Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by G{alpha}12 gene knockout. G{alpha}12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did G{alpha}13 deficiency. The absence of G{alpha}12, but not of G{alpha}13, increased protein kinase C {delta} (PKC {delta}) activation and the PKC {delta}-mediated serine phosphorylation of Nrf2. G{alpha}13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by G{alpha}12 deficiency, suggesting that relief from G{alpha}12 repression leads to the G{alpha}13-mediated activation of Nrf2. Constitutive activation of G{alpha}13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC {delta} activation, corroborating positive regulation by G{alpha}13. In summary, G{alpha}12 and G{alpha}13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas G{alpha}13 regulates Rho-PKC {delta}-mediated Nrf2 phosphorylation, which is negatively balanced by G{alpha}12

The Largest Known Survival Analysis of Patients with Brain Metastasis from Thyroid Cancer Based on Prognostic Groups

To analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM) from differentiated thyroid cancer (DTC).A total of 37 patients with DTC who were diagnosed with BM between 1995 and 2014 were included. We reviewed the clinical characteristics, treatment modalities, and image findings of BM. Factors associated with survival were evaluated, and the patients were divided into three prognostic groups (Groups A, B, and C) for comparative analysis.The median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs) were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A) had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B) had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C) had the least favorable prognosis with a median survival of 1.5 months.The survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors

In-situ fabrication of cobalt-doped SrFe2As2 thin films by using pulsed laser deposition with excimer laser

The remarkably high superconducting transition temperature and upper critical field of iron(Fe)-based layered superconductors, despite ferromagnetic material base, open the prospect for superconducting electronics. However, success in superconducting electronics has been limited because of difficulties in fabricating high-quality thin films. We report the growth of high-quality c-axis-oriented cobalt(Co)-doped SrFe2As2 thin films with bulk superconductivity by using an in-situ pulsed laser deposition technique with a 248-nm-wavelength KrF excimer laser and an arsenic(As)-rich phase target. The temperature and field dependences of the magnetization showing strong diamagnetism and transport critical current density with superior Jc-H performance are reported. These results provide necessary information for practical applications of Fe-based superconductors.Comment: 8 pages, 3figures. to be published at Appl. Phys. Let

The Effects of d_{x^2-y^2}-d_{xy} Mixing on Vortex Structures and Magnetization

The structure of an isolated single vortex and the vortex lattice, and the magnetization in a $d$-wave superconductor are investigated within a phenomenological Ginzburg-Landau (GL) model including the mixture of the $d_{x^2-y^2}$-wave and $d_{xy}$-wave symmetry. The isolated single vortex structure in a week magnetic field is studied both numerically and asymptotically. Near the upper critical field $H_{c2}$, the vortex lattice structure and the magnetization are calculated analytically.Comment: 14 pages, REVTeX, 2 EPS figures, Journal of Physics: Condensed Matter (in press

Neuroprotective Effects of a Traditional Multi-Herbal Medicine Kyung-Ok-Ko in an Animal Model of Parkinson's Disease: Inhibition of MAPKs and NF-κB Pathways and Activation of Keap1-Nrf2 Pathway

Kyung-Ok-Ko (KOK), a traditional multi-herbal medicine, has been widely used in Oriental medicine as a restorative that can enforce vitality of whole organs and as a medicine that can treat age-related symptoms including lack of vigor and weakened immunity. However, the beneficial effect of KOK on neurological diseases such as Parkinson's diseases (PD) is largely unknown. Thus, the objective of this study was to examine the protective effect of KOK on neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pre-treatment with KOK at 1 or 2 g/kg/day (p.o.) showed significant mitigating effects on neurological dysfunction (motor and welfare) based on pole, rotarod, and nest building tests. It also showed effects on survival rate. These positive effects of KOK were related to inhibition of loss of tyrosine hydroxylase–positive neurons, reduction of MitoSOX activity, increased apoptotic cells, microglia activation, and upregulation of inflammatory factors [interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide], and reduced blood-brain barrier (BBB) disruption in the substantia nigra pars compacta (SNpc) and/or striatum after MPTP intoxication. Interestingly, these effects of KOK against MPTP neurotoxicity were associated with inhibition of phosphorylation of mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways along with up-regulation of nuclear factor erythroid 2-related factor 2 pathways in SNpc and/or striatum. Collectively, our findings suggest that KOK might be able to mitigate neurotoxicity in MPTP-induced mouse model of PD via multi-effects, including anti-neuronal and anti-BBB disruption activities through its anti-inflammatory and anti-oxidative activities. Therefore, KOK might have potential for preventing and/or treating PD

Are Portable Imaging Intraoperative Radiographs Helpful for Assessing Adequate Acetabular Cup Positioning in Total Hip Arthroplasty?

Despite advances in surgical techniques and instrumentation, current intra-operative estimations of acetabular version in total hip arthroplasty are of limited accuracy. In the present study, two experienced orthopedic surgeons compared intra-operatively measured (using portable imaging) anteversions and vertical inclinations of acetabular components with those measured using standardized radiographs post-operatively in 40 patients. Of the all vertical inclinations measured from intra-operative radiographs, 72.5% (n=29) were within ±2°, and 97.5% (n=39) were within ±5° of those determined using post-operative radiographs, and for anteversion, 52.5% (n=21) were within ±2°, and 97.5% (n=39) were within ±5°. Post-operative radiographs demonstrated that 90.0% (n=36) of vertical inclinations and anteversions were within the adequate zone. Obviously, our method has its limitations, but the authors conclude that the method described in this article better allows surgeons to verify acetabular version intra-operatively. In particular, the described method is suitable in cases with a deformed acetabular anatomy and difficult revision surgery

Mesenteric Pseudocyst of the Small Bowel in Gastric Cancer Patient: A Case Report

Mesenteric pseudocyst is rare. This term is used to describe the abdominal cystic mass, without the origin of abdominal organ. We presented a case of mesenteric pseudocyst of the small bowel in a 70-year-old man. Esophago-gastro-duodenoscopy showed a 3.5 cm sized excavated lesion on the posterior wall of angle. Endocopic biopsy confirmed a histologic diagnosis of the poorly differentiated adenocarcinoma, which includes the signet ring cell component. Abdominal computed tomography scan showed a focal mucosal enhancement in the posterior wall of angle of the stomach, a 2.4 cm sized enhancing mass on the distal small bowel loop, without distant metastases or ascites in rectal shelf, and multiple gallbladder stones. The patient underwent subtotal gastrectomy with gastroduodenostomy, segmental resection of the small bowel, and cholecystectomy. The final pathological diagnosis was mesenteric pseudocyst. This is the first case report describing incidentally detected mesenteric pseudocyst of the small bowel in gastric cancer patients