

Background/aims: Phosphatidylinositol (PI) regulates a variety of cell processes. The present study investigated the antitumor action of 1,2-dioleoyl-sn-glycero-3-phospho-(1'-myo-inositol)(DOPI) and 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-myo-inositol)(DPPI) on human malignant pleural mesothelioma (MPM) cell lines such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells.

Methods: MTT assay, TUNEL staining, flow cytometry using propidium iodide (PI) and annexin V (AV), enzymatic caspase assay, and nuclear staining using DAPI were carried out, and mitochondrial membrane potentials and intracellular distribution of apoptosis-inducing factor (AIF) were monitored in cells with and without the siRNA silencing the Bid-targeted gene.

Diarachidonoylphosphoethanolamine induces necrosis/necroptosis of malignant pleural mesothelioma cells.

The present study investigated 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE)-induced cell death in malignant pleural mesothelioma (MPM) cells. DAPE reduced cell viability in NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H MPM cell lines in a concentration (1-100μM)-dependent manner. In the flow cytometry using propidium iodide (PI) and annexin V (AV), DAPE significantly increased the population of PI-positive and AV-negative cells, corresponding to primary necrosis, and that of PI-positive and AV-positive cells, corresponding to late apoptosis/secondary necrosis, in NCI-H28 cells.

Irinotecan induces cell cycle arrest, but not apoptosis or necrosis, in Caco-2 and CW2 colorectal cancer cell lines.

Irinotecan, a topoisomerase I inhibitor, is clinically used as an anticancer drug. The present study investigated the anticancer effect of irinotecan on p53-negative Caco-2 and p53-positive CW2 human colorectal cancer cell lines. Cell viability for both Caco-2 and CW2 cells was little affected by treatment with irinotecan at concentrations ranging from 0.

The newly synthesized anticancer drug HUHS1015 is useful for treatment of human gastric cancer.

Naftopidil is clinically for treatment of benign prostate hyperplasia, and emerging evidence has pointed to its anticancer effect. To obtain the anticancer drug with the potential greater than that of naftopidil, we have newly synthesized the naftopidil analogue HUHS1015. The present study investigated the mechanism underlying HUHS1015-induced apoptosis of human gastric cancer cells and assessed the possibility for clinical use as an innovative anticancer drug.

1-[2-(2-Methoxyphenylamino)ethylamino]-3-(naphthalene-1- yloxy)propan-2-ol may be a promising anticancer drug.

We have originally synthesized the naftopidil analogue 1-[2-(2-methoxyphenylamino)ethylamino]-3-(naphthalene-1-yloxy)propan-2-ol (HUHS 1015) as a new anticancer drug. HUHS1015 induces cell death in a wide variety of human cancer cell lines originated from malignant pleural mesothelioma, lung cancer, hepatoma, gastric cancer, colorectal cancer, bladder cancer, prostate cancer, and renal cancer. HUHS1015-induced cell death includes necrosis (necroptosis) and apoptosis, and the underlying mechanism differs depending upon cancer cell types.

Oleic acid stimulates glucose uptake into adipocytes by enhancing insulin receptor signaling.

The present study investigated cis-unsaturated free fatty acid (FFA)-regulated glucose uptake. In the cell-free assay of protein tyrosine phosphatase 1B (PTP1B), cis-unsaturated FFAs such as linoleic, linolenic, and oleic acid significantly suppressed PTP1B activity in a concentration (1 - 100 μM)-dependent manner, with the highest potential for oleic acid. Oleic acid (1 μM) stimulated insulin (0.

Naftopidil is useful for the treatment of malignant pleural mesothelioma.

Naftopidil, an α1-adrenoceptor blocker, induced apoptosis of human malignant pleural mesothelioma NCI-H2052 cells. Naftopidil upregulated the expression of tumor necrosis factor-α (TNF-α) mRNA in these cells. Naftopidil, alternatively, increased FasL secretion from NCI-H2052 cells, without affecting the expression of FasL mRNA and protein, and activated caspase-3 and -8 in NCI-H2052 cells.

HUHS1015 induces necroptosis and caspase-independent apoptosis of MKN28 human gastric cancer cells in association with AMID accumulation in the nucleus.

The newly synthesized naftopidil analogue HUHS1015 reduced viability of MKN28 and MKN45 human gastric cancer cells in a concentration (0.3-100 μM)-dependent manner, with the potential greater than that for naftopidil. In the cell cycle analysis, HUHS1015 significantly increased the proportion at the subG1 phase of cell cycling in MKN28 cells.

Hyperphosphorylation of Tau at Ser396 occurs in the much earlier stage than appearance of learning and memory disorders in 5XFAD mice.

The present study investigated the relation of age-dependent spatial learning/memory impairment and Tau phosphorylation in 5XFAD mice, a model of Alzheimer's disease. In the water maze test, the acquisition and retention latencies for 5XFAD mice at 6 months, but not 2 months, of age was significantly longer than those for wild-type mice at the same months of age, without difference in the swim speed and visual acuity between two groups. The level of glycogen synthase kinase 3β (GSK-3β) phosphorylation at Ser9 in the hippocampus for the 5XFAD mice at >4 months of age was significantly lesser than that for wild-type mice at the same months of age, while a robust increase in the Tyr216 phosphorylation of GSK-3β was found both in wild-type and 5XFAD mice at 6 months of age, without no significant difference in the extent between two groups.

Dipalmitoleoylphosphoethanolamine as a PP2A enhancer obstructs insulin signaling by promoting Ser/Thr dephosphorylation of Akt.

Background/aims: The phospholipid phosphatidylethanolamine is implicated in the regulation of a variety of cellular processes. The present study investigated the effect of phosphatidylethanolamines such as 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE), 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (DLPE), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine (DPPE) on protein phosphatases, Akt1/2 activity, GLUT4 mobilizations, and glucose uptake into cells.

Methods: Activity of protein phosphatase 2A (PP2A) was assayed under the cell-free conditions, and Western blotting, intracellular GLUT4 trafficking, and glucose uptake into cells were monitored using differentiated 3T3-L1-GLUT4myc adipocytes.

Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-κB Activation.

A library of oxygenated natural steroids, including physalins, withanolides, and perulactones, coupled with the synthetic cage-shaped right-side structure of type B physalins, was constructed. SAR studies for inhibition of NF-κB activation showed the importance of both the B-ring and the oxygenated right-side partial structure. The 5β,6β-epoxy derivatives of both physalins and withanolides showed similar profiles of inhibition of NF-κB activation and appeared to act on NF-κB signaling via inhibition of phosphorylation and degradation of IκBα.