bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Do Homeless Families Exit and Return the Homeless Shelter? Factors Affecting the Risk of Family Homelessness in Salt Lake County (Utah, United States) as a Case Study
Authors: Kim Keuntae , Garcia Ivis
Published: November 2019

Previous quantitative research on family homelessness has addressed a question of why some households become homeless. However, why some homeless families return the shelter to repeat their homelessness has not been explored well. This study aims at providing a comprehensive insight into the dynamics of homeless families by identifying the physical, social, and economic characteristics of a homeless family affecting the likelihood of their decision to stay, exit, and return the shelter. The relationships of factors with shelter exit and return were examined using Kaplan-Meier estimates of survival times and Cox Proportional Hazard regression analysis. This study employs a sample of 2348 historical records for 1462 homeless families registered to the Homeless Management Information System (HMIS) database between January 1, 2015 and December 31, 2017. The results indicate that structural factors such as subsidized housing program enrollment during a homeless episode and prior income play a significant role in reducing the risks of shelter exit and return rather than physical characteristics of a homeless family. Additionally, results show that variations in prior residence and exit destination of homeless families serve as factors determining the length of their shelter stay and the likelihood to return to the shelter. Integration of both shelter exit and return analysis results make policymakers and urban planners think about developing policies for coordination of housing and economic stability to address family homelessness.
Genomics of Particulate Matter Exposure Associated Cardiopulmonary Disease: A Narrative Review
Authors: Citron Julia , Willcocks Emma , Crowley George , Kwon Sophia , Nolan Anna
Published: November 2019

Particulate matter (PM) exposure is associated with the development of cardiopulmonary disease. Our group has studied the adverse health effects of World Trade Center particulate matter (WTC-PM) exposure on firefighters. To fully understand the complex interplay between exposure, organism, and resultant disease phenotype, it is vital to analyze the underlying role of genomics in mediating this relationship. A PubMed search was performed focused on environmental exposure, genomics, and cardiopulmonary disease. We included original research published within 10 years, on epigenetic modifications and specific genetic or allelic variants. The initial search resulted in 95 studies. We excluded manuscripts that focused on work-related chemicals, heavy metals and tobacco smoke as primary sources of exposure, as well as reviews, prenatal research, and secondary research studies. Seven full-text articles met pre-determined inclusion criteria, and were reviewed. The effects of air pollution were evaluated in terms of methylation (n = 3), oxidative stress (n = 2), and genetic variants (n = 2). There is evidence to suggest that genomics plays a meditating role in the formation of adverse cardiopulmonary symptoms and diseases that surface after exposure events. Genomic modifications and variations affect the association between environmental exposure and cardiopulmonary disease, but additional research is needed to further define this relationship.
Hand Preference and Performance in Basketball Tasks
Authors: Gualdi-Russo Emanuela , Rinaldo Natascia , Pasini Alba , Zaccagni Luciana
Published: November 2019

The aims of this study were to develop and validate an instrument to quantitatively assess the handedness of basketballers in basketball tasks (Basketball Handedness Inventory, BaHI) and to compare it with their handedness in daily activities by the Edinburgh Handedness Inventory (EHI). The participants were 111 basketballers and 40 controls. All subjects completed the EHI and only basketballers filled in the BaHI. To validate the BaHI, a voluntary subsample of basketballers repeated the BaHI. Exploratory and confirmatory factor analyses supported a two-factor model. Our results show that: (i) Handedness score (R) in daily actions did not differ between basketball players (R by EHI = 69.3 ± 44.6) and the control group (R by EHI = 64.5 ± 58.6); (ii) basketballers more frequently favored performing certain sport tasks with the left hand or mixed hands (as highlighted by R by BaHI = 50.1 ± 47.1), although their choice was primarily the right hand in everyday gestures; and (iii) this preference was especially true for athletes at the highest levels of performance (R by BaHI of A1 league = 38.6 ± 58.3) and for those playing in selected roles (point guard’s R = 29.4 ± 67.4). Our findings suggest that professional training induces handedness changes in basketball tasks. The BaHI provides a valid and reliable measure of the skilled hand in basketball. This will allow coaches to assess mastery of the ball according to the hand used by the athlete in the different tasks and roles.
Walking Green: Developing an Evidence Base for Nature Prescriptions
Authors: Koselka Elizabeth P.D. , Weidner Lucy C. , Minasov Arseniy , Berman Marc G. , Leonard William R. , Santoso Marianne V. , de Brito Junia N. , Pope Zachary C. , Pereira Mark A. , Horton Teresa H.
Published: November 2019

Although the health benefits of exercise and exposure to nature are well established, most evidence of their interaction comes from acute observations of single sessions of activity. However, documenting improved health outcomes requires ongoing interventions, measurement of multiple outcomes, and longitudinal analyses. We conducted a pilot study to guide the development of a protocol for future longitudinal studies that would assess multiple physiological and psychological outcomes. Herein, we report psychological outcomes measured from thirty-eight participants before and after three conditions: a 50 min walk on a forest path, a 50 min walk along a busy road, and a period of activities of daily living. Changes in positive and negative affect, anxiety, perceived stress, and working memory are reported. We benchmark these results to existing studies that used similar protocols and also identify elements of the protocol that might impair recruitment or retention of subjects in longer-term studies. Linear mixed-models regression revealed that walking improved psychological state when compared to activities of daily living, regardless of walk environment (p < 0.05). Comparison of mean differences showed that forest walks yielded the largest and most consistent improvements in psychological state. Thus, despite a protocol that required a 3.5 h time commitment per laboratory visit, the beneficial effects of walking and exposure to a forested environment were observed.
Effect of Sex on the Association Between Nonmedical Use of Opioids and Sleep Disturbance Among Chinese Adolescents: A Cross-Sectional Study
Authors: Xiao Di , Guo Lan , Zhao Meijun , Zhang Sheng , Li Wenyan , Zhang Wei-Hong , Lu Ciyong
Published: November 2019

Sleep disturbance and non-medical prescription opioid use (NMPOU) are currently growing public health concerns, and sex differences may result in differential exposure to frequency of NMPOU or sleep disturbance. This study aimed to explore the association between the frequency of lifetime or past-year NMPOU and sleep disturbance and to evaluate whether there was any sex difference in this association among Chinese adolescents. A cross-sectional study was performed in seven randomly selected Chinese provinces through the 2015 School-Based Chinese Adolescents Health Survey. A total of 159,640 adolescents were invited to participate and among them, 148,687 adolescents’ questionnaires were completed and qualified for this study (response rate: 93.14%). All analyses were performed for boys and girls separately. There were significant sex differences in the prevalence of lifetime or past-year opioid misuse and sleep disturbance (p < 0.05). Among girls, frequent lifetime NMPOU (adjusted odds ratio [aOR] = 2.09, 95% CI = 1.80–2.44) and past-year NMPOU (aOR = 2.16, 95% CI = 1.68–2.77) were positively associated with sleep disturbance. Among boys, these associations were also statistically significant, while the magnitudes of associations between frequent lifetime NMPOU or past-year NMPOU and sleep disturbance were greater in girls than those in boys. There is a significant sex difference in the prevalence of lifetime or past-year NMPOU and sleep disturbance. Furthermore, exposure to more frequent lifetime or past-year NMPOU is associated with a greater risk of sleep disturbance, especially among girls. Taking into account the sex difference for lifetime or past-year NMPOU may help to decrease the risk of sleep disturbance.
Influence of Adjacent Teeth Absence or Extraction on the Outcome of Non-Surgical Periodontal Therapy
Authors: Lin Jia-Hong , Tu Che-Chang , Chen Yi-Wen , Wang Chen-Ying , Liu Cheing-Meei , Kuo Mark Yen-Ping , Chang Po-Chun
Published: November 2019

Background: Extraction of periodontally compromised or strategically non-important teeth is often an integral part of non-surgical periodontal treatment (NSPT). This study evaluated the association between the status of adjacent teeth and the outcome of NSPT on molars. Methods: Charting data of patients with generalized chronic periodontitis receiving NSPT in 2012–2014 were included. The association between initial clinical parameters and significant clinical improvement, including the reductions of probing pocket depth (PPD) and clinical attachment loss (CAL), in molar teeth with severe periodontitis after NSPT was assessed by a generalized linear model and logistic regression. Results: ≥7 mm PPD and <2 mm gingival recession (REC) at the tooth level, and ≥7 mm PPD, ≥7 mm CAL and <2 mm REC at the site level, were associated with significant clinical improvement. Absence or extraction of an adjacent tooth achieved an additional 0.22–0.23 mm and 0.60–0.83 mm clinical improvement. Among the interproximal sites, ≥7 mm PPD, <2 mm REC, ≥7 mm CAL, <Degree II furcation involvement, and absence of an adjacent tooth were associated with significant clinical improvement. Conclusion: Absence or extraction of teeth during NSPT significantly improves the PPD and CAL of the adjacent periodontal sites of molars.
Analysis of the Effect of Backpack Design with Reduced Load Moment Arm on Spinal Alignment
Authors: Kim Kyung-hun , Ann Jihyeon , Jang Sang-hun
Published: November 2019

In this study, we designed a backpack that can reduce the moment arm of backpack load by placing the center of gravity of the backpack close to the axis of the spine. In order to investigate the effect of sagittal spinal alignment compared with the general backpack, we conducted the study using radiological images. The participants in this study were 18 adults (8 males and 10 females). The subjects participated in the experiment without carrying the backpack, wearing the normal backpack, and wearing a backpack designed to reduce the load moment arm by placing the center of gravity close to the body. Spinal alignment parameters were measured and analyzed using 3D radiography measurement software based on radiographic images taken under three conditions. The overall angle of lumbar lordosis, upper arc, lower arc, difference between pelvic incidence and lumbar lordosis, lower cervical lordosis, and sagittal vertical axis were measured. In the case of wearing the backpack rather than without the backpack, there was a significant difference in the overall angle of lumbar lordosis, lower arc, lower cervical spine angle, difference between pelvic incidence and lumbar lordosis, and sagittal vertical axis. In the case of wearing the backpack with reduced moment arm, the overall angle and lower arc of lumbar lordosis were significantly increased compared to those with the normal backpack. The difference between pelvic incidence and lumbar lordosis was significantly decreased. The results showed that a normal backpack caused imbalance of sagittal spinal alignment, and the backpack reducing the load moment arm by placing the backpack’s center of gravity close to the vertebral joint played a positive role in reducing the change of lumbar alignment compared with the normal backpack.
Construction and Verification of a High-Precision Base Map for an Autonomous Vehicle Monitoring System
Authors: Ham Sungil , Im Junhyuck , Kim Minjun , Cho Kuk
Published: November 2019

For autonomous driving, a control system that supports precise road maps is required to monitor the operation status of autonomous vehicles in the research stage. Such a system is also required for research related to automobile engineering, sensors, and artificial intelligence. The design of Google Maps and other map services is limited to the provision of map support at 20 levels of high-resolution precision. An ideal map should include information on roads, autonomous vehicles, and Internet of Things (IOT) facilities that support autonomous driving. The aim of this study was to design a map suitable for the control of autonomous vehicles in Gyeonggi Province in Korea. This work was part of the project “Building a Testbed for Pilot Operations of Autonomous Vehicles”. The map design scheme was redesigned for an autonomous vehicle control system based on the “Easy Map” developed by the National Geography Center, which provides free design schema. In addition, a vector-based precision map, including roads, sidewalks, and road markings, was produced to provide content suitable for 20 levels. A hybrid map that combines the vector layer of the road and an unmanned aerial vehicle (UAV) orthographic map was designed to facilitate vehicle identification. A control system that can display vehicle and sensor information based on the designed map was developed, and an environment to monitor the operation of autonomous vehicles was established. Finally, the high-precision map was verified through an accuracy test and driving data from autonomous vehicles.
The Effect of NDVI Time Series Density Derived from Spatiotemporal Fusion of Multisource Remote Sensing Data on Crop Classification Accuracy
Authors: Sun Rui , Chen Shaohui , Su Hongbo , Mi Chunrong , Jin Ning
Published: November 2019

Remote sensing data with high spatial and temporal resolutions can help to improve the accuracy of the estimation of crop planting acreage, and contribute to the formulation and management of agricultural policies. Therefore, it is important to determine whether multisource sensors can obtain high spatial and temporal resolution remote sensing data for the target sensor with the help of the spatiotemporal fusion method. In this study, we employed three different sensor datasets to obtain one normalized difference vegetation index (NDVI) time series dataset with a 5.8-m spatial resolution using a spatial and temporal adaptive reflectance fusion model (STARFM). We studied the effectiveness of using multisource remote sensing data to extract crop classifications and analyzed whether the increase in the NDVI time series density could significantly improve the accuracy of the crop classification. The results indicated that multisource sensor data could be used for crop classification after spatiotemporal fusion and that the data source was not limited by the sensor platform. With the increase in the number of NDVI phases, the classification accuracy of the support vector machine (SVM) and the random forest (RF) classifier gradually improved. If the added NDVI phases were not in the optimal time period for wheat recognition, the classification accuracy was not greatly improved. Under the same conditions, the classification accuracy of the RF classifier was higher than that of the SVM. In addition, this study can serve as a good reference for the selection of the optimal time range for base image pairs in the spatiotemporal fusion method for high accuracy mapping of crops, and help avoid excessive data collection and processing.
Utilizing BIM and GIS for Representation and Visualization of 3D Cadastre
Authors: Sun Jing , Mi Siying , Olsson Per-ola , Paulsson Jenny , Harrie Lars
Published: November 2019

The current three-dimensionally (3D) delimited property units are in most countries registered using two-dimensional (2D) documentation and textual descriptions. This approach has limitations if used for representing the actual extent of complicated 3D property units, in particular in city centers. 3D digital models such as building information model (BIM) and 3D geographic information system (GIS) could be utilized for accurate identification of property units, better representation of cadastral boundaries, and detailed visualization of complex buildings. To facilitate this, several requirements need to be identified considering organizational, legal, and technical aspects. In this study, we formulate these requirements and then develop a framework for integration of 3D cadastre and 3D digital models. The aim of this paper is that cadastral information stored based on the land administration domain model (LADM) are integrated with BIM on building level for accurate representation of legal boundaries and with GIS on city level for visualization of 3D cadastre in urban environments. The framework is implemented and evaluated against the requirements in a practical case study in Sweden. The conclusion is that the integration of the cadastral information and BIM/GIS is possible on both conceptual level and data level which will facilitate that organizations dealing with cadastral information (cadastral units), BIM models (architecture, engineering, and construction companies), and GIS (surveying units on e.g., municipality level) can exchange information; this facilitates better representation and visualization of 3D cadastral boundaries.
Numerical Study of Bubble Breakup in Fractal Tree-Shaped Microchannels
Authors: Zhang Chengbin , Zhang Xuan , Li Qianwen , Wu Liangyu
Published: November 2019

Hydrodynamic behaviors of bubble stream flow in fractal tree-shaped microchannels is investigated numerically based on a two-dimensional volume of fluid (VOF) method. Bubble breakup is examined in each level of bifurcation and the transition of breakup regimes is discussed in particular. The pressure variations at the center of different levels of bifurcations are analyzed in an effort to gain further insight into the underlying mechanism of bubble breakup affected by multi-levels of bifurcations in tree-shaped microchannel. The results indicate that due to the structure of the fractal tree-shaped microchannel, both lengths of bubbles and local capillary numbers decrease along the microchannel under a constant inlet capillary number. Hence the transition from the obstructed breakup and obstructed-tunnel combined breakup to coalescence breakup is observed when the bubbles are flowing into a higher level of bifurcations. Compared with the breakup of the bubbles in the higher level of bifurcations, the behaviors of bubbles show stronger periodicity in the lower level of bifurcations. Perturbations grow and magnify along the flow direction and the flow field becomes more chaotic at higher level of bifurcations. Besides, the feedback from the unequal downstream pressure to the upstream lower level of bifurcations affects the bubble breakup and enhances the upstream asymmetrical behaviors.
First Insights on the Presence of the Unfolded Protein Response in Human Spermatozoa
Authors: Santiago Joana , Silva Joana Vieira , Fardilha Margarida
Published: November 2019

The unfolded protein response (UPR) is involved in protein quality control and is activated in response to several stressors. Although in testis the UPR mechanisms are well described, their presence in spermatozoa is contentious. We aimed to investigate the presence of UPR-related proteins in human sperm and the impact of oxidative stress induction in UPR activation. To identify UPR-related proteins in human sperm, a bioinformatic approach was adopted. To explore the activation of UPR, sperm were exposed to hydrogen peroxide (H2O2) and motility, vitality, and the levels of UPR-related proteins were assessed. We identified 97 UPR-related proteins in human sperm and showed, for the first time, the presence of HSF1, GADD34, and phosphorylated eIF2α. Additionally, the exposure of human sperm to H2O2 resulted in a significant decrease in sperm viability and motility and an increase in the levels of HSF1, HSP90, HSP60, HSP27, and eIF2α; all proteins involved in sensing and response to unfolded proteins. This study gave us a first insight into the presence of UPR mechanisms in the male gamete. However, the belief that sperm are devoid of transcription and translation highlight the need to clarify if these pathways are activated in sperm in the same way as in somatic cells.
Irrigation-Induced Changes in Chemical Composition and Quality of Seeds of Yellow Lupine (Lupinus luteus L.)
Authors: Polit Justyna , Ciereszko Iwona , Dubis Alina , Leśniewska Joanna , Basa Anna , Winnicki Konrad , Żabka Aneta , Audzei Marharyta , Sobiech Łukasz , Faligowska Agnieszka , Skrzypczak Grzegorz , Maszewski Janusz
Published: November 2019

The quality and amount of yellow lupine yield depend on water availability. Water scarcity negatively affects germination, flowering, and pod formation, and thus introduction of an artificial irrigation system is needed. The aim of this study was to evaluate the influence of irrigation on the quality of yellow lupine seeds. Raining was applied with a semi-solid device with sprinklers during periods of greatest water demand. It was shown that watered plants produced seeds of lesser quality, having smaller size and weight. To find out why seeds of irrigated plants were of poor quality, interdisciplinary research at the cellular level was carried out. DNA cytophotometry evidenced the presence of nuclei with lower polyploidy in the apical zone of mature seeds. This may lead to formation of smaller cells and reduce depositing of storage materials. The electrophoretic and Fourier transform infrared spectroscopic analyses revealed differences in protein and cuticular wax profiles, while scanning electron microscopy and energy dispersive spectroscopy revealed, among various chemical elements, decreased calcium content in one of seed zones (near plumule). Seeds from irrigated plants showed slightly higher germination dynamics but growth rate of seedlings was slightly lower. The studies showed that irrigation of lupine affected seed features and their chemical composition, an ability to germination and seedlings growth.
RETRACTED: AEG-1/miR-221 Axis Cooperatively Regulates the Progression of Hepatocellular Carcinoma by Targeting PTEN/PI3K/AKT Signaling Pathway
Authors: Kannan Maheshkumar , Jayamohan Sridharan , Moorthy Rajesh , Chabattula Siva , Ganeshan Mathan , Arockiam Antony
Published: November 2019

Hepatocellular carcinoma (HCC) is the third leading malignancy worldwide, causing mortality in children and adults. AEG-1 is functioned as a scaffold protein for the proper assembly of RNA-induced silencing complex (RISC) to optimize or increase its activity. The increased activity of oncogenic miRNAs leads to the degradation of target tumor suppressor genes. miR-221 is an oncogenic miRNA, that plays a seminal role in carcinogenesis regulation of HCC. However, the molecular mechanism and biological functions of the miR-221/AEG-1 axis have not been investigated extensively in HCC. Here, the expression of miR-221/AEG-1 and their target/associate genes was analyzed by qRT-PCR and Western blot. The role of the miR-221/AEG-1 axis in HCC was evaluated by proliferation assay, migration assay, invasion assay, and flow cytometry analysis. The expression level of miR-221 decreased in AEG-1 siRNA transfected HCC cells. On the other hand, there were no significant expression changes of AEG-1 in miR-221 mimic and miR-221 inhibitor transfected HCC cells and inhibition of miR-221/AEG-1 axis decreased cell proliferation, invasion, migration, and angiogenesis and induced apoptosis, cell cycle arrest by upregulating p57, p53, PTEN, and RB and downregulating LSF, MMP9, OPN, Bcl-2, PI3K, AKT, and LC3A in HCC cells. Furthermore, these findings suggest that the miR-221/AEG-1 axis plays a seminal oncogenic role by modulating PTEN/PI3K/AKT signaling pathway in HCC. In conclusion, the miR-221/AEG-1 axis may serve as a potential target for therapeutics, diagnostics, and prognostics of HCC.
Transcriptome Analysis Implicates Involvement of Long Noncoding RNAs in Cytoplasmic Male Sterility and Fertility Restoration in Cotton
Authors: Zhang Bingbing , Zhang Xuexian , Zhang Meng , Guo Liping , Qi Tingxiang , Wang Hailin , Tang Huini , Qiao Xiuqin , Shahzad Kashif , Xing Chaozhu , Wu Jianyong
Published: November 2019

The cytoplasmic male sterility (CMS)/restorer-of-fertility system is an important tool to exploit heterosis during commercially hybrid seed production. The importance of long noncoding RNAs (lncRNAs) in plant development is recognized, but few analyses of lncRNAs during anther development of three-line hybrid cotton (CMS-D2 line A, maintainer line B, restorer-of-fertility line R) have been reported. Here, we performed transcriptome sequencing during anther development in three-line hybrid cotton. A total of 80,695 lncRNAs were identified, in which 43,347 and 44,739 lncRNAs were differentially expressed in A–B and A–R comparisons, respectively. These lncRNAs represent functional candidates involved in CMS and fertility restoration. GO analysis indicated that cellular hormone metabolic processes and oxidation–reduction reaction processes might be involved in CMS, and cellular component morphogenesis and small molecular biosynthetic processes might participate in fertility restoration. Additionally, 63 lncRNAs were identified as putative precursors of 35 miRNAs, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed a similar expression pattern to RNA-seq data. Furthermore, construction of lncRNA regulatory networks indicated that several miRNA–lncRNA–mRNA networks might be involved in CMS and fertility restoration. Our findings provide systematic identification of lncRNAs during anther development and lays a solid foundation for the regulatory mechanisms and utilization in hybrid cotton breeding.
Impaired Expression of Ectonucleotidases in Ectopic and Eutopic Endometrial Tissue Is in Favor of ATP Accumulation in the Tissue Microenvironment in Endometriosis
Authors: Trapero Carla , Vidal August , Fernández-Montolí Maria Eulàlia , Coroleu Buenaventura , Tresserra Francesc , Barri Pere , Gómez de Aranda Inmaculada , Sévigny Jean , Ponce Jordi , Matias-Guiu Xavier , Martín-Satué Mireia
Published: November 2019

Endometriosis is a prevalent disease defined by the presence of endometrial tissue outside the uterus. Adenosine triphosphate (ATP), as a proinflammatory molecule, promotes and helps maintain the inflammatory state of endometriosis. Moreover, ATP has a direct influence on the two main symptoms of endometriosis: infertility and pain. Purinergic signaling, the group of biological responses to extracellular nucleotides such as ATP and nucleosides such as adenosine, is involved in the biology of reproduction and is impaired in pathologies with an inflammatory component such as endometriosis. We have previously demonstrated that ectonucleotidases, the enzymes regulating extracellular ATP levels, are active in non-pathological endometria, with hormone-dependent changes in expression throughout the cycle. In the present study we have focused on the expression of ectonucleotidases by means of immunohistochemistry and in situ activity in eutopic and ectopic endometrial tissue of women with endometriosis, and we compared the results with endometria of women without the disease. We have demonstrated that the axis CD39-CD73 is altered in endometriosis, with loss of CD39 and CD73 expression in deep infiltrating endometriosis, the most severe, and most recurring, endometriosis subtype. Our results indicate that this altered expression of ectonucleotidases in endometriosis boosts ATP accumulation in the tissue microenvironment. An important finding is the identification of the nucleotide pyrophophatase/phosphodiesterase 3 (NPP3) as a new histopathological marker of the disease since we have demonstrated its expression in the stroma only in endometriosis, in both eutopic and ectopic tissue. Therefore, targeting the proteins directly involved in ATP breakdown could be an appropriate approach to consider in the treatment of endometriosis.
Curcumin Ameliorates Benzo[a]pyrene-Induced DNA Damages in Stomach Tissues of Sprague-Dawley Rats
Authors: Kim Kyeong Seok , Kim Na Yoon , Son Ji Yeon , Park Jae Hyeon , Lee Su Hyun , Kim Hae Ri , Kim Boomin , Kim Yoon Gyoon , Jeong Hye Gwang , Lee Byung Mu , Kim Hyung Sik
Published: November 2019

Benzo[a]pyrene (BaP) is a well-known carcinogen formed during the cooking process. Although BaP exposure has been implicated as one of the risk factors for lung cancer in animals and humans, there are only limited data on BaP-induced gastrointestinal cancer. Therefore, this study investigated the protective effects of curcumin on BaP-induced DNA damage in rat stomach tissues. BaP (20 mg/kg/day) and curcumin (50, 100, or 200 mg/kg) were administered daily to Sprague-Dawley rats by oral gavage over 30 days. Curcumin was pre-administered before BaP exposure. All rats were euthanized, and liver, kidney, and stomach tissues were removed at 24 h after the last treatment. We observed that aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose levels were significantly reduced in rats treated with high dose co-administration of curcumin (200 mg/kg) compared to BaP alone. The expression levels of cytochrome P450 (CYP) 1A1 and CYP1B1 were significantly increased in the liver of rats treated with BaP. However, co-administration of curcumin (200 mg/kg) with BaP markedly reduced CYP1A1 expression in a dose-dependent manner. Furthermore, plasma levels of BaP-diolepoxide (BPDE) and BaP metabolites were significantly reduced by co-administration of curcumin (200 mg/kg). Additionally, co-administration of curcumin (200 mg/kg) with BaP significantly reduced the formation of BPDE-I-DNA and 8-hydroxydeoxy guanosine (8-OHdG) adducts in the liver, kidney, and stomach tissues. The inhibition of these adduct formations were more prominent in the stomach tissues than in the liver. Overall, our observations suggest that curcumin might inhibit BaP-induced gastrointestinal tumorigenesis and shows promise as a chemopreventive agent.
Farnesiferol C Induces Apoptosis in Chronic Myelogenous Leukemia Cells as an Imatinib Sensitizer via Caspase Activation and HDAC (Histone Deacetylase) Inactivation
Authors: Jung Ji Hoon , Park Ji Eon , Sim Deok Yong , Im Eunji , Park Woon Yi , Lee Duckgue , Shim Bum-Sang , Kim Sung-Hoon
Published: November 2019

Herein the underlying apoptotic mechanism of Farnesiferol C (FC) derived from Ferula assafoetida was elucidated in chronic myelogenous leukemia (CML) K562 and KBM5 cells. FC showed significant cytotoxicity in K562 and KBM5 cells, more so than in U937 and UL-60 acute myeloid leukemia (AML) cells. Cleaved PARP and caspase 9/3 attenuated the expression of Bcl2 and induced G1 arrest in K562 and KBM5 cells. Also, FC effectively abrogated the expression of cell cycle related proteins, such as: Cyclin D1, Cyclin E, Cyclin B1 in K562, and KBM5 cells, but caspase 3 inhibitor Z-DEVD-FMK rescued the cleavages of caspase 3 and PARP induced by FC in K562 cells. Of note, FC decreased histone deacetylase 1 (HDAC1) and HDAC2, and enhanced histone H3 acetylation K18 (Ac-H3K18) in K562 and KBM5 cells. Furthermore, combination of FC and Imatinib enhanced the apoptotic effect of Imatinib as a potent Imatinib sensitizer in K562 cells. Overall, our findings provide scientific evidence that inactivation of HDAC and caspase activation mediate FC induced apoptosis in CML cells.
Efficacy and Safety of Pemafibrate, a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα): Pooled Analysis of Phase 2 and 3 Studies in Dyslipidemic Patients with or without Statin Combination
Authors: Yamashita Shizuya , Arai Hidenori , Yokote Koutaro , Araki Eiichi , Matsushita Mitsunori , Nojima Toshiaki , Suganami Hideki , Ishibashi Shun
Published: November 2019

Hypertriglyceridemia has emerged as an independent risk factor for cardiovascular events, despite low-density lipoprotein-cholesterol (LDL-C) well-controlled with statins. We pooled data from the first 12 weeks of six randomized double-blind placebo-controlled studies of pemafibrate in Japan and investigated its efficacy and safety with and without statins, particularly focusing on patients with renal dysfunction. Subjects were 1253 patients (677 in the “with-statin” group and 576 in the “without-statin” group). At Week 12 (last observation carried forward), triglyceride (TG) was significantly reduced at all pemafibrate doses (0.1, 0.2, and 0.4 mg/day), both with and without statin, compared to placebo (p < 0.001 vs. placebo for all groups). In the “with-statin” group, the estimated percent change from baseline was −2.0% for placebo and −45.1%, −48.5%, and −50.0%, respectively, for the pemafibrate groups. Findings for both groups showed significant decreases in TG-rich lipoproteins and atherogenic lipid parameters compared to placebo. The incidence of adverse events was similar between the pemafibrate and placebo groups and was also similar for patients with and without renal dysfunction in the “with-statin” group. Pemafibrate lowered TG and improved atherogenic dyslipidemia without a significant increase in adverse events in comparison to the placebo, even among “with-statin” patients who had renal dysfunction.
MicroRNAs as Potential Biomarkers in Atherosclerosis
Authors: Churov Alexey , Summerhill Volha , Grechko Andrey , Orekhova Varvara , Orekhov Alexander
Published: November 2019

Atherosclerosis is a complex multifactorial disease that, despite advances in lifestyle management and drug therapy, remains to be the major cause of high morbidity and mortality rates from cardiovascular diseases (CVDs) in industrialized countries. Therefore, there is a great need in reliable diagnostic/prognostic biomarkers and effective treatment alternatives to reduce its burden. It was established that microRNAs (miRNAs/miRs), a class of non-coding single-stranded RNA molecules, can regulate the expression of genes at the post-transcriptional level and, accordingly, coordinate the cellular protein expression. Thus, they are involved not only in cell-specific physiological functions but also in the cellular and molecular mechanisms of human pathologies, including atherosclerosis. MiRNAs may be significant in the dysregulation that affects endothelial integrity, the function of vascular smooth muscle and inflammatory cells, and cellular cholesterol homeostasis that drives the initiation and growth of an atherosclerotic plaque. Besides, distinct expression patterns of several miRNAs are attributed to atherosclerotic and cardiovascular patients. In this article, the evidence indicating the multiple critical roles of miRNAs and their relevant molecular mechanisms related to atherosclerosis development and progression was reviewed. Moreover, the effects of miRNAs on atherosclerosis enabled to exploit them as novel diagnostic biomarkers and therapeutic targets that may lead to better management of atherosclerosis and CVDs.
Wnt Signaling and Biological Therapy in Rheumatoid Arthritis and Spondyloarthritis
Authors: Cici Daniela , Corrado Addolorata , Rotondo Cinzia , Cantatore Francesco P.
Published: November 2019

The Wnt signaling pathway plays a key role in several biological processes, such as cellular proliferation and tissue regeneration, and its dysregulation is involved in the pathogenesis of many autoimmune diseases. Several evidences support its role especially in bone complications of rheumatic diseases. In Rheumatoid Arthritis (RA), the Wnt signaling is implicated in systemic and localized bone loss, while available data of its role in Spondyloarthritis (SpA) are conflicting. In the last few decades, the quality of life of rheumatic patients has been dramatically improved by biological therapy, targeting cytokines involved in the pathogenesis of these diseases like tumor necrosis factor (TNF)α, interleukin (IL)-1, IL-6, IL-17. In this review, we reviewed the role of Wnt signaling in RA and SpA, focusing on the effect of biological therapy on this pathway and its possible clinical implications.
Degradation of High Energy Materials Using Biological Reduction: A Rational Way to Reach Bioremediation
Authors: Aguero Stephanie , Terreux Raphaël
Published: November 2019

Explosives molecules have been widely used since World War II, leading to considerable contamination of soil and groundwater. Recently, bioremediation has emerged as an environmentally friendly approach to solve such contamination issues. However, the 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) explosive, which has very low solubility in water, does not provide satisfying results with this approach. In this study, we used a rational design strategy for improving the specificity of the nitroreductase from E. Cloacae (PDB ID 5J8G) toward HMX. We used the Coupled Moves algorithm from Rosetta to redesign the active site around HMX. Molecular Dynamics (MD) simulations and affinity calculations allowed us to study the newly designed protein. Five mutations were performed. The designed nitroreductase has a better fit with HMX. We observed more H-bonds, which productively stabilized the HMX molecule for the mutant than for the wild type enzyme. Thus, HMX’s nitro groups are close enough to the reductive cofactor to enable a hydride transfer. Also, the HMX affinity for the designed enzyme is better than for the wild type. These results are encouraging. However, the total reduction reaction implies numerous HMX derivatives, and each of them has to be tested to check how far the reaction can’ go.
Identification of Novel 1,3,5-Triphenylbenzene Derivative Compounds as Inhibitors of Hen Lysozyme Amyloid Fibril Formation
Authors: Ramshini Hassan , Tayebee Reza , Bigi Alessandra , Bemporad Francesco , Cecchi Cristina , Chiti Fabrizio
Published: November 2019

Deposition of soluble proteins as insoluble amyloid fibrils is associated with a number of pathological states. There is a growing interest in the identification of small molecules that can prevent proteins from undergoing amyloid fibril formation. In the present study, a series of small aromatic compounds with different substitutions of 1,3,5-triphenylbenzene have been synthesized and their possible effects on amyloid fibril formation by hen egg white lysozyme (HEWL), a model protein for amyloid formation, and of their resulting toxicity were examined. The inhibitory effect of the compounds against HEWL amyloid formation was analyzed using thioflavin T and Congo red binding assays, atomic force microscopy, Fourier-transform infrared spectroscopy, and cytotoxicity assays, such as the 3-(4,5-Dimethylthiazol)-2,5-Diphenyltetrazolium Bromide (MTT) reduction assay and caspase-3 activity measurements. We found that all compounds in our screen were efficient inhibitors of HEWL fibril formation and their associated toxicity. We showed that electron-withdrawing substituents such as –F and –NO2 potentiated the inhibitory potential of 1,3,5-triphenylbenzene, whereas electron-donating groups such as –OH, –OCH3, and –CH3 lowered it. These results may ultimately find applications in the development of potential inhibitors against amyloid fibril formation and its biologically adverse effects.
Anti-Cancer Activity of a 5-Aminopyrazole Derivative Lead Compound (BC-7) and Potential Synergistic Cytotoxicity with Cisplatin against Human Cervical Cancer Cells
Authors: Swanepoel Bresler , Nitulescu George Mihai , Olaru Octavian Tudorel , Venables Luanne , van de Venter Maryna
Published: November 2019

The use of some very well-known chemotherapeutic agents, such as cisplatin, is limited by toxicity in normal tissues and the development of drug resistance. In order to address drug resistance and the side-effects of anti-cancer agents, recent research has focused on finding novel combinations of anti-cancer agents with non-overlapping mechanisms of action. The cytotoxic effect of the synthetic 5-aminopyrazole derivative N-[[3-(4-bromophenyl)-1H-pyrazol-5-yl]-carbamothioyl]-4-chloro-benzamide (BC-7) was evaluated by the bis-Benzamide H 33342 trihydrochloride/propidium iodide (Hoechst 33342/PI) dual staining method against HeLa, MeWo, HepG2, Vero, and MRHF cell lines. Quantitative fluorescence image analysis was used for the elucidation of mechanism of action and synergism with cisplatin in HeLa cells. BC-7 displayed selective cytotoxicity towards HeLa cells (IC50 65.58 ± 8.40 μM) and induced apoptosis in a mitochondrial- and caspase dependent manner. This was most likely preceded by cell cycle arrest in the early M phase and the onset of mitotic catastrophe. BC-7 increased the cytotoxic effect of cisplatin in a synergistic manner with combination index (CI) values less than 0.9 accompanied by highly favourable dose reduction indices. Therefore, the results obtained support the implication that BC-7 has potential anti-cancer properties and that combinations of BC-7 with cisplatin should be further investigated for potential clinical applications.
Water Extract of Cryphaea heteromalla (Hedw.) D. Mohr Bryophyte as a Natural Powerful Source of Biologically Active Compounds
Authors: Provenzano Fiorenza , Sánchez Jesús Lozano , Rao Estella , Santonocito Radha , Ditta Lorena Anna , Borrás Linares Isabel , Passantino Rosa , Campisi Patrizia , Dia Maria Giovanna , Costa Maria Assunta , Segura-Carretero Antonio , San Biagio Pier Luigi , Giacomazza Daniela
Published: November 2019

Bryophytes comprise of the mosses, liverworts, and hornworts. Cryphaea heteromalla, (Hedw.) D. Mohr, is a non-vascular lower plant belonging to mosses group. To the date, the most chemically characterized species belong to the liverworts, while only 3.2% and 8.8% of the species belonging to the mosses and hornworts, respectively, have been investigated. In this work, we present Folin–Ciocalteu and oxygen radical absorbance capacity (ORAC) data related to crude extracts of C. heteromalla obtained by three different extraction solvents: pure water (WT), methanol:water (80:20 v/v) (MET), and ethanol:water (80:20 v/v) (ETH). The water extract proved to be the best solvent showing the highest content of biophenols and the highest ORAC value. The C. heteromalla-WT extract was investigated by HPLC-TOF/MS (High Performance Liquid Chromatography-Time of Flight/Mass Spectrometry) allowing for the detection of 14 compounds, five of which were phenolic compounds, derivatives of benzoic, caffeic, and coumaric acids. Moreover, the C. heteromalla WT extract showed a protective effect against reactive oxygen species (ROS) generation induced by tert-butyl hydroperoxide (TBH) on the murine NIH-3T3 fibroblast cell line.
Inflammation and Coronary Microvascular Dysfunction in Autoimmune Rheumatic Diseases
Authors: Zanatta Elisabetta , Colombo Claudia , D’Amico Gianpiero , d’Humières Thomas , Dal Lin Carlo , Tona Francesco
Published: November 2019

Autoimmune rheumatic diseases (ARDs) form a heterogeneous group of disorders that include systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIMs), and systemic vasculitis. Coronary microvascular dysfunction (CMD) is quite common in patients with ARDs and is linked to increased cardiovascular morbidity and mortality. Inflammation plays a crucial role in the pathogenesis of both accelerated atherosclerosis and CMD in ARDs, especially in patients affected by SLE and RA. In this regard, some studies have highlighted the efficacy of immunosuppressants and/or biologics in restoring CMD in these patients. By contrast, the role of inflammation in the pathogenesis of CMD-SSc appears to be much less relevant compared to endothelial dysfunction and microvascular ischemia, with calcium-channel blockers providing some benefits. Few studies have endeavored to assess the occurrence of CMD in IIMs and systemic vasculitis, thus warranting further investigations. The present review summarizes the current evidence on the occurrence of CMD in ARDs, focusing on the role of inflammation and possible therapeutic approaches.
Systematic Enzyme Mapping of Cellular Metabolism by Phasor-Analyzed Label-Free NAD(P)H Fluorescence Lifetime Imaging
Authors: Leben Ruth , Köhler Markus , Radbruch Helena , Hauser Anja E. , Niesner Raluca A.
Published: November 2019

In the past years, cellular metabolism of the immune system experienced a revival, as it has become clear that it is not merely responsible for the cellular energy supply, but also impacts on many signaling pathways and, thus, on diverse cellular functions. Label-free fluorescence lifetime imaging of the ubiquitous coenzymes NADH and NADPH (NAD(P)H-FLIM) makes it possible to monitor cellular metabolism in living cells and tissues and has already been applied to study metabolic changes both under physiologic and pathologic conditions. However, due to the complex distribution of NAD(P)H-dependent enzymes in cells, whose distribution continuously changes over time, a thorough interpretation of NAD(P)H-FLIM results, in particular, resolving the contribution of various enzymes to the overall metabolic activity, remains challenging. We developed a systematic framework based on angle similarities of the phase vectors and their length to analyze NAD(P)H-FLIM data of cells and tissues based on a generally valid reference system of highly abundant NAD(P)H-dependent enzymes in cells. By using our analysis framework, we retrieve information not only about the overall metabolic activity, i.e., the fraction of free to enzyme-bound NAD(P)H, but also identified the enzymes predominantly active within the sample at a certain time point with subcellular resolution. We verified the performance of the approach by applying NAD(P)H-FLIM on a stromal-like cell line and identified a different group of enzymes that were active in the cell nuclei as compared to the cytoplasm. As the systematic phasor-based analysis framework of label-free NAD(P)H-FLIM can be applied both in vitro and in vivo, it retains the unique power to enable dynamic enzyme-based metabolic investigations, at subcellular resolution, in genuine environments.
Identification and Characterization of a Fatty Acid- and Retinoid-Binding Protein Gene (Ar-far-1) from the Chrysanthemum Foliar Nematode, Aphelenchoides ritzemabosi
Authors: Ding Shan-Wen , Wang Dong-Wei , Xiang Yu , Xu Chun-Ling , Xie Hui
Published: November 2019

The chrysanthemum foliar nematode (CFN), Aphelenchoides ritzemabosi, is a migratory, plant-parasitic nematode that is widely distributed and infects the aboveground parts of many plants. The fatty acid- and retinoid-binding proteins (FAR) are nematode-specific proteins that are involved in the development, reproduction, and infection of nematodes and are secreted into the tissues to disrupt the plant defense reaction. In this study, we obtained the full-length sequence of the FAR gene (Ar-far-1) from CFN, which is 727 bp and includes a 546 bp ORF that encodes 181 amino acids. Ar-FAR-1 from CFN has the highest sequence similarity to Ab-FAR-1 from A. besseyi, and they are located within the same branch of the phylogenetic tree. Fluorescence-based ligand-binding analysis confirmed that recombinant Ar-FAR-1 was bound to fatty acids and retinol. Ar-far-1 mRNA was expressed in the muscle layer, intestine, female genital system, and egg of CFN, and more highly expressed in females than in males among the four developmental stages of CFN. We demonstrated that the reproduction number and infection capacity of CFN decreased significantly when Ar-far-1 was effectively silenced by in vitro RNAi. Ar-far-1 plays an important role in the development, reproduction, infectivity, and pathogenesis of CFN and may be used as an effective target gene for the control of CFN. The results provide meaningful data about the parasitic and pathogenic genes of CFN to study the interaction mechanism between plant-parasitic nematodes and hosts.