bluuebunny/crossref_metadata_2025 huggingface dataset:
The Link Between Angiogenesis and Endothelial Metabolism
Authors: Potente Michael , Carmeliet Peter
Published: December 2016

Angiogenesis has traditionally been viewed from the perspective of how endothelial cells (ECs) coordinate migration and proliferation in response to growth factor activation to form new vessel branches. However, ECs must also coordinate their metabolism and adapt metabolic fluxes to the rising energy and biomass demands of branching vessels. Recent studies have highlighted the importance of such metabolic regulation in the endothelium and uncovered core metabolic pathways and mechanisms of regulation that drive the angiogenic process. In this review, we discuss our current understanding of EC metabolism, how it intersects with angiogenic signal transduction, and how alterations in metabolic pathways affect vessel morphogenesis. Understanding EC metabolism promises to reveal new perspectives on disease mechanisms in the vascular system with therapeutic implications for disorders with aberrant vessel growth and function.
Smoking, Mental Illness, and Public Health
Authors: Prochaska Judith J. , Das Smita , Young-Wolff Kelly C.
Published: December 2016

Tobacco use remains the leading preventable cause of death worldwide. In particular, people with mental illness are disproportionately affected with high smoking prevalence; they account for more than 200,000 of the 520,000 tobacco-attributable deaths in the United States annually and die on average 25 years prematurely. Our review aims to provide an update on smoking in the mentally ill. We review the determinants of tobacco use among smokers with mental illness, presented with regard to the public health HAVE framework of “the host” (e.g., tobacco user characteristics), the “agent” (e.g., nicotine product characteristics), the “vector” (e.g., tobacco industry), and the “environment” (e.g., smoking policies). Furthermore, we identify the significant health harms incurred and opportunities for prevention and intervention within a health care systems and larger health policy perspective. A comprehensive effort is warranted to achieve equity toward the 2025 Healthy People goal of reducing US adult tobacco use to 12%, with attention to all subgroups, including smokers with mental illness.
Prognostic Relevance of Nonsustained Ventricular Tachycardia in Patients with Pulmonary Hypertension
Authors: Bandorski Dirk , Bogossian Harilaos , Stempfl Johanna , Seeger Werner , Hecker Matthias , Ghofrani Ardeschir , Hoeltgen Reinhard , Gall Henning
Published: December 2016

Background.Increased pulmonary vascular resistance in patients with pulmonary hypertension (PH) leads to an increased afterload of right heart and cardiac remodeling which could provide the substrate or trigger for arrhythmias. Supraventricular arrhythmias were associated with clinical deterioration but were not associated with sudden cardiac death (SCD). SCD has been reported to account for approximately 30% of deaths in patients with pulmonary arterial hypertension (PAH).Objective.The role of nonsustained ventricular tachycardia (nsVT) and its prognostic relevance in patients with PH remains unclear. This study evaluated the prognostic relevance of nsVT in patients with PAH and chronic thromboembolic pulmonary hypertension (CTEPH).Methods.Retrospectively, patients with PAH and CTEPH who underwent Holter ECG monitoring and available data of survival were investigated.Results.Seventy-eight (PAH: 55, CTEPH: 23) patients were evaluated. Holter ECG revealed nsVT in 12 patients. Twenty-one patients died during follow-up. In patients with nsVT, tricuspid annular plane systolic excursion was lower(p=0.001), and systolic pulmonary arterial pressure was higher(p=0.163). Mean survival of patients without/with nsVT was 155.2 ± 8.5/146.4 ± 21.4 months(p=0.690). The association between arrhythmias and survival was not confounded by age(p=0.681), gender(p=0.752), 6-MW distance(p=0.196), or arterial hypertension(p=0.238).Conclusions.In patients with PH, nsVT occurs more often than previously reported, and patients with PH group 1 seem to be more at risk.
Structure Prior Effects in Bayesian Approaches of Quantitative Susceptibility Mapping
Authors: Wang Shuai , Chen Weiwei , Wang Chunmei , Liu Tian , Wang Yi , Pan Chu , Mu Ketao , Zhu Ce , Zhang Xiang , Cheng Jian
Published: December 2016

Quantitative susceptibility mapping (QSM) has shown its potential for anatomical and functional MRI, as it can quantify, for in vivo tissues, magnetic biomarkers and contrast agents which have differential susceptibilities to the surroundings substances. For reconstructing the QSM with a single orientation, various methods have been proposed to identify a unique solution for the susceptibility map. Bayesian QSM approach is the major type which uses various regularization terms, such as a piece-wise constant, a smooth, a sparse, or a morphological prior. Six QSM algorithms with or without structure prior are systematically discussed to address the structure prior effects. The methods are evaluated using simulations, phantom experiments with the given susceptibility, and human brain data. The accuracy and image quality of QSM were increased when using structure prior in the simulation and phantom compared to same regularization term without it, respectively. The image quality of QSM method using the structure prior is better comparing, respectively, to the method without it by either sharpening the image or reducing streaking artifacts in vivo. The structure priors improve the performance of the various QSMs using regularized minimization including L1, L2, and TV norm.
Carotid Intima-Media Thickness and Visit-to-Visit HbA1c Variability Predict Progression of Chronic Kidney Disease in Type 2 Diabetic Patients with Preserved Kidney Function
Authors: Takenouchi Akiko , Tsuboi Ayaka , Kurata Miki , Fukuo Keisuke , Kazumi Tsutomu
Published: December 2016

Background/Aims. Subclinical atherosclerosis and long-term glycemic variability have been reported to predict incident chronic kidney disease (CKD) in the general population. However, these associations have not been investigated in patients with type 2 diabetes with preserved kidney function.Methods. We prospectively followed up 162 patients with type 2 diabetes (mean age, 62.3 years; 53.6% men) and assessed whether carotid intima-media thickness (IMT) measured by B-mode ultrasound and visit-to-visit HbA1c variability are associated with deterioration of CKD (incident CKD defined as estimated GFR [eGFR] < 60 mL/min/1.73 m2and progression of CKD stages) over a median follow-up of 6.0 years. At baseline, 25 patients (15.4%) had CKD. Cox proportional hazards regression models were used for identifying associated factors of CKD deterioration.Results.Estimated GFR decreased from75.8±16.3to67.4±18.2 mL/min/1.73 m2(p<0.01). Of 162 patients, 32 developed CKD and 8 made a progression of CKD stages. Multivariate Cox regression analysis revealed that carotid IMT (HR: 4.0, 95% CI: 1.1–14.226.7, andp=0.03) and coefficient of variation of HbA1c (HR: 1.12, 95%: 1.04–1.21, andp=0.003) were predictors of deterioration of CKD independently of age, mean HbA1c, urinary albumin/creatinine ratio, baseline eGFR, uric acid, and leucocyte count.Conclusions.Subclinical atherosclerosis and long-term glycemic variability predict deterioration of chronic kidney disease (as defined by incident or worsening CKD) in type 2 diabetic patients with preserved kidney function.
Genome-Wide Identification of Long Noncoding RNAs in Human Intervertebral Disc Degeneration by RNA Sequencing
Authors: Zhao Bo , Lu Minjuan , Wang Dong , Li Haopeng , He Xijing
Published: December 2016

Long noncoding RNAs (lncRNAs) are emerging as crucial players in a myriad of biological processes. However, the precise mechanism and functions of most lncRNAs are poorly characterized. In this study, we presented genome-wide identification of lncRNAs in the patients with intervertebral disc degeneration (IDD) and spinal cord injury (control) using RNA sequencing (RNA-seq). A total of 124.6 million raw reads were yielded using Hiseq 2500 platform and approximately 88% clean reads could be aligned to human reference genome in both IDD and control groups. RNA-seq profiling indicated that 1,854 lncRNAs were differentially expressed (log2 fold change ≥ 1 or ≤-1, p<0.05), in which 1,530 could potentially target 6,386 genes via cis-regulatory effects. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for these target genes suggested that lncRNAs were involved in diverse pathways, such as lysosome, focal adhesion, and MAPK signaling. In addition, a competing endogenous RNA (ceRNA) network was constructed for analyzing the function of lncRNAs. Further, quantitative real time PCR (qRT-PCR) was used to confirm the differentially expressed lncRNAs and ceRNA network. In conclusion, our results present the first global identification of lncRNAs in IDD and may provide candidate diagnostic biomarkers for IDD treatment.
Cytokine Changes following Acute Ethanol Intoxication in Healthy Men: A Crossover Study
Authors: Neupane Sudan Prasad , Skulberg Andreas , Skulberg Knut Ragnvald , Aass Hans Christian D. , Bramness Jørgen G.
Published: December 2016

Alcohol is a known modulator of the innate immune system. Owing to the absence of human studies, alcohol’s effect on circulating cytokine profile remains unclear. We investigated the effect of acute high dose alcohol consumption on systemic cytokine release. After an overnight fasting, alcohol-experienced healthy male volunteers (N=20) aged 25–45 years were given oral ethanol in the form of vodka (4.28 mL/kg) which they drank over a period of 30 minutes reaching peak blood alcohol concentration of 0.12% (SD 0.028). Blood samples were obtained prior to alcohol intake as well as 2, 7, and 12 hours thereafter. Serum levels of the inflammatory cytokines IL-1β, IL-1Ra, IL-6, IL-10, IL-17, IFN-γ, MCP-1, and TNF-αwere determined by the multibead-based assay. Baseline cytokine levels were not related to BMI, hepatic parameters, electrolytes, glucose, or morning cortisol levels. Within 2 hours of alcohol intake, levels of IL-1Ra were elevated and remained so throughout the assessment period (pfor trend = 0.015). In contrast, the levels of the chemokine MCP-1 dropped acutely followed by steadily increasing levels during the observation period (p<0.001). The impact of sustained elevated levels of MCP-1 even after the clearance of blood alcohol content deserves attention.
The Power of CRISPR-Cas9-Induced Genome Editing to Speed Up Plant Breeding
Authors: Cao Hieu X. , Wang Wenqin , Le Hien T. T. , Vu Giang T. H.
Published: December 2016

Genome editing with engineered nucleases enabling site-directed sequence modifications bears a great potential for advanced plant breeding and crop protection. Remarkably, the RNA-guided endonuclease technology (RGEN) based on the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) is an extremely powerful and easy tool that revolutionizes both basic research and plant breeding. Here, we review the major technical advances and recent applications of the CRISPR-Cas9 system for manipulation of model and crop plant genomes. We also discuss the future prospects of this technology in molecular plant breeding.
Intrapulpal Thermal Changes during Setting Reaction of Glass Carbomer® Using Thermocure Lamp
Authors: Kahvecioglu Firdevs , Tosun Gül , Ülker Hayriye Esra
Published: December 2016

Objectives. To measure the temperature increase induced during thermocure lamp setting reaction of glass carbomer and to compare it with those induced by visible light curing of a resin-modified glass ionomer and a polyacid-modified composite resin in primary and permanent teeth. Materials and Methods. Nonretentive class I cavities were prepared in extracted primary and permanent molars. Glass carbomer (GC) was placed in the cavity and set at 60°C for 60 sn using a special thermocure lamp. Resin-modified glass ionomer (RMGIC) and polyacid-modified composite resin (PMCR) were placed in the cavities and polymerized with an LED curing unit. Temperature increases during setting reactions were measured with a J-type thermocouple wire connected to a data logger. Data were examined using two-way analysis of variance and Tukey’s honestly significant difference tests. Results. The use of GC resulted in temperature changes of 5.17 ± 0.92°C and 5.32 ± 0.90°C in primary and permanent teeth, respectively (p>0.05). Temperature increases were greatest in the GC group, differing significantly from those in the PMCR group (p<0.05). Conclusion. Temperature increases during polymerization and setting reactions of the materials were below the critical value in all groups. No difference was observed between primary and permanent teeth, regardless of the material used.
Effects of Morinda officinalis Polysaccharide on Experimental Varicocele Rats
Authors: Zhang Lihong , Zhao Xiaozhen , Wang Feng , Lin Qing , Wang Wei
Published: December 2016

Morinda officinalis is a traditional Chinese herbal medicine, which has been used to tonify the kidney and strengthen yang for a long time in China. In this study, the effects of M. officinalis Polysaccharide (MOP) on experimental varicocele adolescent rats were investigated. The result showed that varicocele destroyed the structure of the seminiferous epithelium and decreased the TJ protein expression (Occludin, Claudin‐11, and ZO‐1), testosterone (T) concentration in the left testicular tissue and serum, and serum levels of inhibin B (INHB), while increasing the levels of cytokines (TGF‐β3 and TNF‐α) in the left testicular tissue, as well as serum levels of gonadotropin‐releasing hormone (GnRH), follicle‐stimulating hormone (FSH), luteinizing hormone (LH), and antisperm antibody (AsAb). MOP repaired the damaged seminiferous epithelium and TJ and reduced the levels of cytokines (TGF‐β3 and TNF‐α) as well as serum levels of GnRH, FSH, LH, and AsAb, while upregulating TJ protein expression, T level in the left testicular tissue and serum, and serum INHB levels. In summary, we conclude that MOP promotes spermatogenesis and counteracts the varicocele‐induced damage to the seminiferous epithelium and TJ, probably via decreasing cytokines (TGF‐β3 and TNF‐α) levels and regulating the abnormal sex hormones levels in experimental varicocele rats.
Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway
Authors: Lu Jingjing , Xu Ying , Wei Xuan , Zhao Zhe , Xue Jing , Liu Peishu
Published: December 2016

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite the anticancer capabilities of emodin observed in many cancers, including EOC, the underlying molecular mechanism remains to be elucidated. A crucial link has been discovered between the acquisition of metastatic traits and the epithelial-mesenchymal transition (EMT). The present study aimed to determine whether emodin could inhibit the EMT of EOC cells and explore the underlying mechanism. The CCK-8 assay and transwell assay showed that emodin effectively repressed the abilities of proliferation, invasion, and migration in A2780 and SK-OV-3 cells. The Western blot showed that emodin upregulated epithelial markers (E-cadherin and Claudin) while it downregulated mesenchymal markers (N-cadherin and Vimentin) and transcription factor (Slug) in a dose-dependent fashion. After transfection of siRNA-Slug, both Slug and N-cadherin were downregulated in EOC cells while E-cadherin was upregulated, which was intensified by emodin. Besides, emodin decreased the expression of ILK, p-GSK-3β,β-catenin, and Slug. Transfection of siRNA-ILK also achieved the same effects, which was further strengthened by following emodin treatment. Nevertheless, SB216763, an inhibitor of GSK-3β, could reverse the effects of emodin except for ILK expression. These findings suggest that emodin inhibited the EMT of EOC cells via ILK/GSK-3β/Slug signaling pathway.
Adaptive Finite-Horizon Group Estimation for Networked Navigation Systems with Remote Sensing Complementary Observations under Mixed LOS/NLOS Environments
Authors: Gao Chao , Lu Jianhua , Zhao Guorong , Pan Shuang
Published: December 2016

Networked navigation system (NNS) enables a wealth of new applications where real-time estimation is essential. In this paper, an adaptive horizon estimator has been addressed to solve the navigational state estimation problem of NNS with the features of remote sensing complementary observations (RSOs) and mixed LOS/NLOS environments. In our approach, it is assumed that RSOs are the essential observations of the local processor but suffer from random transmission delay; a jump Markov system has been modeled with the switching parameters corresponding to LOS/NLOS errors. An adaptive finite-horizon group estimator (AFGE) has been proposed, where the horizon size can be adjusted in real time according to stochastic parameters and random delays. First, a delay-aware FIR (DFIR) estimator has been derived with observation reorganization and complementary fusion strategies. Second, an adaptive horizon group (AHG) policy has been proposed to manage the horizon size. The AFGE algorithm is thus realized by combining AHG policy and DFIR estimator. It is shown by a numerical example that the proposed AFGE has a more robust performance than the FIR estimator using constant optimal horizon size.
Benefit of Leukocyte- and Platelet-Rich Plasma in Operative Wound Closure in Oral and Maxillofacial Surgery
Authors: Cieślik-Bielecka Agata , Glik Justyna , Skowroński Rafał , Bielecki Tomasz
Published: December 2016

This article reports the influence of an autologous leukocyte- and platelet-rich plasma (L-PRP) injection as a minimally invasive method on supporting wound healing processes after a mandibular odontogenic cystectomy and double mandibular fracture fixation. 113 patients were enrolled into a control group (received no L-PRP injection) and 102 patients were enrolled into an L-PRP group with an oral mucosa incision. 18 patients after a double mandibular fracture were operated on using 2 external submandibular approaches receiving no fluids in the right site (a control group) and an L-PRP injection in the left incision (L-PRP group). Clinical observations showed that the oral mucosa healed faster in patients treated with L-PRP, in comparison to cases where inductive biomaterial was not added. Pain at the L-PRP injection site was relieved within few hours after an operation in patients with double mandibular fractures. However, there were no differences observed in the progression of the healing process. L-PRP possesses inductive properties that could stimulate healing processes and it seems to be one of the most promising methods in the future for the treatment of soft tissue defects.
From Blank Canvas to Masterwork: Creating a Professional Practice Model at a Magnet Hospital
Authors: Dimitroff Lynda J. , Tydings Donna M. , Nickoley Sue , Nichols Lynn W. , Krenzer Maureen E.
Published: December 2016

Objective. The purpose of this study was to engage registered nurses (RNs) in the creation of a Professional Practice Model (PPM).Background. PPMs are essential as the philosophical underpinnings for nursing practice. The study institution created a new PPM utilizing the voice of their RNs.Methods. Qualitative inquiry with focus groups was conducted to explore RNs values and beliefs about their professional practice. Constant-comparative analysis was used to code data and identify domains.Results. The 92 RN participants represented diverse roles and practice settings. The four domains identified were caring, knowing, navigating, and leading.Conclusions. Nurse leaders face the challenge of assisting nurses in articulating their practice using a common voice. In this study, nurses described their identity, their roles, and how they envisioned nursing should be practiced. The results align with the ANCC Magnet® Model, ANA standards, and important foundational and organization specific documents.
Downregulation of PGC-1αPrevents the Beneficial Effect of EET-Heme Oxygenase-1 on Mitochondrial Integrity and Associated Metabolic Function in Obese Mice
Authors: Singh Shailendra P. , Bellner Lars , Vanella Luca , Cao Jian , Falck John R. , Kappas Attallah , Abraham Nader G.
Published: December 2016

Background/Objectives. Obesity and metabolic syndrome and associated adiposity are a systemic condition characterized by increased mitochondrial dysfunction, inflammation, and inhibition of antioxidant genes, HO-1, and EETs levels. We postulate that EETs attenuate adiposity by stimulating mitochondrial function and induction of HO-1 via activation of PGC-1αin adipose and hepatic tissue.Methods. Cultured murine adipocytes and mice fed a high fat (HF) diet were used to assess the functional relationship among EETs, PGC-1α, HO-1, and mitochondrial signaling using an EET-agonist (EET-A) and PGC-1α-deficient cells and mice using lentiviral PGC-1α(sh).Results. EET-A is a potent inducer of PGC-1α, HO-1, mitochondrial biogenesis (cytochrome oxidase subunits 1 and 4 and SIRT3), fusion proteins (Mfn1/2and OPA1) and fission proteins (DRP1 and FIS1) (p<0.05), fasting glucose, BW, and blood pressure. These beneficial effects were prevented by administration of lenti-PGC-1α(sh). EET-A administration prevented HF diet induced mitochondrial and dysfunction in adipose tissue and restored VO2effects that were abrogated in PGC-1α-deficient mice.Conclusion. EET is identified as an upstream positive regulator of PGC-1αthat leads to increased HO-1, decreased BW and fasting blood glucose and increased insulin receptor phosphorylation, that is, increased insulin sensitivity and mitochondrial integrity, and possible use of EET-agonist for treatment of obesity and metabolic syndrome.
Molecular Detection of Anaplasma spp. and Ehrlichia spp. in Ruminants from Twelve Provinces of China
Authors: Qiu Haixiang , Kelly Patrick John , Zhang Jilei , Luo Qinghua , Yang Yi , Mao Yongjiang , Yang Zhangping , Li Jing , Wu Hongzhuan , Wang Chengming
Published: December 2016

Anaplasma spp. and Ehrlichia spp. are tick-transmitted bacteria that are of significant economic importance as they can infect large and small ruminants and also people. There is little information on anaplasmosis and ehrlichiosis in ruminants in China. 16S rRNA FRET-qPCRs were used to screen convenience whole blood samples from 2,240 domestic ruminants in 12 provinces of China for Anaplasma spp. and Ehrlichia spp. Positive samples were further analyzed with a standard PCR for the gltA. Anaplasma spp. DNA was detected in the sheep (11.7%; 13/111), goats (81.8%; 219/270), cattle (13.2%; 241/1,830), and water buffaloes (6.9%; 2/29). Ehrlichia spp. DNA was detected in sheep (1.8%; 2/111), goats (1.1%; 3/270), and cattle (3.6%; 65/1830) but not in water buffaloes (0/29). Sequencing of gltA PCR products showed that A. marginale, A. ovis, Ehrlichia canis, and Ehrlichia sp. (JX629807) were present in ruminants from China, while the 16S rRNA FRET-qPCR sequence data indicated that there might also be A. platys, A. phagocytophilum, Anaplasma sp. BL126-13 (KJ410243), and Anaplasma sp. JC3-6 (KM227012). Our study shows that domestic ruminants from China are not uncommonly infected with a variety of Anaplasma spp. and Ehrlichia spp.
Effects of Renal Ischemic Postconditioning on Myocardial Ultrastructural Organization and Myocardial Expression of Bcl-2/Bax in Rabbits
Authors: Zhang Wen-zhong , Li Rong , Liu Song , Zhang Ji-dong , Ning Xian-feng , Cai Shang-lang
Published: December 2016

We investigated the cardioprotective effect of renal ischemic postconditioning (RI-PostC) and its mechanisms in a rabbit model. Rabbits underwent 60 min of left anterior descending coronary artery occlusion (LADO) and 6 h of reperfusion. The ischemia-reperfusion (IR) group underwent LADO and reperfusion only. In the RI-PostC group, the left renal artery underwent 3 cycles of occlusion for 30 seconds and release for 30 seconds, before the coronary artery was reperfused. In the RI-PostC + GF109203X group, the rabbits received 0.05 mg/kg GF109203X (protein kinase C inhibitor) intravenously for 10 min followed by RI-PostC. Light microscopy and electron microscopy demonstrated that the RI-PostC group showed less pronounced changes, a smaller infarct region, and less apoptosis than the other two groups. Bcl-2 and Bax protein expression did not differ between the IR and RI-PostC + GF109203X groups. However, in the RI-PostC group, Bcl-2 protein expression was significantly higher and Bax protein expression was significantly lower than in the other two groups (P<0.05). Changes in heart rate and mean arterial pressure were also smaller in the RI-PostC group than in the other two groups. These results indicate that RI-PostC can ameliorate myocardial ischemia-reperfusion injury and increase the Bcl-2/Bax ratio through a mechanism involving protein kinase C.
A Comparative Chemical Study of Calcium Silicate-Containing and Epoxy Resin-Based Root Canal Sealers
Authors: Reszka Przemysław , Nowicka Alicja , Lipski Mariusz , Dura Włodzimierz , Droździk Agnieszka , Woźniak Krzysztof
Published: December 2016

Objective.The present study assessed the chemical elements in two novel calcium silicate-containing root canal sealers, BioRoot RCS and Well-Root ST, compared to a calcium silicate-containing root canal sealer that has been on the market for several years, MTA Fillapex, and epoxy resin-based sealer AHPlus.Material and Methods.The sealers were mixed and manipulated according to the manufacturers’ instructions. Twelve cylindrical molds (inner diameter 4 mm; height 3 mm) were placed on a glass petri dish and packed with the materials. The dish was transferred to an incubator. After 72 h the molds were examined by scanning electron microscopy and energy dispersive X-ray microanalysis.Results.BioRoot RCS and Well-Root ST had high peaks of calcium, zirconium, oxygen, carbon, silicon, and chlorine. Well-Root ST also had sodium, magnesium, aluminum, and titanium peaks. MTA Fillapex and AHPlus had carbon, oxygen, calcium, titanium, and bismuth peaks. A silicon peak was also observed for MTA Fillapex, and zirconium and tungsten peaks for AHPlus.Conclusion.BioRoot RSC had the highest degree of purity. The clinical implication of metals contained in the other sealers needs to be investigated.
Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR Activation
Authors: Malakar Pushkar , Shilo Asaf , Mogilevsky Adi , Stein Ilan , Pikarsky Eli , Nevo Yuval , Benyamini Hadar , Elgavish Sharona , Zong Xinying , Prasanth Kannanganattu V. , Karni Rotem
Published: December 2016

Several long noncoding RNAs (lncRNA) are abrogated in cancer but their precise contributions to oncogenesis are still emerging. Here we report that the lncRNA MALAT1 is upregulated in hepatocellular carcinoma and acts as a proto-oncogene through Wnt pathway activation and induction of the oncogenic splicing factor SRSF1. Induction of SRSF1 by MALAT1 modulates SRSF1 splicing targets, enhancing the production of antiapoptotic splicing isoforms and activating the mTOR pathway by modulating the alternative splicing of S6K1. Inhibition of SRSF1 expression or mTOR activity abolishes the oncogenic properties of MALAT1, suggesting that SRSF1 induction and mTOR activation are essential for MALAT1-induced transformation. Our results reveal a mechanism by which lncRNA MALAT1 acts as a proto-oncogene in hepatocellular carcinoma, modulating oncogenic alternative splicing through SRSF1 upregulation. Cancer Res; 77(5); 1155–67. ©2016 AACR.
Safety and Preclinical Efficacy of Aerosol Pioglitazone on Lung Adenoma Prevention in A/J Mice
Authors: Seabloom Donna E. , Galbraith Arthur R. , Haynes Anna M. , Antonides Jennifer D. , Wuertz Beverly R. , Miller Wendy A. , Miller Kimberly A. , Steele Vernon E. , Suen Chen S. , O'Sullivan M. Gerard , Ondrey Frank G.
Published: December 2016

Pioglitazone is a PPARγ agonist commonly prescribed for the clinical treatment of diabetes. We sought to expand its use to lung cancer prevention in a benzo[a]pyrene (B[a]P) mouse model with direct lung delivery via inhalation. Initially, we conducted inhalational toxicity experiments with 0, 15, 50, 150, and 450 μg/kg body weight/day pioglitazone in 40 A/J mice. We examined the animals for any physical toxicity and bronchoalveolar lavage fluids for inflammatory and cytotoxicity markers. Doses up to and including 450 μg/kg bw/d failed to demonstrate toxicity with aerosol pioglitazone. For chemoprevention experiments, A/J mice were randomized to treatment groups of inhaled doses of 0, 50, 150, or 450 μg/kg bw/d pioglitazone 1 or 8 weeks after the last dose of B[a]P. For the early treatment group, we found up to 32% decrease in lung adenoma formation with 450 μg/kg bw/d pioglitazone. We repeated the treatments in a second late-stage experiment and found up to 44% decreases in lung adenoma formation in doses of pioglitazone of 150 and 450 μg/kg bw/day. Both the early- and the late-stage experiments demonstrated biologically relevant and statistically significant decreases in adenoma formation. We conclude that aerosol pioglitazone is well-tolerated in the A/J mouse model and a promising chemoprevention agent for the lower respiratory tract. Cancer Prev Res; 10(2); 124–32. ©2016 AACR.
Spontaneous Isolated Superior Mesenteric Artery Dissection
Authors: Nath Anand , Yewale Sayali , Kousha Mohammad
Published: December 2016

A true isolated superior mesenteric artery (SMA) dissection is a rare occurrence. The increasing use of diagnostic imaging studies has resulted in this rare disease being more recognized. A 68-year-old Caucasian female presented with sharp upper abdominal pain. Computed tomography (CT) of the abdomen showed dissection with thrombosis in the proximal SMA. Conservative management with bowel rest, blood pressure control, and anticoagulation relieved her symptoms. Follow-up CT showed stable dissection. Physicians should consider the diagnosis of isolated spontaneous SMA dissection after excluding more common causes. The optimal management pathway has not been firmly established. Conservative management with anticoagulation appears to be a safe first-line therapy in selected patients.
Immunothrombosis in Acute Respiratory Distress Syndrome: Cross Talks between Inflammation and Coagulation
Authors: Frantzeskaki Frantzeska , Armaganidis Apostolos , Orfanos Stylianos E.
Published: December 2016

Acute respiratory distress syndrome (ARDS) is defined as a syndrome of acute onset, with bilateral opacities on chest imaging and respiratory failure not caused by cardiac failure, leading to mild, moderate, or severe oxygenation impairment. The syndrome is most commonly a manifestation of sepsis-induced organ dysfunction, characterized by disruption of endothelial barrier integrity and diffuse lung damage. Imbalance between coagulation and inflammation is a predominant characteristic of ARDS, leading to extreme inflammatory response and diffuse fibrin deposition in vascular capillary bed and alveoli. Activated platelets, neutrophils, endothelial cells, neutrophil extracellular traps, microparticles, and coagulation proteases, participate in the complex process of immunothrombosis, which is a key event in ARDS pathophysiology. The present review is focused on the elucidation of immunothrombosis in ARDS and the potential therapeutic implications.
Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone
Authors: Ju Ting , Li Yuru , Wang Xiaoran , Xiao Lifeng , Jiang Li , Zhou Shanshan , Yang Meimei , Zhao Tingting , Sun Lina , Liu Tingjiao , Lin Jinghan , Xu Yi , Zhang Liming
Published: December 2016

Background: Streptozotocin (STZ) has served as an agent to generate an Alzheimer's disease (AD) model in rats, while edaravone (EDA), a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. Methods: Through measures of evoked excitatory postsynaptic currents (eEPSCs), AMPAR-mediated eEPSCs (eEPSCsAMPA), evoked inhibitory postsynaptic currents (eIPSCs), evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR) and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR), it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. Results: Our results showed that STZ (1000 µM) significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM) attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. Conclusion: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.
RASD1 Knockdown Results in Failure of Oocyte Maturation
Authors: Lee Youngeun , Kim Kyeoung-Hwa , Yoon Hyemin , Lee Ok-Hee , Kim Eunyoung , Park Miseon , Jang Hoon , Hong Kwonho , Song Hyuk , Ko Jung Jae , Lee Woo Sik , Lee Kyung-Ah , Chang Eun Mi , Choi Youngsok
Published: December 2016

Background: Ras dexamethasone-induced protein (RASD1) is a member of Ras superfamily of small GTPases. RASD1 regulates various signaling pathways involved in iron homeostasis, growth hormone secretion, and circadian rhythm. However, RASD1 function in oocyte remains unknown. Methods: Using immunohistochemistry, immunofluorescence, and quantitative real-time RT-PCR, RASD1 expression in mouse ovary and RASD1 role in oocyte maturation-related gene expression, spindle formation, and chromosome alignment were analyzed. RNAi microinjection and time-lapse video microscopy were used to examine the effect of Rasd1 knockdown on oocyte maturation. Results: RASD1 was highly detected in oocytes transitioning from primordial to secondary follicles. Rasd1 was highly expressed in germinal vesicle (GV), during GV breakdown, and in metaphase I (MI) stage as oocytes mature, and its expression was significantly downregulated in MII stage. With knockdown of Rasd1, maturation in GV oocytes was arrested at MI stage, showing disrupted meiotic spindling and chromosomal misalignment. In addition, Obox4 and Arp2/3, engaged in MI-MII transition and cytokinesis, respectively, were misregulated in GV oocytes by Rasd1 knockdown. Conclusion: These findings suggest that RASD1 is a novel factor in MI-MII oocyte transition and may be involved in regulating the progression of cytokinesis and spindle formation, controlling related signaling pathways during oocyte maturation.
1α,25(OH)2D3 Induces Actin Depolymerization in Endometrial Carcinoma Cells by Targeting RAC1 and PAK1
Authors: Zeng Ni , Salker Madhuri S. , Zhang Shaqiu , Singh Yogesh , Shi Bing , Stournaras Christos , Lang Florian
Published: December 2016

Background: Cell proliferation and motility require actin reorganization, which is under control of various signalling pathways including ras-related C3 botulinum toxin substrate 1 (RAC1), p21 protein-activated kinase 1 (PAK1) and actin related protein 2 (ARP2). Tumour cell proliferation is modified by 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. The present study explored whether 1α,25(OH)2D3 modifies actin cytoskeleton in Ishikawa cells, a well differentiated endometrial carcinoma cell line. Methods: To this end, actin cytoskeleton was visualized by confocal microscopy. Globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry, transcript levels by qRT-PCR and protein abundance by immunoblotting. Results: A 24 hour treatment with 1α,25(OH)2D3 (100 nM) significantly decreased RAC1 and PAK1 transcript levels and activity, decreased ARP2 protein levels and depolymerized actin. The effect of 1α,25(OH)2D3 on actin polymerization was mimicked by pharmacological inhibition of RAC1 and PAK1. Conclusions: 1α,25(OH)2D3 leads to disruption of RAC1 and PAK1 activity with subsequent actin depolymerization of endometrial carcinoma cells.
The Relationship of Plasma miR-29a and Oxidized Low Density Lipoprotein with Atherosclerosis
Authors: Huang Yu-Qing , Cai An-Ping , Chen Ji-Yan , Huang Cheng , Li Jie , Feng Ying-Qing
Published: December 2016

Background/Aims: Atherosclerosis is a chronic inflammatory condition associated with a variety of vascular diseases. Previous studies showed that both miR-29a and oxidized low density lipoprotein (ox-LDL) were vital in the development of atherosclerosis. However, the relationship between miR-29a and ox-LDL remains unknown. This study was designed to investigate the association of miR-29a and ox-LDL and to test whether circulating miR-29a and ox-LDL levels could predict atherosclerosis. Methods: In 170 participants, plasma levels of miR-29a were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) while plasma ox-LDL levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. The relationship between miR-29a level and ox-LDL and carotid intima-media thickness (cIMT) was assessed using the Spearman correlation coefficient and multiple liner regression. Results: Compared with the normal cIMT group, the increased cIMT group had higher levels of ox-LDL (0.47 ± 0.08 vs 0.29 ± 0.06 ng/ml, p = 0.003) and miR-29a (32.93 ± 4.26 vs 26.37 ± 1.04, p < 0.001). A positive correlation was found between ox-LDL and miR-29a (r = 0.695, p < 0.001), and both the ox-LDL (r = 0.857, p < 0.001) and the miR-29a (r = 0.753, p < 0.001) were positively related to cIMT. Furthermore, multiple liner regression indicated that a significant correlation between ox-LDL and cIMT (β = 0.768, p < 0.001), as well as between miR-29a and cIMT (β = 0.686, p <0.001). The combination of miR-29a and ox-LDL (AUC = 0.926, p < 0.001) offered a better predictive value for atherosclerosis than either miR-29a (AUC = 0.759, p < 0.001) or ox-LDL (AUC = 0.762, p < 0.001) alone. Conclusion: Increased miR-29a and ox-LDL levels were associated with an early stage of atherosclerosis, and the combination of miR-29a and ox-LDL offered better predictive values for atherosclerosis than either alone.
The Natural Plant Product Rottlerin Activates Kv7.1/KCNE1 Channels
Authors: Matschke Veronika , Piccini Ilaria , Schubert Janina , Wrobel Eva , Lang Florian , Matschke Johann , Amedonu Elsie , Meuth Sven G. , Strünker Timo , Strutz-Seebohm Nathalie , Greber Boris , Scherkenbeck Jürgen , Seebohm Guiscard
Published: December 2016

Background/Aims: Acquired as well as inherited channelopathies are disorders that are caused by altered ion channel function. A family of channels whose malfunction is associated with different channelopathies is the Kv7 K+ channel family; and restoration of normal Kv7 channel function by small molecule modulators is a promising approach for treatment of these often fatal diseases. Methods: Here, we show the modulation of Kv7 channels by the natural compound Rottlerin heterologously expressed in Xenopus laevis oocytes and on iPSC cardiomyocytes overexpressing Kv7.1 channels. Results: We show that currents carried by Kv7.1 (EC50 = 1.48 μM), Kv7.1/KCNE1 (EC50 = 4.9 μM), and Kv7.4 (EC50 = 0.148 μM) are strongly enhanced by the compound, whereas Kv7.2, Kv7.2/Kv7.3, and Kv7.5 are not sensitive to Rottlerin. Studies on Kv7.1/KCNE1 mutants and in silico modelling indicate that Rottlerin binds to the R-L3-activator site. Rottlerin mediated activation of Kv7.1/KCNE1 channels might be a promising approach in long QT syndrome. As a proof of concept, we show that Rottlerin shortens cardiac repolarisation in iPSC-derived cardiomyocytes expressing Kv7.1.Conclusion: Rottlerin or an optimized derivative holds a potential as QT interval correcting drug.
A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness
Authors: Liu Chang-Yuan , Huang Qi-Fang , Cheng Yi-Bang , Guo Qian-Hui , Chen Qi , Li Yan , Wang Ji-Guang
Published: December 2016

Background: We compared skin and plasma measurements of advanced glycation end products (AGEs), with particular focus on their levels in the presence of hypertension or diabetes and prediabetes and their associations with arterial stiffness in outpatients with suspected or diagnosed hypertension. Methods: Skin AGE accumulation was measured as autofluorescence on the left forearm using the skin autofluorescence Reader and expressed in arbitrary units in the range from 0 to 25. Plasma AGE concentration was measured by the enzyme-linked immunosorbent assay method and logarithmically transformed for statistical analysis. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV) using the SphygmoCor system (Sydney, Australia). Results: The 218 participants (96 [44.0%] men, mean age 51.9 years) had a mean skin autofluorescence of 1.89 arbitrary units, plasma AGE concentration of 4.47 μg/ml, and cfPWV of 8.0 m/s. Skin autofluorescence was significantly correlated with plasma AGEs in diabetic or prediabetic patients (n = 31, r = 0.37, p = 0.04) but not in subjects with normoglycemia (n = 187, r = -0.05, p = 0.48). Nonetheless, both measurements were significantly (p ≤ 0.001) higher in men (2.00 arbitrary units and 6.73 μg/ml, respectively) than women (1.81 arbitrary units and 3.60 μg/ml, respectively) and in diabetic or prediabetic (2.03 arbitrary units and 6.61 μg/ml, respectively) than normoglycemia subjects (1.87 arbitrary units and 4.17 μg/ml, respectively), but similar in hypertensive (n = 105) and normotensive subjects (n = 113, p ≥ 0.35). In adjusted multiple regression analyses, plasma AGE concentration, but not skin autofluorescence (p ≥ 0.37), was significantly associated with cfPWV in all subjects (β 0.44 m/s for each 10-fold increase; p = 0.04) and in subgroups of men and diabetes and prediabetes (β 0.12-0.55 m/s for each 10-fold increase; p ≤ 0.02). Conclusions: Although skin and plasma AGEs were similarly associated with gender and diabetes or prediabetes, they might measure something different and have different clinical relevance, such as for arterial stiffness.
Os despachantes documentalistas na era do profissionalismo organizacional
Authors: Bonelli Maria Da Gloria
Published: December 2016

O artigo analisa o processo de profissionalização dos despachantes documentalistas, após o impacto da terceirização desses serviços para o Poupatempo, com a introdução de processos globalizantes de acesso a cidadania documentada, que encolheram o mercado da intermediação. Em substituição ao modelo tradicional das relações entre estado e sociedade para obtenção de serviços públicos que envolviam o “jeitinho”, os despachantes buscam o profissionalismo organizacional e a criação de conselhos estaduais e federal. Além das lutas concorrenciais entre os pares que se desdobram na judicialização desses conflitos, eles enfrentam a condenação moral, que se seguiu à perda de relevância social da atividade. A pesquisa se baseia em fontes documentais primárias e secundárias, em um  survey com 107 despachantes e em entrevistas qualitativas com lideranças profissionais.
O caudilho da sociologia mexicana: Pablo González Casanova e A democracia no México
Authors: Jackson Luiz Carlos , Blanco Alejandro Raul
Published: December 2016

O artigo discute a trajetória do sociólogo mexicano Pablo González Casanova no interior do proceso de institucionalização das ciências sociais no México, comparando-a com as de Gino Germani, na Argentina, e Florestan Fernandes, no Brasil.
Sexual Orientation and Wage Differentials in Brazilian Labour Market
Authors: Suliano Daniel , Irffi Guilherme , Corrêa Márcio V. , Calvancante Alexsandre , Oliveira Jimmy
Published: December 2016

Este trabalho analisa o diferencial de salários no Brasil a partir da orientação sexual com base no Censo 2010. Não foram observados padrões sistemáticos nas estimações tanto em homens como em mulheres, mas diferenças estatisticamente significativas a favor dos casais do mesmo sexo. Destaca-se que os casais gays ganham, em média, 25,11% a mais que os casais heterossexuais, mantendo fixas suas condições de ocupação e ramos de atividade nas estimativas de MQO. No que tange às mulheres, casais de lésbicas ganham, em média, 13,84% a mais nos modelos de correção de seletividade amostral com controle de todas as características observadas
Self-Selection of Return Migrants in Brazil and Inequality
Authors: Tai Silvio H. T. , Ribeiro Ana Carolina B. M.
Published: December 2016

Esse artigo estuda a autosseleção dos emigrantes retornados no Brasil, de 2001 a 2010. Verificou-se empiricamente o impacto da desigualdade de renda na autosseleção através de dois canais opostos. Em primeiro lugar, os custos de migração impedem indivíduos com baixa qualificação de emigrar, o que contribui para a seleção positiva. Essa seleção é acentuada em locais com muita desigualdade. Em segundo lugar, indivíduos com baixa qualificação têm incentivos salariais para emigrar de estados mais desiguais, o que contribui para a seleção negativa. Considerando os dois canais, os efeitos dos custos de emigração são mais importantes, com predominância da seleção positiva
Receptores muscarínicos na doença pulmonar obstrutiva crônica: o que é importante saber da Biologia à prática clínica?
Authors: Rodrigues Letícia Ubaldo , Soares Caio Teixeira , Venuto Daniel Brandão , Santana Renan Guimarães , Xavier Analúcia Rampazzo , Silva Junior Cyro Teixeira da , Araujo Elizabeth Giestal de
Published: December 2016

A doença pulmonar obstrutiva crônica (DPOC) caracteriza-se por persistente e geralmente progressiva limitação do fluxo de ar associada com uma resposta inflamatória crônica nas vias aéreas e pulmões em resposta a partículas ou gases nocivos. A prescrição de medicamentos como os antimuscarínicos é um item importante para a reabilitação pulmonar em pacientes com DPOC porque melhoram os sintomas, particularmente a dispneia e a capacidade de fazer as atividades diárias. Há evidências de alguns estudos de que também reduzam a tendência a exacerbações. Não há evidências de que broncodilatadores reduzam complicações sistêmicas, comorbidades ou tenham influência sobre a mortalidade.