bluuebunny/crossref_metadata_2025 huggingface dataset:
Projective Verse: The Spiritual Legacy of the Beat Generation
Authors: Nelson Paul E.
Published: October 2018

Allen Ginsberg’s poetry, poetics or cultural activism; Jack Kerouac’s prose, poetry and his method of composition; Gary Snyder’s environmental and Buddhist consciousness and bioregional ethos, or the opening made by the Beats for Eastern spirituality in the west are of intrinsic value and will be for generations, this paper seeks to posit that it is Michael McClure’s use of Projective Verse, that future generations of writers and readers will come to appreciate as that movement’s spiritual legacy.
Perspectives on Inclusive Education of Preschool Children with Autism Spectrum Disorders and Other Developmental Disabilities in Iran
Authors: Samadi Sayyed Ali , McConkey Roy
Published: October 2018

Background: Iranian children with disabilities invariably attend special schools and many may be excluded from education entirely. Information on preschool education is limited but probably mirrors the situation in schools. There is a lack of information in terms of parental preferences for schooling and teachers’ experiences of inclusion in Iran. Method: Two feasibility studies were undertaken; one with 89 parents of children with autism or intellectual disabilities, and another with the head teachers of two private kindergartens. Results: Two-thirds of parents favored inclusive schools; most parents whose children had autism or were verbally proficient were in favor of their child attending ordinary schools, even if their child had been placed in a specialist preschool facility. The head teachers justified inclusion in terms of children’s rights but identified three main challenges: coping with the diverse level of functioning, the need for special devices and training of teachers, and challenging the negative reactions of parents of non-disabled children. Conclusions: Further exploration of the views of those who have experienced inclusion would further challenge existing practices. Moreover, the training and preparation of teachers is key to reforming schools. However, wider social values and beliefs towards disabilities also need to change.
Prevalence of Integrons and Insertion Sequences in ESBL-Producing E. coli Isolated from Different Sources in Navarra, Spain
Authors: Pérez-Etayo Lara , Berzosa Melibea , González David , Vitas Ana Isabel
Published: October 2018

Mobile genetic elements play an important role in the dissemination of antibiotic resistant bacteria among human and environmental sources. Therefore, the aim of this study was to determine the occurrence and patterns of integrons and insertion sequences of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolated from different sources in Navarra, northern Spain. A total of 150 isolates coming from food products, farms and feeds, aquatic environments, and humans (healthy people and hospital inpatients), were analyzed. PCRs were applied for the study of class 1, 2, and 3 integrons (intI1, intI2, and intI3), as well as for the determination of insertion sequences (IS26, ISEcp1, ISCR1, and IS903). Results show the wide presence and dissemination of intI1 (92%), while intI3 was not detected. It is remarkable, the prevalence of intI2 among food isolates, as well as the co-existence of class 1 and class 2 (8% of isolates). The majority of isolates have two or three IS elements, with the most common being IS26 (99.4%). The genetic pattern IS26–ISEcp1 (related with the pathogen clone ST131) was present in the 22% of isolates (including human isolates). In addition, the combination ISEcp1–IS26–IS903–ISCR1 was detected in 11 isolates being, to our knowledge, the first study that describes this genetic complex. Due to the wide variability observed, no relationship was determined among these mobile genetic elements and β-lactam resistance. More investigations regarding the genetic composition of these elements are needed to understand the role of multiple types of integrons and insertion sequences on the dissemination of antimicrobial resistance genes among different environments.
Increased Health and Wellbeing in Preschools (DAGIS) Study—Differences in Children’s Energy Balance-Related Behaviors (EBRBs) and in Long-Term Stress by Parental Educational Level
Authors: Lehto Elviira , Ray Carola , Vepsäläinen Henna , Korkalo Liisa , Lehto Reetta , Kaukonen Riikka , Suhonen Eira , Nislin Mari , Nissinen Kaija , Skaffari Essi , Koivusilta Leena , Sajaniemi Nina , Erkkola Maijaliisa , Roos Eva
Published: October 2018

This paper describes the Increased Health and Wellbeing in Preschools (DAGIS) survey process and socioeconomic status (SES) differences in children’s energy balance-related behaviors (EBRBs), meaning physical activity, sedentary and dietary behaviors, and long-term stress that serve as the basis for the intervention development. A cross-sectional survey was conducted during 2015–2016 in 66 Finnish preschools in eight municipalities involving 864 children (3–6 years old). Parents, preschool personnel, and principals assessed environmental factors at home and preschool with questionnaires. Measurement of children’s EBRBs involved three-day food records, food frequency questionnaires (FFQ), seven-day accelerometer data, and seven-day sedentary behavior diaries. Children’s long-term stress was measured by hair cortisol concentration. Parental educational level (PEL) served as an indicator of SES. Children with low PEL had more screen time, more frequent consumption of sugary beverages and lower consumption of vegetables, fruit, and berries (VFB) than those with high PEL. Children with middle PEL had a higher risk of consuming sugary everyday foods than children with high PEL. No PEL differences were found in children’s physical activity, sedentary time, or long-term stress. The DAGIS intervention, aiming to diminish SES differences in preschool children’s EBRBs, needs to have a special focus on screen time and consumption of sugary foods and beverages, and VFB.
Effects of Participation in Social Activities on Cognitive Function Among Middle-Aged and Older Adults in Korea
Authors: Hwang Jongnam , Park Sangmin , Kim Sujin
Published: October 2018

Cognitive function is a critical health issue in later life, the decline of which disrupts well-being and daily life function. Cognitive decline in older ages can also be understood in the context of the social environment such as social connectedness and engagement in personal life. This study aimed to examine: (1) whether participation in social activities contributes to preventing cognitive decline, and (2) what type of social activities are beneficial to maintaining cognitive function. Data from the Korean Longitudinal Study of Aging (KLOSA) 2006–2014, a longitudinal survey of the household-dwelling population aged 45 and older in Korea were used. The results revealed that Mini-Mental State Examination (MMSE) scores decreased with increasing age, at a rate of approximately 0.18 units across all age-gender groups, and the decrease was steeper for adults aged 65 and over. Participation in social gatherings was likely to delay the decline in cognitive function after the age of 65. In a gender-stratified model, social activity may not have an impact on the decline of cognitive function for men, whereas participation in social gatherings was negatively related to the decline of MMSE scores in women. This study suggests the need for a gender-stratified policy for preventing the decline of cognitive function while promoting engagement in social activities in Korean older adults.
You Can’t Find Healthy Food in the Bush: Poor Accessibility, Availability and Adequacy of Food in Rural Australia
Authors: Whelan Jill , Millar Lynne , Bell Colin , Russell Cherie , Grainger Felicity , Allender Steven , Love Penelope
Published: October 2018

In high-income countries, obesity disproportionately affects those from disadvantaged and rural areas. Poor diet is a modifiable risk factor for obesity and the food environment a primary driver of poor diet. In rural and disadvantaged communities, it is harder to access affordable and nutritious food, affecting both food insecurity and the health of rural residents. This paper aims to describe the food environment in a rural Australian community (approx. 7000 km2 in size) to inform the development of community-relevant food supply interventions. We conducted a census audit of the food environment (ground truthing) of a local government area (LGA). We used the Nutrition Environment Measurement tools (NEMS-S and NEMS-R) to identify availability of a range of food and non-alcoholic beverages, the relative price of a healthy compared to a less healthy option of a similar food type (e.g., bread), the quality of fresh produce and any in-store nutrition promotion. Thirty-eight food retail outlets operated at the time of our study and all were included, 11 food stores (NEMS-S) and 27 food service outlets (NEMS-R). The mean NEMS-S score for all food stores was 21/54 points (39%) and mean NEMS-R score for all food service outlets was 3/23 points (13%); indicative of limited healthier options at relatively higher prices. It is difficult to buy healthy food beyond the supermarkets and one (of seven) cafés across the LGA. Residents demonstrate strong loyalty to local food outlets, providing scope to work with this existing infrastructure to positively impact poor diet and improve food security.
Parenting Desire and Minority Stress in Lesbians and Gay Men: A Mediation Framework
Authors: Amodeo Anna Lisa , Esposito Concetta , Bochicchio Vincenzo , Valerio Paolo , Vitelli Roberto , Bacchini Dario , Scandurra Cristiano
Published: October 2018

Despite the rapid increase in lesbian and gay (LG) people who desire and decide to become parents, LG childless individuals may encounter serious obstacles in the parenthood process, such as minority stress. Notwithstanding, the psychological processes by which prejudice events might affect the desire to become parents are still understudied. As an extension of the minority stress theory, the psychological mediation framework sheds light on these psychological processes, as it encompasses a more clinical view of stress. Within this framework, the current study aimed at assessing the role of prejudice events in affecting parenting desire in 290 childless Italian LG individuals (120 lesbians and 170 gay men), as well as the role of internalized heterosexism and sexual orientation concealment in mediating the relationship between prejudice events and parenting desire. The results suggest that only in lesbians prejudice events were negatively associated with parenting desire, and that sexual orientation concealment and internalized heterosexism were also negatively associated with parenting desire. Furthermore, sexual orientation concealment, and not internalized heterosexism, mediated the relationship between prejudice events and parenting desire in lesbians, but not gay men. The findings have important implications for clinical practice.
Fear of Missing Out as a Predictor of Problematic Social Media Use and Phubbing Behavior among Flemish Adolescents
Authors: Franchina Vittoria , Vanden Abeele Mariek , Van Rooij Antonius J. , Lo Coco Gianluca , De Marez Lieven
Published: October 2018

Fear-of-missing-out (FOMO) refers to feelings of anxiety that arise from the realization that you may be missing out on rewarding experiences that others are having. FOMO can be identified as an intra-personal trait that drives people to stay up to date of what other people are doing, among others on social media platforms. Drawing from the findings of a large-scale survey study among 2663 Flemish teenagers, this study explores the relationships between FOMO, social media use, problematic social media use (PSMU) and phubbing behavior. In line with our expectations, FOMO was a positive predictor of both how frequently teenagers use several social media platforms and of how many platforms they actively use. FOMO was a stronger predictor of the use of social media platforms that are more private (e.g., Facebook, Snapchat) than platforms that are more public in nature (e.g., Twitter, Youtube). FOMO predicted phubbing behavior both directly and indirectly via its relationship with PSMU. These findings support extant research that points towards FOMO as a factor explaining teenagers’ social media use.
Phenolic Compounds Diminish Antibiotic Resistance of Staphylococcus Aureus Clinical Strains
Authors: Miklasińska-Majdanik Maria , Kępa Małgorzata , Wojtyczka Robert D. , Idzik Danuta , Wąsik Tomasz J.
Published: October 2018

There is a growing body of evidence that flavonoids show antibacterial activity against both Gram-positive and Gram-negative bacteria. The mechanisms of action of phenolic compounds on bacterial cell have been partially attributed to damage to the bacterial membrane, inhibition of virulence factors such as enzymes and toxins, and suppression of bacterial biofilm formation. What is more, some natural polyphenols, aside from direct antibacterial activity, exert a synergistic effect when combined with common chemotherapeutics. Many studies have proved that in synergy with antibiotics plant flavonoids pose a promising alternative for therapeutic strategies against drug resistant bacteria. In this review most recent reports on antimicrobial action of polyphenols on Staphylococcus aureus strains are described, highlighting where proven, the mechanisms of action and the structure–activity relationships. Since many reports in this field are, to some extent, conflicting, a unified in vitro and in vivo susceptibility testing algorithms should be introduced to ensure the selection of effective antibacterial polyphenolic compounds with low cytotoxicity and minimal side effects.
Physical Activity, Residential Environment, and Nature Relatedness in Young Men—A Population-Based MOPO Study
Authors: Puhakka Soile , Pyky Riitta , Lankila Tiina , Kangas Maarit , Rusanen Jarmo , Ikäheimo Tiina M. , Koivumaa-Honkanen Heli , Korpelainen Raija
Published: October 2018

Background: In general, nature relatedness is positively associated with physical activity, health, and subjective well-being. However, increased residence in urban areas, and the decrease in natural spaces, may affect the younger generation most adversely. The associated environmental changes can increase youths’ risk of spending most of their time indoors, and weaken their nature relatedness, making them less likely to enjoy nature’s health benefits. This is a serious public health issue, since inadequate physical activity, combined with minimum time spent in green space, can affect health across the whole lifespan. Thus, to develop effective interventions for physical activation and promote health and well-being among young men, further knowledge of the determinants of their nature relatedness is necessary. Aims: To explore factors related to nature relatedness, including physical activity, physical activity with parents, and residential environment. Methods: The study population consisted of all 914 young men (mean—17.8 years; SD—0.5) who participated in mandatory call-ups for military service and completed the study questionnaire in 2013. The questionnaire inquired about their nature relatedness, demographic characteristics, socioeconomic status, physical activity, health, and subjective well-being. A geographic information system (GIS) was used to assess the features of their residential environments. Multivariable linear regression was used to analyze the data. Results: Physical activity (p = 0.021) and physical activity with parents at primary school age (p = 0.007), and currently (p = 0.001) as well as good self-rated health (p = 0.001), and father’s higher socioeconomic status (p = 0.041), were positively connected to nature relatedness. Conclusions: Physical activity in general, physical activity with parents, and nature relatedness were positively related. This knowledge can be utilized in promoting physical activity and health among young men.
Impacts of Individual Daily Greenspace Exposure on Health Based on Individual Activity Space and Structural Equation Modeling
Authors: Zhang Lin , Zhou Suhong , Kwan Mei-Po , Chen Fei , Lin Rongping
Published: October 2018

Previous studies on the effects of greenspace exposure on health are largely based on static contextual units, such as residential neighborhoods, and other administrative units. They tend to ignore the spatiotemporal dynamics of individual daily greenspace exposure and the mediating effects of specific activity type (such as physical activity). Therefore, this study examines individual daily greenspace exposure while taking into account people’s daily mobility and the mediating role of physical activity between greenspace exposure and health. Specifically, using survey data collected in Guangzhou, China, and high-resolution remote sensing images, individual activity space for a weekday is delineated and used to measure participants’ daily greenspace exposure. Structural equation modeling is then applied to analyze the direct effects of individual daily greenspace exposure on health and its indirect effects through the mediating variable of physical activity. The results show that daily greenspace exposure directly influences individual health and also indirectly affects participants’ health status through physical activity. With respect to the total effects, daily greenspace exposure helps improve participants’ mental health and contributes to promoting their social health. It also helps improve participants’ physical health, although to a lesser extent. In general, the higher the daily greenspace exposure, the higher the physical activity level and the better the overall health (including physical, mental, and social health).
Metallothionein and Superoxide Dismutase—Antioxidative Protein Status in Fullerene-Doxorubicin Delivery to MCF-7 Human Breast Cancer Cells
Authors: Kepinska Marta , Kizek Rene , Milnerowicz Halina
Published: October 2018

Doxorubicin (DOX) is one of the most frequently used anticancer drugs in breast cancer treatment. However, clinical applications of DOX are restricted, largely due to the fact that its action disturbs the pro/antioxidant balance in both cancerous and non-cancerous cells. The aim of this study was to investigate the influence of fullerene (C60) in cell treatment by DOX on the proliferation of human breast cancer cells (MCF-7), concentration of metallothionein (MT) and superoxide dismutase (SOD), and SOD activity in these cells. The use of C60 in complexes with DOX causes a change in the level of cell proliferation of about 5% more than when caused by DOX alone (from 60–65% to 70%). The use of C60 as a DOX nanotransporter reduced the MT level increase induced by DOX. C60 alone caused an increase of SOD1 concentration. On the other hand, it led to a decrease of SOD activity. C60 in complex with DOX caused a decrease of the DOX-induced SOD activity level. Exposure of MCF-7 cells to DOX-C60 complexes results in a decrease in viable cells and may become a new therapeutic approach to breast cancer. The effects of C60 in complexes with DOX on MCF-7 cells included a decreased enzymatic (SOD activity) and nonenzymatic (MT) antioxidant status, thus indicating their prooxidant role in MCF-7 cells.
Bivalent Ligand UDCA-LPE Inhibits Pro-Fibrogenic Integrin Signalling by Inducing Lipid Raft-Mediated Internalization
Authors: Su Jie , Gan-Schreier Hongying , Goeppert Benjamin , Chamulitrat Walee , Stremmel Wolfgang , Pathil Anita
Published: October 2018

Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a synthetic bile acid-phospholipid conjugate with profound hepatoprotective and anti-fibrogenic functions in vitro and in vivo. Herein, we aimed to demonstrate the inhibitory effects of UDCA-LPE on pro-fibrogenic integrin signalling. UDCA-LPE treatment of human embryonic liver cell line CL48 and primary human hepatic stellate cells induced a non-classical internalization of integrin β1 resulting in dephosphorylation and inhibition of SRC and focal adhesion kinase (FAK). Signalling analyses suggested that UDCA-LPE may act as a heterobivalent ligand for integrins and lysophospholipid receptor1 (LPAR1) and co-immunoprecipitation demonstrated the bridging effect of UDCA-LPE on integrin β1 and LPAR1. The disruption of either the UDCA-moiety binding to integrins by RGD-containing peptide GRGDSP or the LPE-moiety binding to LPAR1 by LPAR1 antagonist Ki16425 reversed inhibitory functions of UDCA-LPE. The lack of inhibitory functions of UDCA-PE and UDCA-LPE derivatives (14:0 and 12:0, LPE-moiety containing shorter fatty acid chain) as well as the consistency of the translocation of UDCA-LPE and integrins, which co-fractionated with LPE but not UDCA, suggested that the observed UDCA-LPE-induced translocation of integrins was mediated by LPE endocytic transport pathway.
Detours to Replication: Functions of Specialized DNA Polymerases during Oncogene-induced Replication Stress
Authors: Tsao Wei-Chung , Eckert Kristin A.
Published: October 2018

Incomplete and low-fidelity genome duplication contribute to genomic instability and cancer development. Difficult-to-Replicate Sequences, or DiToRS, are natural impediments in the genome that require specialized DNA polymerases and repair pathways to complete and maintain faithful DNA synthesis. DiToRS include non B-DNA secondary structures formed by repetitive sequences, for example within chromosomal fragile sites and telomeres, which inhibit DNA replication under endogenous stress conditions. Oncogene activation alters DNA replication dynamics and creates oncogenic replication stress, resulting in persistent activation of the DNA damage and replication stress responses, cell cycle arrest, and cell death. The response to oncogenic replication stress is highly complex and must be tightly regulated to prevent mutations and tumorigenesis. In this review, we summarize types of known DiToRS and the experimental evidence supporting replication inhibition, with a focus on the specialized DNA polymerases utilized to cope with these obstacles. In addition, we discuss different causes of oncogenic replication stress and its impact on DiToRS stability. We highlight recent findings regarding the regulation of DNA polymerases during oncogenic replication stress and the implications for cancer development.
C-C Motif Ligand 20 (CCL20) and C-C Motif Chemokine Receptor 6 (CCR6) in Human Peripheral Blood Mononuclear Cells: Dysregulated in Ulcerative Colitis and a Potential Role for CCL20 in IL-1β Release
Authors: Skovdahl Helene Kolstad , Damås Jan Kristian , Granlund Atle van Beelen , Østvik Ann Elisabet , Doseth Berit , Bruland Torunn , Mollnes Tom Eirik , Sandvik Arne Kristian
Published: October 2018

The chemokine C-C motif ligand 20 (CCL20) is increased in the colonic mucosa during active inflammatory bowel disease (IBD) and can be found both in the epithelium and immune cells in the lamina propria. The present study investigated CCL20 and C-C motif Chemokine Receptor 6 (CCR6) in peripheral blood mononuclear cells (PBMCs) (n = 40) from IBD patients and healthy controls, to identify inductors of CCL20 release encountered in a local proinflammatory environment. CCL20 release from PBMCs was increased when activating TLR2/1 or NOD2, suggesting that CCL20 is part of a first line response to danger-associated molecular patterns also in immune cells. Overall, ulcerative colitis (UC) had a significantly stronger CCL20 release than Crohn’s disease (CD) (+242%, p < 0.01), indicating that the CCL20-CCR6 axis may be more involved in UC. The CCL20 receptor CCR6 is essential for the chemotactic function of CCL20. UC with active inflammation had significantly decreased CCR6 expression and a reduction in CCR6+ cells in circulation, indicating chemoattraction of CCR6+ cells from circulation towards peripheral tissues. We further examined CCL20 induced release of cytokines from PBMCs. Stimulation with CCL20 combined with TNF increased IL-1β release from PBMCs. By attracting additional immune cells, as well as inducing proinflammatory IL-1β release from immune cells, CCL20 may protract the inflammatory response in ulcerative colitis.
Pazopanib, Cabozantinib, and Vandetanib in the Treatment of Progressive Medullary Thyroid Cancer with a Special Focus on the Adverse Effects on Hypertension
Authors: Milling Rikke Vilsbøll , Grimm Daniela , Krüger Marcus , Grosse Jirka , Kopp Sascha , Bauer Johann , Infanger Manfred , Wehland Markus
Published: October 2018

Medullary thyroid cancer (MTC) is a rare malignancy with a poor prognosis. First line therapy is surgery, which is the only curative method of the disease. However, in non-operable cases or with tumor progression and metastases, a systemic treatment is necessary. This form of cancer is often insensitive to conventional chemotherapy, but the use of tyrosine kinase inhibitors (TKIs), such as pazopanib, cabozantinib, and vandetanib, has shown promising results with an increase in progression-free survival and prolonged lifetime. Therefore, we focused on the pharmacological characteristics of TKIs, their mechanism of action, their application as a secondary treatment option for MTC, their efficacy as a cancer drug treatment, and reviewed the ongoing clinical trials. TKIs also act systemically causing various adverse events (AEs). One common AE of this treatment is hypertension, known to be associated with cardiovascular disease and can therefore potentially worsen the well-being of the treated patients. The available treatment strategies of drug-induced hypertension were discussed. The mechanism behind the development of hypertension is still unclear. Therefore, the treatment of this AE remains symptomatic. Thus, future studies are necessary to investigate the link between tumor growth inhibition and hypertension. In addition, optimized, individual treatment strategies should be implemented.
Integrative Analysis of lncRNAs, miRNAs, and mRNA-Associated ceRNA Network in an Atopic Dermatitis Recurrence Model
Authors: Wang Xiaoyu , Bao Kaifan , Wu Peng , Yu Xi , Wang Can , Ji Lv , Hong Min
Published: October 2018

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.
Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer
Authors: Gurunathan Sangiliyandi , Kang Min-Hee , Qasim Muhammad , Kim Jin-Hoi
Published: October 2018

Cancer represents a group of heterogeneous diseases characterized by uncontrolled growth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significant role in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Some of the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeutic window and undesired side effects of available anticancer drugs and the limitations of anticancer drugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranostic carriers, liposomes, carbon nanotubes, quantum dots, polymeric micelles, dendrimers and metallic nanoparticles. However, nonbiodegradable nanoparticles causes high tissue accumulation and leads to toxicity. MDR is considered a major impediment to cancer treatment due to metastatic tumors that develop resistance to chemotherapy. MDR contributes to the failure of chemotherapies in various cancers, including breast, ovarian, lung, gastrointestinal and hematological malignancies. Moreover, the therapeutic efficiency of anticancer drugs or nanoparticles (NPs) used alone is less than that of the combination of NPs and anticancer drugs. Combination therapy has long been adopted as the standard first-line treatment of several malignancies to improve the clinical outcome. Combination therapy with anticancer drugs has been shown to generally induce synergistic drug actions and deter the onset of drug resistance. Therefore, this review is designed to report and analyze the recent progress made to address combination therapy using NPs and anticancer drugs. We first provide a comprehensive overview of the angiogenesis and of the different types of NPs currently used in treatments of cancer; those emphasized in this review are liposomes, polymeric NPs, polymeric micelles (PMs), dendrimers, carbon NPs, nanodiamond (ND), fullerenes, carbon nanotubes (CNTs), graphene oxide (GO), GO nanocomposites and metallic NPs used for combination therapy with various anticancer agents. Nanotechnology has provided the convenient tools for combination therapy. However, for clinical translation, we need continued improvements in the field of nanotechnology.
Anti-Cancer and Protective Effects of Royal Jelly for Therapy-Induced Toxicities in Malignancies
Authors: Miyata Yasuyoshi , Sakai Hideki
Published: October 2018

Royal jelly (RJ) is a glandular secretion produced by worker honeybees and is a special food for the queen honeybee. It results in a significant prolongation of the lifespan of the queen honeybee compared with the worker honeybees through anti-inflammatory, anti-oxidant and anti-microbial activities. Consequently, RJ is used as cosmetic and dietary supplement throughout the world. In addition, in vitro studies and animal experiments have demonstrated that RJ inhibits cell proliferation and stimulates apoptosis in various types of malignant cells and affects the production of various chemokines, anti-oxidants and growth factors and the expression of cancer-related molecules in patients with malignancies, especially in patients treated with anti-cancer agents. Therefore, RJ is thought to exert anti-cancer effects on tumor growth and exhibit protective functions against drug-induced toxicities. RJ has also been demonstrated to be useful for suppression of adverse events, the maintenance of the quality of life during treatment and the improvement of prognosis in animal models and patients with malignancies. To understand the mechanisms of the beneficial effects of RJ, knowledge of the changes induced at the molecular level by RJ with respect to cell survival, inflammation, oxidative stress and other cancer-related factors is essential. In addition, the effects of combination therapies of RJ and other anti-cancer agents or natural compounds are important to determine the future direction of RJ-based treatment strategies. Therefore, in this review, we have covered the following five issues: (1) the anti-cancer effects of RJ and its main component, 10-hydroxy-2-decenoic acid; (2) the protective effects of RJ against anti-cancer agent-induced toxicities; (3) the molecular mechanisms of such beneficial effects of RJ; (4) the safety and toxicity of RJ; and (5) the future directions of RJ-based treatment strategies, with a discussion on the limitations of the study of the biological activities of RJ.
Transcription Factor ANAC074 Binds to NRS1, NRS2, or MybSt1 Element in Addition to the NACRS to Regulate Gene Expression
Authors: He Lin , Xu Jingyu , Wang Yucheng , Yang Kejun
Published: October 2018

NAC (NAM, ATAF1/2, and CUC2) transcription factors play important roles in many biological processes, and mainly bind to the NACRS with core sequences “CACG” or “CATGTG” to regulate gene expression. However, whether NAC proteins can bind to other motifs without these core sequences remains unknown. In this study, we employed a Transcription Factor-Centered Yeast one Hybrid (TF-Centered Y1H) screen to study the motifs recognized by ANAC074. In addition to the NACRS core cis-element, we identified that ANAC074 could bind to MybSt1, NRS1, and NRS2. Y1H and GUS assays showed that ANAC074 could bind the promoters of ethylene responsive genes and stress responsive genes via the NRS1, NRS2, or MybSt1 element. ChIP study further confirmed that the bindings of ANAC074 to MybSt1, NRS1, and NRS2 actually occurred in Arabidopsis. Furthermore, ten NAC proteins from different NAC subfamilies in Arabidopsis thaliana were selected and confirmed to bind to the MybSt1, NRS1, and NRS2 motifs, indicating that they are recognized commonly by NACs. These findings will help us to further reveal the functions of NAC proteins.
Structural Analysis of Variability and Interaction of the N-terminal of the Oncogenic Effector CagA of Helicobacter pylori with Phosphatidylserine
Authors: Ulloa-Guerrero Cindy P. , Delgado Maria del Pilar , Jaramillo Carlos A.
Published: October 2018

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA’s translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the phosphatidylserine and the docking of three mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA–Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score; mutations in this position were evaluated to observe the differences in intermolecular forces for the CagA–Phosphatidylserine complex. We evaluated the docking of three mutations: K636A, K636R and K636N. The crystal and mutation models presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG ( χ 2 ( 1 ) = 93.82 , p-value < 2.2 × 10 − 16 ) and the H-bonds ( χ 2 ( 1 ) = 91.93 , p-value < 2.2 × 10 − 16 ). Overall, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA–Phosphatidylserine complex interaction.
Neuroimmunological Implications of Subclinical Lipopolysaccharide from Salmonella Enteritidis
Authors: Mikołajczyk Anita , Złotkowska Dagmara
Published: October 2018

Mounting evidence has indicated that lipopolysaccharide (LPS) is implicated in neuroimmunological responses, but the body’s response to subclinical doses of bacterial endotoxin remains poorly understood. The influence of a low single dose of LPS from Salmonella Enteritidis, which does not result in any clinical symptoms of intoxication (subclinical lipopolysaccharide), on selected cells and signal molecules of the neuroimmune system was tested. Five juvenile crossbred female pigs were intravenously injected with LPS from S. Enteritidis (5 μg/kg body weight (b.w.)), while five pigs from the control group received sodium chloride in the same way. Our data demonstrated that subclinical LPS from S. Enteritidis increased levels of dopamine in the brain and neuropeptides such as substance P (SP), galanin (GAL), neuropeptide Y (NPY), and active intestinal peptide (VIP) in the cervical lymph nodes with serum hyperhaptoglobinaemia and reduction of plasma CD4 and CD8 T-lymphocytes seven days after lipopolysaccharide administration. CD4 and CD8 T-lymphocytes from the cervical lymph node and serum interleukin-6 and tumour necrosis factor α showed no significant differences between the control and lipopolysaccharide groups. Subclinical lipopolysaccharide from S. Enteritidis can affect cells and signal molecules of the neuroimmune system. The presence of subclinical lipopolysaccharide from S. Enteritidis is associated with unknown prolonged consequences and may require eradication and a deeper search into the asymptomatic carrier state of Salmonella spp.
Dietary Supplementation with Trihexanoin Enhances Intestinal Function of Weaned Piglets
Authors: Wu Tao , Li Kang , Yi Dan , Wang Lei , Zhao Di , Lv Yang , Zhang Lin , Chen Hongbo , Ding Binying , Hou Yongqing , Wu Guoyao
Published: October 2018

Trihexanoin is a short-chain triglyceride (SCT). Many studies have reported that SCTs play important roles in the maintenance of intestinal epithelial structure and function. The present work was to investigate the effects of trihexanoin on growth performance, carbohydrate and fat metabolism, as well as intestinal morphology and function in weaned piglets. Twenty weaned piglets (21 ± 2 d) were randomly allocated to one of two treatment groups: The control group (basal diet supplemented with 0.5% soya oil); the TH group (basal diet supplemented with 0.5% trihexanoin). Dietary trihexanoin supplementation significantly reduced diarrhea rate; increased the concentrations of LDL, HDL and total protein in plasma; decreased cholesterol concentrations and glutamyl transpeptidase activity in plasma; improved intestinal morphologic structure; altered the mRNA levels and abundances of proteins related to glycogen and fat metabolism, mucosal barrier function, antioxidant capacity and water transport capacity; and altered the community of intestinal microflora. These results indicate that dietary trihexanoin supplementation could reduce diarrhea, regulate carbohydrate and fat metabolism, exert beneficial effects on the intestinal mucosal barrier, protect the intestinal mucosa from injuries, improve intestinal transport and absorption, and enhance antioxidant capacity. In conclusion, dietary supplementation with 0.5% trihexanoin improves the intestinal function and health of weaned piglets.
Crosstalk between Brassinosteroids and Ethylene during Plant Growth and under Abiotic Stress Conditions
Authors: Jiroutova Petra , Oklestkova Jana , Strnad Miroslav
Published: October 2018

Plant hormones through signaling networks mutually regulate several signaling and metabolic systems essential for both plant development and plant responses to different environmental stresses. Extensive research has enabled the main effects of all known phytohormones classes to be identified. Therefore, it is now possible to investigate the interesting topic of plant hormonal crosstalk more fully. In this review, we focus on the role of brassinosteroids and ethylene during plant growth and development especially flowering, ripening of fruits, apical hook development, and root and shoot growth. As well as it summarizes their interaction during various abiotic stress conditions.
Novel Transcriptional Mechanisms for Regulating Metabolism by Thyroid Hormone
Authors: Singh Brijesh Kumar , Sinha Rohit Anthony , Yen Paul Michael
Published: October 2018

The thyroid hormone plays a key role in energy and nutrient metabolisms in many tissues and regulates the transcription of key genes in metabolic pathways. It has long been believed that thyroid hormones (THs) exerted their effects primarily by binding to nuclear TH receptors (THRs) that are associated with conserved thyroid hormone response elements (TREs) located on the promoters of target genes. However, recent transcriptome and ChIP-Seq studies have challenged this conventional view as discordance was observed between TH-responsive genes and THR binding to DNA. While THR association with other transcription factors bound to DNA, TH activation of THRs to mediate effects that do not involve DNA-binding, or TH binding to proteins other than THRs have been invoked as potential mechanisms to explain this discrepancy, it appears that additional novel mechanisms may enable TH to regulate the mRNA expression. These include activation of transcription factors by SIRT1 via metabolic actions by TH, the post-translational modification of THR, the THR co-regulation of transcription with other nuclear receptors and transcription factors, and the microRNA (miR) control of RNA transcript expression to encode proteins involved in the cellular metabolism. Together, these novel mechanisms enlarge and diversify the panoply of metabolic genes that can be regulated by TH.
Association between Sarcopenic Obesity, Type 2 Diabetes, and Hypertension in Overweight and Obese Treatment-Seeking Adult Women
Authors: Kreidieh Dima , Itani Leila , El Masri Dana , Tannir Hana , Citarella Roberto , El Ghoch Marwan
Published: October 2018

The last decade has seen a new condition that describes the coexistence of obesity and sarcopenia, termed sarcopenic obesity (SO). We aimed to assess the prevalence of SO in overweight and obese treatment-seeking adult women and the association with type 2 diabetes, hypertension, and dyslipidemia. A body composition assessment was conducted with an InBody bioimpedance analyser in 154 overweight and obese women referred to the Outpatient Clinic in the Department of Nutrition and Dietetics at Beirut Arab University (BAU) in Lebanon, and 30 normal-weight participants of similar age. The overweight and obese patients were then categorized as being with or without sarcopenia. Thirty-one out of the 154 overweight or obese participants met the criteria for SO and displayed a significantly higher prevalence of type 2 diabetes and hypertension than those without SO. Logistic regression analysis showed that SO increases the odds of having type 2 diabetes and hypertension by nearly 550% (odds ratio = 5.42, 95% confidence interval = 1.37–21.40, p < 0.05) after adjusting for central fat, eating habits, level of physical activity, and smoking. SO affects nearly 20% of treatment-seeking overweight and obese adult women. Moreover, SO seems to be strongly associated with type 2 diabetes and hypertension.
Metabolic Profile of Patients with Premature Ovarian Insufficiency
Authors: Podfigurna Agnieszka , Stellmach Angelika , Szeliga Anna , Czyzyk Adam , Meczekalski Blazej
Published: October 2018

Premature ovarian insufficiency (POI) is hypogonadism associated with amenorrhea, increased levels of gonadotropins, and hypoestrogenism. Deficiency of estrogens may contribute to higher risk of cardiovascular diseases and death. POI patients present several risk factors for the development of cardiovascular diseases (CVD): endothelial dysfunction, abnormal lipid profile, insulin resistance, and insulin action disturbances. Therefore, patients present a higher risk of developing metabolic syndrome. Materials and methods: Follicle stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid stimulating hormone (TSH), thyroxine (fT4), fasting serum glucose and insulin concentrations, homeostatic model for insulin resistance (HOMA-IR), and lipid profiles were assessed in 56 women (mean age: 30.7 ± 6.9) suffering from POI diagnosed according to European Society of Human Reproduction and Embryology (ESHRE) criteria and 68 healthy age-and-weight matched women (mean age: 27.3 ± 4.5). Results: After regression analysis with BMI and age correction, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) serum concentrations were found to be significantly higher in the POI group, when compared to healthy subjects, whilst triglycerides, glucose, insulin serum concentrations, HOMA-IR, as well as systolic (SBP) and diastolic blood pressure (DBP) did not differ significantly between both groups. A significant positive correlation was identified between TC and LDL-C levels, regardless of BMI and age, whilst SBP correlated only with serum glucose concentration. Additionally, FSH correlated positively with fasting serum glucose concentration after BMI and age correction. Conclusions: Certain metabolic parameters appeared to correlate with POI and these correlations persisted after correction for BMI and age. More research is required to determine the influence of absent ovulatory function on metabolic profiles in POI women. This information may additionally help in early identification of CVD risk factors in those patients.
The Anti-Inflammatory Effects of Fermented Herbal Roots of Asparagus cochinchinensis in an Ovalbumin-Induced Asthma Model
Authors: Choi Jun Young , Kim Ji Eun , Park Jin Ju , Lee Mi Rim , Song Bo Ram , Park Ji Won , Kang Mi Ju , Lee Hee Seob , Son Hong Joo , Hong Jin Tae , Hwang Dae Youn
Published: October 2018

Introduction: Roots of Asparagus cochinchinensis, which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that had been fermented with Weissella cibaria (BAW) and its possible underlying cholinergic regulation. Methods: Alterations of the anti-asthmatic markers and the molecular response factors were measured in an ovalbumin (OVA)-induced asthma model after treatment with BAW. Results: Treatment with BAW decreased the intracellular reactive oxygen species (ROS) production in lipopolysaccharides (LPS) activated RAW264.7 cells. The results of the animal experiments revealed lower infiltration of inflammatory cells and bronchial thickness, and a significant reduction in the number of macrophages and eosinophils, concentration of OVA-specific IgE, and expression of Th2 cytokines in the OVA + BAW treated group. In addition, a significant recovery of goblet cell hyperplasia, MMP-9 expression, and the VEGF signaling pathway was observed upon airway remodeling in the OVA + BAW treated group. Furthermore, these responses of BAW were linked to recovery of acetylcholine esterase (AChE) activity and muscarinic acetylcholine receptor (mAChR) M3 downstream signaling pathway in epithelial cells, smooth muscle cells, and afferent sensory nerves of OVA + BAW-treated mice. Conclusion: Overall, these findings are the first to provide evidence that the therapeutic effects of BAW can prevent airway inflammation and remodeling through the recovery of cholinergic regulation in structural cells and inflammatory cells of the chronic asthma model.
I Spy in the Developing Fly a Multitude of Ways to Die
Authors: Yalonetskaya Alla , Mondragon Albert A. , Elguero Johnny , McCall Kimberly
Published: October 2018

Cell proliferation and cell death are two opposing, yet complementary fundamental processes in development. Cell proliferation provides new cells, while developmental programmed cell death adjusts cell numbers and refines structures as an organism grows. Apoptosis is the best-characterized form of programmed cell death; however, there are many other non-apoptotic forms of cell death that occur throughout development. Drosophila is an excellent model for studying these varied forms of cell death given the array of cellular, molecular, and genetic techniques available. In this review, we discuss select examples of apoptotic and non-apoptotic cell death that occur in different tissues and at different stages of Drosophila development. For example, apoptosis occurs throughout the nervous system to achieve an appropriate number of neurons. Elsewhere in the fly, non-apoptotic modes of developmental cell death are employed, such as in the elimination of larval salivary glands and midgut during metamorphosis. These and other examples discussed here demonstrate the versatility of Drosophila as a model organism for elucidating the diverse modes of programmed cell death.