bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Intrastriatal Applications of Botulinum Neurotoxin-A: A Review
Authors: Hawlitschka Alexander , Wree Andreas
Published: May 2018

Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. Its main pathophysiological characteristic is the loss of dopaminergic neurons in the substantia nigra pars compacta followed by a lack of striatal dopaminergic input and a consequent disinhibition of tonically active cholinergic interneurons. The resulting striatal hypercholinism causes major motor symptoms in PD. Anticholinergic pharmacotherapies have antiparkinsonian effects on motor symptoms, but, due to systemic actions, also numerous severe side effects occur on a regular basis. To circumvent these side effects, a local anticholinergic therapy acting exclusively in the striatum would be reasonable. Botulinum neurotoxin-A (BoNT-A) is synthesized by Clostridium botulinum and blocks the release of acetylcholine from the presynaptic bouton. For several decades, BoNT-A has been used successfully for medical and cosmetic purposes to induce controlled paralyses of single muscles. Our group and others investigated the experimental treatment of striatal hypercholinism by the direct injection of BoNT-A into the striatum of rats and mice as well as of hemiparkinsonian animal models. This review gives an overview of the most important results of the experimental intrastriatal BoNT-A application, with a focus on hemiparkinsonian rats.
New Insight into the Octamer of TYMS Stabilized by Intermolecular Cys43-Disulfide
Authors: Xie Dan , Wang Lulu , Xiao Qi , Wu Xiaoyan , Zhang Lin , Yang Qingkai , Wang Lina
Published: May 2018

Thymidylate synthase (TYMS) is an essential enzyme for the de novo synthesis of deoxythymidine monophosphate (dTMP) and has been a primary target for cancer chemotherapy. Although the physical structure of TYMS and the molecular mechanisms of TYMS catalyzing the conversion of deoxyuridine monophosphate (dUMP) to dTMP have been the subject of thorough studies, its oligomeric structure remains unclear. Here, we show that human TYMS not only exists in dimer form but also as an octamer by intermolecular Cys43-disulfide formation. We optimized the expression conditions of recombinant human TYMS using the Escherichia coli system. Using high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS), we have shown that purified TYMS has catalytic activity for producing dTMP. In the absence of reductant β-mercaptoethanol, SDS-PAGE and size exclusion chromatography (SEC) showed that the size of the TYMS protein is about 35 kDa, 70 kDa, and 280 kDa. When the Cys43 was mutated to Gly, the band of ~280 kDa and the peak of the octamer disappeared. Therefore, TYMS was determined to form an octamer, depending on the presence of Cys43-disulfide. By measuring steady-state parameters for the monomer, dimer, and octamer, we found the kcat of the octamer was increased slightly more than the monomer. On the basis of these findings, we suggest that the octamer in the active state might have a potential influence on the design of new drug targets.
Caffeic Acid Phenethyl Ester Induces N-myc Downstream Regulated Gene 1 to Inhibit Cell Proliferation and Invasion of Human Nasopharyngeal Cancer Cells
Authors: Chiang Kun-Chun , Yang Shih-Wei , Chang Kai-Ping , Feng Tsui-Hsia , Chang Kang-Shuo , Tsui Ke-Hung , Shin Yi-Syuan , Chen Chiu-Chun , Chao Mei , Juang Horng-Heng
Published: May 2018

Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis, is widely studied due to its anti-cancer effect. Nasopharyngeal carcinoma (NPC) is distinct from other head and neck carcinomas and has a high risk of distant metastases. N-myc downstream regulated gene 1 (NDRG1) is demonstrated as a tumor suppressor gene in several cancers. Our result showed that CAPE treatment could repress NPC cell growth, through induction of S phase cell cycle arrest, and invasion. CAPE treatment stimulated NDRG1 expression in NPC cells. NDRG1 knockdown increased NPC cell proliferation and invasion and rendered NPC cells less responsive to CAPE growth-inhibiting effect, indicating CAPE repressed NPC cell growth partly through NDRG1indcution. CAPE treatment increased phosphorylation of ERK, JNK, and p38 in a dose- and time-dependent manner. Pre-treatments by inhibitors of ERK (PD0325901), JNK (SP600125), or p38 (SB201290), respectively, all could partly inhibit the CAPE effect on NDRG1 induction in NPC cells. Further, STAT3 activity was also repressed by CAPE in NPC cells. In summary, CAPE attenuates NPC cell proliferation and invasion by upregulating NDRG1 expression via MAPK pathway and by inhibiting phosphorylation of STAT3. Considering the poor prognosis of NPC patients with metastasis, CAPE could be a promising agent against NPC.
High-Throughput Sequencing of microRNAs in Glucocorticoid Sensitive Paediatric Inflammatory Bowel Disease Patients
Authors: De Iudicibus Sara , Lucafò Marianna , Vitulo Nicola , Martelossi Stefano , Zimbello Rosanna , De Pascale Fabio , Forcato Claudio , Naviglio Samuele , Di Silvestre Alessia , Gerdol Marco , Stocco Gabriele , Valle Giorgio , Ventura Alessandro , Bramuzzo Matteo , Decorti Giuliana
Published: May 2018

The aim of this research was the identification of novel pharmacogenomic biomarkers for better understanding the complex gene regulation mechanisms underpinning glucocorticoid (GC) action in paediatric inflammatory bowel disease (IBD). This goal was achieved by evaluating high-throughput microRNA (miRNA) profiles during GC treatment, integrated with the assessment of expression changes in GC receptor (GR) heterocomplex genes. Furthermore, we tested the hypothesis that differentially expressed miRNAs could be directly regulated by GCs through investigating the presence of GC responsive elements (GREs) in their gene promoters. Ten IBD paediatric patients responding to GCs were enrolled. Peripheral blood was obtained at diagnosis (T0) and after four weeks of steroid treatment (T4). MicroRNA profiles were analyzed using next generation sequencing, and selected significantly differentially expressed miRNAs were validated by quantitative reverse transcription-polymerase chain reaction. In detail, 18 miRNAs were differentially expressed from T0 to T4, 16 of which were upregulated and 2 of which were downregulated. Out of these, three miRNAs (miR-144, miR-142, and miR-96) could putatively recognize the 3’UTR of the GR gene and three miRNAs (miR-363, miR-96, miR-142) contained GREs sequences, thereby potentially enabling direct regulation by the GR. In conclusion, we identified miRNAs differently expressed during GC treatment and miRNAs which could be directly regulated by GCs in blood cells of young IBD patients. These results could represent a first step towards their translation as pharmacogenomic biomarkers.
Human Macrophages Preferentially Infiltrate the Superficial Adipose Tissue
Authors: Cappellano Giuseppe , Morandi Evi M. , Rainer Johannes , Grubwieser Philipp , Heinz Katharina , Wolfram Dolores , Bernhard David , Lobenwein Susanne , Pierer Gerhard , Ploner Christian
Published: May 2018

Human abdominal subcutaneous adipose tissue consists of two individual layers—the superficial adipose tissue (SAT) and deep adipose tissue (DAT)—separated by the Scarpa’s fascia. The present study focuses on the analysis of morphological and immunological differences of primary adipocytes, adipose-derived stem cells (ASC), and tissue-infiltrating immune cells found in SAT and DAT. Adipocytes and stromal vascular fraction (SVF) cells were isolated from human SAT and DAT specimens and phenotypically characterized by in vitro assays. Ex vivo analysis of infiltrating immune cells was performed by flow cytometry. Primary adipocytes from SAT are larger in size but did not significantly differ in cytokine levels of LEPTIN, ADIPOQ, RBP4, CHEMERIN, DEFB1, VISFATIN, MCP1, or MSCF. ASC isolated from SAT proliferated faster and exhibited a higher differentiation potential than those isolated from DAT. Flow cytometry analysis indicated no specific differences in the relative numbers of ASC, epithelial progenitor cells (EPC), or CD3+ T-cells, but showed higher numbers of tissue-infiltrating macrophages in SAT compared to DAT. Our findings suggest that ASC isolated from SAT have a higher regenerative potential than DAT-ASC. Moreover, spatial proximity to skin microbiota might promote macrophage infiltration in SAT.
From Structure to Phenotype: Impact of Collagen Alterations on Human Health
Authors: Arseni Lavinia , Lombardi Anita , Orioli Donata
Published: May 2018

The extracellular matrix (ECM) is a highly dynamic and heterogeneous structure that plays multiple roles in living organisms. Its integrity and homeostasis are crucial for normal tissue development and organ physiology. Loss or alteration of ECM components turns towards a disease outcome. In this review, we provide a general overview of ECM components with a special focus on collagens, the most abundant and diverse ECM molecules. We discuss the different functions of the ECM including its impact on cell proliferation, migration and differentiation by highlighting the relevance of the bidirectional cross-talk between the matrix and surrounding cells. By systematically reviewing all the hereditary disorders associated to altered collagen structure or resulting in excessive collagen degradation, we point to the functional relevance of the collagen and therefore of the ECM elements for human health. Moreover, the large overlapping spectrum of clinical features of the collagen-related disorders makes in some cases the patient clinical diagnosis very difficult. A better understanding of ECM complexity and molecular mechanisms regulating the expression and functions of the various ECM elements will be fundamental to fully recognize the different clinical entities.
The Role of scaRNAs in Adjusting Alternative mRNA Splicing in Heart Development
Authors: Nagasawa Chloe , Ogren Allison , Kibiryeva Nataliya , Marshall Jennifer , O’Brien James , Kenmochi Naoya , Bittel Douglas
Published: May 2018

Congenital heart disease (CHD) is a leading cause of death in children <1 year of age. Despite intense effort in the last 10 years, most CHDs (~70%) still have an unknown etiology. Conotruncal based defects, such as Tetralogy of Fallot (TOF), a common complex of devastating heart defects, typically requires surgical intervention in the first year of life. We reported that the noncoding transcriptome in myocardial tissue from children with TOF is characterized by significant variation in levels of expression of noncoding RNAs, and more specifically, a significant reduction in 12 small cajal body-associated RNAs (scaRNAs) in the right ventricle. scaRNAs are essential for the biochemical modification and maturation of small nuclear RNAs (spliceosomal RNAs), which in turn are critical components of the spliceosome. This is particularly important because we also documented that splicing of mRNAs that are critical for heart development was dysregulated in the heart tissue of infants with TOF. Furthermore, we went on to show, using the zebrafish model, that altering the expression of these same scaRNAs led to faulty mRNA processing and heart defects in the developing embryo. This review will examine how scaRNAs may influence spliceosome fidelity in exon retention during heart development and thus contribute to regulation of heart development.
Preschoolers’ Technology-Assessed Physical Activity and Cognitive Function: A Cross-Sectional Study
Authors: Quan Minghui , Zhang Hanbin , Zhang Jiayi , Zhou Tang , Zhang Jinming , Zhao Guanggao , Fang Hui , Sun Shunli , Wang Ru , Chen Peijie
Published: May 2018

Early childhood is a critical period for development of cognitive function, but research on the association between physical activity and cognitive function in preschool children is limited and inconclusive. This study aimed to examine the association between technology-assessed physical activity and cognitive function in preschool children. A cross-sectional analysis of baseline data from the Physical Activity and Cognitive Development Study was conducted in Shanghai, China. Physical activity was measured with accelerometers for 7 consecutive days, and cognitive functions were assessed using the Chinese version of Wechsler Young Children Scale of Intelligence (C-WYCSI). Linear regression analyses were used to assess the association between physical activity and cognitive function. A total of 260 preschool children (boys, 144; girls, 116; mean age: 57.2 ± 5.4 months) were included in analyses for this study. After adjusting for confounding factors, we found that Verbal Intelligence Quotient, Performance Intelligence Quotient, and Full Intelligence Quotient were significantly correlated with light physical activity, not moderate to vigorous physical activity, in boys. Standardized coefficients were 0.211, 0.218, and 0.242 (all p < 0.05) in three different models, respectively. However, the correlation between physical activity and cognitive functions were not significant in girls (p > 0.05). These findings suggest that cognitive function is apparently associated with light physical activity in boys. Further studies are required to clarify the sex-specific effect on physical activity and cognitive functions.
Experimental and Modeling Study of Liquid-Assisted—Laser Beam Micromachining of Smart Ceramic Materials
Authors: Parmar Mayur , James Sagil
Published: May 2018

Smart ceramic materials are next generation materials with the inherent intelligence to adapt to change in the external environment. These materials are destined to play an essential role in several critical engineering applications. Machining these materials using traditional machining processes is a challenge. The laser beam micromachining (LBMM) process has the potential to machine such smart materials. However, laser machining when performed in air induces high thermal stress on the surface, often leading to crack formation, recast and re-deposition of ablated material, and large heat-affected zones (HAZ). Performing laser beam machining in the presence of a liquid medium could potentially resolve these issues. This research investigates the possibility of using a Liquid Assisted—Laser Beam Micromachining (LA-LBMM) process for micromachining smart ceramic materials. Experimental studies are performed to compare the machining quality of laser beam machining process in air and in a liquid medium. The study reveals that the presence of liquid medium helps in controlling the heat-affected zone and the taper angle of the cavity drilled, thereby enhancing the machining quality. Analytical modeling is developed for the prediction of HAZ and cavity diameter both in air and underwater conditions, and the model is capable of predicting the experimental results to within 10% error.
Prediction of Propeller-Induced Hull Pressure Fluctuations via a Potential-Based Method: Study of the Effects of Different Wake Alignment Methods and of the Rudder
Authors: Su Yiran , Kim Seungnam , Kinnas Spyros A.
Published: May 2018

In order to predict ship hull pressure fluctuations induced by marine propellers, a combination of several numerical schemes is used. The propeller perturbation flow is solved by the boundary element method (BEM), while the coupling between a BEM solver and a Reynolds-averaged Navier-Stokes (RANS) solver can efficiently predict the effective wake. Based on the BEM solution under the predicted effective wake, the propeller-induced potential on the ship hull can be evaluated. Then, a pressure-BEM solver is used to solve the diffraction pressure on the hull in order to obtain the solid boundary factor which leads to the total hull pressure. This paper briefly introduces the schemes and numerical models. To avoid numerical instability, several simplifications need to be made. The effects of these simplifications are studied, including the rudder effect and the wake alignment model effect.
Low-Cost IoT: A Holistic Approach
Authors: Ciuffoletti Augusto
Published: May 2018

The key factors for a successful smart-city project are its initial cost and its scalability. The initial cost depends on several inter-related aspects that cannot be designed and optimized separately. After the pilot deployment, scaling-up takes place only if the cost remains affordable: an initial financial support may induce dependencies from technologies that become unsustainable in the long period. In addition, the initial adoption of an emerging technology that fails to affirm may jeopardize investment return. This paper investigates a smart-village use case, the success of which strongly depends on the initial cost and scalability, exploring a low-cost way for Internet of Things (IoT). We propose a simple conceptual framework for cost evaluation, and we verify its effectiveness with an exhaustive use case: a prototype sensor designed and tested with its surrounding eco-system. Using experimental results, we can estimate both performance and cost for a pilot system made of fifty sensors deployed in an urban area. We show that such cost grows linearly with system size, taking advantage of widely adopted technologies. The code and the design of the prototype are available, so that all steps are reproducible.
Mineral Surface-Templated Self-Assembling Systems: Case Studies from Nanoscience and Surface Science towards Origins of Life Research
Authors: Gillams Richard J. , Jia Tony Z.
Published: May 2018

An increasing body of evidence relates the wide range of benefits mineral surfaces offer for the development of early living systems, including adsorption of small molecules from the aqueous phase, formation of monomeric subunits and their subsequent polymerization, and supramolecular assembly of biopolymers and other biomolecules. Each of these processes was likely a necessary stage in the emergence of life on Earth. Here, we compile evidence that templating and enhancement of prebiotically-relevant self-assembling systems by mineral surfaces offers a route to increased structural, functional, and/or chemical complexity. This increase in complexity could have been achieved by early living systems before the advent of evolvable systems and would not have required the generally energetically unfavorable formation of covalent bonds such as phosphodiester or peptide bonds. In this review we will focus on various case studies of prebiotically-relevant mineral-templated self-assembling systems, including supramolecular assemblies of peptides and nucleic acids, from nanoscience and surface science. These fields contain valuable information that is not yet fully being utilized by the origins of life and astrobiology research communities. Some of the self-assemblies that we present can promote the formation of new mineral surfaces, similar to biomineralization, which can then catalyze more essential prebiotic reactions; this could have resulted in a symbiotic feedback loop by which geology and primitive pre-living systems were closely linked to one another even before life’s origin. We hope that the ideas presented herein will seed some interesting discussions and new collaborations between nanoscience/surface science researchers and origins of life/astrobiology researchers.
Macro-Scale Strength and Microstructure of ZrW2O8 Cementitious Composites with Tunable Low Thermal Expansion
Authors: Ouyang Jianshu , Li Yangbo , Chen Bo , Huang Dahai
Published: May 2018

Concretes with engineered thermal expansion coefficients, capable of avoiding failure or irreversible destruction of structures or devices, are important for civil engineering applications, such as dams, bridges, and buildings. In natural materials, thermal expansion usually cannot be easily regulated and an extremely low thermal expansion coefficient (TEC) is still uncommon. Here we propose a novel cementitious composite, doped with ZrW2O8, showing a wide range of tunable thermal expansion coefficients, from 8.65 × 10−6 °C−1 to 2.48 × 10−6 °C−1. Macro-scale experiments are implemented to quantify the evolution of the thermal expansion coefficients, compressive and flexural strength over a wide range of temperature. Scanning Electron Microscope (SEM) imaging was conducted to quantify the specimens’ microstructural characteristics including pores ratio and size. It is shown that the TEC of the proposed composites depends on the proportion of ZrW2O8 and the ambient curing temperature. Macro-scale experimental results and microstructures have a good agreement. The TEC and strength gradually decrease as ZrW2O8 increases from 0% to 20%, subsequently fluctuates until 60%. The findings reported here provide a new routine to design cementitious composites with tunable thermal expansion for a wide range of engineering applications.
Experimentally Achievable Accuracy Using a Digital Image Correlation Technique in measuring Small-Magnitude (<0.1%) Homogeneous Strain Fields
Authors: Acciaioli Alice , Lionello Giacomo , Baleani Massimiliano
Published: May 2018

Measuring small-magnitude strain fields using a digital image correlation (DIC) technique is challenging, due to the noise-signal ratio in strain maps. Here, we determined the level of accuracy achievable in measuring small-magnitude (<0.1%) homogeneous strain fields. We investigated different sets of parameters for image processing and imaging pre-selection, based on single-image noise level. The trueness of DIC was assessed by comparison of Young’s modulus (E) and Poisson’s ratio (ν) with values obtained from strain gauge measurements. Repeatability was improved, on average, by 20–25% with experimentally-determined optimal parameters and image pre-selection. Despite this, the intra- and inter-specimen repeatability of strain gauge measurements was 5 and 2.5 times better than DIC, respectively. Moreover, although trueness was also improved, on average, by 30–45%, DIC consistently overestimated the two material parameters by 1.8% and 3.2% for E and ν, respectively. DIC is a suitable option to measure small-magnitude homogeneous strain fields, bearing in mind the limitations in achievable accuracy.
In Vitro Comparative Study of Oxygen Plasma Treated Poly(Lactic–Co–Glycolic) (PLGA) Membranes and Supported Nanostructured Oxides for Guided Bone Regeneration Processes
Authors: Torres-Lagares Daniel , Castellanos-Cosano Lizett , Serrera-Figallo Maria-Angeles , López-Santos Carmen , Barranco Angel , Rodríguez-González-Elipe Agustín , Gutierrez-Perez Jose-Luis
Published: May 2018

(1) Background: The use of physical barriers to prevent the invasion of gingival and connective tissue cells into bone cavities during the healing process is called guided bone regeneration. The objective of this in-vitro study was to compare the growth of human osteoblasts on Poly(Lactic–co–Glycolic) (PLGA) membranes modified with oxygen plasma and Hydroxyapatite (HA), silicon dioxide (SiO2), and titanium dioxide (TiO2) composite nanoparticles, respectively. (2) Methods: All the membranes received a common treatment with oxygen plasma and were subsequently treated with HA nanostructured coatings (n = 10), SiO2 (n = 10) and TiO2 (n = 10), respectively and a PLGA control membrane (n = 10). The assays were performed using the human osteoblast line MG-63 acquired from the Center for Scientific Instrumentation (CIC) from the University of Granada. The cell adhesion and the viability of the osteoblasts were analyzed by means of light-field microphotographs of each condition with the inverted microscope Axio Observer A1 (Carl Zeiss). For the determination of the mitochondrial energy balance, the MitoProbe™ JC-1 Assay Kit was employed. For the determination of cell growth and the morphology of adherent osteoblasts, two techniques were employed: staining with phalloidin-TRITC and staining with DAPI. (3) Results: The modified membranes that show osteoblasts with a morphology more similar to the control osteoblasts follow the order: PLGA/PO2/HA > PLGA/PO2/SiO2 > PLGA/PO2/TiO2 > PLGA (p < 0.05). When analysing the cell viability, a higher percentage of viable cells bound to the membranes was observed as follows: PLGA/PO2/SiO2 > PLGA/PO2/HA > PLGA/PO2/TiO2 > PLGA (p < 0.05), with a better energy balance of the cells adhered to the membranes PLGA/PO2/HA and PLGA/PO2/SiO2. (4) Conclusion: The membrane in which osteoblasts show characteristics more similar to the control osteoblasts is the PLGA/PO2/HA, followed by the PLGA/PO2/SiO2.
Prevention of Amyloid-Beta Oligomer-Induced Neuronal Death by EGTA, Estradiol, and Endocytosis Inhibitor
Authors: Čižas Paulius , Jekabsonė Aistė , Borutaitė Vilmantė , Morkūnienė Ramunė
Published: May 2018

Background and objective. Alzheimer’s disease is a progressive neurodegenerative disease that is biochemically characterized by the accumulation of amyloid beta (Aβ) peptides in the brain. The current hypothesis suggests that Aβ oligomers rather than fibrillar aggregates are the most toxic species of Aβ though the mechanisms of their neurotoxicity are unclear. The authors have previously shown that small Aβ1–42 oligomers at around 1 μM concentration caused rapid (in 24 h) neuronal death in cerebellar granule cell (CGC) cultures. In this study, we aimed to investigate whether protracted (up to 7 days) incubation of CGC cultures with lower submicromolar concentration of various aggregates of Aβ1–42 had an effect on viability of neurons. In order to get some insight into the mechanism of Aβ-induced cell death, we also sought to determine whether extracellular Ca2+ and process of endocytosis contributed to Aβ oligomer-induced neurotoxicity and whether pharmacological interventions into these processes would prevent Aβ oligomer-induced cell death. Material and Methods. Primary cultures of CGC were treated with various aggregate forms of Aβ1–42. Cell viability was assessed by fluorescent microscopy using propidium iodide and Hoechst 33342 staining. Results. Exposure of neurons to 500 nM Aβ1–42 oligomers for 72–168 h caused extensive neuronal necrosis. Lower concentrations (100–250 nM) were not toxic to cells during 7 days of incubation. Aβ1–42 monomers and fibrils had no effect on neuronal viability even after 7 days of incubation. Treatment of neurons with EGTA, steroid hormone 17β-estradiol, and methyl-β-cyclodextrin significantly reduced Aβ1-42 oligomers-induced neuronal death. Conclusions. The results show that submicromolar concentrations of Aβ1-42 oligomers were highly toxic to neurons during protracted incubation inducing neuronal necrosis that can be prevented by chelating extracellular Ca2+ with EGTA, inhibiting endocytosis with methyl-β-cyclodextrin, or by estradiol, which may protect against mitochondrial permeability transition pore opening.
Mikrosatelitų nestabilumas ir heterozigotiškumo praradimas sergant vėžiu
Authors: Didžiapetrienė Janina , Kanopienė Daiva , Valuckas Konstantinas , Uleckienė Saulė , Atkočius Vydmantas , Mickė Ingrida , Sužiedėlis Kęstutis
Published: May 2018

Straipsnyje pateikiami literatūros duomenys apie mikrosatelitų nestabilumą ir heterozigotiškumo praradimą sergant įvairių lokalizacijų vėžiu. Šie genetiniai pokyčiai yra svarbūs kancerogenezei. Mikrosatelitų nestabilumo ir heterozigotiškumo praradimas gali būti prognoziniu, o kai kuriais atvejais predikciniu žymeniu (rodyti atsaką į gydymą). Daugiausia duomenų yra apie mikrosatelitų nestabilumą sergant storosios žarnos vėžiu. Duomenys apie mikrosatelitų nestabilumą kitų lokalizacijų vėžio atvejais dar kaupiami, taigi, šia tema publikuojamų straipsnių skaičius auga.
Complexity, Coordination, and Health: Avoiding Pitfalls and Erroneous Interpretations in Fractal Analyses
Authors: Marmelat Vivien , Delignières Didier
Published: May 2018

Background and Objective. The analysis of fractal fluctuation has become very popular because of the close relationships between health, adaptability, and long-range correlations. 1/f noise is considered a “magical” threshold, characterizing optimal functioning, and a decrease or conversely and increase of serial correlations, with respect to 1/f noise, is supposed to sign a kind of disadaptation of the system. Empirical results, however, should be interpreted with caution. In experimental series, serial correlations often present a complex pattern, resulting from the combination of long-range and short-term correlated processes. We show, in the present paper, that an increase in serial correlations cannot be directly interpreted as an increase in long-range correlations. Material and Methods. Eleven participants performed four walking bouts following 4 individually determined velocities (slow, comfortable, high, and critical). Series of 512 stride intervals were collected under each condition. The strength of serial correlation was measured by the detrended fluctuation analysis. The effective presence of 1/f fluctuation was tested through ARFIMA modeling. Results. The strength of serial correlations tended to increase with walking velocity. However, the ARFIMA modeling showed that long-range correlations were significantly present only at slow and comfortable velocities. Conclusions. The strength of correlations, as measured by classical methods, cannot be considered as predictive of the genuine presence of long-range correlations. Sometimes systems can present the moderate levels of effective long-range correlations, whereas in others cases, series can present high correlation levels without being long-range correlated.
Skeletal Muscle-Derived Stem Cells: Implications for Cell-Mediated Therapies
Authors: Ūsas Arvydas , Mačiulaitis Justinas , Mačiulaitis Romaldas , Jakubonienė Neli , Milašius Arvydas , Huard Johnny
Published: May 2018

Current advances in stem cell research and innovative biological approaches in the field of tissue engineering and regenerative medicine could eventually translate into prospective clinical applications. Various adult organs and tissues harbor stem and progenitor cells that could potentially be used to repair, regenerate, and restore a variety of different tissues following acute injury or tissue destructive diseases. Skeletal muscle is a very convenient and plentiful source of somatic stem cells. It contains several distinct populations of myogenic stem cells including satellite cells that are mainly responsible for muscle growth and regeneration, and multipotent muscle-derived stem cells (MDSCs). Although both cell populations share some phenotypic similarities, MDSCs display a much greater differentiation potential in vitro and are capable of regenerating various tissues in vivo. Furthermore, these cells not only participate in the regeneration process by differentiating into tissue-specific cell types, but also promote endogenous tissue repair by secreting a multitude of trophic factors. In this article, we describe the biological aspects of MDSC isolation and characterization and provide an overview of potential therapeutic application of these cells for the treatment of cardiac and skeletal muscle injuries and diseases, urological dysfunction, and bone and cartilage defects. We also discuss major challenges and limitations currently faced by MDSC-based therapies that await resolution before these techniques can be applied clinically.
Effectiveness of the Second-Stage Rehabilitation in Stroke Patients With Cognitive Impairment
Authors: Milinavičienė Eglė , Rastenytė Daiva , Kriščiūnas Aleksandras
Published: May 2018

The aim of this study was to evaluate the recovery of functional status and effectiveness of the second-stage rehabilitation depending on the degree of cognitive impairment in stroke patients. Material and Methods. The study sample comprised 226 stroke patients at the Viršužiglis Hospital of Rehabilitation, Hospital of Lithuanian University of Health Sciences. Functional status was evaluated with the Functional Independence Measure, cognitive function with the Mini-Mental Status Examination scale, and severity of neurologic condition with the National Institutes of Health Stroke Scale. The patients were divided into 4 study groups based on cognitive impairment: severe, moderate, mild, or no impairment. Results. More than half (53%) of all cases were found to have cognitive impairment, while patients with different degree of cognitive impairment were equally distributed: mild impairment (18%), moderate impairment (17%), and severe impairment (18%). Improvement of functional status was observed in all study groups (P<0.001). In the patients with moderate and severe cognitive impairment, cognitive recovery was significantly more expressed than in other study groups (P<0.001). Insufficient recovery of functional status was significantly associated with hemiplegia (OR, 11.15; P=0.015), urinary incontinence (OR, 14.91; P<0.001), joint diseases (OR, 5.52; P=0.022), heart diseases (OR, 4.10; P=0.041), and severe cognitive impairment (OR, 15.18; P<0.001), while moderate and mild cognitive impairment was not associated with the recovery of functional status. Conclusions. During the second-stage rehabilitation of stroke patients, functional status as well as cognitive and motor skills were improved both in patients with and without cognitive impairment; however, the patients who were diagnosed with severe or moderate cognitive impairment at the beginning of second-stage rehabilitation showed worse neurological and functional status during the whole second-stage rehabilitation than the patients with mild or no cognitive impairment.
The Influence of Health Care Reforms on Work-Related Attitudes and Anxieties of Primary Care Physicians
Authors: Günvar Tolga , Kartal Mehtap , Toksun Aynur , Yemez Beyazıt , Güldal Dilek
Published: May 2018

Background and Objective. Reforming primary healthcare services has been the core agenda of health policies of the developing countries in accordance with the recommendations of the World Health Organization. In Turkey, the Transformation in Health Project brings along many changes in all aspects of primary health care services, such as organization and financing of services and employment of healthcare workers. The aim of this study was to determine the effects of health care reforms on primary care physicians working in Izmir. Material and Methods. A questionnaire and an anxiety scale were applied to a sample of primary care physicians in Izmir in 2007 and 2009. The questionnaire consisted of questions about demographic characteristics and expressions regarding the effect of reforms on physicians organized on a 7-point Likert scale. The State-Trait Anxiety Inventory was used as an anxiety scale. Results. The mean scores given by physicians working in family health centers were significantly higher than those of physicians working in public institutions. The score for “My responsibilities are well defined” statement given by physicians working in family health centers decreased significantly in the second survey. The necessity of reforms in the health care system and primary care health services was more significantly favored by physicians working in family health centers. Persistent anxiety of physicians working in community health centers was significantly higher in both surveys. Conclusions. Our study showed that health reforms had a substantial impact on work-related attitudes and anxieties of primary care physicians, and this effect was maintained over time.
Cloacal Exstrophy: A Case Report and Literature Review
Authors: Varygin Vitalij , Bernotas Šarūnas , Gurskas Pranas , Karmanovas Valerijus , Strupas Sigitas , Zimanaitė Olga , Verkauskas Gilvydas
Published: May 2018

Cloacal exstrophy is an extremely rare congenital malformation resulting in an exstrophy of the urinary, intestinal, and genital organs and associated with anomalies of other organ systems. We present a complicated case of cloacal exstrophy and the recent progress in the management of this probably most complicated anomaly in pediatric urology and surgery.
Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells
Authors: Mombeini Maryam , Saki Ghasem , Khorsandi Layasadat , Bavarsad Neda
Published: May 2018

Background and objective: Previous studies have demonstrated the anti-cancer effects of silymarin (SLM). However, the low bioavailability of SLM has restricted its use. This study investigated the toxic effect of nanostructured SLM encapsulated in micelles (Nano-SLM) on the growth of the HT-29 human colon cancer cell line. Materials and methods: HT-29 cells were treated with 25 μM/mL of SLM or Nano-SLM for 48 h. MTT and colony formation assays were used to assess the cytotoxicity and proliferation of HT-29 cells, respectively. The cells were stained with annexin V/PI for assessment of apoptosis. Results: MTT assays revealed that Nano-SLM treatment was able to exert a more pronounced toxic effect on the HT-29 cells as compared to free SLM treatment (p < 0.01). In the Nano-SLM-treated cells, colony numbers were significantly reduced in comparison to the free SLM-treated cells (p < 0.01). Apoptotic and necrotic indexes of Nano-SLM-treated HT-29 cells were also significantly increased in comparison to those of the free SLM-treated cells (p < 0.01). The viability, proliferation and apoptosis of healthy cells (NIH-3T3 cells) were not changed in response to Nano-SLM or SLM. Conclusions: Our results indicate that Nano-SLM enhances the anti-cancer effects of SLM against human colon cancer cells.
Prevalence and Risk Factors of Amblyopia among Refractive Errors in an Eastern European Population
Authors: Mocanu Valeria , Horhat Raluca
Published: May 2018

Background and objective: Amblyopia is the leading cause of visual impairment in children and adults and is very common during childhood. The aim of this study was to identify the prevalence and the risk factors of amblyopia in a pediatric population with refractive errors from an Eastern European country. Materials and methods: A total of 1231 children aged 5–16 years, who had refractive errors and were examined from January to August 2017, were enrolled in a cross-sectional population-based study. Every child underwent a complete ophthalmological exam. Amblyopia was defined as a visual acuity (VA) of less than 0.63. The study respected the Multi-Ethnic Pediatric Eye Disease Study (MEPEDS) criteria for defining amblyopia (MEPEDS, 2008). Parents participated in a face-to-face interview. The questionnaire contained details about their family history of amblyopia; the child’s maternal nutritional status in the preconception period; their history of maternal smoking or work in a toxic environment; the child’s birth, and the child’s history of congenital naso-lacrimal duct obstruction (CNLDO). Results: Amblyopia was identified in 2.8% of the participants. The ocular conditions hyperopia (p = 0.0079), astigmatism (p = 0.046), anisometropia (p < 0.001), esotropia (p < 0.001), exotropia (p = 0.0195), and CNLDO (p < 0.001), as well as a family history of amblyopia (p < 0.001), were associated with amblyopia. The non-ocular risk factors for amblyopia that were found in the study included low birth weight (p < 0.0009), prematurity (p < 0.001), an Apgar score under 7 (p = 0.0008), maternal age, maternal smoking history or work in toxic environment (p < 0.001), and maternal body mass index in the preconception period (p < 0.003). Conclusions: Some of the risk factors we identified for amblyopia are modifiable factors. This is an important observation as an adequate health education program can provide the relevant information for future mothers that will allow for a better management of the condition. We also wanted to highlight the need for amblyopia screening starting from the age of 3 years in case of significant parental refractive errors, strabismus, prematurity, and maternal risk factors.
Angiogenesis: Managing the Culprits behind Tumorigenesis and Metastasis
Authors: Yehya Ashwaq , Asif Muhammad , Petersen Sven , Subramaniam Ayappa , Kono Koji , Majid Amin , Oon Chern
Published: May 2018

Deregulated angiogenesis has been identified as a key contributor in a number of pathological conditions including cancer. It is a complex process, which involves highly regulated interaction of multiple signalling molecules. The pro-angiogenic signalling molecule, vascular endothelial growth factor (VEGF) and its cognate receptor 2 (VEGFR-2), which is often highly expressed in majority of human cancers, plays a central role in tumour angiogenesis. Owing to the importance of tumour vasculature in carcinogenesis, tumour blood vessels have emerged as an excellent therapeutic target. The anti-angiogenic therapies have been shown to arrest growth of solid tumours through multiple mechanisms, halting the expansion of tumour vasculature and transient normalization of tumour vasculature which help in the improvement of blood flow resulting in more uniform delivery of cytotoxic agents to the core of tumour mass. This also helps in reduction of hypoxia and interstitial pressure leading to reduced chemotherapy resistance and more uniform delivery of cytotoxic agents at the targeted site. Thus, complimentary combination of different agents that target multiple molecules in the angiogenic cascade may optimize inhibition of angiogenesis and improve clinical benefit in the cancer patients. This review provides an update on the current trend in exploitation of angiogenesis pathways as a strategy in the treatment of cancer.
An Effect of Culture Media on Epithelial Differentiation Markers in Breast Cancer Cell Lines MCF7, MDA-MB-436 and SkBr3
Authors: Pirsko Valdis , Cakstina Inese , Priedite Marta , Dortane Rasma , Feldmane Linda , Nakazawa-Miklasevica Miki , Daneberga Zanda , Gardovskis Janis , Miklasevics Edvins
Published: May 2018

Background and objectives: Cell culture is one of the mainstays in the research of breast cancer biology, although the extent to which this approach allows to preserve the original characteristics of originating tumor and implications of cell culture findings to real life situations have been widely debated in the literature. The aim of this study was to determine the role of three cell culture media on transcriptional expression of breast cancer markers in three breast cancer reference cell lines (MCF7, SkBr3 and MDA-MB-436). Materials and methods: Cell lines were conditioned in three studied media (all containing 5% fetal bovine serum (FBS) + hormones/growth factors; different composition of basal media) for four passages. Population growth was characterized by cumulative population doubling levels, average generation time, cell yield and viability at the fourth passage. Transcriptional expression of breast cancer differentiation markers and regulatory transcriptional programs was measured by qPCR. Results: Differences in the composition of growth media significantly influenced the growth of studied cell lines and the expression of mammary lineage governing transcriptional programs and luminal/basal markers. Effects of media on transcriptional expression were more pronounced in luminal cell lines (MCF7, SkBr3), than in the basal cell line (MDA-MB-436). Changes in growth media in terms of supplementation and basal medium delayed growth of cells, but improved cell yields. Conclusions: The expression of breast cancer cell differentiation phenotypic markers depends on the composition of cell growth medium, therefore cell culture as a tool in phenotypic studies should be used considering this effect. The findings of such studies should always be interpreted with caution. The formulation of cell growth media has greater effect on the expression of phenotypic markers in luminal, rather than basal cell lines. Media containing mitogens and higher vitamin content improved efficacy of cell culture in terms of cell yields, although greatly increased growth times.
Development of the Lithuanian Version of Sniffin’ Sticks 12 Odor Identification Test
Authors: Čičelienė Jolita , Vaičys Žygimantas , Rastenytė Daiva
Published: May 2018

Background: Evaluation of smell function is essential especially in cases of gradual deterioration, e.g., in neurodegenerative diseases, where rates of unawareness of the disorder are high and the importance of screening for olfactory dysfunction is increasing. To date, none of the tests for evaluation of olfactory dysfunction has been validated in Lithuania. The aim of the study was to develop a Lithuanian version of Sniffin’ Sticks 12 (SS12) odor identification test. Materials and Methods: The study was performed in 4 stages. The first stage included translation and back-translation from German, pilot group testing and language adaptation of the original SS12 test. In the second stage a survey group of 99 subjects was questioned for familiarity with the descriptors, used in the original version of the test. In the third stage after replacement of the least familiar distracters, a modified version of SS12 was created. Original and modified versions of SS12 were tested on 112 and 119 healthy subjects accordingly. The fourth stage of the study proved necessary as neither of the two SS12 versions turned out to be valid. After another round of replacement of the misleading distracters the second modified version of SS12 was created and it was tested on 115 healthy subjects. Results: Unsatisfactory correct identification rates of less than 75 percent in the same one item (lemon) were observed using both original and modified SS12 versions. With the second modification of distracters of SS12, identification of lemon increased significantly and overcame 75 percent. The decrease of SS12 scores in relation to age was ascertained in the study sample. Gender and smoking status did not prove to be independent predictors of SS12 scores in multiple linear regression analysis. Conclusion: The study presents an olfactory testing tool, which is adapted and modified culturally for use in the Lithuanian population.
Curcumin Effect on Copper Transport in HepG2 Cells
Authors: Berzina Anita , Martinsone Inese , Svirskis Simons , Murovska Modra , Kalis Martins
Published: May 2018

Background and Objective: In Wilson’s disease, copper metabolism is impaired due to defective copper transporting protein ATP7B, resulting in copper accumulation in liver and brain and causing damage to liver and brain tissues. Published data suggest that one of the possible treatments for Wilson’s disease is curcumin—a compound found in the root of Curcuma longa. In this study, we tested whether curcumin affects copper transport and excretion in HepG2 hepatocytes carrying wildtype ATP7B. Materials and Methods: We examined the impact of 5 µM and 25 µM curcumin on the transport of copper in HepG2 cells incubated with 20 µM and 100 µM CuCl2, as well as copper excretion from cells. First, immunofluorescent staining and co-localization analysis were carried out in HepG2 cells using confocal laser scanning microscope and Nikon NIS Elements software. Second, a concentration of copper extracted into cell culture medium was determined using atomic absorption spectrometry. Results: The analysis of the co-localization between Golgi complex and ATP7B revealed that both 5 µM and 25 µM doses of curcumin improve the ability of liver cells to transport copper to plasma membrane at 20 µM CuCl2, but not at 100 µM CuCl2 concentration. However, atomic absorption spectrometry showed that curcumin rather promotes copper absorption into liver cell line HepG2 than excretion of it. Conclusions: Curcumin accelerates the transport of copper within liver cells, but does not promote copper excretion from HepG2 cells.