bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-Scale Assessment of Function and Disability in Patients with Parkinson’s Disease Using the Functioning Disability Evaluation Scale-Adult Version
Authors: Hsu Tzu-Herng , Liou Tsan-Hon , Chou Kuei-Ru , Chi Wen-Chou , Yen Chia-Feng , Liao Hua-Fang , Tseng Ing-Jy
Published: December 2018

This study assesses the functioning and disability related to Parkinson’s disease using the Functioning Disability Evaluation Scale-Adult Version (FUNDES-Adult), based on the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) in a large-scale database; this study describes, discusses and clarifies the predictive factor of not being in an ambulatory status. Of 7455 patients included in this study, 3561 were not ambulatory and 3894 were ambulatory or assisted ambulatory. Patients with poor walking status revealed higher FUNDES-Adult scores in all domains. Age, modified Hoehn–Yahr stage, living in an institution and the standardized score of FUNDES-Adult domains 1 and 2 were positive independent predictors of the not ambulatory status. The FUNDES-Adult could evaluate multifaceted disability and predict the walking status in patients with Parkinson’s disease.
Types of Milk and/or Its Substitutes Given to Children (6–36 Months) in Nurseries in Poland: Data from the Research and Education Project “Eating Healthy, Growing Healthy”
Authors: Harton Anna , Myszkowska-Ryciak Joanna
Published: December 2018

The purpose of the study was to evaluate the types of milk and/or its substitutes given to children (aged 6–36 months) in nurseries in Poland. Methods: The study was conducted in 211 nurseries across Poland. The supply of milk and its substitutes was checked in ten-day menus and inventory documents. In total, 211 ten-day menus and 2110 daily inventory reports were analyzed. Additionally, data were obtained by interviews with day-care center (DCC) directors and/or staff responsible for nutrition. Results: Compared to non-public nurseries, public ones were characterized by a higher average number of children, most often maintained their own kitchens, and charged a lower financial fee. Public DCCs also more often employed dietitians. The type of milk and its substitutes offered to children in nurseries was dependent on the age of the children and type of DCC. In a larger percentage of public DCCs infants received a milk formula, and in smaller percentage they received breast milk. This regularity also occurred in older children’s diets (13–36 months). In toddlers’ diets in public nurseries, cow’s milk was more common. The share of other milk substitutes in the nutrition of children from both age groups was negligible. Conclusion: The types of milk given to children in nurseries in Poland varied and depended on the age of children and the type of DCCs. It is necessary to provide education to DCC staff regarding the type of milk recommended for children under one year of age.
Association Between Sport Participation, Body Composition, Physical Fitness, and Social Correlates Among Adolescents: The PAHL Study
Authors: Agata Korcz , Monyeki Makama Andries
Published: December 2018

Background: Evidence suggests that social support impacts on participation in sport or physical activity (PA), and is associated with health benefits, although the link is complex and not well understood. The study aim was to examine whether participation in organized sports is related to body composition, physical fitness, and social correlates for PA. Methods: Cross-sectional data on 238 adolescents (90 boys and 148 girls), mean age 14.9 ± 0.8 years, who were participants in the Physical Activity and Health Longitudinal Study, were collected. The participants were divided into two groups: sport participation (SP) and non-sport participation (NSP). Height, weight, and triceps and subscapular skinfolds were assessed according to standard procedures. Weight (kg) and height (m2) were used to calculate body mass index (BMI), and skinfolds were used to calculate body fat percentage. The European Test of Physical Fitness (EUROFIT) battery of tests was used to assess physical fitness. The standardized International Physical Activity Questionnaire Short Form and Social Support for PA questionnaires were used to obtain information on PA and social correlates for PA, respectively. Participants were asked to choose between participation and non-participation in sport. Results: The SP group had lower BMI component values (p = 0.011, d = 0.52 for percentage body fat (%BF); p = 0.011, d = 0.53 for sum of skinfolds (∑SKF) obtained higher physical fitness scores in selected items (p = 0.003, d = 0.64 for sit ups (SUP); p < 0.000, d = 0.96 for maximal oxygen consumption VO2max) and received higher social support (p < 0.001, d = 0.86 for social support (SS)), than the NSP group. The social support received by those participating in sport correlated positively with most fitness components (p = 0.013, r2 = 18% for bent arm hang (BAH); p = 0.000, r2 = 12% for sit ups (SUP); p = 0.000, r2 = 17% for VO2max). Physical fitness components were negatively associated with most body composition components for both groups. Conclusions: The results provide a better understanding of sport participation in organized sports-related, body composition-related and physical fitness-related associations with changes in social support received by adolescents and may contribute to the development of more accurate promotive strategies to increase children’s and adolescents’ engagement in sport and PA.
Methods for Evaluating the Combined Effects of Chemical and Nonchemical Exposures for Cumulative Environmental Health Risk Assessment
Authors: Payne-Sturges Devon C. , Scammell Madeleine K. , Levy Jonathan I. , Cory-Slechta Deborah A. , Symanski Elaine , Carr Shmool Jessie L. , Laumbach Robert , Linder Stephen , Clougherty Jane E.
Published: December 2018

Cumulative risk assessment (CRA) has been proposed as a means of evaluating possible additive and synergistic effects of multiple chemical, physical and social stressors on human health, with the goal of informing policy and decision-making, and protecting public health. Routine application of CRA to environmental regulatory and policy decision making, however, has been limited due to a perceived lack of appropriate quantitative approaches for assessing combined effects of chemical and nonchemical exposures. Seven research projects, which represented a variety of disciplines, including population health science, laboratory science, social sciences, geography, statistics and mathematics, were funded by the US Environmental Protection Agency (EPA) to help address this knowledge gap. We synthesize key insights from these unique studies to determine the implications for CRA practice and priorities for further research. Our analyses of these seven projects demonstrate that the necessary analytical methods to support CRA are available but are ultimately context-dependent. These projects collectively provided advancements for CRA in the areas of community engagement, characterization of exposures to nonchemical stressors, and assessment of health effects associated with joint exposures to chemical and psychosocial stressors.
Delivery of Fall Prevention Interventions for At-Risk Older Adults in Rural Areas: Findings from a National Dissemination
Authors: Smith Matthew , Towne Samuel , Herrera-Venson Angelica , Cameron Kathleen , Horel Scott , Ory Marcia , Gilchrist Chelsea , Schneider Ellen , DiCocco Casey , Skowronski Shannon
Published: December 2018

Falls incidence rates and associated injuries are projected to increase among rural-dwelling older adults, which highlights the need for effective interventions to prevent falls and manage fall-related risks. The purpose of this descriptive study was to identify the geospatial dissemination of eight evidence-based fall prevention programs (e.g., A Matter of Balance, Stepping On, Tai Chi, Otago Exercise Program) across the United States (U.S.) in terms of participants enrolled, workshops delivered, and geospatial reach. These dissemination characteristics were compared across three rurality designations (i.e., metro areas; non-metro areas adjacent to metro areas; and, non-metro areas not adjacent to metro areas). Data were analyzed from a national repository of 39 Administration for Community Living (ACL) grantees from 2014–2017 (spanning 22 states). Descriptive statistics were used to assess program reach, delivery-site type, and completion rate by rurality. Geographic information systems (GIS) geospatially represented the collective reach of the eight interventions. Of the 45,812 participants who attended a fall prevention program, 12.7% attended workshops in non-metro adjacent areas and 6.6% attended workshops in non-metro non-adjacent areas. Of the 3755 workshops delivered (in over 550 unique counties), most were delivered in senior centers (26%), residential facilities (20%), healthcare organizations (13%), and faith-based organizations (9%). On average, the workshop attendance/retention rates were consistent across rurality (~70%). Findings highlight the need to diversify the delivery infrastructure for fall prevention programs to adequately serve older adults in rural areas. Ongoing efforts are needed to offer sustainable technical assistance and to develop scalable clinical-community referral systems to increase fall prevention program participation among rural-dwelling older adults.
Levels of Burnout and Risk Factors in Medical Area Nurses: A Meta-Analytic Study
Authors: Molina-Praena Jesús , Ramirez-Baena Lucia , Gómez-Urquiza José L. , Cañadas Gustavo R. , De la Fuente Emilia I. , Cañadas-De la Fuente Guillermo A.
Published: December 2018

Research findings concerning burnout prevalence rate among nurses from the medical area are contradictory. The aim of this study was to analyse associated factors, to determine nurse burnout levels and to meta-analyse the prevalence rate of each burnout dimension. A systematic review, with meta-analysis, was conducted in February 2018, consulting the next scientific databases: PubMed, CUIDEN, CINAHL, Scopus, LILACS, PsycINFO and ProQuest Health & Medical Complete. In total, 38 articles were extracted, using a double-blinded procedure. The studies were classified by the level of evidence and degrees of recommendation. The 63.15% (n = 24) of the studies used the MBI. High emotional exhaustion was found in the 31% of the nurses, 24% of high depersonalisation and low personal accomplishment was found in the 38%. Factors related to burnout included professional experience, psychological factors and marital status. High emotional exhaustion prevalence rates, high depersonalisation and inadequate personal accomplishment are present among medical area nurses. The risk profile could be a single nurse, with multiple employments, who suffers work overload and with relatively little experience in this field. The problem addressed in this study influence the quality of care provided, on patients’ well-being and on the occupational health of nurses.
Relationships between Meteorological Parameters and Particulate Matter in Mae Hong Son Province, Thailand
Authors: Kliengchuay Wissanupong , Cooper Meeyai Aronrag , Worakhunpiset Suwalee , Tantrakarnapa Kraichat
Published: December 2018

Meteorological parameters play an important role in determining the prevalence of ambient particulate matter (PM) in the upper north of Thailand. Mae Hong Son is a province located in this region and which borders Myanmar. This study aimed to determine the relationships between meteorological parameters and ambient concentrations of particulate matter less than 10 µm in diameter (PM10) in Mae Hong Son. Parameters were measured at an air quality monitoring station, and consisted of PM10, carbon monoxide (CO), ozone (O3), and meteorological factors, including temperature, rainfall, pressure, wind speed, wind direction, and relative humidity (RH). Nine years (2009–2017) of pollution and climate data obtained from the Thai Pollution Control Department (PCD) were used for analysis. The results of this study indicate that PM10 is influenced by meteorological parameters; high concentration occurred during the dry season and northeastern monsoon seasons. Maximum concentrations were always observed in March. The PM10 concentrations were significantly related to CO and O3 concentrations and to RH, giving correlation coefficients of 0.73, 0.39, and −0.37, respectively (p-value < 0.001). Additionally, the hourly PM10 concentration fluctuated within each day. In general, it was found that the reporting of daily concentrations might be best suited to public announcements and presentations. Hourly concentrations are recommended for public declarations that might be useful for warning citizens and organizations about air pollution. Our findings could be used to improve the understanding of PM10 concentration patterns in Mae Hong Son and provide information to better air pollution measures and establish a warning system for the province.
Tuberculosis Transmission in Households and Classrooms of Adolescent Cases Compared to the Community in China
Authors: Pan Dongxiang , Lin Mei , Lan Rushu , Graviss Edward , Lin Dingwen , Liang Dabin , Long Xi , Qin Huifang , Huang Liwen , Huang Minying , Chongsuvivatwong Virasakdi
Published: December 2018

The aim of this paper is to evaluate the link between the history of exposure to tuberculosis (TB) in the household and diagnosed TB cases at school, and to compare the detection rate of active TB among household contacts and classroom contacts of adolescent TB cases with the rates among contacts of healthy controls. From November 2016 to December 2017, a prospective matched case-control study was conducted using passively identified index adolescent student cases from the TB surveillance system and healthy controls (matched by county, school type, sex, age and ethnicity). Contacts in households and classrooms of index cases and of controls were investigated. Matched tabulation of 117 case-control pairs revealed exposure to TB in the household as a strong risk factor (odds ratio (OR) = 21.0, 95% confidence interval (CI): 3.4, 868.6). Forty-five (case detection rate 0.69%) and two (case detection rate 0.03%) new active TB cases were detected among 6512 and 6480 classroom contacts of the index cases and controls, respectively. Having an index case in the classroom significantly increased the risk of classmates contracting active TB (OR = 22.5, 95% CI: 5.9, 191.4). Our findings suggested that previous exposure to TB in the household could lead a child to catch TB at school, then spread TB to classmates.
Psychological Benefits of Walking through Forest Areas
Authors: Song Chorong , Ikei Harumi , Park Bum-Jin , Lee Juyoung , Kagawa Takahide , Miyazaki Yoshifumi
Published: December 2018

This study aimed to clarify the psychological benefits of brief walks through forest areas. In addition, we aimed to examine the associations between psychological responses and trait anxiety levels. Five-hundred-and-eighty-five participants (mean age, 21.7 ± 1.6 years) were instructed to walk predetermined courses through forest (test) and city (control) areas for 15 min. The Profile of Mood State (POMS) questionnaire and State-Trait Anxiety Inventory were used to assess participants’ psychological responses and trait anxiety levels, respectively. The results revealed that walking through forest areas decreased the negative moods of “depression-dejection”, “tension-anxiety”, “anger-hostility”, “fatigue”, and “confusion” and improved the participants’ positive mood of “vigor” compared with walking through city areas. Furthermore, a significant correlation was found between participants’ trait anxiety levels and their changes in the subscale of “depression-dejection” of POMS after walking through forest areas. A more effective reduction in the feeling of “depression-dejection” after walking through forest areas was observed for participants with high trait anxiety levels than for those with normal and low trait anxiety levels. This study showed the psychological benefits of walking through forest areas and identified a significant correlation between psychological responses to walking through forests and trait anxiety levels.
Chronic Musculoskeletal Pain, Self-Reported Health and Quality of Life among Older Populations in South Africa and Uganda
Authors: Wang Chao , Pu Run , Ghose Bishwajit , Tang Shangfeng
Published: December 2018

Chronic musculoskeletal pain (CMP) is a serious health concern especially among the elderly population and has significant bearing on health and quality of life. Not much is known about the relationship between chronic pain with self-reported health and quality of life among older populations in low-resource settings. Based on sub-national data from South Africa and Uganda, the present study aimed to explore whether the older population living with CMP report health and quality of life differently compared to those with no CMP complaints. This study was based on cross-sectional data on 1495 South African and Ugandan men and women collected from the SAGE Well-Being of Older People Study. Outcome variables were self-reported physical and mental health and quality of life (QoL). Mental health was assessed by self-reported depressive symptoms during the last 12 months. CMP was assessed by self-reported generalised pain as well as back pain. Multivariable logistic regression models were used to measure the association between health and QoL with CMP by adjusting for potential demographic and environmental confounders. The prevalence of poor self-rated health (61.2%, 95% CI = 51.7, 70.0), depression (37.2%, 95% CI = 34.8, 39.6) and QoL (80.5%, 95% CI = 70.8, 87.5) was considerably high in the study population. Mild/moderate and Severe/extreme generalised pain were reported respectively by 34.5% (95% CI = 28.9, 40.5) and 15.7% (95% CI = 12.2, 19.9) of the respondents, while back pain was reported by 53.3% (95% CI = 45.8, 60.4). The prevalence of both types was significantly higher among women than in men (p < 0.001). In the multivariate analysis, both generalised pain and back pain significantly predicted poor health, depression and QoL, however, it varied between the two different populations. Back pain was associated with higher odds of poor self-rated health [OR = 1.813, 95% CI = 1.308, 2.512], depression [1.640, 95% CI = 1.425, 3.964] and poor QoL [1.505, 95% CI = 1.028, 2.202] in South Africa, but not in Uganda. Compared to having no generalised pain, having Mild/Moderate [OR = 2.309, 95% CI = 1.219, 7.438] and Severe/Extreme [OR = 2.271, 95% CI = 1.447, 4.143] generalised pain was associated with significantly higher odds of poor self-rated health in South Africa. An overwhelmingly high proportion of the sample population reported poor health, quality of life and depression. Among older individuals, health interventions that address CMP may help promote subjective health and quality and life and improve psychological health.
Network Design for Municipal Solid Waste Collection: A Case Study of the Nanjing Jiangbei New Area
Authors: Liang Jing , Liu Ming
Published: December 2018

Garbage collection is an important part of municipal engineering. An effective service network design can help to reduce the municipal operation cost and improve its service level. In this paper, we propose an optimization model for the network design of municipal solid waste (MSW) collection in the Nanjing Jiangbei new area. The problem was formulated as a mixed integer nonlinear programming (MINLP) model with an emphasis on minimizing the annual operation cost. The model simultaneously decides on the optimal number of refuse transfer stations (RTSs), determines the relative size and location for each RTS, allocates each community to a specific RTS, and finally identifies the annual operation cost and service level for the optimal scenario as well as other scenarios. A custom solution procedure which hybrids an enumeration rule and a genetic algorithm was designed to solve the proposed model. A sensitivity analysis was also conducted to illustrate the impact of changes in parameters on the optimality of the proposed model. Test results revealed that our model could provide tangible policy recommendations for managing the MSW collection.
Assessment of Displacements of Linestrings Based on Homologous Vertexes
Authors: Mozas-Calvache Antonio Tomás , Ariza-López Francisco Javier
Published: December 2018

This study describes a new method that was developed in order to assess the displacements between two linestrings that represent the same element in two datasets based on their shape. Until now, all existing line-based methods have been focused on the calculation of distances or buffer inclusions between the two linestrings. However, these approaches assess a spatial difference between two linestrings, but they can hide the displacements that were suffered because of the geometry of the linestrings themselves. In our approach, the shapes of the linestrings are taken into account in order to identify homologous vertexes and estimate real displacements. Between two lines a pair of homologous vertices are defined as those that represent in reality the same characteristic feature of the line. Homologous vertexes can be detected by means of any appropriate algorithm. In order to test this method, we developed a design of experiment that was based on its application to a large dataset of lines classified into five sinuosity classes. These datasets were obtained from an external source that contains perturbed linestrings with several known random and systematic disturbances. 496 linestrings and 59 configurations were used in this experiment. The results have demonstrated the viability of the proposed method in estimating the real displacement of the lines, and consequently assessing their positional accuracy.
TGFβ Superfamily Members as Regulators of B Cell Development and Function—Implications for Autoimmunity
Authors: Tamayo Esther , Alvarez Pilar , Merino Ramón
Published: December 2018

The TGFβ superfamily is composed of more than 33 growth and differentiation factors, including TGFβ1, β2, β3, BMPs, GDFs, nodal-related proteins, and activins. These members usually exert pleiotropic actions on several tissues and control multiple cellular processes, such as cell growth, cell survival, cell migration, cell fate specification, and differentiation, both during embryonic development and postnatal life. Although the effects of these factors on immune responses were elucidated long ago, most studies have been focused on the actions of TGFβs on T cells, as major regulators of adaptive immunity. In this review, we discuss new findings about the involvement of TGFβ superfamily members in the control of B cell development and function. Moreover, the potential contribution of TGFβ signaling to control B cell-mediated autoimmune diseases and its utility in the design of new therapies are also discussed.
Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer
Authors: Mazloumi Gavgani Fatemeh , Smith Arnesen Victoria , Jacobsen Rhîan G. , Krakstad Camilla , Hoivik Erling A. , Lewis Aurélia E.
Published: December 2018

The phosphoinositide 3-kinase (PI3K) signalling pathway is highly dysregulated in cancer, leading to elevated PI3K signalling and altered cellular processes that contribute to tumour development. The pathway is normally orchestrated by class I PI3K enzymes and negatively regulated by the phosphatase and tensin homologue, PTEN. Endometrial carcinomas harbour frequent alterations in components of the pathway, including changes in gene copy number and mutations, in particular in the oncogene PIK3CA, the gene encoding the PI3K catalytic subunit p110α, and the tumour suppressor PTEN. PIK3CB, encoding the other ubiquitously expressed class I isoform p110β, is less frequently altered but the few mutations identified to date are oncogenic. This isoform has received more research interest in recent years, particularly since PTEN-deficient tumours were found to be reliant on p110β activity to sustain transformation. In this review, we describe the current understanding of the common and distinct biochemical properties of the p110α and p110β isoforms, summarise their mutations and highlight how they are targeted in clinical trials in endometrial cancer.
A Conserved Glycine Is Identified to be Essential for Desaturase Activity of IpFAD2s by Analyzing Natural Variants from Idesia polycarpa
Authors: Wu Pan , Zhang Lingling , Feng Tao , Lu Wenying , Zhao Huayan , Li Jianzhong , Lü Shiyou
Published: December 2018

High amounts of polyunsaturated fatty acids (PUFAs) in vegetable oil are not desirable for biodiesel or food oil due to their lower oxidative stability. The oil from Idesia polycarpa fruit contains 65–80% (mol%) linoleic acid (C18:2). Therefore, development of Idesia polycarpa cultivars with low PUFAs is highly desirable for Idesia polycarpa oil quality. Fatty acid desaturase 2 (FAD2) is the key enzyme converting oleic acid (C18:1) to C18:2. We isolated four FAD2 homologs from the fruit of Idesia polycarpa. Yeast transformed with IpFAD2-1, IpFAD2-2 and IpFAD2-3 can generate appreciable amounts of hexadecadienoic acid (C16:2) and C18:2, which are not present in wild-type yeast cells, revealing that the proteins encoded by these genes have Δ12 desaturase activity. Only trace amounts of C18:2 and little C16:2 were detected in yeast cells transformed with IpFAD2-4, suggesting IpFAD2-4 displays low activity. We also analyzed the activity of several FAD2 natural variants of Idesia polycarpa in yeast and found that a highly conserved Gly376 substitution caused the markedly reduced products catalyzed by IpFAD2-3. This glycine is also essential for the activity of IpFAD2-1 and IpFAD2-2, but its replacement in other plant FAD2 proteins displays different effects on the desaturase activity, suggesting its distinct roles across plant FAD2s proteins.
Anticancer Action and Mechanism of Ergosterol Peroxide from Paecilomyces cicadae Fermentation Broth
Authors: He Linfu , Shi Wenjing , Liu Xiaocui , Zhao Xiaohuan , Zhang Zhicai
Published: December 2018

Isaria cicadae, a medicinal food fungus, is a fruit from Paecilomyces cicadae. In this study, we purified ergosterol peroxide (EP) from the fermentation broth of P. cicadae and investigated its effects on renal cell carcinoma (RCC) cells, in vitro. EP was purified from P. cicadae fermentation broth. The human RCC cell line 786-0 was used to analyze the anticancer mechanism of EP and inhibit its effect on cancer cell proliferation, in vitro. EP with a validated structure showed a yield rate of 20.1 mg/L and a purity of 96%. EP significantly inhibited RCC cell growth and clone formation in vitro. In addition, EP suppressed the migration and invasion, triggered the apoptosis, and modulated the cell cycle of RCC cells, in a dose-dependent manner. It also downregulated β-catenin expression. EP could be routinely produced through P. cicadae. It fights RCC cells in vitro through multiple mechanisms, including suppressing cell growth, colonization, migration, and invasion, arresting the cell cycle, attenuating β-catenin pathways, and triggering apoptosis.
Effects of Reduced Graphene Oxides on Apoptosis and Cell Cycle of Glioblastoma Multiforme
Authors: Szczepaniak Jaroslaw , Strojny Barbara , Sawosz Chwalibog Ewa , Jaworski Slawomir , Jagiello Joanna , Winkowska Magdalena , Szmidt Maciej , Wierzbicki Mateusz , Sosnowska Malwina , Balaban Jasmina , Winnicka Anna , Lipinska Ludwika , Witkowska Pilaszewicz Olga , Grodzik Marta
Published: December 2018

Graphene (GN) and its derivatives (rGOs) show anticancer properties in glioblastoma multiforme (GBM) cells in vitro and in tumors in vivo. We compared the anti-tumor effects of rGOs with different oxygen contents with those of GN, and determined the characteristics of rGOs useful in anti-glioblastoma therapy using the U87 glioblastoma line. GN/ExF, rGO/Term, rGO/ATS, and rGO/TUD were structurally analysed via transmission electron microscopy, Raman spectroscopy, FTIR, and AFM. Zeta potential, oxygen content, and electrical resistance were determined. We analyzed the viability, metabolic activity, apoptosis, mitochondrial membrane potential, and cell cycle. Caspase- and mitochondrial-dependent apoptotic pathways were investigated by analyzing gene expression. rGO/TUD induced the greatest decrease in the metabolic activity of U87 cells. rGO/Term induced the highest level of apoptosis compared with that induced by GN/ExF. rGO/ATS induced a greater decrease in mitochondrial membrane potential than GN/ExF. No significant changes were observed in the cytometric study of the cell cycle. The effectiveness of these graphene derivatives was related to the presence of oxygen-containing functional groups and electron clouds. Their cytotoxicity mechanism may involve electron clouds, which are smaller in rGOs, decreasing their cytotoxic effect. Overall, cytotoxic activity involved depolarization of the mitochondrial membrane potential and the induction of apoptosis in U87 glioblastoma cells.
MiR-19a Overexpression in FTC-133 Cell Line Induces a More De-Differentiated and Aggressive Phenotype
Authors: Calabrese Giovanna , Dolcimascolo Anna , Torrisi Filippo , Zappalà Agata , Gulino Rosario , Parenti Rosalba
Published: December 2018

In recent years, microRNAs (miRNAs) have received increasing attention for their important role in tumor initiation and progression. MiRNAs are a class of endogenous small non-coding RNAs that negatively regulate the expression of several oncogenes or tumor suppressor genes. MiR-19a, a component of the oncogenic miR-17-92 cluster, has been reported to be highly expressed only in anaplastic thyroid cancer, the most undifferentiated, aggressive and lethal form of thyroid neoplasia. In this work, we evaluated the putative contribution of miR-19a in de-differentiation and aggressiveness of thyroid tumors. To this aim, we induced miR-19a expression in the well-differentiated follicular thyroid cancer cell line and evaluated proliferation, apoptosis and gene expression profile of cancer cells. Our results showed that miR-19a overexpression stimulates cell proliferation and alters the expression profile of genes related to thyroid cell differentiation and aggressiveness. These findings not only suggest that miR-19a has a possible involvement in de-differentiation and malignancy, but also that it could represent an important prognostic indicator and a good therapeutic target for the most aggressive thyroid cancer.
Activated Rho GTPases in Cancer—The Beginning of a New Paradigm
Authors: Aspenström Pontus
Published: December 2018

Involvement of Rho GTPases in cancer has been a matter of debate since the identification of the first members of this branch of the Ras superfamily of small GTPases. The Rho GTPases were ascribed important roles in the cell, although these were restricted to regulation of cytoskeletal dynamics, cell morphogenesis, and cell locomotion, with initially no clear indications of direct involvement in cancer progression. This paradigm has been challenged by numerous observations that Rho-regulated pathways are often dysregulated in cancers. More recently, identification of point mutants in the Rho GTPases Rac1, RhoA, and Cdc42 in human tumors has finally given rise to a new paradigm, and we can now state with confidence that Rho GTPases serve as oncogenes in several human cancers. This article provides an exposé of current knowledge of the roles of activated Rho GTPases in cancers.
Search of Allosteric Inhibitors and Associated Proteins of an AKT-like Kinase from Trypanosoma cruzi
Authors: Ochoa Rodrigo , Rocha-Roa Cristian , Marín-Villa Marcel , Robledo Sara M. , Varela-M Rubén E.
Published: December 2018

Proteins associated to the PI3K/AKT/mTOR signaling pathway are widely used targets for cancer treatment, and in recent years they have also been evaluated as putative targets in trypanosomatids parasites, such as Trypanosoma cruzi. Here, we performed a virtual screening approach to find candidates that can bind regions on or near the Pleckstrin homology domain of an AKT-like protein in T. cruzi. The compounds were also evaluated in vitro. The in silico and experimental results allowed us to identify a set of compounds that can potentially alter the intracellular signaling pathway through the AKT-like kinase of the parasite; among them, a derivative of the pyrazolopyridine nucleus with an IC50 of 14.25 ± 1.00 μM against amastigotes of T. cruzi. In addition, we built a protein–protein interaction network of T. cruzi to understand the role of the AKT-like protein in the parasite, and look for additional proteins that can be postulated as possible novel molecular targets for the rational design of compounds against T. cruzi.
Comparative Proteomic Analysis during the Involvement of Nitric Oxide in Hydrogen Gas-Improved Postharvest Freshness in Cut Lilies
Authors: Huo Jianqiang , Huang Dengjing , Zhang Jing , Fang Hua , Wang Bo , Wang Chunlei , Ma Zhanjun , Liao Weibiao
Published: December 2018

Our previous studies suggested that both hydrogen gas (H2) and nitric oxide (NO) could enhance the postharvest freshness of cut flowers. However, the crosstalk of H2 and NO during that process is unknown. Here, cut lilies (Lilium “Manissa”) were used to investigate the relationship between H2 and NO and to identify differentially accumulated proteins during postharvest freshness. The results revealed that 1% hydrogen-rich water (HRW) and 150 μM sodium nitroprusside (SNP) significantly extended the vase life and quality, while NO inhibitors suppressed the positive effects of HRW. Proteomics analysis found 50 differentially accumulated proteins in lilies leaves which were classified into seven functional categories. Among them, ATP synthase CF1 alpha subunit (chloroplast) (AtpA) was up-regulated by HRW and down-regulated by NO inhibitor. The expression level of LlatpA gene was consistent with the result of proteomics analysis. The positive effect of HRW and SNP on ATP synthase activity was inhibited by NO inhibitor. Meanwhile, the physiological-level analysis of chlorophyll fluorescence and photosynthetic parameters also agreed with the expression of AtpA regulated by HRW and SNP. Altogether, our results suggested that NO might be involved in H2-improved freshness of cut lilies, and AtpA protein may play important roles during that process.
Temporary Loading Prevents Cancer Progression and Immune Organ Atrophy Induced by Hind-Limb Unloading in Mice
Authors: Takahashi Akihisa , Wakihata Shoto , Ma Liqiu , Adachi Takuya , Hirose Hiroki , Yoshida Yukari , Ohira Yoshinobu
Published: December 2018

Although the body’s immune system is altered during spaceflight, the effects of microgravity (μG) on tumor growth and carcinogenesis are, as yet, unknown. To assess tumor proliferation and its effects on the immune system, we used a hind-limb unloading (HU) murine model to simulate μG during spaceflight. HU mice demonstrated significantly increased tumor growth, metastasis to the lung, and greater splenic and thymic atrophy compared with mice in constant orthostatic suspension and standard housing controls. In addition, mice undergoing temporary loading during HU (2 h per day) demonstrated no difference in cancer progression and immune organ atrophy compared with controls. Our findings suggest that temporary loading can prevent cancer progression and immune organ atrophy induced by HU. Further space experiment studies are warranted to elucidate the precise effects of μG on systemic immunity and cancer progression.
Stimulation of Peritoneal Mesothelial Cells to Secrete Matrix Metalloproteinase-9 (MMP-9) by TNF-α: A Role in the Invasion of Gastric Carcinoma Cells
Authors: Oku Teruaki , Shimada Kentaro , Kenmotsu Hiroki , Ando Yusuke , Kurisaka Chisato , Sano Rikio , Tsuiji Makoto , Hasegawa Shinya , Fukui Tetsuya , Tsuji Tsutomu
Published: December 2018

It has recently been recognized that inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), upregulate the secretion of matrix metalloproteinase-9 (MMP-9) from cancer cells and thereby promote peritoneal dissemination. In this study, we found that TNF-α also stimulated peritoneal mesothelial cells to secrete MMP-9 as assessed by zymography. MMP-9 gene expression in mesothelial cells induced by TNF-α was confirmed by quantitative RT-PCR analysis. We then utilized the reconstituted artificial mesothelium, which was composed of a monolayer of mesothelial cells cultured on a Matrigel layer in a Boyden chamber system, to examine the effects of TNF-α on carcinoma cell invasion. The transmigration of MKN1 human gastric carcinoma cells through the reconstituted mesothelium was promoted by TNF-α in a dose-dependent manner. The increased MKN1 cell migration was partially inhibited by the anti-α3 integrin antibody, indicating that the invasion process involves an integrin-dependent mechanism. Finally, we observed that the invasion of MMP-9-knockdown MKN1 cells into Matrigel membranes was potentiated by the exogenous addition of purified proMMP-9. These results suggest that TNF-α-induced MMP-9 secretion from mesothelial cells plays an important role in the metastatic dissemination of gastric cancer.
Potential Role of Fluoride in the Etiopathogenesis of Alzheimer’s Disease
Authors: Goschorska Marta , Baranowska-Bosiacka Irena , Gutowska Izabela , Metryka Emilia , Skórka-Majewicz Marta , Chlubek Dariusz
Published: December 2018

The etiopathogenesis of Alzheimer’s disease has not been fully explained. Now, the disease is widely attributed both to genetic and environmental factors. It is believed that only a small percentage of new AD cases result solely from genetic mutations, with most cases attributed to environmental factors or to the interaction of environmental factors with preexistent genetic determinants. Fluoride is widespread in the environment and it easily crosses the blood–brain barrier. In the brain fluoride affects cellular energy metabolism, synthesis of inflammatory factors, neurotransmitter metabolism, microglial activation, and the expression of proteins involved in neuronal maturation. Finally, and of specific importance to its role in Alzheimer’s disease, studies report fluoride-induced apoptosis and inflammation within the central nervous system. This review attempts to elucidate the potential relationship between the effects of fluoride exposure and the pathogenesis of Alzheimer’s disease. We describe the impact of fluoride-induced oxidative stress and inflammation in the pathogenesis of AD and demonstrate a role for apoptosis in disease progression, as well as a mechanism for its initiation by fluoride. The influence of fluoride on processes of AD initiation and progression is complex and warrants further investigation, especially considering growing environmental fluoride pollution.
Genome-Wide Identification and Analysis of HAK/KUP/KT Potassium Transporters Gene Family in Wheat (Triticum aestivum L.)
Authors: Cheng Xiyong , Liu Xiaodan , Mao Weiwei , Zhang Xurui , Chen Shulin , Zhan Kehui , Bi Huihui , Xu Haixia
Published: December 2018

In plants, the HAK (high-affinity K+)/KUP (K+ uptake)/KT (K+ transporter) family represents a large group of potassium transporters that play important roles in plant growth and environmental adaptation. Although HAK/KUP/KT genes have been extensively investigated in many plant species, they remain uncharacterized in wheat, especially those involved in the response to environmental stresses. In this study, 56 wheat HAK/KUP/KT (hereafter called TaHAKs) genes were identified by a genome-wide search using recently released wheat genomic data. Phylogenetic analysis grouped these genes into four clusters (Ι, II, III, IV), containing 22, 19, 7 and 8 genes, respectively. Chromosomal distribution, gene structure, and conserved motif analyses of the 56 TaHAK genes were subsequently performed. In silico RNA-seq data analysis revealed that TaHAKs from clusters II and III are constitutively expressed in various wheat tissues, while most genes from clusters I and IV have very low expression levels in the examined tissues at different developmental stages. qRT-PCR analysis showed that expression levels of TaHAK genes in wheat seedlings were significantly up- or downregulated when seedlings were exposed to K+ deficiency, high salinity, or dehydration. Furthermore, we functionally characterized TaHAK1b-2BL and showed that it facilitates K+ transport in yeast. Collectively, these results provide valuable information for further functional studies of TaHAKs, and contribute to a better understanding of the molecular basis of wheat development and stress tolerance.
Novel Clofarabine-Based Combinations with Polyphenols Epigenetically Reactivate Retinoic Acid Receptor Beta, Inhibit Cell Growth, and Induce Apoptosis of Breast Cancer Cells
Authors: Lubecka Katarzyna , Kaufman-Szymczyk Agnieszka , Cebula-Obrzut Barbara , Smolewski Piotr , Szemraj Janusz , Fabianowska-Majewska Krystyna
Published: December 2018

An epigenetic component, especially aberrant DNA methylation pattern, has been shown to be frequently involved in sporadic breast cancer development. A growing body of literature demonstrates that combination of agents, i.e. nucleoside analogues with dietary phytochemicals, may provide enhanced therapeutic effects in epigenetic reprogramming of cancer cells. Clofarabine (2-chloro-2′-fluoro-2′-deoxyarabinosyladenine, ClF), a second-generation 2′-deoxyadenosine analogue, has numerous anti-cancer effects, including potential capacity to regulate epigenetic processes. Our present study is the first to investigate the combinatorial effects of ClF (used at IC50 concentration) with epigallocatechin-3-gallate (EGCG, tea catechin) or genistein (soy phytoestrogen), at physiological concentrations, on breast cancer cell growth, apoptosis, and epigenetic regulation of retinoic acid receptor beta (RARB) transcriptional activity. In MCF7 and MDA-MB-231 cells, RARB promoter methylation and expression of RARB, modifiers of DNA methylation reaction (DNMT1, CDKN1A, TP53), and potential regulator of RARB transcription, PTEN, were estimated using methylation-sensitive restriction analysis (MSRA) and quantitative real-time polymerase chain reaction (qPCR), respectively. The combinatorial exposures synergistically or additively inhibited the growth and induced apoptosis of breast cancer cells, followed by RARB hypomethylation with concomitant multiple increase in RARB, PTEN, and CDKN1A transcript levels. Taken together, our results demonstrate the ability of ClF-based combinations with polyphenols to promote cancer cell death and reactivate DNA methylation-silenced tumor suppressor genes in breast cancer cells with different invasive potential.
Involvement of Gastrin-Releasing Peptide Receptor in the Regulation of Adipocyte Differentiation in 3T3-L1 Cells
Authors: Kim Mi-Kyoung , Park Hyun-Joo , Kim Yeon , Bae Soo-Kyung , Kim Hyung Joon , Bae Moon-Kyoung
Published: December 2018

Gastrin-releasing peptide (GRP), a member of bombesin-like peptides, and its receptor (GRP-R) play an important role in various physiological and pathological conditions. In this work, we investigated the role of GRP-R on adipogenesis in 3T3-L1 adipocytes. The expression of GRP-R was significantly increased during the adipocyte differentiation of 3T3-L1 cells. The inhibition of GRP-R by the antagonist RC-3095 affected adipogenesis in 3T3-L1 cells, which reduced lipid accumulation and regulated the expression of adipogenic genes. Moreover, cyclic AMP response element-binding protein (CREB) directly bound to the GRP-R promoter upon exposure to adipogenic stimuli. The down-regulation of GRP-R by the knockdown of CREB inhibited adipocyte differentiation of 3T3-L1 cells. Together these results suggest that the regulation of GRP-R activity or expression has an influence on adipogenesis through regulating adipogenic related genes.
From Neuronal Differentiation of iPSCs to 3D Neuro-Organoids: Modelling and Therapy of Neurodegenerative Diseases
Authors: Bordoni Matteo , Rey Federica , Fantini Valentina , Pansarasa Orietta , Di Giulio Anna Maria , Carelli Stephana , Cereda Cristina
Published: December 2018

In the last decade, the advances made into the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) led to great improvements towards their use as models of diseases. In particular, in the field of neurodegenerative diseases, iPSCs technology allowed to culture in vitro all types of patient-specific neural cells, facilitating not only the investigation of diseases’ etiopathology, but also the testing of new drugs and cell therapies, leading to the innovative concept of personalized medicine. Moreover, iPSCs can be differentiated and organized into 3D organoids, providing a tool which mimics the complexity of the brain’s architecture. Furthermore, recent developments in 3D bioprinting allowed the study of physiological cell-to-cell interactions, given by a combination of several biomaterials, scaffolds, and cells. This technology combines bio-plotter and biomaterials in which several types of cells, such as iPSCs or differentiated neurons, can be encapsulated in order to develop an innovative cellular model. IPSCs and 3D cell cultures technologies represent the first step towards the obtainment of a more reliable model, such as organoids, to facilitate neurodegenerative diseases’ investigation. The combination of iPSCs, 3D organoids and bioprinting will also allow the development of new therapeutic approaches. Indeed, on the one hand they will lead to the development of safer and patient-specific drugs testing but, also, they could be developed as cell-therapy for curing neurodegenerative diseases with a regenerative medicine approach.
From mRNA Expression of Drug Disposition Genes to In Vivo Assessment of CYP-Mediated Biotransformation during Zebrafish Embryonic and Larval Development
Authors: Verbueken Evy , Bars Chloé , Ball Jonathan S. , Periz-Stanacev Jelena , Marei Waleed F. A. , Tochwin Anna , Gabriëls Isabelle J. , Michiels Ellen D. G. , Stinckens Evelyn , Vergauwen Lucia , Knapen Dries , Van Ginneken Chris J. , Van Cruchten Steven J.
Published: December 2018

The zebrafish (Danio rerio) embryo is currently explored as an alternative for developmental toxicity testing. As maternal metabolism is lacking in this model, knowledge of the disposition of xenobiotics during zebrafish organogenesis is pivotal in order to correctly interpret the outcome of teratogenicity assays. Therefore, the aim of this study was to assess cytochrome P450 (CYP) activity in zebrafish embryos and larvae until 14 d post-fertilization (dpf) by using a non-specific CYP substrate, i.e., benzyloxy-methyl-resorufin (BOMR) and a CYP1-specific substrate, i.e., 7-ethoxyresorufin (ER). Moreover, the constitutive mRNA expression of CYP1A, CYP1B1, CYP1C1, CYP1C2, CYP2K6, CYP3A65, CYP3C1, phase II enzymes uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and sulfotransferase 1st1 (SULT1ST1), and an ATP-binding cassette (ABC) drug transporter, i.e., abcb4, was assessed during zebrafish development until 32 dpf by means of quantitative PCR (qPCR). The present study showed that trancripts and/or the activity of these proteins involved in disposition of xenobiotics are generally low to undetectable before 72 h post-fertilization (hpf), which has to be taken into account in teratogenicity testing. Full capacity appears to be reached by the end of organogenesis (i.e., 120 hpf), although CYP1—except CYP1A—and SULT1ST1 were shown to be already mature in early embryonic development.