Far-infrared irradiation increases the uptake of LDL cholesterol by downregulating PCSK9 through the activation of TRPV4 calcium channels in HepG2 cells.

This study investigated the effects of far-infrared (FIR) irradiation on low-density lipoprotein cholesterol (LDL-C) uptake by human hepatocellular carcinoma G2 (HepG2) cells via the regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9). FIR irradiation for 30 min significantly decreased PCSK9 expression (p < 0.01) in HepG2 cells. FIR irradiation substantially increased the low-density lipoprotein receptor (p < 0.0001) and LDL-C uptake (p < 0.01). Activation of transient receptor potential vanilloid (TRPV) channels mimicked the effects of FIR irradiation, significantly decreasing the protein expression of PCSK9 (p < 0.05). Conversely, inhibition of TRP channels using ruthenium red reversed the reduction in PCSK9 protein expression following FIR irradiation (p < 0.01). The specific activation of TRPV4 using 4α-PDD mimicked the effect of FIR irradiation (p < 0.01), whereas PCSK9 reduction by FIR irradiation was significantly reversed by the inhibition of TRPV4 using RN1734 (p < 0.05). These findings implied that FIR irradiation emitted from a ceramic lamp specifically increased TRPV4 activity. These findings provide insights into a novel therapeutic approach using FIR irradiation for LDL-C regulation and its implications for cardiovascular health.

Reliable synaptic plasticity of InGaZnO transistor with TiO2interlayer.

We demonstrate an InGaZnO (IGZO)-based synaptic transistor with a TiO2buffer layer. The structure of the synaptic transistor with TiO2inserted between the Ti metal electrode and an IGZO semiconductor channel O2trapping layer produces a large hysteresis window, which is crucial for achieving synaptic functionality. The Ti/TiO2/IGZO synaptic transistor exhibits reliable synaptic plasticity features such as excitatory post-synaptic current, paired-pulse facilitation, and potentiation and depression, originating from the reversible charge trapping and detrapping in the TiO2layer. Finally, the pattern recognition accuracy of Modified National Institute of Standards and Technology handwritten digit images was modeled using CrossSim simulation software. The simulation results present a high image recognition accuracy of ∼89%. Therefore, this simple approach using an oxide buffer layer can aid the implementation of high-performance synaptic devices for neuromorphic computing systems.

Increased Mobility and Reduced Hysteresis of MoS2 Field-Effect Transistors via Direct Surface Precipitation of CsPbBr3-Nanoclusters for Charge Transfer Doping.

Transition-metal dichalcogenides (TMDs) and metal halide perovskites (MHPs) have been investigated for various applications, owing to their unique physical properties and excellent optoelectronic functionalities. TMD monolayers synthesized via chemical vapor deposition (CVD), which are advantageous for large-area synthesis, exhibit low mobility and prominent hysteresis in the electrical signals of field-effect transistors (FETs) because of their native defects. In this study, we demonstrate an increase in electrical mobility by ∼170 times and reduced hysteresis in the current-bias curves of MoS2 FETs hybridized with CsPbBr3 for charge transfer doping, which is implemented via solution-based CsPbBr3-nanocluster precipitation on CVD-grown MoS2 monolayer FETs. Electrons injected from CsPbBr3 into MoS2 induce heavy n-doping and heal point defects in the MoS2 channel layer, thus significantly increasing mobility and reducing hysteresis in the hybrid FETs. Our results provide a foundation for improving the reliability and performance of TMD-based FETs by hybridizing them with solution-based perovskites.

Conduction Mechanism in Acceptor- or Donor-Doped ZrO2 Bulk and Thin Films.

The leakage current in capacitors in future electronics should be highly suppressed to achieve low power consumption, high reliability, and fast data processing. Although considerable efforts have been directed at reducing the leakage current, fundamental studies on the effects of doping on bulk and thin-film materials have rarely been conducted. Herein, we investigated the effects of doping with acceptor and donor elements on the conduction of bulk and thin-film ZrO2 and elucidated the underlying charge conduction mechanism. In the case of bulk ZrO2, the electrical conductivity was reliably modulated by the type of dopant element, which is highly consistent with defect chemistry theory. However, unlike in the bulk material, in acceptor- and donor-doped thin-film ZrO2, the leakage current was suppressed, indicating that the factors determining the electrical property in thin films are different from those in bulk materials.

Oleracone F Alleviates Cognitive Impairment and Neuropathology in APPswe/PSEN1dE9 Mice by Reducing the Expression of Vascular Cell Adhesion Molecule and Leukocyte Adhesion to Brain Vascular Endothelial Cells.

Alzheimer's disease (AD) is the most common neurodegenerative disease and the blood-brain barrier dysfunction has been suggested as a key pathological feature of the disease. Our research group successfully established a synthetic protocol for oleracones, a novel series of flavonoids isolated from the plant extract of Portulaca oleracea L. (PO). PO extract was reported to have anti-inflammatory and antioxidant effects, enhancing cognitive function. Thus, we investigated the effects and mechanism of oleracones on cognition using AD model transgenic mice (Tg; APPswe/PSEN1dE9). Oleracone F treatment significantly improved memory dysfunction in Tg mice. Oleracone F decreased the number, burden, and immunoreactivity of amyloid plaques and amyloid precursor protein (APP) protein levels in the brains of Tg mice compared to wild-type mice. Oleracone F also alleviated inflammation observed in Tg mice brains. In vitro studies in human microvascular endothelial cells (HBMVECs) demonstrated that oleracones D, E, and F blocked the elevations in VCAM-1 protein induced by tumor necrosis factor-α (TNF-α), hindering leukocyte adhesion to HBMVECs. Taken together, our results suggest that oleracones ameliorated cognitive impairment by blocking TNF-α-induced increases in VCAM-1, thereby reducing leukocyte infiltration to the brain and modulating brain inflammation.

CD49f and CD146: A Possible Crosstalk Modulates Adipogenic Differentiation Potential of Mesenchymal Stem Cells.

BACKGROUND: The lack of appropriate mesenchymal stem cells (MSCs) selection methods has given the challenges for standardized harvesting, processing, and phenotyping procedures of MSCs. Genetic engineering coupled with high-throughput proteomic studies of MSC surface markers arises as a promising strategy to identify stem cell-specific markers. However, the technical limitations are the key factors making it less suitable to provide an appropriate starting material for the screening platform. A more accurate, easily accessible approach is required to solve the issues. METHODS: This study established a high-throughput screening strategy with forward versus side scatter gating to identify the adipogenesis-associated markers of bone marrow-derived MSCs (BMSCs) and tonsil-derived MSCs (TMSCs). We classified the MSC-derived adipogenic differentiated cells into two clusters: lipid-rich cells as side scatter (SSC)-high population and lipid-poor cells as SSC-low population. By screening the expression of 242 cell surface proteins, we identified the surface markers which exclusively found in lipid-rich subpopulation as the specific markers for BMSCs and TMSCs. RESULTS: High-throughput screening of the expression of 242 cell surface proteins indicated that CD49f and CD146 were specific for BMSCs and TMSCs. Subsequent immunostaining confirmed the consistent specific expression of CD49f and CD146 and in BMSCs and TMSCs. Enrichment of MSCs by CD49f and CD146 surface markers demonstrated that the simultaneous expression of CD49f and CD146 is required for adipogenesis and osteogenesis of mesenchymal stem cells. Furthermore, the fate decision of MSCs from different sources is regulated by distinct responses of cells to differentiation stimulations despite sharing a common CD49f+CD146+ immunophenotype. CONCLUSIONS: We established an accurate, robust, transgene-free method for screening adipogenesis associated cell surface proteins. This provided a valuable tool to investigate MSC-specific markers. Additionally, we showed a possible crosstalk between CD49f and CD146 modulates the adipogenesis of MSCs.

Basic Fibroblast Growth Factor Induces Cholinergic Differentiation of Tonsil-Derived Mesenchymal Stem Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are considered a potential tool for regenerating damaged tissues due to their great multipotency into various cell types. Here, we attempted to find the appropriate conditions for neuronal differentiation of tonsil-derived MSCs (TMSCs) and expand the potential application of TMSCs for treating neurological diseases. METHODS: The TMSCs were differentiated in DMEM/F-12 (Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12) supplemented with various neurotrophic factors for 7-28 days to determine the optimal neuronal differentiation condition for the TMSCs. The morphologies as well as the levels of the neural markers and neurotransmitters were assessed to determine neuronal differentiation potentials and the neuronal lineages of the differentiated TMSCs. RESULTS: Our initial study demonstrated that DMEM/F12 supplemented with 50 ng/mL basic fibroblast growth factor with 10 µM forskolin was the optimal condition for neuronal differentiation for the TMSCs. TMSCs had higher protein expression of neuronal markers, including neuron-specific enolase (NSE), GAP43, postsynaptic density protein 95 (PSD95), and synaptosomal-associated protein of 25 kDa (SNAP25) compared to the undifferentiated TMSCs. Immunofluorescence staining also validated the increased mature neuron markers, NeuN and synaptophysin, in the differentiated TMSCs. The expression of glial fibrillar acidic protein and ionized calcium-binding adaptor molecule 1 the markers of astrocytes and microglia, were also slightly increased. Additionally, the differentiated TMSCs released a significantly higher level of acetylcholine, the cholinergic neurotransmitter, as analyzed by the liquid chromatography-tandem mass spectrometry and showed an enhanced choline acetyltransferase immunoreactivity compared to the undifferentiated cells. CONCLUSION: Our study suggests that the optimized condition favors the TMSCs to differentiate into cholinergic neuron-like phenotype, which could be used as a possible therapeutic tool in treating certain neurological disorders such as Alzheimer's disease.

Indolo[3,2,1-jk]carbazole-Derived Narrowband Violet-Blue Fluorophores: Tuning the Optical and Electroluminescence Properties by Chromophore Juggling.

The development of rigid polyaromatic building blocks for narrowband violet fluorophores has received tremendous attention. Herein, we designed and synthesized two new triangle-shaped rigid building blocks, namely, 2,5-di-tert-butylindolo[3,2,1-jk]carbazole (tBuICz) and 2,11-di-tert-butylindolo[3,2,1-jk]carbazole-4-carbonitrile (tBuICzCN), and tethered them with different chromophores to yield a series of violet-blue fluorophores, viz., ICzTPA-ICzPICN, and studied their structure-function relationship. The appended chromophores and cyano unit played a vital role in controlling the optical and electrical properties of the compounds. Except triphenylamine-substituted derivatives, the compounds showed pure violet emission (λem ≤ 403 nm). Intriguingly, the compounds exhibited narrow-band emission with a full-width at half-maximum ≤ 40 nm, attributed to the rigidity of the ICz core. The emission of the compounds displayed positive solvatochromism, which is ascribed to the photoinduced intramolecular charge transfer in the excited state. The compounds revealed excellent thermal robustness with T5d ≥ 363 °C. The triphenylamine-featuring derivatives displayed a high-lying HOMO compared to their congeners due to their electron-rich nature. When we applied these materials in organic light-emitting diodes, ICzPI outperformed in the series with an EQEmax of 3.07% and a current efficiency of 1.04 cd/A. Notably, its CIEy ∼ 0.046 precisely matched with the Rec.2020 standard of deep-blue color (CIEy ∼ 0.046).

In-depth analysis on electrical parameters of floating gate IGZO synaptic transistor affecting pattern recognition accuracy.

The reliable conductance modulation of synaptic devices is key when implementing high-performance neuromorphic systems. Herein, we propose a floating gate indium gallium zinc oxide (IGZO) synaptic device with an aluminum trapping layer to investigate the correlation between its diverse electrical parameters and pattern recognition accuracy. Basic synaptic properties such as excitatory postsynaptic current, paired pulse facilitation, long/short term memory, and long-term potentiation/depression are demonstrated in the IGZO synaptic transistor. The effects of pulse tuning conditions associated with the pulse voltage magnitude, interval, duration, and cycling number of the applied pulses on the conductance update are systematically investigated. It is discovered that both the nonlinearity of the conductance update and cycle-to-cycle variation should be critically considered using an artificial neural network simulator to ensure the high pattern recognition accuracy of Modified National Institute of Standards and Technology (MNIST) handwritten digit images. The highest recognition rate of the MNIST handwritten dataset is 94.06% for the most optimized pulse condition. Finally, a systematic study regarding the synaptic parameters must be performed to optimize the developed synapse device.

In-depth analysis on electrical parameters of floating gate IGZO synaptic transistor affecting pattern recognition accuracy.

The reliable conductance modulation of synaptic devices is key when implementing high-performance neuromorphic systems. Herein, we propose a floating gate IGZO synaptic device with an aluminum trapping layer to investigate the correlation between its diverse electrical parameters and pattern recognition accuracy. Basic synaptic properties such as excitatory postsynaptic current, paired pulse facilitation, long/short term memory, and long-term potentiation/depression are demonstrated in the IGZO synaptic transistor. The effects of pulse tuning conditions associated with the pulse voltage magnitude, interval, duration, and cycling number of the applied pulses on the conductance update are systematically investigated. It is discovered that both the nonlinearity of the conductance update and cycle-to-cycle variation should be critically considered using an artificial neural network simulator to ensure the high pattern recognition accuracy of Modified National Institute of Standards and Technology (MNIST) handwritten digit images. The highest recognition rate of the MNIST handwritten dataset is 94.06% for the most optimized pulse condition. Finally, a systematic study regarding the synaptic parameters must be performed to optimize the developed synapse device.

Valproic Acid-Induced CCN1 Promotes Osteogenic Differentiation by Increasing CCN1 Protein Stability through HDAC1 Inhibition in Tonsil-Derived Mesenchymal Stem Cells.

Our previous study found that the level of CCN1 increases as osteogenic differentiation progresses in tonsil-derived mesenchymal stem cells (TMSCs). This study investigated how CCN1 is regulated through HDAC inhibition in TMSCs and their relationship with osteogenesis. Valproic acid (VPA) (1-5 mM), a well-known histone deacetylase (HDAC) inhibitor, strongly inhibited TMSC proliferation without altering MSC-specific surface markers, CD14, 34, 45, 73, 90 and 105. However, CD146 expression increased at 5 mM VPA. VPA increased osteogenic differentiation of TMSCs but decreased adipogenesis and chondrogenesis, as evidenced by the cell-specific staining of differentiation. The former was validated by the increased osteocalcin (OCN). The changes in CCN1 by VPA was biphasic; it increased until 48 h and decreased thereafter. Knockdown of CCN1 by using siRNA inhibited the osteogenic effect of VPA. VPA had no effect on CCN1 mRNA expression, but inhibition of protein synthesis by cycloheximide showed that VPA slowed down the CCN1 protein degradation. Moreover, overexpression of HDAC1 completely inhibited VPA-induced CCN1. Our results indicate that VPA inhibits the HDAC1, inducing CCN1 protein stability rather than gene expression, thereby promoting osteogenic differentiation of TMSCs. These findings present the noble implication of VPA as an inhibitor of HDAC1 to facilitate CCN1-induced osteogenic differentiation of MSCs.

Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells.

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.

Tonsil-derived mesenchymal stem cells incorporated in reactive oxygen species-releasing hydrogel promote bone formation by increasing the translocation of cell surface GRP78.

Controlling the senescence of mesenchymal stem cells (MSCs) is essential for improving the efficacy of MSC-based therapies. Here, a model of MSC senescence was established by replicative subculture in tonsil-derived MSCs (TMSCs) using senescence-associated ß-galactosidase, telomere-length related genes, stemness, and mitochondrial metabolism. Using transcriptomic and proteomic analyses, we identified glucose-regulated protein 78 (GRP78) as a unique MSC senescence marker. With increasing cell passage number, GRP78 gradually translocated from the cell surface and cytosol to the (peri)nuclear region of TMSCs. A gelatin-based hydrogel releasing a sustained, low level of reactive oxygen species (ROS-hydrogel) was used to improve TMSC quiescence and self-renewal. TMSCs expressing cell surface-specific GRP78 (csGRP78+), collected by magnetic sorting, showed better stem cell function and higher mitochondrial metabolism than unsorted cells. Implantation of csGRP78+ cells embedded in ROS-hydrogel in rats with calvarial defects resulted in increased bone regeneration. Thus, csGRP78 is a promising biomarker of senescent TMSCs, and the combined use of csGRP78+ cells and ROS-hydrogel improved the regenerative capacity of TMSCs by regulating GRP78 translocation.

Zearalenone Induces Endothelial Cell Apoptosis through Activation of a Cytosolic Ca2+/ERK1/2/p53/Caspase 3 Signaling Pathway.

Zearalenone (ZEN) is a mycotoxin that has been reported to damage various types of cells/tissues, yet its effects on endothelial cells (ECs) have never been investigated. Therefore, this study investigates the potential effects of ZEN using bovine aortic ECs (BAECs). In this study, we found that ZEN induced apoptosis of BAECs through increased cleavage of caspase 3 and poly ADP-ribose polymerase (PARP). ZEN also increased phosphorylation of ERK1/2 and p53, and treatment with the ERK1/2 or p53 inhibitor reversed ZEN-induced EC apoptosis. Transfection of BAECs with small interfering RNA against ERK1/2 or p53 revealed ERK1/2 as an upstream target of p53 in ZEN-stimulated apoptosis. ZEN increased the production of reactive oxygen species (ROS), yet treatment with the antioxidant did not prevent EC apoptosis. Similarly, blocking of estrogen receptors by specific inhibitors also did not prevent ZEN-induced apoptosis. Finally, chelation of cytosolic calcium (Ca2+) using BAPTA-AM or inhibition of endoplasmic reticulum (ER) Ca2+ channel using 2-APB reversed ZEN-induced EC apoptosis, but not by inhibiting ER stress using 4-PBA. Together, our findings demonstrate that ZEN induces EC apoptosis through an ERK1/2/p53/caspase 3 signaling pathway activated by Ca2+ release from the ER, and this pathway is independent of ROS production and estrogen receptor activation.

Symptom distress and quality of life among Black Americans with cancer and their family caregivers.

OBJECTIVE: Black Americans are disproportionately affected by cancer and chronic diseases. Black patients with cancer and their family caregivers may concurrently experience symptoms that influence their wellbeing. This study investigates the influence of mental and physical symptom distress on quality of life (QOL) among Black Americans with cancer and their family caregivers from a dyadic perspective. METHODS: One hundred and fifty-one dyads comprised of a Black American with breast, colorectal, lung or prostate cancer and a Black family caregiver were included in this secondary analysis of pooled baseline data from three studies. Self-reports of problems managing 13 symptoms were used to measure mental and physical symptom distress. Descriptive statistics and the actor-partner interdependence model were used to examine symptom prevalence and the influence of each person's symptom distress on their own and each other's QOL. RESULTS: Fatigue, sleep problems, pain and mental distress were prevalent. Patients and caregivers reported similar levels of mental distress; however, patients reported higher physical distress. Increased patient mental distress was associated with decreased patient QOL (overall, emotional, social, functional). Increased patient physical distress was associated with decreased patient QOL (overall, physical, emotional, functional) and decreased caregiver emotional wellbeing. Increased caregiver mental distress was associated with decreased caregiver QOL (overall, emotional, social, functional) and decreased patient overall QOL. Increased caregiver physical distress was associated with decreased caregiver QOL (overall, physical, functional), decreased patient emotional wellbeing, and better patient social wellbeing. CONCLUSIONS: Supporting symptom management in Black patient/caregiver dyads may improve their QOL.

Transient receptor potential vanilloid 2 mediates the inhibitory effect of far-infrared irradiation on adipogenic differentiation of tonsil-derived mesenchymal stem cells.

AIMS: Far-infrared (FIR) irradiation inhibits adipogenic differentiation of tonsil-derived mesenchymal stem cells (TMSCs) by activating Ca2+-dependent protein phosphatase 2B (PP2B), but it stimulates osteogenic differentiation in a PP2B-independent pathway. We investigated the potential involvement of transient receptor potential vanilloid (TRPV) channels, a well-known Ca2+-permeable channel, in the effects of FIR irradiation on adipogenic or osteogenic differentiation of TMSCs. METHODS: TMSCs, in the absence or presence of activators or inhibitors, were exposed to FIR irradiation followed by adipogenic or osteogenic differentiation, which was assessed using Oil red O or Alizarin red S staining, respectively. RT-PCR, qRT-PCR, and Western blotting were used to determine gene and protein expression of calcium channels and adipocyte-specific markers. RESULTS: Treatment with the calcium ionophore ionomycin simulated the inhibitory effect of FIR irradiation on adipogenic differentiation but had no effect on osteogenic differentiation, indicating the involvement of intracellular Ca2+ in adipogenic differentiation. Inhibition of pan-TRP channels using ruthenium red reversed the FIR irradiation-induced inhibition of adipogenic differentiation. Among the TRP channels tested, inhibition of the TRPV2 channel by tranilast or siRNA against TRPV2 attenuated the inhibitory effect of FIR irradiation on adipogenic differentiation, accompanied by a decrease in intracellular Ca2+ levels. By contrast, activation of the TRPV2 channel by probenecid simulated FIR irradiation-induced inhibition of adipogenic differentiation. Expectedly, the stimulatory effect of FIR irradiation on osteogenic differentiation was independent of the TRPV2 channel. CONCLUSION: Our data demonstrate that the TRPV2 channel is a sensor/receptor for the inhibited adipogenic differentiation of TMSCs associated with FIR irradiation.

High-Detectivity Perovskite Photodetector Using Combustion-Processed NiOx as p-Type Buffer Layer.

We fabricated a photodetector device consisting of ITO/NiOx/Perovskite/PC60BM/BCP/Ag. The NiOx layer was deposited using the sol-gel and combustion processes. Combustion-processed NiOx films have advantages such as low annealing temperature, improved perovskite film quality, and better photodetector performance compared to the sol-gel processed NiOx film. The improved film quality, improved charge transfer, and reduced dark current of the device using combustion-processed NiOx film were investigated by measuring the current-voltage characteristics, transient photocurrent, and impedance analysis. The photodetector using the combustion-processed NiOx achieved a high detectivity of 1.20×1013 Jones and bandwidth of over 2 MHz at -0.1 V and 550 nm.

A transcriptomic analysis of serial-cultured, tonsil-derived mesenchymal stem cells reveals decreased integrin α3 protein as a potential biomarker of senescent cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have been widely used for stem cell therapy, and serial passage of stem cells is often required to obtain sufficient cell numbers for practical applications in regenerative medicine. A long-term serial cell expansion can potentially induce replicative senescence, which leads to a progressive decline in stem cell function and stemness, losing multipotent characteristics. To improve the therapeutic efficiency of stem cell therapy, it would be important to identify specific biomarkers for senescent cells. METHODS: Tonsil-derived mesenchymal stem cells (TMSCs) with 20-25 passages were designated as culture-aged TMSCs, and their mesodermal differentiation potentials as well as markers of senescence and stemness were compared with the control TMSCs passaged up to 8 times at the most (designated as young). A whole-genome analysis was used to identify novel regulatory factors that distinguish between the culture-aged and control TMSCs. The identified markers of replicative senescence were validated using Western blot analyses. RESULTS: The culture-aged TMSCs showed longer doubling time compared to control TMSCs and had higher expression of senescence-associated (SA)-ß-gal staining but lower expression of the stemness protein markers, including Nanog, Oct4, and Sox2 with decreased adipogenic, osteogenic, and chondrogenic differentiation potentials. Microarray analyses identified a total of 18,614 differentially expressed genes between the culture-aged and control TMSCs. The differentially expressed genes were classified into the Gene Ontology categories of cellular component (CC), functional component (FC), and biological process (BP) using KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis. This analysis revealed that those genes associated with CC and BP showed the most significant difference between the culture-aged and control TMSCs. The genes related to extracellular matrix-receptor interactions were also shown to be significantly different (p < 0.001). We also found that culture-aged TMSCs had decreased expressions of integrin α3 (ITGA3) and phosphorylated AKT protein (p-AKT-Ser473) compared to the control TMSCs. CONCLUSIONS: Our data suggest that activation of ECM-receptor signaling, specifically involved with integrin family-mediated activation of the intracellular cell survival-signaling molecule AKT, can regulate stem cell senescence in TMSCs. Among these identified factors, ITGA3 was found to be a representative biomarker of the senescent TMSCs. Exclusion of the TMSCs with the senescent TMSC markers in this study could potentially increase the therapeutic efficacy of TMSCs in clinical applications.

Zearalenone-Induced Interaction between PXR and Sp1 Increases Binding of Sp1 to a Promoter Site of the eNOS, Decreasing Its Transcription and NO Production in BAECs.

Zearalenone (ZEN) is a non-steroidal mycotoxin that has various toxicological impacts on mammalian health. Here, we found that ZEN significantly affected the production of nitric oxide (NO) and the expression of endothelial NO synthase (eNOS) of bovine aortic endothelial cells (BAECs). A promoter analysis using 5'-serially deleted human eNOS promoter revealed that the proximal region (-135 to +22) was responsible for ZEN-mediated reduction of the human eNOS promoter activity. This effect was reversed by mutation of two specificity protein 1 (Sp1) binding elements in the human eNOS promoter. A chromatin immunoprecipitation assay revealed that ZEN increased Sp1 binding to the bovine eNOS promoter region (-113 to -12), which is homologous to -135 to +22 of the human eNOS promoter region. We also found that ZEN promoted the binding of the pregnane X receptor (PXR) to Sp1 of the bovine eNOS, consequently decreasing eNOS expression. This reduction of eNOS could have contributed to the decreased acetylcholine-induced vessel relaxation upon ZEN treatment in our ex vivo study using mouse aortas. In conclusion, our data demonstrate that ZEN decreases eNOS expression by enhancing the binding of PXR-Sp1 to the eNOS promoter, thereby decreasing NO production and potentially causing vessel dysfunction.

Chronic Disease Among African American Families: A Systematic Scoping Review.

INTRODUCTION: Chronic diseases are common among African Americans, but the extent to which research has focused on addressing chronic diseases across multiple members of African American families is unclear. This systematic scoping review summarizes the characteristics of research addressing coexisting chronic conditions among African American families, including guiding theories, conditions studied, types of relationships, study outcomes, and intervention research. METHODS: The literature search was conducted in PsycInfo, PubMed, Social Work Abstracts, Sociological Abstracts, CINAHL, and Family and Society Studies Worldwide to identify relevant articles published from January 2000 through September 2016. We screened the title and abstracts of 9,170 articles, followed by full-text screening of 530 articles, resulting in a final sample of 114 articles. Fifty-seven percent (n = 65) of the articles cited a guiding theory/framework, with psychological theories (eg, social cognitive theory, transtheoretical model) being most prominent. The most common conditions studied in families were depression (70.2%), anxiety (23.7%), and diabetes (22.8%), with most articles focusing on a combination of physical and mental health conditions (47.4%). RESULTS: In the 114 studies in this review, adult family members were primarily the index person (71.1%, n = 81). The index condition, when identified (79.8%, n = 91), was more likely to be a physical health condition (46.5%, n = 53) than a mental health condition (29.8%, n = 34). Among 343 family relationships examined, immediate family relationships were overwhelmingly represented (85.4%, n = 293); however, extended family (12.0%, n = 41) and fictive kin (0.6%, n = 2) were included. Most (57.0%, n = 65) studies focused on a single category of outcomes, such as physical health (eg, obesity, glycemic control), mental health (eg, depression, anxiety, distress), psychosocial outcomes (eg, social support, caregiver burden), or health behaviors (eg, medication adherence, disease management, health care utilization); however, 43.0% (n = 49) of studies focused on outcomes across multiple categories. Sixteen intervention articles (14.0%) were identified, with depression the most common condition of interest. CONCLUSION: Recognizing the multiple, simultaneous health issues facing families through a lens of family comorbidity and family multimorbidity may more accurately mirror the lived experiences of many African American families and better elucidate intervention opportunities than previous approaches.