Tunable multi-responsive nano-gated mesoporous silica nanoparticles as drug carriers.

Tunable multi-responsive mesoporous silica nanoparticles were prepared by post-condensation/surface modification of MCM-41 nanoparticles. Surface grafting of a poly(N,N-dimethylaminoethyl methacrylate)-based polymer containing disulfide bonds was achieved by a click reaction. Chemical modification, morphological characteristics, and textural properties of the nanoparticles were studied using multiple characterization techniques such as Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, small-angle X-ray scattering, and nitrogen adsorption/desorption behavior.

Production of Inflected Novel Words in Older Adults With and Without Dementia.

While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know.

Potentiation of TRAIL‑induced cell death by nonsteroidal anti‑inflammatory drug in human hepatocellular carcinoma cells through the ER stress‑dependent autophagy pathway.

Hepatocellular carcinoma (HCC) is the most commonly diagnosed primary liver malignancy. The limited success with relapse of the disease in HCC therapy is frequently associated with the acquired resistance to anticancer drugs. To develop a strategy and design for overcoming the resistance of HCC cells to TNF‑related apoptosis inducing ligand (TRAIL)‑induced cell death, we evaluated the efficacy of a non‑steroidal anti‑inflammatory drug (NSAID) in combination with TRAIL against TRAIL‑resistant HCC cells expressing a high level of CD44.

Lexical Decision Task for Studying Written Word Recognition in Adults with and without Dementia or Mild Cognitive Impairment.

Older adults are slower at recognizing visual objects than younger adults. The same is true for recognizing that a letter string is a real word. People with Alzheimer's disease (AD) or Mild Cognitive Impairment (MCI) demonstrate even longer responses in written word recognition than elderly controls.

Nonsteroidal Anti-inflammatory Drugs Sensitize CD44-Overexpressing Cancer Cells to Hsp90 Inhibitor Through Autophagy Activation.

Recently, novel therapeutic strategies have been designed with the aim of killing cancer stem-like cells (CSCs), and considerable interest has been generated in the development of specific therapies that target stemness-related marker of CSCs. In this study, nonsteroidal anti-inflammatory drugs (NSAIDs) significantly potentiated Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-mediated cytotoxicity through apoptotic and autophagic cell death induction, but COX-2-inhibitory function was not required for NSAID-induced autophagy in CD44-overexpressing human chronic myeloid leukemia K562 (CD44K562) cells. Importantly, we found that treatment with NSAIDs resulted in a dose-dependent increase in LC3-II level and decrease in p62 level and simultaneous reduction in multiple stemness-related markers including CD44, Oct4, c-Myc, and mutant p53 (mutp53) in CD44K562 cells, suggesting that NSAIDs could induce autophagy, which might mediate degradation of stemness-related marker proteins.

Preferential Disruption of Auditory Word Representations in Primary Progressive Aphasia With the Neuropathology of FTLD-TDP Type A.

Four patients with primary progressive aphasia displayed a greater deficit in understanding words they heard than words they read, and a further deficiency in naming objects orally rather than in writing. All four had frontotemporal lobar degeneration-transactive response DNA binding protein Type A neuropathology, three determined postmortem and one surmised on the basis of granulin gene (GRN) mutation. These features of language impairment are not characteristic of any currently recognized primary progressive aphasia variant.

Effects of morphological family on word recognition in normal aging, mild cognitive impairment, and Alzheimer's disease.

Reading a word activates morphologically related words in the mental lexicon. People with Alzheimer's disease (AD) or Mild Cognitive Impairment (MCI) often have difficulty retrieving words, though the source of this problem is not well understood. To better understand the word recognition process in aging and in neurodegenerative disorders such as MCI and AD, we investigated the nature of the activation of morphologically related family members in 22 Finnish speakers with AD, 24 with MCI, and 17 cognitively healthy elderly.

Sensitization of multidrug-resistant cancer cells to Hsp90 inhibitors by NSAIDs-induced apoptotic and autophagic cell death.

NSAIDs (non-steroidal anti-inflammatory drugs) have potential use as anticancer agents, either alone or in combination with other cancer therapies. We found that NSAIDs including celecoxib (CCB) and ibuprofen (IBU) significantly potentiated the cytotoxicity of Hsp90 inhibitors in human multidrug-resistant (MDR) cells expressing high levels of mutant p53 (mutp53) protein and P-glycoprotein (P-gp), and reversed Hsp90 inhibitor resistance caused by activation of heat shock factor 1 (HSF1) and by up-regulation of heat shock proteins (Hsps) and P-gp. Inhibition of Akt/mTOR and STAT3 pathways by CCB induced autophagy, which promoted the degradation of mutp53, one of Hsp90 client proteins, and subsequently down-regulated HSF1/Hsps and P-gp.

Decreased Muc5AC expression is associated with poor prognosis in gastric cancer.

Mucins reportedly play numerous key roles in carcinogenesis, including in tumor invasion, regulation of differentiation and tumor cell proliferation. We investigated the effect of Muc5AC, a secreted mucin, on the invasiveness/migratory capability of gastric cancer cells and the prognostic significance of Muc5AC in gastric cancer patients. The clinicopathological and prognostic significance of Muc5AC expression was validated using immunohistochemical analysis in 412 gastric cancer patients.

S100A8 and S100A9 promotes invasion and migration through p38 mitogen-activated protein kinase-dependent NF-κB activation in gastric cancer cells.

S100A8 and S100A9 (S100A8/A9) are low-molecular weight members of the S100 family of calcium-binding proteins. Recent studies have reported S100A8/A9 promote tumorigenesis. We have previously reported that S100A8/A9 is mostly expressed in stromal cells and inflammatory cells between gastric tumor cells.

Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer.

Background: Epithelial-mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer.

Identification of S100A8 and S100A9 as negative regulators for lymph node metastasis of gastric adenocarcinoma.

With increasing therapeutic use of minimally invasive therapy for treatment of early gastric cancer, prediction of lymph node metastasis is important. In search of tissue biomarkers for prediction of lymph node metastasis of gastric adenocarcinoma, we analyzed gastric adenocarcinoma tissue using proteomic methods. We have done 2D-PAGE and MALDI-TOF MS analysis in matched normal and gastric cancer tissues.

Bilateral brain regions associated with naming in older adults.

To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall, several regions showed that greater gray and white matter volume/integrity measures were associated with better task performance. Left peri-Sylvian language regions and their right-hemisphere counterparts, plus left mid-frontal gyrus correlated with accuracy and/or negatively with response time (RT) on the naming tests.

Cancer-derived lysophosphatidic acid stimulates differentiation of human mesenchymal stem cells to myofibroblast-like cells.

Lysophosphatidic acid (LPA) is enriched in ascites of ovarian cancer patients and is involved in growth and invasion of ovarian cancer cells. Accumulating evidence suggests cancer-associated myofibroblasts play a pivotal role in tumorigenesis through secreting stromal cell-derived factor-1 (SDF-1). In the present study, we demonstrate that LPA induces expression of alpha-smooth muscle actin (alpha-SMA), a marker for myofibroblasts, in human adipose tissue-derived mesenchymal stem cells (hADSCs).

Sphingosylphosphorylcholine stimulates expression of fibronectin through TGF-beta1-Smad-dependent mechanism in human mesenchymal stem cells.

Sphingosylphosphorylcholine (SPC) has been reported to stimulate the expression of fibronectin (FN), which plays a key role in cell recruitment and adhesion during wound healing. In a previous study, we reported that SPC induces differentiation of human adipose tissue-derived mesenchymal stem cells (hATSCs) to smooth muscle-like cell types through ERK-dependent autocrine secretion of TGF-beta1 and delayed activation of the TGF-beta1-Smad pathway. In the present study, we demonstrated that SPC dose- and time-dependently increased the expression of FN in hATSCs.

Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-beta-dependent mechanism.

Mesenchymal stem cells (MSCs) can differentiate into diverse cell types including adipogenic, osteogenic, chondrogenic and myogenic lineages. In the present study, we demonstrated for the first time that sphingosylphosphorylcholine (SPC) induces differentiation of human adipose-tissue-derived mesenchymal stem cells (hATSCs) to smooth-muscle-like cell types. SPC increased the expression levels of several smooth-muscle-specific genes, such as those for alpha-smooth-muscle actin (alpha-SMA), h1-calponin and SM22alpha, as effectively as transforming growth factor beta (TGF-beta1) and TGF-beta3.

The effect of nanofiller on the opacity of experimental composites.

The purpose of this study was to evaluate the effect of the nanofiller in experimental composites on opacity (contrast ratio). Thirteen experimental composites were prepared with three different sizes of fillers: barium glass minifiller (1 microm; 69-76 wt %), silica microfiller (0.04 microm; 0-6 wt %), and silica nanofiller (7 nm; 0-7 wt %).

Sphingosylphosphorylcholine induces proliferation of human adipose tissue-derived mesenchymal stem cells via activation of JNK.

Sphingosylphosphorylcholine (SPC) has been implicated in a variety of cellular responses, including proliferation and differentiation. In this study, we demonstrate that d-erythro-SPC, but not l-threo-SPC, stereoselectively stimulated the proliferation of human adipose tissue-derived mesenchymal stem cells (hADSCs), with a maximal increase at 5 microM, and increased the intracellular concentration of Ca(2+) ([Ca(2+)](i)) in hADSCs, which do not express known SPC receptors (i.e.