Who are the most vulnerable populations for primary care? Avoidable hospitalizations across individuals with different types of disabilities in South Korea.

BACKGROUND: Individuals with disabilities have limited access to primary care, the quality of care must be examined. OBJECTIVE: To examine avoidable hospitalizations among individuals with disabilities and determine the most vulnerable populations across types of disabilities. METHODS: Using the Korean National Health Insurance Claims Database, we compared hypertension- and diabetes-related avoidable hospitalizations (HRAH and DRAH, respectively) across disability status and disability type based on age-sex standardized rates from 2011 to 2020 and logistic regression. RESULTS: The gap between those with and without disabilities in age-sex standardized HRAH and DRAH increased over 10 years. Odds ratios for HRAH were higher for those with disabilities, with individuals with mental disabilities having the highest odds ratio, followed by those with intellectual/developmental disabilities, then those with physical disabilities; for DRAH, the three highest odds ratios belonged to individuals with mental, intellectual/developmental, and visual disabilities. Among those with disabilities, HRAH was higher for those with mental, intellectual/developmental, and severe physical disabilities, whereas DRAH was higher for those with mental, severe visual, and intellectual/developmental disabilities compared to those with mild physical disabilities. CONCLUSION: This study reveals high avoidable hospitalization rates among individuals with disabilities and calls for policies supporting quality primary care and comprehensively addressing disparities.

AMP-activated protein kinase contributes to ROS-mediated p53 activation in cisplatin-induced nephrotoxicity.

OBJECTIVE: Cisplatin is a widely used anticancer drug that provokes various side effects. Nephrotoxicity is one of the well-known major side effects in the chemotherapeutic use of cisplatin. Reactive oxygen species (ROS) and p53 play important roles in cisplatin-induced nephrotoxicity. AMP-activated protein kinase (AMPK) is known to be sensitively activated by ROS and can directly activate p53. The present study investigated the role of AMPK on cisplatin-induced apoptosis in rat renal epithelial NRK-52E cells. MATERIALS AND METHODS: NRK-52E cells were treated with cisplatin in the absence or presence of specific ROS scavenger and AMPK inhibitor for indicated times under the serum-free condition. The expression and phosphorylation levels of proteins were evaluated by Western blot and densitometry analysis. RESULTS: Cisplatin induced apoptotic cell death through ROS-mediated p53 activation, which is associated with AMPK activation. AMPK inhibitor suppressed cisplatin-induced p53 activation, as well as AMPK activation. Interestingly, ROS scavenger also diminished cisplatin-induced p53 activation and AMPK activation. Furthermore, cisplatin induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), which attenuated p53 activation, but did not affect the expression levels of total p53, cleaved caspase-3 and PARP. Meanwhile, inhibition of AMPK induced premature phosphorylation of eIF2α in cisplatin-treated cells. CONCLUSIONS: Taken together, these suggest that AMPK may be required for activation of p53 by oxidative stress in cisplatin-induced nephrotoxicity. Moreover, eIF2α phosphorylation may interrupt the AMPK-activated p53 in NRK-52E cells exposed to cisplatin, but does not critically affect cisplatin-induced nephrotoxicity because AMPK activation can be disrupted eIF2α phosphorylation.

Antifungal activity of streptavidin C1 and C2 against pathogens causing Fusarium wilt.

Fusarium wilt is caused by the soil-inhabiting fungus Fusarium oxysporum ff. spp. and is one of the most devastating plant diseases, resulting in losses and decreasing the quality and safety of agricultural crops. We recently reported the structures and biochemical properties of two biotin-binding proteins, streptavidin C1 and C2 (isolated from Streptomyces cinnamonensis strain KPP02129). In the present study, the potential of the biotin-binding proteins as antifungal agent for Fusarium wilt pathogens was investigated using recombinant streptavidin C1 and C2. The minimum inhibitory concentration of streptavidin C2 was found to be 16 µg ml-1 for inhibiting the mycelial growth of F. oxysporum f.sp. cucumerinum and F. oxysporum f.sp. lycopersici, while that of streptavidin C1 was found to be 64 µg ml-1 . Compared with the nontreated control soil, the population density of F. oxysporum f.sp. lycopersici in the soil was reduced to 49·5% and 39·6% on treatment with streptavidin C1 (500 µg ml-1 ) and C2 (500 µg ml-1 ), respectively. A greenhouse experiment revealed that Fusarium wilt of tomato plants was completely inhibited on soil drenching using a 50-ml culture filtrate of the streptavidin-producing strain KPP02129.

Cigarette smoke extraxt influences intracellular calcium concentration in A549 cells.

Cigarette smoking is a major risk factor for pulmonary diseases, including chronic obstructive pulmonary disease (COPD) and cancer. Cigarette smoke is reported to contain over 4,000 chemical compounds. Therefore, it needs to study the effects of cigarette smoke extract (CSE) administration on intracellular calcium concentration. In this study, we investigated how CSE influences intracellular calcium concentration in human lung adenocarcinoma A549 cells. The CSE concentrations used (0.4, 2, 3%) did not influence cell viability. However, at these CSE concentrations, calcium influx transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential vanilloid 6 (TRPV6) proteins significantly increased, whereas calcium efflux sodium-calcium exchanger (NCX1) and plasma membrane Ca2+ ATPase (PMCA1) proteins significantly decreased from those of the control cells. The 3% CSE treatment produced an intracellular calcium concentration higher than that of the control treatment through methods of co-transfection of pGP-CMV-GCaMP6f/CMV-R-GECO1.2 and Rhod-4 Assay. CSE induced concentration-dependent increments in hypoxia-inducible factor (HIF)-1α and HIF-2α protein levels. Moreover, phosphorylation of ERK and Akt was induced by CSE treatment. Also, mitochondrial marker B-cell lymphoma 2 (Bcl-2) protein level decreased and Bcl-2-associated X (Bax) protein level increased following CSE treatment. Also, endoplasmic reticulum (ER) stress markers BiP, CHOP, p-SAPK, and p-eIF2α levels were increased by CSE treatment. These results suggest that CSE may increase the concentration of intracellular calcium, thus increasing mitochondrial and ER stress.

Comparison of open and pneumovesical approaches for Politano-Leadbetter ureteric reimplantation: a single-center long-term follow-up study.

PURPOSE: To report our experience with the laparoscopic pneumovesical approach for Politano-Leadbetter ureteric reimplantation and to compare the results to those obtained using a traditional open approach. METHODS: We retrospectively reviewed the medical records of 52 patients who underwent Politano-Leadbetter ureteral reimplantation between 2012 and 2017. The peri-operative parameters, postoperative outcomes, and complication rates of patients who underwent the open approach for the Politano-Leadbetter procedure and those who underwent the laparoscopic pneumovesical approach were compared. RESULTS: During the study period, 52 ureteric reimplantation procedures were analyzed. Among these, 28 and 24 patients underwent surgery using the open and pneumovesical approaches, respectively. The mean operative time did not differ between the groups (143.64 min vs. 128.12 min, P = 0.092). However, the pneumovesical group had a shorter duration of hospital stay (5.08 days vs 7.43 days, P = 0.001) and required less morphine analgesic for pain than did the open group (7.7% vs 32.1%, P = 0.027). No significant differences in the success rates (94.9% vs 92.5%, P = 0.512) or procedure-related complications were noted between the pneumovesical and open techniques. CONCLUSIONS: The transvesicoscopic Politano-Leadbetter technique with pneumovesicum is safe and effective for ureteric reimplantation and is comparable to the open approach.

Cognitive decline in association with hyposmia in idiopathic rapid eye movement sleep behavior disorder: a prospective 2-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to analyze the characteristics and progression of cognitive dysfunction in non-demented idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with baseline olfactory function. METHODS: From a prospective polysomnography-confirmed iRBD cohort, 25 patients (16 patients in 2-year follow-up) and 13 normal controls were included. Initial and 2-year follow-up cognitive functions were analyzed with olfactory function and 18 F-fluorinated-N-3-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)-nortropane (18 F-FP-CIT) uptake in deep nuclei initially. RESULTS: Idiopathic RBD patients had impaired attention, memory and executive function compared to controls. Baseline cognitive tests were comparable between the iRBD subgroups with and without hyposmia. 18 F-FP-CIT uptake tended to be lower in the hyposmic group than in the normosmic group. The olfactory test score was positively correlated with amygdala uptake in iRBD patients (P = 0.027). After 2 years, visuospatial and verbal memory dysfunction worsened more in hyposmics than in normosmics. Lower initial olfactory test score was associated with more severe declines in verbal memory function. CONCLUSIONS: Hyposmia may be a predictive sign of cognitive decline in iRBD patients.

Regulatory effect of dexamethasone on tracheal calcium processing proteins and mucosal secretion.

Dexamethasone inhibits mucin secretion considering the primary option for treating acute asthma exacerbation. However, the mechanism underlying dexamethasone-induced decreased in mucosecretion is unclear. Recent studies have reported that dexamethasone exerts an inhibitory effect on mucosecretion in the lung by modulating the expression of calcium processing genes. However, the expression of the calcium processing genes in the trachea is not examined yet. Thus, the present study is the first to report the localization of calcium processing proteins such as transient receptor potential vanilloid-4 (Trpv4), transient receptor potential vanilloid-6 (Trpv6), calbindin-D9k (CaBP-9k) and plasma membrane Ca2+-ATPase 1 (Pmca1) in the mouse trachea and their glucocorticoid-induced response. In this study, mice were subcutaneously injected with dexamethasone for 5 days, and their tracheal samples were collected by dividing the trachea into the cervical, and thoracic sections based on its anatomical structure. The localization of TRPV4, TRPV6, CaBP-9k, and PMCA1 proteins was detected in the tracheal epithelium, submucosal glands, cartilages and muscles. Dexamethasone treatment downregulated the mRNA expression of the four calcium processing genes and mucin producing genes. The dexamethasone-induced decrease in the secretion of mucosubstances in the trachea was determined by performing Alcian blue-periodic acid-Schiff staining. Thus, the findings of the present study suggest that glucocorticoids simultaneously can regulate the expression of calcium processing genes and tracheal mucosecretion.

The clinical efficacy of stem cell therapy for complex perianal fistulas: a meta-analysis.

BACKGROUND: Treatment of complex anal fistulas remains difficult. However, treatment with stem cells has had an encouraging success rate when applied to complex perianal fistulas. We systematically reviewed the current evidence through meta-analysis. METHODS: We performed an electronic literature search on PubMed, Embase, and the Cochrane Library and identified studies (published between January 1946 and August 2017) that used stem cells to treat patients with complex perianal fistula. Each paper was evaluated for treatment success rate, target patients, types of stem cells used, number of cells used, and criteria for complete healing. Potential publication bias was assessed via visual inspection of a funnel plot and Orwin's fail-safe N. Out of 171 papers, 16 were included in the meta-analysis. RESULTS: The overall healing rate of stem cell injection therapy for patients with complex perianal fistulas was 62.8% (95% CI 53.5-71.2, I2 = 54.05%), whereas those for patients with Crohn's perianal fistulas alone and complex anal fistulas not associated with Crohn's disease were 64.1% and 61.5% (p = 0.840), respectively. Healing rates for autologous and allogenic stem cell treatment were 69.4% and 50.7% (p = 0.020), respectively. Four comparative studies out of 16 studies were analyzed separately. Stem cell therapy increased the healing rate compared to the control groups (OR 0.379, 95% CI 0.152-0.947). CONCLUSIONS: Stem cell therapy is a good treatment option for complex perianal fistulas, which cannot be healed by conventional operative procedures. However, further research for additional supportive evidence, such as a large-scale randomized controlled trial, is required.

The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding.

This corrects the article DOI: 10.1038/onc.2011.331.

Borrelia Species Detected in Ticks Feeding on Wild Korean Water Deer (Hydropotes inermis) Using Molecular and Genotypic Analyses.

Lyme borreliosis is a vector-borne disease transmitted through the bite of ticks infected by Borrelia burgdorferi sensu lato group, including B. burgdorferi sensu stricto, B. afzelii, and B. garinii. The goal of the present study was to detect Borrelia species in ticks infesting wild Korean water deer (KWD; Hydropotes inermis Swinhoe), using molecular and genotypic analyses. In total, 48 ticks were collected from KWD, all of which were morphologically identified as Haemaphysalis longicornis Neumann that is dominant in Korea. Nested PCR was performed to detect the Borrelia-specific 5S (rrf)-23S (rrl) intergenic spacer region and the outer surface protein A (ospA) genes in ticks. Both rrf-rrl and ospA were amplified from one of the 48 ticks (2.1%) and were identified as B. afzelii. To our knowledge, this study constitutes the first molecular detection of B. afzelii in Haemaphysalis ticks in Korea. Because B. afzelii is a zoonotic tick-borne pathogen, understanding the molecular characteristics of this bacterium is important for preventing the transmission of Borrelia from ticks to other animals and humans.

Licorice and its active compound glycyrrhizic acid ameliorates cisplatin-induced nephrotoxicity through inactivation of p53 by scavenging ROS and overexpression of p21 in human renal proximal tubular epithelial cells.

OBJECTIVE: Nephrotoxicity is one of the major side effects that limit the use of cisplatin in cancer therapy. Cisplatin-induced apoptosis in renal cells is associated with reactive oxygen species (ROS)-mediated p53 activation. Licorice (Glycyrrhiza uralensis Fischer) is one of the most widely used medicinal herbs in Korea, China and Japan. The aim of the study was to evaluate the protective effects of licorice extract (LE) and its active compound glycyrrhizic acid (GA) against cisplatin-induced nephrotoxicity in human renal proximal tubular epithelial (HK-2) cells. MATERIALS AND METHODS: HK-2 cells were pretreated with LE or GA for 1 h and then treated with 40 µM of cisplatin for indicated times under the serum-free condition. Cell viability was evaluated by MTT assay. Apoptosis was evaluated by flow cytometric analysis and caspase-3 activity. The intracellular ROS levels were determined by DCFH-DA assay. The expression and phosphorylation levels of protein were evaluated by Western blot and densitometry analysis. RESULTS: When treating HK-2 cells with LE or GA, both of them alleviated cisplatin-induced cytotoxicity and apoptosis. LE and GA inhibited caspase-3 activity and polymerase (PARP) cleavage in cisplatin-treated cells. LE and GA also inhibited p53 expression and its phosphorylation as well as ROS production in cells exposed to cisplatin. Meanwhile, LE and GA enhanced cisplatin-induced p21 expression, which then led to S-phase arrest in cell cycle and limited cell growth. Presumably, increased p21 expression may contribute to cellular prevention from cisplatin-induced apoptosis, because p21 is the key molecule to cytoprotection during cisplatin-induced nephrotoxicity. CONCLUSIONS: These results suggest that LE and GA ameliorate cisplatin-induced apoptosis through reduction of ROS-mediating p53 activation and promotion of p21 expression in HK-2 cells.

Interplay of charge density wave and multiband superconductivity in 2H-PdxTaSe2.

2H-TaSe2 has been one of unique transition metal dichalcogenides exhibiting several phase transitions due to a delicate balance among competing electronic ground states. An unusual metallic state at high-T is sequentially followed by an incommensurate charge density wave (ICDW) state at ≈122 K and a commensurate charge density wave (CCDW) state at ≈90 K, and superconductivity at TC ~ 0.14 K. Upon systematic intercalation of Pd ions into TaSe2, we find that CCDW order is destabilized more rapidly than ICDW to indicate a hidden quantum phase transition point at x ~ 0.09-0.10. Moreover, TC shows a dramatic enhancement up to 3.3 K at x = 0.08, ~24 times of TC in 2H-TaSe2, in proportional to the density of states N(EF). Investigations of upper critical fields Hc2 in single crystals reveal evidences of multiband superconductivity as temperature-dependent anisotropy factor γH = , quasi-linear increase of , and an upward, positive-curvature in near TC. Furthermore, analysis of temperature-dependent electronic specific heat corroborates the presence of multiple superconducting gaps. Based on above findings and electronic phase diagram vs x, we propose that the increase of N(EF) and effective electron-phonon coupling in the vicinity of CDW quantum phase transition should be a key to the large enhancement of TC in PdxTaSe2.

Antifungal activity of rimocidin and a new rimocidin derivative BU16 produced by Streptomyces mauvecolor BU16 and their effects on pepper anthracnose.

AIMS: The objective of this study was to explore antifungal metabolites targeting fungal cell envelope and to evaluate the control efficacy against anthracnose development in pepper plants. METHODS AND RESULTS: A natural product library comprising 3000 microbial culture extracts was screened via an adenylate kinase (AK)-based cell lysis assay to detect antifungal metabolites targeting the cell envelope of plant-pathogenic fungi. The culture extract of Streptomyces mauvecolor strain BU16 displayed potent AK-releasing activity. Rimocidin and a new rimocidin derivative, BU16, were identified from the extract as active constituents. BU16 is a tetraene macrolide containing a six-membered hemiketal ring with an ethyl group side chain instead of the propyl group in rimocidin. Rimocidin and BU16 showed broad-spectrum antifungal activity against various plant-pathogenic fungi and demonstrated potent control efficacy against anthracnose development in pepper plants. CONCLUSIONS: Antifungal metabolites produced by S. mauvecolor strain BU16 were identified to be rimocidin and BU16. The compounds displayed potent control efficacy against pepper anthracnose. SIGNIFICANCE AND IMPACT OF THE STUDY: Rimocidin and BU16 would be active ingredients of disease control agents disrupting cell envelope of plant-pathogenic fungi. The structure and antifungal activity of rimocidin derivative BU16 is first described in this study.

Exogenous administration of DLK1 ameliorates hepatic steatosis and regulates gluconeogenesis via activation of AMPK.

BACKGROUND/OBJECTIVES: Activation of Notch signaling pathologically enhances lipogenesis and gluconeogenesis in the liver causing non-alcoholic fatty liver disease (NAFLD) and diabetes. Delta-like 1 homolog (DLK1), an imprinted gene that can modulate adipogenesis and muscle development in mice, was found as an inhibitory regulator of Notch signaling. Therefore, we investigated the metabolic effect of exogenous DLK1 in vitro and in vivo. SUBJECTS/METHODS: A soluble DLK1 peptide was generated with fusion between a human Fc fragment and extracellular domain of DLK1. Male db/db mice were randomly assigned to two groups: vehicle treated and DLK1-treated group (25 mg kg(-1), intraperitoneal injection, twice a week for 4 weeks). Primary mice hepatocytes and HepG2 cells were used for in vitro experiments. RESULTS: After 4 weeks of DLK1 administration, hepatic triglyceride content and lipid droplets in liver tissues, as well as serum levels of liver enzymes, were markedly decreased in db/db mice. DLK1 treatment induced phosphorylation of AMPK and ACC and suppressed nuclear expression of SREBP-1c in the mouse liver or hepatocytes, indicating regulation of fatty acid oxidation and synthesis pathways. Furthermore, DLK1-treated mice showed significantly lower levels of fasting and random glucose, with improved glucose and insulin tolerance compared with the vehicle-treated group. Macrophage infiltration and proinflammatory cytokine levels in the epididymal fat were decreased in DLK1-treated db/db mice. Moreover, DLK1 suppressed glucose production from hepatocytes, which was blocked after co-administration of an AMPK inhibitor, compound C. DLK1-treated hepatocytes and mouse liver tissues showed lower PEPCK and G6Pase expression. DLK1 triggered AKT phosphorylation followed by cytosolic translocation of FOXO1 from the nucleus in hepatocytes. CONCLUSIONS: The present study demonstrated that exogenous administration of DLK1 reduced hepatic steatosis and hyperglycemia via AMPK activation in the liver. This result suggests that DLK1 may be a novel therapeutic approach for treating NAFLD and diabetes.

Microscopic mechanism underlying double-state lasing in an InAs/GaAs quantum dot laser diode elucidated using coupled rate equations and the spontaneous emission recorded from a window structure.

We investigated the microscopic mechanism underlying the double-state lasing behavior (simultaneous lasing at the ground state [GS] and excited state [ES]) in InAs/GaAs quantum dot (QD) laser diodes. The ES and GS lasing processes that contributed to double-state lasing were examined experimentally and theoretically. Experiments were conducted in which spontaneous emission from a window of a QD laser diode was examined under lasing conditions, and numerical simulations were performed using a coupled rate equation model of the QD microstates. The findings showed that, when carrier relaxation from the ES to the GS was sufficiently slow, double-state lasing occurred. Additionally, ES lasing was found to arise not from the QD group undergoing GS lasing, but rather from another QD group in which the states were lower in energy and outside of the homogeneous bandwidth.

Differentiation of Parkinsonism-Predominant Multiple System Atrophy from Idiopathic Parkinson Disease Using 3T Susceptibility-Weighted MR Imaging, Focusing on Putaminal Change and Lesion Asymmetry.

BACKGROUND AND PURPOSE: Asymmetric presentation of clinical feature in parkinsonism is common, but correlatable radiologic feature is not clearly defined. Our aim was to evaluate 3T susceptibility-weighted imaging findings for differentiating parkinsonism-predominant multiple system atrophy from idiopathic Parkinson disease, focusing on putaminal changes and lesion asymmetry. MATERIALS AND METHODS: This retrospective cohort study included 27 patients with parkinsonism-predominant multiple system atrophy and 50 patients with idiopathic Parkinson disease diagnosed clinically. Twenty-seven age-matched subjects without evidence of movement disorders who underwent SWI were included as the control group. A consensus was reached by 2 radiologists who visually assessed SWI for the presence of putaminal atrophy and marked signal hypointensity on each side of the posterolateral putamen. We also quantitatively measured putaminal width and phase-shift values. RESULTS: The mean disease duration was 4.7 years for the patients with parkinsonism-predominant multiple system atrophy and 7.8 years for the patients with idiopathic Parkinson disease. In the patients with parkinsonism-predominant multiple system atrophy, putaminal atrophy was frequently observed (14/27, 51.9%) and was most commonly found in the unilateral putamen (13/14). Marked signal hypointensity was observed in 12 patients with parkinsonism-predominant multiple system atrophy (44.4%). No patients with idiopathic Parkinson disease or healthy controls showed putaminal atrophy or marked signal hypointensity. Quantitatively measured putaminal width, phase-shift values, and the ratio of mean phase-shift values for the dominant and nondominant sides were significantly different between the parkinsonism-predominant multiple system atrophy group and the idiopathic Parkinson disease and healthy control groups (P < .001). CONCLUSIONS: 3T SWI can visualize putaminal atrophy and marked signal hypointensity in patients with parkinsonism-predominant multiple system atrophy with high specificity. Furthermore, it clearly demonstrates the dominant side of putaminal changes, which correlate with the contralateral symptomatic side of patients.

Conventional and real-time PCR targeting 16S ribosomal RNA for the detection of Mycobacterium tuberculosis complex.

SETTING: Conventional diagnostic methods for tuberculosis (TB) have limited sensitivity and specificity or are time-consuming. OBJECTIVE: 16S rDNA and 16S rRNA of Mycobacterium tuberculosis complex (MTC) were used as targets to develop sensitive and specific polymerase chain reactions (PCRs) to improve the diagnosis of MTC. DESIGN: We developed conventional and real-time PCRs targeting 16S rDNA and rRNA of MTC. RESULTS: PCRs targeting 16S rRNA had a 10-100 times lower limit of detection for M. tuberculosis than PCRs targeting 16S rDNA. The sensitivities of the 16S rDNA PCR, 16S rRNA reverse transcription PCR (RT-PCR), 16S rDNA real-time PCR and 16S rRNA real-time RT-PCR for sputum specimens were respectively 92%, 94.6%, 96% and 100%. Real-time PCR showed no cross-reactivity, but conventional PCR had cross-reactivity to M. avium, M. gastri and M. nonchromogenicum. CONCLUSION: PCRs targeting the 16S rRNA of MTC were more sensitive than those targeting 16S rDNA; 16S rRNA real-time RT-PCR showed the highest sensitivity and specificity for MTC.

Apigenin inhibits indoxyl sulfate-induced endoplasmic reticulum stress and anti-proliferative pathways, CHOP and IL-6/p21, in human renal proximal tubular cells.

OBJECTIVE: Indoxyl sulfate (IS) has been reported to induce endoplasmic reticulum (ER) stress in tubular cells and to inhibit the cell proliferation via ER stress and ERK/IL-6/p21 pathways. This study has investigated the effect of apigenin on IS-induced ER stress in immortalized human renal proximal tubular HK-2 cells. MATERIALS AND METHODS: Human Kidney 2 (HK-2) cells were treated with IS (5 mM) in the absence or presence of apigenin (10 µM) or salubrinal (20 µM) for indicated times under the serum-free condition. Cell viability was evaluated by MTT assay. The levels of protein expression and phosphorylation were evaluated by Western blot analysis. RESULTS: In HK-2 cells, apigenin completely inhibited IS-induced ER stress, as indicated by decreased expression of CHOP, ATF4 and GRP78, although the phosphorylated level of eIF2α did not decrease. IS-induced expression levels of IL-6 and p21 proteins were also inhibited by apigenin, with no significant changes in ERK activation. The suppression of cell proliferation by IS was abolished by salubrinal, an ER stress inhibitor, but not by apigenin. Apigenin inhibited the phosphorylation of Akt and GSK-3ß in IS-treated HK-2 cells. The phosphorylation of GSK-3ß, which was inhibited by apigenin, resulted in hypo-phosphorylation of retinoblastoma (Rb) protein, which was associated with the decrease in cyclin D1 expression. CONCLUSIONS: These results suggest that apigenin may inhibit IS-induced ER stress and expression of IL-6 and p21 proteins in HK-2 cells. It is most likely that apigenin, together with its inhibitory effect on ER stress, may also suppress the cell growth by inducing the loss of Rb phosphorylation, which was associated with the decrease in cyclin D1 expression by GSK-3ß activation through the inhibition of PI3K/Akt pathway.

Suppression of creep-regime dynamics in epitaxial ferroelectric BiFeO3 films.

Switching dynamics of ferroelectric materials are governed by the response of domain walls to applied electric field. In epitaxial ferroelectric films, thermally-activated 'creep' motion plays a significant role in domain wall dynamics, and accordingly, detailed understanding of the system's switching properties requires that this creep motion be taken into account. Despite this importance, few studies have investigated creep motion in ferroelectric films under ac-driven force. Here, we explore ac hysteretic dynamics in epitaxial BiFeO3 thin films, through ferroelectric hysteresis measurements, and stroboscopic piezoresponse force microscopy. We reveal that identically-fabricated BiFeO3 films on SrRuO3 or La0.67Sr0.33MnO3 bottom electrodes exhibit markedly different switching behaviour, with BiFeO3/SrRuO3 presenting essentially creep-free dynamics. This unprecedented result arises from the distinctive spatial inhomogeneities of the internal fields, these being influenced by the bottom electrode's surface morphology. Our findings further highlight the importance of controlling interface and defect characteristics, to engineer ferroelectric devices with optimised performance.