bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Uron and Chlorobenzene Derivatives, as Potential Endocrine Disrupting Compounds, in the Secretion of ACTH and PRL
Authors: Sepp Krisztian , Laszlo Anna M. , Molnar Zsolt , Serester Andrea , Alapi Tunde , Galfi Marta , Valkusz Zsuzsanna , Radacs Marianna
Published: May 2018

Uron herbicides polluting the environment represent a serious concern for environmental health and may be regarded as endocrine-disrupting compounds (EDCs), which influence the regulation of human homeostasis. We aimed to investigate the effect of EDC urons (phenuron: PU, monuron: MU, and diuron: DU) and chlorobenzenes on the basal release of the adrenocorticotropic hormone (ACTH), which is a part of the adenohypophysis-adrenocortical axis. Hormone secretion in the presence of EDC was studied in two cell types: normal adenohypophysis cells (AdH) and cells of prolactinomas (PRLOMA). PRLOMA was induced in female Wistar rats by subcutaneously injecting them with estrone acetate for 6 months. AdH and PRLOMA were separated from treated and untreated experimental animals, dissociated enzymatically and mechanically in order to create monolayer cell cultures, which served as an experimentalin vitromodel. We investigated the effects of ED agents separately and in combination on ACTH and prolactin (PRL) release through the hypophyseal-adrenal axis. Hormone determination was carried out by the luminescent immunoassay and the radioimmunoassay methods. Our results showed that (1) uron agents separately did not change ACTH and PRL release in AdH culture; (2) ACTH secretion in arginine vasopressin- (AVP-) activated AdH cells was significantly increased by EDC treatment; (3) ED agents increased the basal hormone release (ACTH, PRL) in PRLOMA cells; and (4) EDC exposure increased ACTH release in AVP-activated PRLOMA cells. We conclude that the herbicides PU, MU, and DU carry EDC effects and show human toxicity potential.
Lysophosphatidic Acid Analogue rather than Lysophosphatidic Acid Promoted the Bone Formation In Vivo
Authors: Yu Zi-Li , Jiao Bin-Fang , Li Zu-Bing
Published: May 2018

Lysophosphatidic acid (LPA), a bioactive lipid molecule, has recently emerged as physiological and pathophysiological regulator in skeletal biology. Here we evaluate the effects of LPA on bone formation in vivo in murine femoral critical defect model. Primary femoral osteoblasts were isolated and treated with osteogenic induction conditional media supplemented with 20 μM LPA or LPA analogue. Mineralized nodules were visualized by Alizarin Red S staining. Forty-five C57BL/6 mice underwent unilateral osteotomy. The femoral osteotomy gap was filled with porous scaffolds of degradable chitosan/beta-tricalcium phosphate containing PBS, LPA, or LPA analogue. 2, 5, and 10 weeks after surgery, mice were sacrificed and femurs were harvested and prepared for Micro-Computed Tomography (Micro-CT) and histological analysis. Alizarin Red S staining showed that LPA and LPA analogue significantly enhanced the mineral deposition in osteoblasts. Micro-CT 3D reconstruction images and HE staining revealed that significantly more newly formed bone in osteotomy was treated with LPA analogue when compared to control and LPA group, which was verified by histological analysis and biomechanical characterization testing. In summary, our study demonstrated that although LPA promotes mineralized matrix formation in vitro, the locally administrated LPA was not effective in promoting bone formation in vivo. And bone formation was enhanced by LPA analogue, administrated locally in vivo. LPA analogue was a potent stimulating factor for bone formation in vivo due to its excellent stability.
Incidence and Comorbidity of Dementia with Lewy Bodies: A Population-Based Cohort Study
Authors: Yang Sheng-Kung , Chen Weishan , Su Chun-Hsien , Liu Chung-Hsiang
Published: May 2018

Background and Aims. Dementia with Lewy bodies (DLB) is the third most common form of dementia. Epidemiological studies of DLB in Taiwan are scarce. In this study, we estimated the incidence of DLB and comorbidity in the population of Taiwan. Methods. Data were obtained from the Taiwan National Health Insurance Research Database (NHIRD). DLB patients between 2000 and 2013 were enrolled in assessments of incidence and comorbidity. Results. The incidence of DLB was shown to be 7.10 per 100,000 person-years (95% CI = 6.63–7.59), which increased with age. The average age at diagnosis was 76.3, and this was higher for males than for females. The comorbidity rates of hypertension and hyperlipidemia in DLB patients were higher in females than in males. Conclusions. Epidemiologic data from large-scale retrospective studies is crucial to the prevention of DLB.
Generalized Pointwise Hölder Spaces Defined via Admissible Sequences
Authors: Kreit Damien , Nicolay Samuel
Published: May 2018

We introduce in this paper a generalization of the pointwise Hölder spaces. We give alternative definitions of these spaces, look at their relationship with the wavelets, and introduce a notion of generalized Hölder exponent.
Dimensional Characteristics of Knitted Fabrics Made from 100% Cotton and Cotton/Elastane Yarns
Authors: Sitotaw Dereje Berihun
Published: May 2018

The dimensional characteristics such as loop length (l), wales per centimeter (wpc), courses per centimeter (cpc), stitch density (s), tightness factor (K), loop shape factor (R) and take-up rate (T) of single jersey, 1x1rib, 1x1 interlock, single pique, and two-thread fleece knitted fabrics made from 100% cotton and cotton/elastane yarns (5% elastane yarn content) are investigated in this research. Dimensional properties of knitted fabrics are an important property and determine the materials consumption during production, productions parameter, and applications of different knitted structures. The sample fabrics have been conditioned for 24 hours at 20±1°C temperature and 65±2% relative humidity. The specimens used for sampling are determined as per the test standards described in the paper for each yarn type, property, and structure. As observed in the result, the properties are related to each other. It is found that the loop length, wpc, cpc, stitch density, tightness factor, loop shape factor and take-up rate of single jersey, 1x1rib, 1x1interlock, single pique, and two-thread fleece knitted fabrics made from 100% cotton and cotton/elastane yarns are significantly influenced by the presence of an elastane yarn. The loop length of single jersey, 1x1rib, and interlock knitted fabrics made from elastane yarns reduced while the single pique and fleece increased. Similarly, other dimensional properties are significantly influenced by the yarn types used during knitting.
Nonredundant, Highly Connected MicroRNAs Control Functionality in Breast Cancer Networks
Authors: de Anda-Jáuregui Guillermo , Espinal-Enríquez Jesús , Drago-García Diana , Hernández-Lemus Enrique
Published: May 2018

Alterations to transcriptional regulation are an important factor in breast cancer. Noncoding RNA, such as microRNA (miR), have very influential roles in the transcriptional regulation of genes. Transcriptional regulation can be successfully modeled and analyzed using complex network theory. Particularly, interactions between two distinct classes of biological elements, such as miR and genes, can be approached through the bipartite network formalism. Based on bipartite network properties, it is possible to identify highly influential miRs in the network, such as those that have a large number of connections indicating regulation of a large set of genes. Some miRs in a network are nonredundant, which indicates that they are solely responsible of the regulation of a particular set of genes, which in turn may be associated to a particular biological process. We hypothesize that highly influential, nonredundant miRs, which we call Commodore miRs (Cdre-miRs), have an important role on the control of biological functions through transcriptional networks. In this work, we analyze the regulation of gene expression by miRs in healthy and cancerous breast tissue using bipartite miR-gene networks inferred from the Cancer Genome Atlas (TCGA) expression data. We observe differences in the degree, clustering coefficient and redundancy distributions for miRs and genes in the network, indicating differences in the way that these elements interact with each other. Furthermore, we identify a small set of five Cdre-miRs in the breast cancer network: miR-190b, miR-let7i, miR-292-b, miR-511, and miR-141. The neighborhood of genes controlled by each of these miRs is involved in particular biological functions such as dynein structure-associated processes, immune response, angiogenesis, cytokine activity, and cell motility. We propose that these Cdre-miRs are important control elements of biological functions deregulated in breast cancer.
Hepatic Abscess in a Returning Traveler with Crohn’s Disease: Differentiating Amebic from Pyogenic Liver Abscess
Authors: Gaut Daria , Shull Hannah , Bejjani Anthony , Kahn Daniel
Published: May 2018

Liver abscess is a rare but serious complication of Crohn’s disease. Patients with Crohn’s disease are at risk for pyogenic liver abscesses due to immunosuppressive therapy, fistulous disease, and intraabdominal abscesses. Inflammatory bowel disease patients are also known to have a greater prevalence of amebiasis compared to the rest of the population; however, a higher incidence of amebic liver abscess has not been reported. We describe a case of a liver abscess in a patient with Crohn’s disease that was initially presumed pyogenic but later determined to be amebic in origin. Epidemiology, clinical presentation, diagnosis, and treatment of amebic and pyogenic liver abscesses are discussed.
miR-30 Family: A Promising Regulator in Development and Disease
Authors: Mao Ling , Liu Shiming , Hu Lin , Jia Li , Wang Hairong , Guo Mengmeng , Chen Chao , Liu Yun , Xu Lin
Published: May 2018

MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate posttranscriptional expression of target genes. Accumulating evidences have demonstrated that the miR-30 family, as a member of microRNAs, played a crucial regulating role in the development of tissues and organs and the pathogenesis of clinical diseases, which indicated that it may be a promising regulator in development and disease. This review aims to clarify the current progress on the regulating role of miR-30 family in tissues and organs development and related disease and highlight their research prospective in the future.
Restraining Network Response to Targeted Cancer Therapies Improves Efficacy and Reduces Cellular Resistance
Authors: Das Tirtha K. , Esernio Jessica , Cagan Ross L.
Published: May 2018

A key tool of cancer therapy has been targeted inhibition of oncogene-addicted pathways. However, efficacy has been limited by progressive emergence of resistance as transformed cells adapt. Here, we use Drosophila to dissect response to targeted therapies. Treatment with a range of kinase inhibitors led to hyperactivation of overall cellular networks, resulting in emergent resistance and expression of stem cell markers, including Sox2. Genetic and drug screens revealed that inhibitors of histone deacetylases, proteasome, and Hsp90 family of proteins restrained this network hyperactivation. These “network brake” cocktails, used as adjuncts, prevented emergent resistance and promoted cell death at subtherapeutic doses. Our results highlight a general response of cells, transformed and normal, to targeted therapies that leads to resistance and toxicity. Pairing targeted therapeutics with subtherapeutic doses of broad-acting “network brake” drugs may provide a means of extending therapeutic utility while reducing whole body toxicity.

Significance: These findings with a strong therapeutic potential provide an innovative approach of identifying effective combination treatments for cancer. Cancer Res; 78(15); 4344–59. ©2018 AACR.
Integrative Modeling Identifies Key Determinants of Inhibitor Sensitivity in Breast Cancer Cell Lines
Authors: Jastrzebski Katarzyna , Thijssen Bram , Kluin Roelof J.C. , de Lint Klaas , Majewski Ian J. , Beijersbergen Roderick L. , Wessels Lodewyk F.A.
Published: May 2018

Cancer cell lines differ greatly in their sensitivity to anticancer drugs as a result of different oncogenic drivers and drug resistance mechanisms operating in each cell line. Although many of these mechanisms have been discovered, it remains a challenge to understand how they interact to render an individual cell line sensitive or resistant to a particular drug. To better understand this variability, we profiled a panel of 30 breast cancer cell lines in the absence of drugs for their mutations, copy number aberrations, mRNA, protein expression and protein phosphorylation, and for response to seven different kinase inhibitors. We then constructed a knowledge-based, Bayesian computational model that integrates these data types and estimates the relative contribution of various drug sensitivity mechanisms. The resulting model of regulatory signaling explained the majority of the variability observed in drug response. The model also identified cell lines with an unexplained response, and for these we searched for novel explanatory factors. Among others, we found that 4E-BP1 protein expression, and not just the extent of phosphorylation, was a determinant of mTOR inhibitor sensitivity. We validated this finding experimentally and found that overexpression of 4E-BP1 in cell lines that normally possess low levels of this protein is sufficient to increase mTOR inhibitor sensitivity. Taken together, our work demonstrates that combining experimental characterization with integrative modeling can be used to systematically test and extend our understanding of the variability in anticancer drug response.

Significance: By estimating how different oncogenic mutations and drug resistance mechanisms affect the response of cancer cells to kinase inhibitors, we can better understand and ultimately predict response to these anticancer drugs.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4396/F1.large.jpg. Cancer Res; 78(15); 4396–410. ©2018 AACR.
SNHG6 Acts as a Genome-Wide Hypomethylation Trigger via Coupling of miR-1297–Mediated S-Adenosylmethionine–Dependent Positive Feedback Loops
Authors: Guo Tao , Wang Hongling , Liu Pengpeng , Xiao Yushao , Wu Ping , Wang Yitao , Chen Baiyang , Zhao Qiu , Liu Zhisu , Liu Quanyan
Published: May 2018

Aberrant genome-wide hypomethylation and long noncoding RNA (lncRNA) dysregulation are associated with hepatocarcinogenesis. However, whether a relationship between the two exists remains largely unknown. S-adenosylmethionine (SAMe)-dependent methylation is a critical factor in genomic methylation. We previously found that SNHG6 lncRNA acted as an oncogene in hepatocarcinogenesis and could be considered a potential prognostic indicator for hepatocellular carcinoma (HCC). Here we verify that SNHG6 leads to genome-wide hypomethylation in hepatoma cells and that SNHG6 negatively correlates with the steady-state SAMe concentration in vivo and in vitro. SNHG6 suppressed MAT1A protein expression by activating the miR-1297/FUS pathway to regulate nucleocytoplasmic shuttling of MAT1A mRNA. In addition, SNHG6 promoted expression of MAT2A by suppressing direct binding of miR-1297 to the MAT2A 3′UTR. SNHG6 regulated steady-state SAMe levels via coupling of two miR-1297–mediated SAMe-dependent positive feedback loops. Interestingly, the effect of SNHG6 on genome-wide methylation was inhibited by exogenous SAMe within a certain concentration range. These results suggest that single lncRNA dysregulation can lead to aberrant genome-wide hypomethylation by inhibiting SAMe production in HCC and that exogenous SAMe may be beneficial in the treatment of HCC.

Significance: These findings explore the role of SNHG6 lncRNA in suppressing production of the universal methyl donor SAMe and its impact on global DNA methylation levels in liver cancer and highlight the potential benefit of SAMe for the treatment of liver cancer. Cancer Res; 78(14); 3849–64. ©2018 AACR.
Glycosyltransferase Gene Expression Identifies a Poor Prognostic Colorectal Cancer Subtype Associated with Mismatch Repair Deficiency and Incomplete Glycan Synthesis
Authors: Noda Masaru , Okayama Hirokazu , Tachibana Kazunoshin , Sakamoto Wataru , Saito Katsuharu , Thar Min Aung Kyi , Ashizawa Mai , Nakajima Takahiro , Aoto Keita , Momma Tomoyuki , Katakura Kyoko , Ohki Shinji , Kono Koji
Published: May 2018

Purpose: We aimed to discover glycosyltransferase gene (glycogene)-derived molecular subtypes of colorectal cancer associated with patient outcomes.

Experimental Design: Transcriptomic and epigenomic datasets of nontumor, precancerous, cancerous tissues, and cell lines with somatic mutations, mismatch repair status, clinicopathologic and survival information were assembled (n = 4,223) and glycogene profiles were analyzed. IHC for a glycogene, GALNT6, was conducted in adenoma and carcinoma specimens (n = 403). The functional role and cell surface glycan profiles were further investigated by in vitro loss-of-function assays and lectin microarray analysis.

Results: We initially developed and validated a 15-glycogene signature that can identify a poor-prognostic subtype, which closely related to deficient mismatch repair (dMMR) and GALNT6 downregulation. The association of decreased GALNT6 with dMMR was confirmed in multiple datasets of tumors and cell lines, and was further recapitulated by IHC, where approximately 15% tumors exhibited loss of GALNT6 protein. GALNT6 mRNA and protein was expressed in premalignant/preinvasive lesions but was subsequently downregulated in a subset of carcinomas, possibly through epigenetic silencing. Decreased GALNT6 was independently associated with poor prognosis in the IHC cohort and an additional microarray meta-cohort, by multivariate analyses, and its discriminative power of survival was particularly remarkable in stage III patients. GALNT6 silencing in SW480 cells promoted invasion, migration, chemoresistance, and increased cell surface expression of a cancer-associated truncated O-glycan, Tn-antigen.

Conclusions: The 15-glycogene signature and the expression levels of GALNT6 mRNA and protein each serve as a novel prognostic biomarker, highlighting the role of dysregulated glycogenes in cancer-associated glycan synthesis and poor prognosis. Clin Cancer Res; 24(18); 4468–81. ©2018 AACR.
Impact of Metamorphopsia on Quality of Life after Successful Retinal Detachment Surgery
Authors: Saleh Maher , Gauthier Anne-Sophie , Delbosc Bernard , Castelbou Marie
Published: May 2018

Purpose: To determine the impact of metamorphopsia on quality of life after successful retinal detachment (RD) surgery and to determine which retinal changes are related to the most severe distortions. Design: This was a prospective, observational, consecutive study. Methods: The study included 58 eyes of 58 consecutive patients who underwent successful RD surgery. At 6 months postoperatively, the incidence and severity of metamorphopsia were assessed by a quality-of-life questionnaire. Microstructure retinal changes were studied with spectral domain optical coherence tomography (OCT). The questionnaire score was compared with pre- and postoperative OCT findings. Results: Overall, 20 patients (34.5%) had metamorphopsia. Outer retinal folds (ORFs) and the macular status before surgery, together with postoperative ORFs and decrease in ellipsoid and/or interdigitation photoreceptor zone reflectivity, were identified as risk factors of developing metamorphopsia (relative risk, 1.7–4.8). The most severe visual distortions were associated with ORFs. Conclusion: Metamorphopsia is a frequent occurrence after RD surgery and its impact on patients’ quality of life appears to be limited. While it may be difficult to prevent photoreceptor loss occurring after surgery, limiting postoperative ORFs may be helpful in reducing their incidence.
Reactive Astrogliosis in an Experimental Model of Fibromyalgia: Effect of Dexmedetomidine
Authors: Abd-ellatief Rasha B. , Mohamed Heba K. , Kotb Hassan I.
Published: May 2018

To our knowledge, this is the first study which investigates the induction of neuroinflammation in rats using an acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception, and astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory responses induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by intramuscular injection of 100 µL of acidic saline on days 0 and 5 resulted in peripheral sensitization (measured using the von Frey test) and significant (p < 0.05) increases in IL-1β (160.2 ± 1.1 to 335.2 ± 1.8), IL-6 (100.1 ± 1.4 to 202.4 ± 1.1), and TNF-α (60.0 ± 0.7 to 115.5 ± 1). Light and electron microscopy revealed degenerative changes in the hippocampus and reactive astrogliosis. Immunohistochemistry showed increased expression of glial fibrillary acid protein and inducible nitric oxide synthase. Surprisingly, treatment with a single dose of an α2-adrenergic agonist, dexmedetomidine (5 µg/kg i.p.), attenuated these changes. This trial suggests that dexmedetomidine possibly directly acts on astrocytes, and a peripheral action is also suggested.
Aromatase/Seladin-1 Interactions in Human Neuronal Cell Culture, the Hippocampus of Healthy Rats and Transgenic Alzheimer’s Disease Mice
Authors: Karahan Hande , Lüle Sevda , Kelicen-Uğur Pelin
Published: May 2018

Background/Aims: Decreasing levels of aromatase and seladin-1 could be one of the molecular mechanisms of Alzheimer’s disease (AD). Aromatase is an enzyme that catalyzes estrogen biosynthesis from androgen precursors, and seladin-1 is an enzyme that converts desmosterol to cholesterol, which is the precursor of all hormones. Verifying the potential relationship between these proteins and accordingly determining new therapeutic targets constitute the aims of this study. Methods: Changes in protein levels were compared in vitro in aromatase and seladin-1 inhibitor-administered human neuroblastoma (SH-SY5Y) cells in vivo in intracerebroventricular (icv) aromatase or seladin-1 inhibitor-administered rats, as well as in transgenic AD mice in which the genes encoding these proteins were knocked out. Results and Conclusions: In the cell cultures, we observed that seladin-1 protein levels increased after aromatase enzyme inhibition. The hippocampal aromatase protein levels decreased following chronic seladin-1 inhibition in icv inhibitor-administered rats; however, the aromatase levels in the dentate gyrus of seladin-1 knockout (SelKO) AD male mice increased. These findings indicate a partial relationship between these proteins and their roles in AD pathology.
Endophytic-Type Endometrial Cancer with Adenomyosis Successfully Diagnosed with Hysteroscopic Endometrial Biopsy Using an 8.3-mm Operative Resectoscope: A Case Report
Authors: Honda Michiko , Tsuchiya Akira , Isono Wataru , Takahashi Mikiko , Fujimoto Akihisa , Kawamoto Masashi , Nishii Osamu
Published: May 2018

In order to diagnose endometrial cancer preoperatively, outpatient endometrial biopsy with a curette is frequently performed owing to its convenience. However, in some cases, gynecologists fail to diagnose endometrial cancer via outpatient endometrial biopsy because of the cancer’s distribution in the uterus and its consistency. A 57-year-old Japanese woman (gravida 4 para 4) presented with a 6-month history of light but intermittent postmenopausal vaginal bleeding. A malignant uterine tumor was strongly suspected after imaging using ultrasound examination and magnetic resonance imaging; however, a precise pathological diagnosis was not achieved despite multiple outpatient endometrial biopsies with the aid of office hysteroscopy. Based on an endometrial biopsy obtained using a cutting loop electrode on an 8.3-mm operative resectoscope, we reached a diagnosis of endophytic-type endometrial cancer, which is in accordance with the final pathological diagnosis after abdominal hysterectomy. Three months after her first visit to our hospital, total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic/para-aortic lymph node dissection were performed. Macroscopically, the endometrium was atrophic, and there was no obvious mass in the uterine cavity; however, microscopically, the cancer cells mainly existed in the deep myometrium and the final diagnosis was International Federation of Gynecology and Obstetrics (FIGO) stage IB endometrial cancer. Operative biopsy of the uterine endometrium and deep myometrium using hysteroscopy confirmed an accurate preoperative diagnosis of uterine endometrial cancer specifically of the endophytic type.
Small-Cell Carcinoma Transformation of Pulmonary Adenocarcinoma after Osimertinib Treatment: A Case Report
Authors: Taniguchi Yuri , Horiuchi Hajime , Morikawa Teppei , Usui Kazuhiro
Published: May 2018

There are various mechanisms underlying the resistance of EGFR-mutant lung adenocarcinoma to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We herein report a case of pulmonary adenocarcinoma with EGFR mutation (exon 19 deletion and T790M) that acquired resistance to osimertinib treatment because of transformation into small-cell lung carcinoma (SCLC). A 67-year-old ex-smoking woman was diagnosed with left upper lobe adenocarcinoma of clinical stage IIIA (cT2bN2M0). She was treated with chemoradiotherapy (cisplatin and vinorelbine plus radiation), gefitinib, cisplatin, and pemetrexed followed by pemetrexed maintenance therapy and erlotinib. Since a sample extracted from the metastatic lung tumor taken obtained via a transbronchial lung biopsy was found to be positive for the T790M mutation at the time of disease progression during erlotinib treatment, she received osimertinib treatment for 15 months until progressive disease. She developed resistance to osimertinib due to the histologic transformation to SCLC. Although the standard chemotherapy of carboplatin and etoposide for SCLC was administered, she died due to metastatic liver failure.
Appetite-Related Eating Behaviours: An Overview of Assessment Methods, Determinants and Effects on Children’s Weight
Authors: Freitas Ana , Albuquerque Gabriela , Silva Cláudia , Oliveira Andreia
Published: May 2018

Identifying the underlying child-eating behaviours that contribute to weight differences across growth has been a constant challenge. This report reviews the various literature approaches for assessing appetite regulation. In doing so, it attempts to understand how appetite control develops and determines the eating habits in early childhood, and its effects on children’s weight status. The interaction between homeostatic and hedonic mechanisms largely explains the appetite regulation process. Homeostatic mechanisms are mediated by the biological need to maintain the body’s energy reserves, increasing the motivation to eat. On the contrary, the hedonic mechanisms are mediated by food reward, increasing the craving for high-palatable foods and triggering the release of dopamine and serotonin. There are many biological methods (plasma measurements of hormones, like leptin, ghrelin and insulin) and behavioural evaluation methods of appetite. The Children’s Eating Behaviour Questionnaire is most commonly used, due to its adequate psychometric properties tested in several population settings. The development of eating behaviours begins in utero, and several determinants may contribute to a decrease in the ability to self-regulate dietary intake. Examples include genetic predisposition, the first taste experiences and the family environment, a key determinant in this process. Several eating behaviours contribute most to childhood obesity. Among them, are the external eating (eating by external stimuli, such as the mere presence of the food or its smell), food restriction (which may potentiate the uninhibited increased intake of the restricted foods) and emotional eating (intake due to emotional variations, especially negative feelings). These eating behaviours have been linked to childhood obesity.
A New 3p14.2 Microdeletion in a Patient with Intellectual Disability and Language Impairment: Case Report and Review of the Literature
Authors: Parmeggiani Giulia , Buldrini Barbara , Fini Sergio , Ferlini Alessandra , Bigoni Stefania
Published: May 2018

Interstitial deletions of chromosome 3p are rare, and specific genotype-phenotype correlations cannot always be assessed. We report the case of a 3p14.2 proximal microdeletion in a 60-year-old female patient with mild intellectual disability, severe speech delay, and mild dysmorphism. An array-CGH analysis detected a 500-kb deletion in the 3p14.2 region, including FEZF2, CADPS, and PTPRG. FEZF2 and CADPS are known to network within the neurodevelopmental pathways. It is possible that their rearrangements lead to the phenotypic features observed in the patient, and therefore, they can be considered candidate genes responsible for such abnormalities.
HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer
Authors: Tang Qing , Hann Swei Sunny
Published: May 2018

Long non-coding RNAs (LncRNAs) represent a novel class of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential and function as novel master regulators in various human diseases, including cancer. Accumulating evidence shows that lncRNAs are dysregulated and implicated in various aspects of cellular homeostasis, such as proliferation, apoptosis, mobility, invasion, metastasis, chromatin remodeling, gene transcription, and post-transcriptional processing. However, the mechanisms by which lncRNAs regulate various biological functions in human diseases have yet to be determined. HOX antisense intergenic RNA (HOTAIR) is a recently discovered lncRNA and plays a critical role in various areas of cancer, such as proliferation, survival, migration, drug resistance, and genomic stability. In this review, we briefly introduce the concept, identification, and biological functions of HOTAIR. We then describe the involvement of HOTAIR that has been associated with tumorigenesis, growth, invasion, cancer stem cell differentiation, metastasis, and drug resistance in cancer. We also discuss emerging insights into the role of HOTAIR as potential biomarkers and therapeutic targets for novel treatment paradigms in cancer.
Erythropoietin Protects the Kidney by Regulating the Effect of TNF-α in L-NAME-Induced Hypertensive Rats
Authors: Ozkurt Mete , Uzuner Kubilay , Erkasap Nilufer , Kus Gokhan , Ozyurt Rumeysa , Uysal Onur , Akyazi Ibrahim , Kutlay Ozden
Published: May 2018

Background/Aims: Hypertension is the leading cause of death worldwide. Chronic high blood pressure induces inflammation. Tumor necrosis factor (TNF)-α plays a major role in inflammation and also depresses the synthesis of erythropoietin, which exerts protective effects on tissue; however, the mechanism is still unclear. We investigated the protective effect of erythropoietin against tissue damage caused by hypertension in the kidney and whether this effect was suppressed by TNF-α. Methods: First, we detected the optimum chronic dose for darbepoetin-α (Depo), which is a long-acting erythropoietin analog for rats. We separated 60 female adult rats into 6 groups: control, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), L-NAME+Depo, L-NAME+Remicade (an anti-TNF-α antibody), L-NAME+Depo+Remicade, Depo, and control. After 1 month of treatment, we measured cardiovascular parameters, took blood samples, sacrificed the rats, and removed kidneys for analyses. Results: The apoptotic index and the plasma and kidney mRNA levels of TNF-α increased in the L-NAME group and decreased in all other treatment groups. Macrophage accumulation increased in the L-NAME and L-NAME+Remicade groups, while it decreased in the Depo group. The mRNA abundance of TNF receptor 1 (TNFR1) decreased slightly in the Depo group and TNFR2 increased significantly in the same group. Conclusion: Erythropoietin protects kidney tissue against hypertension by preventing the apoptotic effects of TNF-α by blocking macrophage accumulation, decreasing TNF-α levels, and switching the TNF-α receptors from the apoptotic receptor TNFR1 to the proliferative receptor TNFR2.
Circulating α-Klotho is Related to Plasma Aldosterone and Its Follow-Up Change Predicts CKD Progression
Authors: Qian Jing , Zhong Jianyong , Yan Minhua , Cheng Ping , Shi Huizhu , Hao Chuanming , Gu Yong , Lai Lingyun
Published: May 2018

Background/Aims: We aimed to determine if soluble α-klotho level was an indicator of chronic kidney disease (CKD) progression and whether α-klotho interacted with aldosterone during the course of further renal damage. Methods: 112 adults with stages 1–5 CKD were enrolled into our cohort study. All of the patients were followed up for 6 years (from January 2010 to December 2015). Serum soluble α-klotho and aldosterone were measured at baseline and at 1.5-years follow-up. The primary outcome was the initiation of renal replacement therapy (RRT) and the secondary outcome was the occurrence of cardio-cerebrovascular events. Long-term progression to RRT and cardio-cerebrovascular events in patients was analyzed with a risk-adjusted Cox proportional hazards regression model. Adjustment included age, gender, eGFR, mean arterial pressure, 24-h protein excretion and the change in α-klotho level from baseline at 1.5-years follow-up. Results: Baseline circulating α-klotho levels were positively associated with baseline estimated glomerular filtration rate (eGFR; r = 0.224, p = 0.017), but not age, calcium, phosphate, or parathyroid hormone levels. The change in α-klotho level from baseline at 1.5-years follow-up (p = 0.002) was independently associated with renal replace treatment (RRT) initiation after adjustment for age, gender, eGFR, mean arterial pressure, and 24-h protein excretion in Cox regression analysis. Aldosterone levels were positively associated with CKD stage, and were inversely correlated with circulating α-klotho levels. Conclusion: The change in concentration of soluble α-klotho during the 1.5-years follow-up was an indicator of CKD progression. Renal damage associated with a reduction of α-klotho may involve the upregulation of plasma aldosterone. Future studies are needed to validate our findings, and to investigate the underlying mechanism by which α-klotho and aldosterone may cause renal damage.
Resveratrol Protects Murine Chondrogenic ATDC5 Cells Against LPS-Induced Inflammatory Injury Through Up-Regulating MiR-146b
Authors: Jin Hui , Zhang Hong , Ma Tingjian , Lan Hongjia , Feng Shibin , Zhu Haiyan , Ji Youbo
Published: May 2018

Background/Aims: Resveratrol (RSV) has been reported as a promising oral supplementation for osteoarthritis treatment, while the mechanism of its action is still unclear. The specific aim of this study is to decode one of the mechanisms by which RSV protects chondrocyte. Methods: Mouse chondrogenic cell line ATDC5 was treated with 30 µM RSV for 24 h, and 10 µg/ml LPS for 12 h, after which cell viability, apoptosis, and the release of pro-inflammatory cytokines were assessed. The expression of miR-146b in ATDC5 cells was silenced by the specific inhibitor transfection, and then cell viability, apoptosis and inflammation were re-assessed. Results: The IC50 value of LPS in ATDC5 cells was about 10.27 µg/ml. LPS with a dosage of 10 µg/ml repressed cell viability, induced apoptosis, and increased the release of IL-1β, IL-6 and TNF-α. RSV pre-treatment (30 µM) significantly alleviated LPS-induced apoptosis and inflammation. More importantly, miR-146b was up-regulated by RSV, and the protective functions of RSV on ATDC5 cells were attenuated by miR-146b silence. Further, NF-κB and p38MAPK pathways were activated by LPS, and were deactivated by RSV. Besides, RSV-induced the deactivation of NF-κB and p38MAPK pathways was reversed by miR-146b silence. Conclusions: Our findings suggest that RSV protects ATDC5 cells from LPS-induced inflammatory and apoptotic injury via up-regulation of miR-146b and thereby deactivation of NF-κB and p38MAPK pathways.
The Critical Role of PTEN/PI3K/AKT Signaling Pathway in Shikonin-Induced Apoptosis and Proliferation Inhibition of Chronic Myeloid Leukemia
Authors: Chen Yu , Wang Tongtong , Du Jing , Li Yanchun , Wang Xin , Zhou Yi , Yu XingXing , Fan Weimin , Zhu Qiaojuan , Tong Xiangmin , Wang Ying
Published: May 2018

Background/Aims: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line. Methods: Firstly, K562 cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry with Annexin V-FITC/PI staining. Cell migration was measured by Transwell migration assay. In addition, western blot was performed to determine the proteins (PI3K, Bax, Bcl-2, cleaved caspase-3, PTEN, p-AKT, AKT, CXCR4, SDF-1, CD44) involved in the mechanism of action of shikonin. Finally, neutrophils from peripheral blood of CML patients were obtained, and cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry. Results: Shikonin reduced the proliferation of K562 cells in a time- and dose-dependent manner and promoted the apoptosis of K562 cells. Moreover, shikonin increased the PTEN level and inactivated the PI3K/AKT signaling pathway, subsequently upregulating BAX in K562 cells. In addition, shikonin could block K562 cell migration via the CXCR4/SDF-1 axis. Finally, shikonin significantly inhibited the proliferation and promoted the apoptosis of neutrophils from CML patients. Conclusion: These results demonstrated that shikonin inhibits CML proliferation and migration and induces apoptosis by the PTEN/PI3K/AKT pathway, revealing the effects of shikonin therapy on CML.
Zurampic Protects Pancreatic β-Cells from High Uric Acid Induced-Damage by Inhibiting URAT1 and Inactivating the ROS/AMPK/ERK Pathways
Authors: Xin Ying , Wang Kun , Jia Zhaotong , Xu Tao , Xu Qiang , Zhang Chao , Liu Jia , Chen Rui , Du Zhongcai , Sun Jianjing
Published: May 2018

Background/Aims: Zurampic is a US FDA approved drug for treatment of gout. However, the influence of Zurampic on pancreatic β-cells remains unclear. The study aimed to evaluate the effects of Zurampic on high uric acid-induced damage of pancreatic β-cells and the possible underlying mechanisms. Methods: INS-1 cells and primary rat islets were stimulated with Zurampic and the mRNA expression of urate transporter 1 (URAT1) was assessed by qRT-PCR. Cells were stimulated with uric acid or uric acid plus Zurampic, and cell viability, apoptosis and ROS release were measured by MTT and flow cytometry assays. Western blot analysis was performed to evaluate the expressions of active Caspase-3 and phosphorylation of AMPK and ERK. Finally, cells were stimulated with uric acid or uric acid plus Zurampic at low/high level of glucose (2.8/16.7 mM glucose), and the insulin release was assessed by ELISA. Results: mRNA expression of URAT1 was decreased by Zurampic in a dose-dependent manner. Uric acid decreased cell viability, promoted cell apoptosis and induced ROS release. Uric acid-induced alterations could be reversed by Zurampic. Activation of Caspase-3 and phosphorylation of AMPK and ERK were enhanced by uric acid, and the enhancements were reversed by Zurampic. Decreased phosphorylation of AMPK and ERK, induced by Zurampic, was further reduced by adding inhibitor of AMPK or ERK. Besides, uric acid inhibited high glucose-induced insulin secretion and the inhibition was rescued by Zurampic. Conclusions: Zurampic has a protective effect on pancreatic β-cells against uric acid induced-damage by inhibiting URAT1 and inactivating the ROS/AMPK/ERK pathway.
The Effects of Angelica Sinensis Polysaccharide on Tumor Growth and Iron Metabolism by Regulating Hepcidin in Tumor-Bearing Mice
Authors: Ren Feng , Li Jian , Wang Yanglin , Wang Yongxia , Feng Sijia , Yuan Zhiqing , Qian Xinlai
Published: May 2018

Background/Aims: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP) to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. Methods: Western blot, RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometer. Results: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6), JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. Conclusion: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.
Haploinsufficiency of the Mouse Atp6v1b1 Gene Leads to a Mild Acid-Base Disturbance with Implications for Kidney Stone Disease
Authors: Bourgeois Soline , Bettoni Carla , Baron Stéphanie , Wagner Carsten A.
Published: May 2018

Background/Aims: Homozygous mutations or deletion of the ATP6V1B1 gene encoding for the B1 subunit of the vacuolar H+-ATPase leads to distal renal tubular acidosis in man and mice. In humans, heterozygous carriers of B1 mutations can develop incomplete dRTA with nephroclacinosis. Here, we investigated whether Atp6v1b1+/- mice also develop acid-base disturbances during an HCl acid load. Methods: We subjected Atp6v1b1+/+, Atp6v1b1+/-, Atp6v1b1-/- to an HCl-load for 7 days and investigated acid-base status, kidney function, and expression of renal acid-base transport proteins. Results: Atp6v1b1-/- mice had more alkaline urine and low ammoniuria, whereas Atp6v1b1+/- mice showed no difference in their urine parameters but higher blood chloride and lower blood pCO2 compared to controls. Subcellular localization of a4 and B2 subunits of H+-ATPase were unchanged within the 3 genotypes and Atp6v1b1+/+ and Atp6v1b1+/- mice exhibited a similar luminal localization of B1 subunit in intercalated cells. However, B1, B2 and a4 expression were decreased in renal membrane fractions from Atp6v1b1+/- mice compared to Atp6v1b1+/+ while B2 and a4 were unchanged and B1 protein was reduced in Atp6v1b+-/- kidneys. Compensatory mechanisms of B1 ablation were found only in the collecting duct with a down-regulation of pendrin in Atp6v1b1-/- mice. Conclusions: In conclusion, 1) Atp6v1b1+/- mice developed a mild incomplete dRTA. dRTA is partly compensated by respiration. 2) Compensatory mechanisms for the absence of B1 take place only in the collecting duct of Atp6v1b1-/- kidneys.
Testes de usabilidade de um controle remoto com idosos: aplicação de testes virtuais em softwares CAD/CAE
Authors: Ramos Mayara , Reis Alexandre Amorim dos
Published: May 2018

O envelhecimento populacional traz a necessidade de desenvolver produtos mais adequados às capacidades dessa população. Uma forma de progredir nesse sentido é a inclusão do público idoso em testes de usabilidade no processo de desenvolvimento de produtos. Essa inclusão pode ser feita com baixo custo e sem exposição do usuário por meio de testes virtuais. O objetivo neste estudo é desenvolver um procedimento para testes de usabilidade virtuais realizados no software SolidWorks que foque nos idosos, realizando um estudo com um controle remoto. Para isso foram feitos tais testes com esse público, sendo um convencional e um com usuários simulados virtualmente, comparando seus resultados. A conclusão indicou que, devido às limitações encontradas neste estudo, o teste virtual na plataforma desse software ainda não substitui os testes tradicionais.
O instrumentalismo na aferição da experiência do usuário
Authors: Demilis Marcelo Pereira , Sousa Richard Perassi Luiz de , Merino Giselle Alves Diaz
Published: May 2018

Instrumentalismo é o nome de uma doutrina no campo de Epistemologia que indica que conhecimento e método científico não são necessariamente falsos ou verdadeiros. Mas, devido ao seu caráter instrumental, esses servem de recursos para lidar com a realidade. Por sua vez, como aspecto da realidade prática na área de Design, observa-se a busca por métodos e outros recursos para mensurar a experiência do usuário (UX), porque, progressivamente, aumentou o interesse em design orientado para a experiência. Contudo, as experiências abrangem uma gama de propriedades e métricas que são variadas, muitas vezes particulares, efêmeras e subjetivas. Por isso, há dificuldades para se encontrar conceitos que designam a experiência do usuário e, consequentemente, recursos instrumentais relacionados com essa temática. Isso caracteriza a problemática desta pesquisa sobre o instrumentalismo na aferição da experiência do usuário. O objetivo foi identificar instrumentos que, de maneira eficiente, auxiliam os designers na projeção e mensuração da experiência do usuário, visando o desenvolvimento coerente de produtos e serviços. O procedimento adotado inicialmente no estudo proposto, como é descrito neste artigo, foi pesquisar trabalhos publicados em periódicos internacionais por meio de uma revisão sistemática. O conhecimento resultante permitiu a sistematização da literatura e a seleção de instrumentos considerados coerentes com o propósito da pesquisa. Portanto, o resultado foi o mapeamento descritivo de instrumentos destinados à aferição da experiência do usuário, para serem aplicados em projetos de design.
The republican face of Augustus political action: a case study of Res Gestae Divi Augusti
Authors: Giacomo Luiz Henrique Souza de
Published: May 2018

O presente texto visa propor um exercício reflexivo em relação a um dos principais expoentes do discurso político de Augusto, o texto de sua res gestae, e analisar quais os mecanismos utilizados por Augusto em sua escrita para reforçar sua ação virtuosa em prol “do povo e do Senado romano” e se apresentar como o restaurador da República.
IG VII 53, an epigraphic rara avis in the corpus of greek metrical inscriptions
Authors: Guijarro Ruano Paloma
Published: May 2018

Este artigo tem como objetivo estudar a inscrição publicada no IG VII 53 de uma perspectiva liguística. Ele consiste de uma seção em prosa que inclui um epigrama dedicado aos Mégaros caídos em combate nas guerras Pérsicas. A inscrição foi supostamente composta no século V a. C., mas o texto preservado não foi inscrito antes do IV século a. C. Após reavaliar a bibliografia principal sobre o texto, que estudou a inscrição principalmente do ponto de vista arqueológico, histórico ou literário, nós aplicamos uma análise linguística em dois níveis, baseada: a) na comparação dos dados linguísticos com a prosa epigráfica ou outras influências literárias, e b) nas restrições métricas que poderiam determinar a escolha entre formas locais ou literárias. Como complemento ao que os estudos atuais sugerem, essa abordagem metodológica nos permite distinguir até que ponto é possível traçar as características linguísticas originais de uma versão anterior do epigrama, bem como se e como a métrica contribui para os preservar.