Description: Consumption of fructose has been linked to the development of metabolic syndrome, whereas the cardiomyopathic changes and cardiac apoptosis of dietary high-fructose intake have not yet been clarified. The purpose of this study was to evaluate the effects of high-fructose on cardiac apoptotic and survival pathways. Thirty-two Wistar rats were randomly divided into a control group (CON), which received a standard chow diet, and a fructose-induced metabolic syndrome group (FIMS), which received a 50% fructose-content diet for 13 weeks. Histopathological analysis, TUNEL assays and Western blotting were performed on the excised hearts from both groups. The blood pressure, glucose, insulin, triglyceride and cholesterol levels were significantly increased in the FIMS group, compared with the CON group. The abnormal myocardial architecture, enlarged interstitial space and increased cardiac TUNEL-positive apoptotic cells were observed in the FIMS group. The TNF- α , TNF receptor 1, Fas ligand, Fas receptor, FADD, and activated caspase-3 and 8 protein levels (Fas pathway) and the Bax, Bak, Bax/Bcl-2, Bak/Bcl-xL, cytosolic cytochrome c , and activated caspase-3 and nine protein levels (mitochondria pathway) were increased in the FIMS group compared with those in the CON group. The IGFI, IGFI-R, p-PI3K, p-Akt, Bcl-2 and Bcl-xL protein levels (survival pathway) were all significantly decreased in the FIMS group compared with those in the CON group. High-fructose intake elevated blood pressure and glucose levels; moreover, high-fructose diet activated cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and suppressed the survival pathway, which might provide one possible mechanism for developing heart failure in patients with metabolic syndrome. Copyright © 2013 John Wiley & Sons, Ltd.

Description: Oral squamous cell carcinoma (OSCC) is a common human malignant tumor with high mortality. So far, the molecular pathogenesis of OSCC remains largely unclear. Heterogeneous nuclear ribonucleoprotein (HnRNP) A1 is an important multi-function splicing factor and closely related to tumorigenesis. HnRNP A1 is overexpressed in various tumors, and promotes aerobic glycolysis and elongation of telomere, but the function of hnRNP A1 in cell cycle and proliferation remains unclear. We found that hnRNP A1 was overexpressed in OSCC tissues, and was required for the growth of OSCC cells. Moreover, hnRNP A1 was highly expressed in the G2/M cell cycle phase. Knockdown of hnRNP A1 induced G2/M arrest. DNA microarray assay result showed that hnRNP A1 regulated the expression of a number of target genes associated with G2/M phase. Moreover, hnRNP A1 controlled the alternative splicing of CDK2 exon 5. These findings suggested that hnRNP A1 plays key roles in the regulation of cell cycle progression and pathogenesis of OSCC. This article is protected by copyright. All rights reserved

Description: ABSTRACT Acute lung injury (ALI) is a serious inflammatory disorder which remains the primary cause of incidence and mortality in patients with acute pulmonary inflammation. However, there is still no effective medical strategy available clinically for the improvement of ALI. Wogonin, isolated from roots of Scutellaria baicalensis Georgi, is a common medicinal herb which presents biological and pharmacological effects, including antioxidation, anti-inflammation, and anticancer. Preadministration of wogonin inhibited not only lung edema but also protein leakage into the alveolar space in murine model of lipopolysaccharide (LPS)-induced ALI. Moreover, wogonin not only reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)−2 but also inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) induced by LPS. We further found wogonin inhibited the phosphorylation of p38 MAPK and JNK at a concentration lower than ERK. In addition, inhibition of lung edema, protein leakage, expression of iNOS and COX-2, and phosphorylation of p38 MAPK and JNK were all observed in a parallel concentration-dependent manner. These results suggest that wogonin possesses potential protective effect against LPS-induced ALI via downregulation of iNOS and COX-2 expression by blocking phosphorylation of p38 MAPK and JNK. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.

Description: Q-ball imaging (QBI) is an imaging technique that is capable of resolving intravoxel fiber crossings; however, the signal readout based on echo-planar imaging (EPI) introduces geometric distortions in the presence of susceptibility gradients. This study proposes an imaging technique that reduces susceptibility distortions in QBI by short-axis PROPELLER EPI acquisition. Conventional QBI and PROPELLER QBI data were acquired from two 3T MR scans of the brains of five healthy subjects. Prior to the PROPELLER reconstruction, residual distortions in single-blade low-resolution b0 and diffusion-weighted images (DWIs) were minimized by linear affine and nonlinear diffeomorphic demon registrations. Subsequently, the PROPELLER keyhole reconstruction was applied to the corrected DWIs to obtain high-resolution PROPELLER DWIs. The generalized fractional anisotropy and orientation distribution function maps contained fewer distortions in PROPELLER QBI than in conventional QBI, and the fiber tracts more closely matched the brain anatomy depicted by turbo spin-echo (TSE) T 2 -weighted imaging (T2WI). Furthermore, for fixed T E , PROPELLER QBI enabled a shorter scan time than conventional QBI. We conclude that PROPELLER QBI can reduce susceptibility distortions without lengthening the acquisition time and is suitable for tracing neuronal fiber tracts in the human brain. Copyright © 2013 John Wiley & Sons, Ltd. This study employed the short-axis PROPELLER EPI technique in conjunction with data-sharing PROPELLER reconstruction to obtain QBI data with reduced susceptibility distortions. The results showed that PROPELLER EPI with affine + demon registrations substantially reduces the susceptibility distortions in PROPELLER EPI. As compared with conventional QBI, the GFA, ODF, and fiber tracts in PROPELLER QBI more closely match their anatomical locations in distortion-free TSE T2WI.

Description: Recent evidence indicates that microRNAs might participate in prostate cancer initiation, progression, and treatment response. Germline variations in microRNAs might alter target gene expression and modify the efficacy of prostate cancer therapy. To determine whether genetic variants in microRNAs and microRNA target sites are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We retrospectively studied two independent cohorts composed of 320 Asian and 526 Caucasian men with pathologically organ-confined prostate cancer who had a median follow-up of 54.7 and 88.8 months after RP, respectively. Patients were systematically genotyped for 64 single-nucleotide polymorphisms (SNPs) in microRNAs and microRNA target sites, and their prognostic significance on BCR was assessed by Kaplan-Meier analysis and Cox regression model. After adjusting for known clinicopathologic risk factors, two SNPs ( MIR605 rs204556 and CDON rs3737336) remained associated with BCR. The numbers of risk alleles showed a cumulative effect on BCR [per-allele hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.16-2.21, P for trend = 0.005] in Asian cohort, and the risk was replicated in Caucasian cohort (HR 1.55, 95% CI 1.15-2.08, P for trend = 0.004) and in combined analysis (HR 1.57, 95% CI 1.26-1.96, P for trend 〈 0.001). Results warrant replication in larger cohorts. This is the first study demonstrating that SNPs in microRNAs and microRNA target sites can be predictive biomarkers for BCR after RP. © 2014 Wiley Periodicals, Inc.

Description: Background Osteoarthritis (OA) is currently still an irreversible degenerative disease of the articular cartilage. Recent, dextrose (D-glucose) intraarticular injection prolotherapy for OA patients has been reported to benefit the chondrogenic stimulation of damaged cartilage. However, the detailed mechanism of glucose's effect on cartilage repair remains unclear. Chitosan, a naturally derived polysaccharide, has recently been investigated as a surgical or dental dressing to control breeding. Therefore, in this study, glucose was adsorbed to chitosan membranes (CTS-Glc), and the study aimed to investigate whether CTS-Glc complex membranes could regulate the proliferation of human OA chondrocytes and to explore the underlying mechanism. Methods Human OA and SW1353 chondrocytes were used in this study. The experiments involving the transfection of cells used SW1353 chondrocytes. A specific inhibitor and siRNAs were used to investigate the mechanism underlying the CTS-Glc-regulated proliferation of human chondrocytes. Results We found that CTS-Glc significantly increased the proliferation of both human OA and SW1353 chondrocytes comparable to glucose- or chitosan-only stimulation. The role of mammalian target of rapamycin complex 1 (mTORC1) signaling, including mTOR, raptor, and S6k proteins, has been demonstrated in the regulation of CTS-Glc-increased human chondrocyte proliferation. mTORC1 signaling increased the expression levels of maturated SREBP-1 and FASN and then induced the expressions of cell cycle regulators, i.e., cyclin D, cyclin-dependent kinase-4 and -6 in human chondrocytes. Conclusions This study elucidates the detailed mechanism behind the effect of CTS-Glc complex membranes in promoting chondrocyte proliferation and proposes a possible clinical application of the CTS-Glc complex in the dextrose intraarticular injection of OA prolotherapy in the future to attenuate the pain and discomfort of OA patients. This article is protected by copyright. All rights reserved

Description: Five new oxygenated lignans with a dibenzocyclooctadiene skeleton, kadsuphilols P–T ( 1 – 5 ), and two new C 19 homolignans, kadsuphilols U and V ( 6 and 7 ), were isolated by chromatographic fractionation of an AcOEt extract of the stems of Kadsura philippinensis. The structures of the isolated metabolites were elucidated through extensive spectroscopic analysis including HR-ESI-MS and 2D-NMR (HMQC, COSY, and HMBC). The configuration at the chiral centers and at the biphenyl moiety were determined by interpretation of NOESY and CD data, respectively.

Description: Our previous hybrid simulation [ Shi et al. , 2013] under a radial interplanetary magnetic field (IMF) and a supercritical solar wind Mach number has shown that foreshock compressional waves originated from the quasi-parallel (Q-∥) shock are mode converted to kinetic Alfvén waves (KAWs) at the Alfvén resonance surface of the subsolar magnetopause. In this paper, three-dimensional global dayside mode conversion is investigated for cases under various solar wind conditions using the global hybrid model. The global patterns and propagations of KAWs are distinguished and presented. Under a near-critical Mach number ( M A =3), KAW structures due to mode conversion exhibit a feature of broader excitation regions in the magnetopause boundary layer (MPBL) compared to super-critical Mach number ( M A =5) shocks. For cases with an oblique IMF with supercritical Mach numbers ( M A =5), the amplitude of magnetosheath compressional waves is larger at the quasi-parallel shock (Q-∥) than at the quasi-perpendicular (Q-⊥) shock. Downstream of the Q-∥ shock, there is a general trend that the perturbations of density ( N ) and magnetic field ( B ) change from predominantly in-phase in the magnetosheath to anti-phase near the MPBL. While downstream of the Q-⊥ shock, an anti-phase relation between N and B is dominant throughout the magnetosheath and magnetopause except near the shock transition. The compressional drivers are found to reach an extended region of the magnetopause due to the combined effects of wave propagation in the plasma frame and flow convection, leading to a broad region of mode conversion at the magnetopause. Subsequently, the resulting KAWs can be carried to the regions downstream of the Q-⊥ shock owing to the ïňĆow convection at the magnetopause. The KAWs propagate poleward along the geomagnetic field lines and meanwhile are carried tailward by the ambient flows, and they are more intense in the downstream of Q-∥ shocks than downstream of Q-⊥ shocks.

Description: BACKGROUND Stereotactic radiosurgery (SRS) alone is an increasingly accepted treatment for brain metastases, but it requires adherence to frequently scheduled follow-up neuroimaging because of the risk of distant brain metastasis. The effect of disparities in access to follow-up care on outcomes after SRS alone is unknown. METHODS This retrospective study included 153 brain metastasis patients treated consecutively with SRS alone from 2010 through 2016 at an academic medical center and a safety-net hospital (SNH) located in Los Angeles, California. Outcomes included neurologic symptoms, hospitalization, steroid use and dependency, salvage SRS, salvage whole-brain radiotherapy, salvage neurosurgery, and overall survival. RESULTS Ninety-three of the 153 patients were private hospital (PH) patients, and 60 were SNH patients. The median follow-up time was 7.7 months. SNH patients received fewer follow-up neuroimaging studies (1.5 vs 3; P  = .008). In a multivariate analysis, the SNH setting was a significant risk factor for salvage neurosurgery (hazard ratio [HR], 13.65; P  〈 .001), neurologic symptoms (HR, 3.74; P  = .002), and hospitalization due to brain metastases (HR, 6.25; P  〈 .001). More clinical visits were protective against hospitalizations due to brain metastases (HR, 0.75; P  = .002), whereas more neuroimaging studies were protective against death (HR, 0.65; P  〈 .001). CONCLUSIONS SNH patients with brain metastases treated with SRS alone had fewer follow-up neuroimaging studies and were at higher risk for neurologic symptoms, hospitalization for brain metastases, and salvage neurosurgery in comparison with PH patients. Clinicians should consider the practice setting and patient access to follow-up care when they are deciding on the optimal strategy for the treatment of brain metastases. Cancer 2017; . © 2017 American Cancer Society .

Description: Ovarian carcinosarcoma cancer is the most lethal form of gynecological malignancy, but the pathogenesis and biological function for this ovarian cancer remain unknown. We establishment the transgenic mouse model of K-ras G12D p53 loxP/loxP and found that K-ras mutation and p53 deletion within the ovarian surface epithelium gave rise to ovarian lesions with a hyperproliferation and endometrioid glandular morphology. Furthermore, double mutant ovaries formed ovarian carcinosarcomas that were high grade and poorly differentiated. Induction was widely metastatic and spread to abdominal organs including liver, spleen, and kidney at 4 wk. We also confirmed the role of K-ras G12D in ovarian cancer cell lines MCAS and PA-1 and showed that K-ras G12D overexpression strongly induced cell proliferation, migration, and invasion. The ovarian cancer model we developed recapitulates the specific tumor histomorphology and the probable mechanism of malignant transformation in endometriosis. This article is protected by copyright. All rights reserved.