bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of COVID−19 on Female Sexual Health
Authors: Fuchs Anna , Matonóg Aleksandra , Pilarska Joanna , Sieradzka Paulina , Szul Mateusz , Czuba Bartosz , Drosdzol-Cop Agnieszka
Published: September 2020

Introduction: Coronavirus disease (COVID−19), announced as a pandemic by the World Health Organization, recently has dominated people’s lifestyle. The impact of COVID−19 seems to be relevant to the sexual health as well. Methods: This prospective study was conducted on two occasions involving 764 female patients between March and April 2020—before and during the time of social quarantine. The sexual function was assessed using the Polish version of the Female Sexual Function Index (FSFI). Every patient filled out the survey concerning socio-demographic characteristics as well as the influence of SARS-CoV−2 pandemic on their lives. Results: The overall FSFI score before the pandemic was 30.1 ± 4.4 and changed to 25.8 ± 9.7 during it. Scores of every domain: desire, arousal, lubrication, orgasm, satisfaction and pain decreased as well (p < 0.001). There was statistically significant association between the workplace and the change of FSFI scores before and during COVID−19 pandemic (p < 0.01). We noticed the biggest decrease in FSFI score in the group of women who did not work at all (5.2 ± 9.9). Religion had a statistically important impact on level of anxiety (p < 0.01). Conclusion: The main finding of our study was the influence of COVID−19 pandemic on the quality of sexual lifestyle and frequency of intercourse among Polish women.
The Effects of Circadian Rhythm Disruption on Mental Health and Physiological Responses among Shift Workers and General Population
Authors: Ahmad Mahadir , Md. Din Nur Syafiqa Balqis , Tharumalay Ruthra Devi , Che Din Normah , Ibrahim Norhayati , Amit Noh , Farah Nor MF , Osman Rose Azzlinda , Abdul Hamid Mohamed Faisal , Ibrahim Ibnor Azli , Jamsari Ezad Azraai , Palil Mohd Rizal , Ahmad Sha’ari
Published: September 2020

Background: The effect of circadian disruption on the bio-psychological clock system has been widely studied. However, the mechanism and the association of circadian rhythm disruption with mental health and physiological responses are still unclear. Therefore, this study was conducted to investigate the effects of circadian rhythm disruption on mental health and physiological responses among shift workers and the general population. Methods: A total of 42 subjects participated in this quasi-experimental study. Participants were divided into a group of shift workers (n = 20) and a general population group (n = 22). Polysomnography tests, blood tests (cortisol, triglycerides and glucose), and psychological tests (Abbreviated Profile of Mood States, General Health Questionnaire-28, Working Memory and Processing Speed Indexes of the Wechsler Adult Intelligent Scale (WAIS-IV) were used to examine the effects of circadian rhythm disruption. Results: The results showed a significant relationship between circadian rhythm disruption and mood (r = 0.305, p < 0.05). The findings of this study also indicated that there was a significant effect of circadian rhythm disruption on mood (F(2,40) = 8.89, p < 0.001, η2 =0.182), processing speed (F(2,40) = 9.17, p < 0.001, η2 = 0.186) and working memory (F(2,40) = 4.963, p < 0.01, η2 = 0.11) in shift workers and the general population. Conclusions: Our findings showed that circadian rhythm disruption affects mood and cognitive performance, but it does not significantly affect psychological wellbeing and physiological responses. Future studies are warranted to examine moderator and mediator variables that could influence the circadian rhythm disruption.
A Quantitative Study on Crucial Food Supplies after the 2011 Tohoku Earthquake Based on Time Series Analysis
Authors: Zhu Xiaoxin , Wang Yanyan , Regan David , Sun Baiqing
Published: September 2020

Awareness of the requested quantity and characteristics of emergency supplies is crucial for facilitating an efficient relief operation. With the aim of focusing on the quantitative study of immediate food supplies, this article estimates the numerical autoregressive integrative moving average (ARIMA) model based on the actual data of 14 key commodities in the Sendai City of Japan during the 2011 Tohoku earthquake. Although the temporal patterns of key food commodity groups are qualitatively similar, the results show that they follow different ARIMA processes, with different autoregressive moving averages and difference order patterns. A key finding is that 3 of the 14 items are significantly related to the number of temporary residents in shelters, revealing that the relatively low number of different items makes it easier to deploy these key supplies or develop regional purchase agreements so as to promptly obtain them from distributors.
Unemployment and Psychological Distress among Young People during the COVID-19 Pandemic: Psychological Resources and Risk Factors
Authors: Achdut Netta , Refaeli Tehila
Published: September 2020

In the wake of COVID-19, unemployment and its potential deleterious consequences have attracted renewed interest. We examined (1) the association between unemployment, occurring upon the coronavirus outbreak, and psychological distress among Israeli young people (20–35-years-old); (2) the associations between various psychological resources/risk factors and psychological distress; and (3) whether these resources and risk factors were moderators in the unemployment-psychological distress link. A real-time survey based on snowball sampling was conducted during the month of April 2020 (N = 390). We employed hierarchical linear models to explore associations between unemployment, psychological resources, risk factors, and psychological distress. Unemployment was independently associated with greater psychological distress. Perceived trust, optimism, and sense of mastery decreased psychological distress, whereas financial strain and loneliness during the crisis increased this distress. The effect of unemployment on psychological distress did not depend on participants’ resource and risk factor levels. Policymakers must develop and extend health initiatives aimed at alleviating the mental health consequences of COVID-19-related unemployment and promote labor market interventions to help young job seekers integrate into employment. These measures, which are in line with the UN sustainable development goals, should be seen as an important route to promote public health.
Hospital and Population-Based Evidence for COVID-19 Early Circulation in the East of France
Authors: Gerbaud Laurent , Guiguet-Auclair Candy , Breysse Franck , Odoul Joséphine , Ouchchane Lemlih , Peterschmitt Jonathan , Dezfouli-Desfer Camille , Breton Vincent
Published: September 2020

Background: Understanding SARS-CoV-2 dynamics and transmission is a serious issue. Its propagation needs to be modeled and controlled. The Alsace region in the East of France has been among the first French COVID-19 clusters in 2020. Methods: We confront evidence from three independent and retrospective sources: a population-based survey through internet, an analysis of the medical records from hospital emergency care services, and a review of medical biology laboratory data. We also check the role played in virus propagation by a large religious meeting that gathered over 2000 participants from all over France mid-February in Mulhouse. Results: Our results suggest that SARS-CoV-2 was circulating several weeks before the first officially recognized case in Alsace on 26 February 2020 and the sanitary alert on 3 March 2020. The religious gathering seems to have played a role for secondary dissemination of the epidemic in France, but not in creating the local outbreak. Conclusions: Our results illustrate how the integration of data coming from multiple sources could help trigger an early alarm in the context of an emerging disease. Good information data systems, able to produce earlier alerts, could have avoided a general lockdown in France.
A Method for 3D Reconstruction of the Ming and Qing Official-Style Roof Using a Decorative Components Template Library
Authors: Huo Pengpeng , Hou Miaole , Dong Youqiang , Li Aiqun , Ji Yuhang , Li Songnian
Published: September 2020

The ancient roof decorative components of the official-style architectures from the Ming and Qing dynasties in China hold both physical and symbolic significance. These roof structures are the essential objects in three-dimensional (3D) modeling of ancient architectures for traditional Chinese cultural preservation. Although ancient architectures can be surveyed by a 3D laser scanner, the complex geometry and diverse pattern of their roof decorative components make the 3D point cloud reconstruction challenging, or at some points, nearly impossible in a fully automated manner. In this paper, we propose a method to ensure that the 3D shape of each roof decorative component is accurately modeled. First, we establish a decorative components template library (or “template library” in short hereafter), which is the first of its kind for the roofs of Ming and Qing official-style architectures. The process of establishing the decorative components template library begins with a remote collection of survey data using a terrestrial laser scanner and digital camera. The next stage involves the design and construction of different 3D decorative components in the template library with reference to the manuscripts written in the Ming and Qing dynasties’ architectural pattern books. With the point cloud data collected on any Ming and Qing official-style architecture, we further propose a geo-registration mechanism to search for an optimal fitting of the decorative components from the template library on the collected point cloud automatically. Based on the experimental results, the accuracy of point cloud registration yields less than 0.02 m, which meets the accuracy of the 3D model at LoD 300 level. Time consumption is less than 5s and stable, for large volume computing capacity has good robustness. The proposed strategy provides a new way for the 3D modeling of large and clustered historical architectures, particularly with complex structures.
Quantitative Evaluation of Spatial Differentiation for Public Open Spaces in Urban Built-Up Areas by Assessing SDG 11.7: A Case of Deqing County
Authors: Chen Qiang , Du Mingyi , Cheng Qianhao , Jing Changfeng
Published: September 2020

Urban public open spaces refer to open space between architectural structures in a city or urban agglomeration that is open for urban residents to conduct public exchanges and hold various activities. Sustainable Development Goal (SDG) 11.7 in the 2030 UN Agenda for Sustainable Development clearly states that the distribution characteristics of public open spaces are important indicators to measure the sustainable development of urban ecological society. In 2018, in order to implement the sustainable development agenda, China offered the example of Deqing to the world. Therefore, taking Deqing as an example, this paper uses geographic statistics and spatial analysis methods to quantitatively evaluate and visualize public open spaces in the built area in 2016 and analyzes the spatial pattern and relationship of the population. The results show that the public open spaces in the built-up area of Deqing have typical global and local spatial autocorrelation. The spatial pattern shows obvious differences in different parts of the built area and attributes of public open spaces. According to the results of correlation analysis, it can be seen that the decentralized characteristics of public open spaces have a significant relationship with the population agglomeration, and this correlation is also related to the types of public open spaces. The assessment results by SDG 11.7.1 indicate that the public open spaces in the built-up area of Deqing conform to the living needs of residents on the whole and have a humanized space design and good accessibility. However, the per capita public open spaces of towns and villages outside the built area are relatively low, and there is an imbalance in public open spaces. Therefore, more attention should be paid to constructing urban public open spaces fairly.
Scalable Model Selection for Spatial Additive Mixed Modeling: Application to Crime Analysis
Authors: Murakami Daisuke , Kajita Mami , Kajita Seiji
Published: September 2020

A rapid growth in spatial open datasets has led to a huge demand for regression approaches accommodating spatial and non-spatial effects in big data. Regression model selection is particularly important to stably estimate flexible regression models. However, conventional methods can be slow for large samples. Hence, we develop a fast and practical model-selection approach for spatial regression models, focusing on the selection of coefficient types that include constant, spatially varying, and non-spatially varying coefficients. A pre-processing approach, which replaces data matrices with small inner products through dimension reduction, dramatically accelerates the computation speed of model selection. Numerical experiments show that our approach selects a model accurately and computationally efficiently, highlighting the importance of model selection in the spatial regression context. Then, the present approach is applied to open data to investigate local factors affecting crime in Japan. The results suggest that our approach is useful not only for selecting factors influencing crime risk but also for predicting crime events. This scalable model selection will be key to appropriately specifying flexible and large-scale spatial regression models in the era of big data. The developed model selection approach was implemented in the R package spmoran.
Boosting the Timeliness of UAV Large Scale Mapping. Direct Georeferencing Approaches: Operational Strategies and Best Practices
Authors: Teppati Losè Lorenzo , Chiabrando Filiberto , Giulio Tonolo Fabio
Published: September 2020

The use of unmanned aerial vehicles (UAVs) is nowadays a standard approach in several application fields. Researches connected with these systems cover several topics and the evolution of these platforms and their applications are rapidly growing. Despite the high level of automatization reached nowadays, there is still a phase of the overall UAVs’ photogrammetric pipeline that requires a high effort in terms of time and resources (i.e., the georeferencing phase). However, thanks to the availability of survey-grade GNSS (Global Navigation Satellite System) receivers embedded in the aerial platforms, it is possible to also enhance this phase of the processing by adopting direct georeferencing approaches (i.e., without using any ground control point and exploiting real time kinematic (RTK) positioning). This work investigates the possibilities offered by a multirotor commercial system equipped with a RTK-enabled GNSS receiver, focusing on the accuracy of the georeferencing phase. Several tests were performed in an ad-hoc case study exploiting different georeferencing solutions and assessing the 3D positional accuracies, thanks to a network of control points. The best approaches to be adopted in the field according to accuracy requirements of the final map products were identified and operational guidelines proposed accordingly.
Chemerin Isoform-Specific Effects on Hepatocyte Migration and Immune Cell Inflammation
Authors: Feder Susanne , Bruckmann Astrid , McMullen Nichole , Sinal Christopher J. , Buechler Christa
Published: September 2020

Murine chemerin is C-terminally processed to the bioactive isoforms, muChem-156 and muChem-155, among which the longer variant protects from hepatocellular carcinoma (HCC). However, the role of muChem-155 is mostly unknown. Here, we aimed to compare the effects of these isoforms on the proliferation, migration and the secretome of the human hepatocyte cell lines HepG2 and Huh7 and the murine Hepa1-6 cell line. Therefore, huChem-157 and -156 were overexpressed in the human cells, and the respective murine variants, muChem-156 and -155, in the murine hepatocytes. Both chemerin isoforms produced by HepG2 and Hepa1-6 cells activated the chemerin receptors chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor 1 (GPR1). HuChem-157 was the active isoform in the Huh7 cell culture medium. The potencies of muChem-155 and muChem-156 to activate human GPR1 and mouse CMKLR1 were equivalent. Human CMKLR1 was most responsive to muChem-156. Chemerin variants showed no effect on cell viability and proliferation. Activation of the mitogen-activated protein kinases Erk1/2 and p38, and protein levels of the epithelial–mesenchymal transition marker, E-cadherin, were not regulated by the chemerin variants. Migration was reduced in HepG2 and Hepa1-6 cells by the longer isoform. Protective effects of chemerin in HCC include the modulation of cytokines but huChem-156 and huChem-157 overexpression did not change IL-8, CCL20 or osteopontin in the hepatocytes. The conditioned medium of the transfected hepatocytes failed to alter these soluble factors in the cell culture medium of peripheral blood mononuclear cells (PBMCs). Interestingly, the cell culture medium of Huh7 cells producing the inactive variant huChem-155 reduced CCL2 and IL-8 in PBMCs. To sum up, huChem-157 and muChem-156 inhibited hepatocyte migration and may protect from HCC metastasis. HuChem-155 was the only human isoform exerting anti-inflammatory effects on immune cells.
Self-Assembly of Supramolecular Architectures by the Effect of Amino Acid Residues of Quaternary Ammonium Pillar[5]arenes
Authors: Nazarova Anastasia , Shurpik Dmitriy , Padnya Pavel , Mukhametzyanov Timur , Cragg Peter , Stoikov Ivan
Published: September 2020

Novel water-soluble multifunctional pillar[5]arenes containing amide-ammonium-amino acid moiety were synthesized. The compounds demonstrated a superior ability to bind (1S)-(+)-10-camphorsulfonic acid (S-CSA) and methyl orange dye depending on the nature of the substituent, resulting in the formation one-to-one complexes with both guests. The formation of host-guest complexes was confirmed by ultraviolet (UV), circular dichroism (CD) and 1H NMR spectroscopy. This work demonstrates the first case of using S-CSA as a chiral template for the non-covalent self-assembly of architectures based on pillar[5]arenes. It was shown that pillar[5]arenes with glycine or L-alanine fragments formed aggregates with average hydrodynamic diameters (d) of 165 and 238 nm, respectively. It was established that the addition of S-CSA to the L-alanine-containing derivative led to the formation of micron-sized aggregates with d of 713 nm. This study may advance the design novel stereoselective catalysts and transmembrane amino acid channels.
Role of SGK1 in the Osteogenic Transdifferentiation and Calcification of Vascular Smooth Muscle Cells Promoted by Hyperglycemic Conditions
Authors: Poetsch Florian , Henze Laura A. , Estepa Misael , Moser Barbara , Pieske Burkert , Lang Florian , Eckardt Kai-Uwe , Alesutan Ioana , Voelkl Jakob
Published: September 2020

In diabetes mellitus, hyperglycemia promotes the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) to enhance medial vascular calcification, a common complication strongly associated with cardiovascular disease and mortality. The mechanisms involved are, however, still poorly understood. Therefore, the present study explored the potential role of serum- and glucocorticoid-inducible kinase 1 (SGK1) during vascular calcification promoted by hyperglycemic conditions. Exposure to high-glucose conditions up-regulated the SGK1 expression in primary human aortic VSMCs. High glucose increased osteogenic marker expression and activity and, thus, promoted the osteogenic transdifferentiation of VSMCs, effects significantly suppressed by additional treatment with the SGK1 inhibitor EMD638683. Moreover, high glucose augmented the mineralization of VSMCs in the presence of calcification medium, effects again significantly reduced by SGK1 inhibition. Similarly, SGK1 knockdown blunted the high glucose-induced osteogenic transdifferentiation of VSMCs. The osteoinductive signaling promoted by high glucose required SGK1-dependent NF-κB activation. In addition, advanced glycation end products (AGEs) increased the SGK1 expression in VSMCs, and SGK1 inhibition was able to interfere with AGEs-induced osteogenic signaling. In conclusion, SGK1 is up-regulated and mediates, at least partly, the osteogenic transdifferentiation and calcification of VSMCs during hyperglycemic conditions. Thus, SGK1 inhibition may reduce the development of vascular calcification promoted by hyperglycemia in diabetes.
Effect of Disulfide Cyclization of Ultrashort Cationic Lipopeptides on Antimicrobial Activity and Cytotoxicity
Authors: Neubauer Damian , Jaśkiewicz Maciej , Sikorska Emilia , Bartoszewska Sylwia , Bauer Marta , Kapusta Małgorzata , Narajczyk Magdalena , Kamysz Wojciech
Published: September 2020

Ultrashort cationic lipopeptides (USCLs) are considered to be a promising class of antimicrobials with high activity against a broad-spectrum of microorganisms. However, the majority of these compounds are characterized by significant toxicity toward human cells, which hinders their potential application. To overcome those limitations, several approaches have been advanced. One of these is disulfide cyclization that has been shown to improve drug-like characteristics of peptides. In this article the effect of disulfide cyclization of the polar head of N-palmitoylated USCLs on in vitro biological activity has been studied. Lipopeptides used in this study consisted of three or four basic amino acids (lysine and arginine) and cystine in a cyclic peptide. In general, disulfide cyclization of the lipopeptides resulted in peptides with reduced cytotoxicity. Disulfide-cyclized USCLs exhibited improved selectivity between Candida sp., Gram-positive strains and normal cells in contrast to their linear counterparts. Interactions between selected USCLs and membranes were studied by molecular dynamics simulations using a coarse-grained force field. Moreover, membrane permeabilization properties and kinetics were examined. Fluorescence and transmission electron microscopy revealed damage to Candida cell membrane and organelles. Concluding, USCLs are strong membrane disruptors and disulfide cyclization of polar head can have a beneficial effect on its in vitro selectivity between Candida sp. and normal human cells.
Functional Characterization of Gomisin N in High-Fat-Induced Drosophila Obesity Models
Authors: Lee Joo Young , Lee Ji Hye , Cheon Chong Kun
Published: September 2020

Gomisin N (GN) is lignin derived from Schisandra chinensis that has been reported to exhibit hepato-protective, anti-cancer, and anti-inflammatory effects. However, its role in whole-body energetic homeostasis remains unclear. In this study, we employed Drosophila melanogaster as a diet-induced obese model to elucidate the effects of GN on lipid and glucose metabolism by measuring climbing activity, triglyceride levels, and lifespan under a rearing condition of a high-fat diet (HFD) containing 20% coconut oil, with or without GN. Constant exposure of flies to an HFD resulted in increased body weight and decreased climbing activity, along with a shortened life span. Importantly, the administration of GN to HFD groups lowered their body weight and induced a specific upregulation of lipid storage droplet (Lsd)-2 and hormone-sensitive lipase (Hsl), in addition to improved lifespan. Importantly, GN in HFD groups appeared to downregulate heat shock protein Hsp90 family member (dGRP94), a key regulator of the endoplasmic reticulum stress response, which may also contribute to improved life span in the presence of GN. Taken together, these in vivo findings suggest that GN could serve as a useful agent for the prevention and treatment of obesity.
Discoidin Domain Receptor 1 Regulates Runx2 during Osteogenesis of Osteoblasts and Promotes Bone Ossification via Phosphorylation of p38
Authors: Chou Liang-Yin , Chen Chung-Hwan , Chuang Shu-Chun , Cheng Tsung-Lin , Lin Yi-Hsiung , Chou Hsin-Chiao , Fu Yin-Chih , Wang Yan-Hsiung , Wang Chau-Zen
Published: September 2020

Discoidin domain receptor 1 (Drd1) is a collagen-binding membrane protein, but its role in osteoblasts during osteogenesis remains undefined. We generated inducible osteoblast-specific Ddr1 knockout (OKOΔDdr1) mice; their stature at birth, body weight and body length were significantly decreased compared with those of control Ddr1f/f-4OHT mice. We hypothesize that Ddr1 regulates osteogenesis of osteoblasts. Micro-CT showed that compared to 4-week-old Ddr1f/f-4OHT mice, OKOΔDdr1 mice presented significant decreases in cancellous bone volume and trabecular number and significant increases in trabecular separation. The cortical bone volume was decreased in OKOΔDdr1 mice, resulting in decreased mechanical properties of femurs compared with those of Ddr1f/f-4OHT mice. In femurs of 4-week-old OKOΔDdr1 mice, H&E staining showed fewer osteocytes and decreased cortical bone thickness than Ddr1f/f-4OHT. Osteoblast differentiation markers, including BMP2, Runx2, alkaline phosphatase (ALP), Col-I and OC, were decreased compared with those of control mice. Ddr1 knockdown in osteoblasts resulted in decreased mineralization, ALP activity, phosphorylated p38 and protein levels of BMP2, Runx2, ALP, Col-I and OC during osteogenesis. Overexpression and knockdown of Ddr1 in osteoblasts demonstrated that DDR1 mediates the expression and activity of Runx2 and the downstream osteogenesis markers during osteogenesis through regulation of p38 phosphorylation.
Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents
Authors: Nishi Mayumi
Published: September 2020

Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.
The Interaction of Innate and Adaptive Immunity and Stabilization of Mast Cell Activation in Management of Infusion Related Reactions in Patients with Fabry Disease
Authors: Limgala Renuka P. , Fikry Jaqueline , Veligatla Vasudha , Goker-Alpan Ozlem
Published: September 2020

Fabry disease (FD) is an X-linked lysosomal disorder caused by mutations in GLA gene resulting in lack of or faulty α-galactosidase A (α-GalA) enzyme. Enzyme replacement therapy (ERT) with recombinant human α-GalA enzyme (agalsidase) is the standard treatment option for FD. Infusion-related reactions (IRRs), with symptoms ranging from rigors, to fever, pain, vomiting, angioedema and diarrhea, are often seen due to immune response against the exogenous enzyme. To elucidate the mechanisms causing the IRRs in FD, eight patients who developed IRRs were investigated. All, except one, tested negative for agalsidase-specific IgE and had normal tryptase levels. Circulating dendritic cells were drastically reduced during IRRs, suggesting possible sequestration to the sites of inflammation. An increase in NK cells and a decrease in T cells were also observed. Cytokines IL-4, IL-8 and TNF-α showed a significant increase, indicating nonspecific degranulation of mast cells. All IRRs were managed successfully using a combination of standard premedications and mast cell stabilizers without any interruption of therapy. Taken together, the results indicate crosstalk between immune cells resulting in IgE-independent mast-cell-specific allergic inflammation. Mast cell stabilizers could be used to control IRRs and for safe reintroduction of agalsidase in patients previously treated with ERT.
NRF2 and PPAR-γ Pathways in Oligodendrocyte Progenitors: Focus on ROS Protection, Mitochondrial Biogenesis and Promotion of Cell Differentiation
Authors: De Nuccio Chiara , Bernardo Antonietta , Troiano Carmen , Brignone Maria Stefania , Falchi Mario , Greco Anita , Rosini Michela , Basagni Filippo , Lanni Cristina , Serafini Melania Maria , Minghetti Luisa , Visentin Sergio
Published: September 2020

An adequate protection from oxidative and inflammatory reactions, together with the promotion of oligodendrocyte progenitor (OP) differentiation, is needed to recover from myelin damage in demyelinating diseases. Mitochondria are targets of inflammatory and oxidative insults and are essential in oligodendrocyte differentiation. It is known that nuclear factor-erythroid 2-related factor/antioxidant responsive element (NRF2/ARE) and peroxisome proliferator-activated receptor gamma/PPAR-γ response element (PPAR-γ/PPRE) pathways control inflammation and overcome mitochondrial impairment. In this study, we analyzed the effects of activators of these pathways on mitochondrial features, protection from inflammatory/mitochondrial insults and cell differentiation in OP cultures, to depict the specificities and similarities of their actions. We used dimethyl-fumarate (DMF) and pioglitazone (pio) as agents activating NRF2 and PPAR-γ, respectively, and two synthetic hybrids acting differently on the NRF2/ARE pathway. Only DMF and compound 1 caused early effects on the mitochondria. Both DMF and pio induced mitochondrial biogenesis but different antioxidant repertoires. Moreover, pio induced OP differentiation more efficiently than DMF. Finally, DMF, pio and compound 1 protected from tumor necrosis factor-alpha (TNF-α) insult, with pio showing faster kinetics of action and compound 1 a higher activity than DMF. In conclusion, NRF2 and PPAR-γ by inducing partially overlapping pathways accomplish complementary functions aimed at the preservation of mitochondrial function, the defense against oxidative stress and the promotion of OP differentiation.
Hyperbaric Oxygen Treatment Following Mid-Cervical Spinal Cord Injury Preserves Diaphragm Muscle Function
Authors: Smuder Ashley J. , Turner Sara M. , Schuster Cassandra M. , Morton Aaron B. , Hinkley J. Matthew , Fuller David D.
Published: September 2020

Oxidative damage to the diaphragm as a result of cervical spinal cord injury (SCI) promotes muscle atrophy and weakness. Respiratory insufficiency is the leading cause of morbidity and mortality in cervical spinal cord injury (SCI) patients, emphasizing the need for strategies to maintain diaphragm function. Hyperbaric oxygen (HBO) increases the amount of oxygen dissolved into the blood, elevating the delivery of oxygen to skeletal muscle and reactive oxygen species (ROS) generation. It is proposed that enhanced ROS production due to HBO treatment stimulates adaptations to diaphragm oxidative capacity, resulting in overall reductions in oxidative stress and inflammation. Therefore, we tested the hypothesis that exposure to HBO therapy acutely following SCI would reduce oxidative damage to the diaphragm muscle, preserving muscle fiber size and contractility. Our results demonstrated that lateral contusion injury at C3/4 results in a significant reduction in diaphragm muscle-specific force production and fiber cross-sectional area, which was associated with augmented mitochondrial hydrogen peroxide emission and a reduced mitochondrial respiratory control ratio. In contrast, rats that underwent SCI followed by HBO exposure consisting of 1 h of 100% oxygen at 3 atmospheres absolute (ATA) delivered for 10 consecutive days demonstrated an improvement in diaphragm-specific force production, and an attenuation of fiber atrophy, mitochondrial dysfunction and ROS production. These beneficial adaptations in the diaphragm were related to HBO-induced increases in antioxidant capacity and a reduction in atrogene expression. These findings suggest that HBO therapy may be an effective adjunctive therapy to promote respiratory health following cervical SCI.
Micro-RNAs: Crossroads between the Exposure to Environmental Particulate Pollution and the Obstructive Pulmonary Disease
Authors: Finicelli Mauro , Squillaro Tiziana , Galderisi Umberto , Peluso Gianfranco
Published: September 2020

Environmental pollution has reached a global echo and represents a serious problem for human health. Air pollution encompasses a set of hazardous substances, such as particulate matter and heavy metals (e.g., cadmium, lead, and arsenic), and has a strong impact on the environment by affecting groundwater, soil, and air. An adaptive response to environmental cues is essential for human survival, which is associated with the induction of adaptive phenotypes. The epigenetic mechanisms regulating the expression patterns of several genes are promising candidates to provide mechanistic and prognostic insights into this. Micro-RNAs (miRNAs) fulfil these features given their ability to respond to environmental factors and their critical role in determining phenotypes. These molecules are present in extracellular fluids, and their expression patterns are organ-, tissue-, or cell-specific. Moreover, the experimental settings for their quantitative and qualitative analysis are robust, standardized, and inexpensive. In this review, we provide an update on the role of miRNAs as suitable tools for understanding the mechanisms behind the physiopathological response to toxicants and the prognostic value of their expression pattern associable with specific exposures. We look at the mechanistic evidence associable to the role of miRNAs in the processes leading to environmental-induced pulmonary disease (i.e., chronic obstructive pulmonary disease).
Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies
Authors: Theotoki Eleni I. , Pantazopoulou Vasiliki I. , Georgiou Stella , Kakoulidis Panos , Filippa Vicky , Stravopodis Dimitrios J. , Anastasiadou Ema
Published: September 2020

Gene expression dictates fundamental cellular processes and its de-regulation leads to pathological conditions. A key contributor to the fine-tuning of gene expression is Dicer, an RNA-binding protein (RBPs) that forms complexes and affects transcription by acting at the post-transcriptional level via the targeting of mRNAs by Dicer-produced small non-coding RNAs. This review aims to present the contribution of Dicer protein in a wide spectrum of human pathological conditions, including cancer, neurological, autoimmune, reproductive and cardiovascular diseases, as well as viral infections. Germline mutations of Dicer have been linked to Dicer1 syndrome, a rare genetic disorder that predisposes to the development of both benign and malignant tumors, but the exact correlation of Dicer protein expression within the different cancer types is unclear, and there are contradictions in the data. Downregulation of Dicer is related to Geographic atrophy (GA), a severe eye-disease that is a leading cause of blindness in industrialized countries, as well as to psychiatric and neurological diseases such as depression and Parkinson’s disease, respectively. Both loss and upregulation of Dicer protein expression is implicated in severe autoimmune disorders, including psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis and autoimmune thyroid diseases. Loss of Dicer contributes to cardiovascular diseases and causes defective germ cell differentiation and reproductive system abnormalities in both sexes. Dicer can also act as a strong antiviral with a crucial role in RNA-based antiviral immunity. In conclusion, Dicer is an essential enzyme for the maintenance of physiology due to its pivotal role in several cellular processes, and its loss or aberrant expression contributes to the development of severe human diseases. Further exploitation is required for the development of novel, more effective Dicer-based diagnostic and therapeutic strategies, with the goal of new clinical benefits and better quality of life for patients.
The Role of SHIP1 on Apoptosis and Autophagy in the Adipose Tissue of Obese Mice
Authors: Jeong Jae Hun , Choi Eun Bee , Jang Hye Min , Ahn Yu Jeong , An Hyeong Seok , Lee Jong Youl , Park Gyeongah , Jeong Eun Ae , Shin Hyun Joo , Lee Jaewoong , Kim Kyung Eun , Roh Gu Seob
Published: September 2020

Obesity-induced adipocyte apoptosis promotes inflammation and insulin resistance. Src homology domain-containing inositol 5′-phosphatase 1 (SHIP1) is a key factor of apoptosis and inflammation. However, the role of SHIP1 in obesity-induced adipocyte apoptosis and autophagy is unclear. We found that diet-induced obesity (DIO) mice have significantly greater crown-like structures and terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive cells than ob/ob or control mice. Using RNA sequencing (RNA-seq) analysis, we identified that the apoptosis- and inflammation-related gene Ship1 is upregulated in DIO and ob/ob mice compared with control mice. In particular, DIO mice had more SHIP1-positive macrophages and lysosomal-associated membrane protein 1 (LAMP1) as well as a higher B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 ratio compared with ob/ob or control mice. Furthermore, caloric restriction attenuated adipose tissue inflammation, apoptosis, and autophagy by reversing increases in SHIP1-associated macrophages, Bax/Bcl2-ratio, and autophagy in DIO and ob/ob mice. These results demonstrate that DIO, not ob/ob, aggravates adipocyte inflammation, apoptosis, and autophagy due to differential SHIP1 expression. The evidence of decreased SHIP1-mediated inflammation, apoptosis, and autophagy indicates new therapeutic approaches for obesity-induced chronic inflammatory diseases.
Immunological Memory in Imiquimod-Induced Murine Model of Psoriasiform Dermatitis
Authors: Fenix Kevin , Wijesundara Danushka K. , Cowin Allison J. , Grubor-Bauk Branka , Kopecki Zlatko
Published: September 2020

Psoriasis is a common chronic inflammatory skin condition manifested by T cell responses and characterized by preferential recurrence at previously inflamed sites upon withdrawal of treatment. The site-specific disease memory in psoriasis has been linked to CD8+CD103+ tissue-resident memory T cells (Trm) in the epidermis which were previously thought to only provide “frontline” protection against pathogens and immunosurveillance during cancer development. In this study, we correlated the presence of a subset of the Trm cells which are also CD49a+ with disease severity in human psoriatic lesions with acute and chronic disease. Using an imiquimod (IMQ)-induced murine model of psoriasiform dermatitis, we also investigated the level of CD49a+ Trm cells in acute, chronic and resolved psoriatic lesions. Investigation of clinical human samples showed that patient disease severity highly correlated with the numbers of epidermal CD49a+ Trm cells. Additionally, this subset of Trm cells was shown to persist in resolved lesions of murine psoriasiform dermatitis once clinical disease features had subsided. Importantly, these CD49a+ Trm cells showed significantly higher levels of granzyme B (GzmB) production compared to acute disease, suggesting a potential role of CD49a+ Trm cells for psoriatic re-occurrence in resolved patients. Better understanding of epidermal CD49a+ Trm cell activity is necessary for development of advanced treatment strategies for psoriasis to permit long-term, continuous disease control.
Differential Effect of Extracellular Acidic Environment on IL-1β Released from Human and Mouse Phagocytes
Authors: Sušjan Petra , Benčina Mojca , Hafner-Bratkovič Iva
Published: September 2020

Areas of locally decreased pH are characteristic for many chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis, acute pathologies such as ischemia reperfusion, and tumor microenvironment. The data on the effects of extracellular acidic pH on inflammation are conflicting with respect to interleukin 1 beta (IL-1β) as one of the most potent proinflammatory cytokines. In this study, we used various mouse- and human-derived cells in order to identify potential species-specific differences in IL-1β secretion pattern in response to extracellular acidification. We found that a short incubation in mild acidic medium caused significant IL-1β release from human macrophages, however, the same effect was not observed in mouse macrophages. Rather, a marked IL-1β suppression was observed when mouse cells were stimulated with a combination of various inflammasome instigators and low pH. Upon activation of cells under acidic conditions, the cytosolic pH was reduced while metabolic activity and the expression of the main inflammasome proteins were not affected by low pH. We show that IL-1β secretion in mouse macrophages is reversible upon restoration of physiological pH. pH sensitivity of NLRP3, NLRC4 and AIM2 inflammasomes appeared to be conferred by the processes upstream of the apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization and most likely contributed by the cell background rather than species-specific amino acid sequences of the sensor proteins.
MicroRNA-31 Regulates Expression of Wntless in Both Drosophila melanogaster and Human Oral Cancer Cells
Authors: Jung Ji Eun , Lee Joo Young , Kim In Ryoung , Park Sang Mee , Kang Ji Wan , Kim Yun Hak , Park Hae Ryoun , Lee Ji Hye
Published: September 2020

Recent comparative studies have indicated distinct expression profiles of short, non-coding microRNAs (miRNAs) in various types of cancer, including oral squamous cell carcinoma (OSCC). In this study, we employed a hybrid approach using Drosophila melanogaster as well as OSCC cell lines to validate putative targets of oral cancer-related miRNAs both in vivo and in vitro. Following overexpression of Drosophila miR-31, we found a significant decrease in the size of the imaginal wing discs and downregulation of a subset of putative targets, including wntless (wls), an important regulator of the Wnt signaling pathway. Parallel experiments performed in OSCC cells have also confirmed a similar miR-31-dependent regulation of human WLS that was not initially predicted as targets of human miR-31. Furthermore, we found subsequent downregulation of cyclin D1 and c-MYC, two of the main transcriptional targets of Wnt signaling, suggesting a potential role of miR-31 in regulating the cell cycle and proliferation of OSCC cells. Taken together, our Drosophila-based in vivo system in conjunction with the human in vitro platform will thus provide a novel insight into a mammal-to-Drosophila-to-mammal approach to validate putative targets of human miRNA and to better understand the miRNA-target relationships that play an important role in the pathophysiology of oral cancer.
Maternal Adenine-Induced Chronic Kidney Disease Programs Hypertension in Adult Male Rat Offspring: Implications of Nitric Oxide and Gut Microbiome Derived Metabolites
Authors: Hsu Chien-Ning , Yang Hung-Wei , Hou Chih-Yao , Chang-Chien Guo-Ping , Lin Sufan , Tain You-Lin
Published: September 2020

Maternal chronic kidney disease (CKD) during pregnancy causes adverse fetal programming. Nitric oxide (NO) deficiency, gut microbiota dysbiosis, and dysregulated renin-angiotensin system (RAS) during pregnancy are linked to the development of hypertension in adult offspring. We examined whether maternal adenine-induced CKD can program hypertension and kidney disease in adult male offspring. We also aimed to identify potential mechanisms, including alterations of gut microbiota composition, increased trimethylamine-N-oxide (TMAO), reduced NO bioavailability, and dysregulation of the RAS. To construct a maternal CKD model, female Sprague-Dawley rats received regular chow (control group) or chow supplemented with 0.5% adenine (CKD group) for 3 weeks before pregnancy. Mother rats were sacrificed on gestational day 21 to analyze placentas and fetuses. Male offspring (n = 8/group) were sacrificed at 12 weeks of age. Adenine-fed rats developed renal dysfunction, glomerular and tubulointerstitial damage, hypertension, placental abnormalities, and reduced fetal weights. Additionally, maternal adenine-induced CKD caused hypertension and renal hypertrophy in adult male offspring. These adverse pregnancy and offspring outcomes are associated with alterations of gut microbiota composition, increased uremic toxin asymmetric and symmetric dimethylarginine (ADMA and SDMA), increased microbiota-derived uremic toxin TMAO, reduced microbiota-derived metabolite acetate and butyrate levels, and dysregulation of the intrarenal RAS. Our results indicated that adenine-induced maternal CKD could be an appropriate model for studying uremia-related adverse pregnancy and offspring outcomes. Targeting NO pathway, microbiota metabolite TMAO, and the RAS might be potential therapeutic strategies to improve maternal CKD-induced adverse pregnancy and offspring outcomes.
Non-Alcoholic Fatty Liver Disease Markers Associated with Fasting Serum Insulin and Urinary Albumin Excretion Independent of Fasting Plasma Glucose
Authors: Katoh Shuichi , Peltonen Markku , Zeniya Mikio , Sakamoto Yoichi , Utsunomiya Kazunori , Nishimura Rimei , Tuomilehto Jaakko
Published: September 2020

Objective: We examined the association between non-alcoholic fatty liver disease (NAFLD) markers and fasting serum immunoreactive insulin (FIRI) and urinary albumin excretion (UAE). Subjects and methods: This study comprised Periods I and II from January 2007 to May 2009, and from June 2009 to December 2011, respectively. After excluding people with ethanol intake ≥210 g/week in men and ≥140 g/week in women, 961 people (613 men, 348 women; mean age: 44 years) were included. We evaluated the fatty liver using ultrasonography score (FLUS) and measured liver enzymes. Results: The mean observation period was 25 ± 9 months. We stratified people into two groups by fasting plasma glucose (FPG) in Period I. The cutoff point between the lower FPG and higher FPG was 100 mg/dL. In regression analysis, serum alanine aminotransferase (ALT) (p < 0.001), FLUS (p < 0.001) and γ-glutamyl transpeptidase (GGTP) (p = 0.022) in Period I were independently associated with FIRI in Period II, whereas in all participants FPG was not. ALT (p < 0.001) and GGTP (p = 0.001) were also independently associated with UAE in people with FPG < 100 mg/dL in Period II. Conclusions: Some NAFLD markers were associated with FIRI and UAE independently of fasting plasma glucose.