bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Gender Role Stereotypes and Patriarchal Culture Affect Nursing Students’ Major Satisfaction?
Authors: Cho Sunhee , Jang Sun Joo
Published: March 2021

This study aimed to identify the relationships between gender role stereotypes (GRS), patriarchal family environment, and major satisfaction (MS) and their associated factors in nursing students. A total of 195 nursing students (154 women, 41 men) were surveyed online in South Korea from May to June 2020. The Gender Role Stereotype Inventory was used to assess gender role stereotypes, while patriarchal family environment and MS were evaluated using a 11-item instrument for testing patriarchal family environment and the Major Satisfaction Inventory, respectively. Men demonstrated stronger gender role stereotypes and patriarchal family culture than women. Patriarchal family culture was significantly correlated with gender role stereotypes and MS. A multiple regression analysis was performed to identify the effects of age, academic performance, motive for MS, intellectual GRS, social GRS, and patriarchal family environment on MS. The explanatory power of this model was 12.2%. Younger age, higher grade point average, voluntary selection of major, lower intellectual gender stereotypes, and higher social gender stereotypes predicted higher MS. Further studies on cultures in Asia and the world are needed to understand the impact of the patriarchal family culture and gender role stereotypes of nursing students on school adaptation.
Private Insurance and Mental Health among Older Adults with Multiple Chronic Conditions: A Longitudinal Analysis by Race and Ethnicity
Authors: Jun Hankyung , Aguila Emma
Published: March 2021

Older adults with multiple chronic conditions have a higher risk than those without multiple conditions of developing a mental health condition. Individuals with both physical and mental conditions face many substantial burdens. Many such individuals also belong to racial and ethnic minority groups. Private insurance coverage can reduce the risks of developing mental illnesses by increasing healthcare utilization and reducing psychological stress related to financial hardship. This study examines the association between private insurance and mental health (i.e., depressive symptoms and cognitive impairment) among older adults in the United States with multiple chronic conditions by race and ethnicity. We apply a multivariate logistic model with individual fixed-effects to 12 waves of the Health and Retirement Study. Among adults with multiple chronic conditions in late middle age nearing entry to Medicare and of all racial and ethnic groups, those without private insurance have a stronger probability of having depressive symptoms. Private insurance and Medicare can mediate the risk of cognitive impairment among non-Hispanic Whites with multiple chronic conditions and among Blacks regardless of the number of chronic conditions. Our study has implications for policies aiming to reduce disparities among individuals coping with multiple chronic conditions.
Effectiveness of Communication Interventions in Obstetrics—A Systematic Review
Authors: Lippke Sonia , Derksen Christina , Keller Franziska Maria , Kötting Lukas , Schmiedhofer Martina , Welp Annalena
Published: March 2021

(1) Background: Obstetric work requires good communication, which can be trained through interventions targeting healthcare providers and pregnant women/patients. This systematic review aims to aggregate the current state of research on communication interventions in obstetrics. (2) Methods: Using the PICOS scheme, we searched for studies published in peer-reviewed journals in English or German between 2000 and 2020. Out of 7018 results, 71 studies were included and evaluated in this synthesis using the Oxford Level of Evidence Scale. (3) Results: The 63 studies that included a communication component revealed a positive effect on different proximal outcomes (i.e., communication skills). Three studies revealed a beneficial effect of communication trainings on distal performance indicators (i.e., patient safety), but only to a limited extent. Most studies simultaneously examined different groups, however, those addressing healthcare providers were more common than those with students (61 vs. 12). Only nine studies targeted expectant mothers. Overall, the evidence level of studies was low (only 11 RCTs), with 24 studies with an evidence level I-II, 35 with level III, and 10 with level IV. (4) Conclusions: Communication trainings should be more frequently applied to improve communication of staff, students, and pregnant women and their partners, thereby improving patient safety.
Induced Effect of Environmental Regulation on Green Innovation: Evidence from the Increasing-Block Pricing Scheme
Authors: Liu Zhangsheng , Yang Liuqingqing , Fan Liqin
Published: March 2021

With increasing constraints on resources and the environment, it is of great practical importance to discover and utilize the induced effect of green technology through market-based tools, in order to simultaneously realize economic development and ecological sustainability. Based on unique patent data from 1999 to 2013, this paper examines the induced effect of China’s increasing-block electricity pricing scheme (IBP) on energy-efficient patents and checks whether the effect is neutral or biased. Furthermore, the quality of the induced patents is identified. The results reveal that increased green innovation is strongly related to the IBP scheme. In addition, the induced effect is biased towards green technology such that, apart from autonomous technological advances, the biased effect of IBP induced two more energy-efficient patents per hundred technological patents. However, the quality of the induced innovation is relatively low: compared to high-quality inventions, low-quality utility models showed greater and more significant growth due to the IBP. Our paper provides quantitative insight into the impact of the IBP and indicates that a reasonable pricing scheme can benefit both the environment and the economy.
A Risk Exchange: Health and Mobility in the Context of Climate and Environmental Change in Bangladesh—A Qualitative Study
Authors: Nayna Schwerdtle Patricia , Baernighausen Kate , Karim Sayeda , Raihan Tauheed Syed , Selim Samiya , Baernighausen Till , Danquah Ina
Published: March 2021

Background: Climate change influences patterns of human mobility and health outcomes. While much of the climate change and migration discourse is invested in quantitative predictions and debates about whether migration is adaptive or maladaptive, less attention has been paid to the voices of the people moving in the context of climate change with a focus on their health and wellbeing. This qualitative research aims to amplify the voices of migrants themselves to add nuance to dominant migration narratives and to shed light on the real-life challenges migrants face in meeting their health needs in the context of climate change. Methods: We conducted 58 semi-structured in-depth interviews with migrants purposefully selected for having moved from rural Bhola, southern Bangladesh to an urban slum in Dhaka, Bangladesh. Transcripts were analysed using thematic analysis under the philosophical underpinnings of phenomenology. Coding was conducted using NVivo Pro 12. Findings: We identified two overarching themes in the thematic analysis: Firstly, we identified the theme “A risk exchange: Exchanging climate change and health risks at origin and destination”. Rather than describing a “net positive” or “net negative” outcome in terms of migration in the context of climate change, migrants described an exchange of hazards, exposures, and vulnerabilities at origin with those at destination, which challenged their capacity to adapt. This theme included several sub-themes—income and employment factors, changing food environment, shelter and water sanitation and hygiene (WaSH) conditions, and social capital. The second overarching theme was “A changing health and healthcare environment”. This theme also included several sub-themes—changing physical and mental health status and a changing healthcare environment encompassing quality of care and barriers to accessing healthcare. Migrants described physical and mental health concerns and connected these experiences with their new environment. These two overarching themes were prevalent across the dataset, although each participant experienced and expressed them uniquely. Conclusion: Migrants who move in the context of climate change face a range of diverse health risks at the origin, en route, and at the destination. Migrating individuals, households, and communities undertake a risk exchange when they decide to move, which has diverse positive and negative consequences for their health and wellbeing. Along with changing health determinants is a changing healthcare environment where migrants face different choices, barriers, and quality of care. A more migrant-centric perspective as described in this paper could strengthen migration, climate, and health governance. Policymakers, urban planners, city corporations, and health practitioners should integrate the risk exchange into practice and policies.
Assessing Commensality in Research
Authors: Scander Henrik , Yngve Agneta , Lennernäs Wiklund Maria
Published: March 2021

This scoping review focuses on the assessment of commensality in research and attempts to identify used methods for performing research on commensality. It reflects a multidisciplinary research field and draws on findings from Web of Science Core Collection, up to April 2019. The empirical material consisted of 61 studies, whereof most were qualitative research, and some were of quantitative character, including very few dietary surveys. The findings show nine papers categorized as using quantitative approaches, 52 papers were categorized as qualitative. The results show a wide variety of different ways to try to find and understand how commensality can be understood and identified. There seems to be a shift in the very concept of commensality as well as some variations around the concept. This paper argues the need to further investigate the importance of commensality for health and wellbeing, as well as the need to gather data on health and health-related behaviors, living conditions and sociodemographic data in parallel. The review shows the broad-ranging areas where commensality is researched, from cultural and historical areas to ethnographic or anthropological areas over to dietary assessment. To complement large dietary surveys with methods of assessing who you are eating with in what environment should be a simple way to further our knowledge on the circumstances of meal intake and the importance of commensality. To add 24-h dietary recall to any study of commensality is another way of identifying the importance of commensality for dietary quality. The use of mixed methods research was encouraged by several authors as a good way forward in the assessment of commensality and its importance.
The Safety of Slaughterhouse Workers during the Pandemic Crisis
Authors: Ursachi Claudiu Ștefan , Munteanu Florentina-Daniela , Cioca Gabriela
Published: March 2021

The working conditions in a slaughterhouse are difficult because of the low temperatures, high humidity, and little natural light. Therefore, in these facilities, there is a high demand in the maintenance of strict hygiene rules. Lately, the new SARS-CoV-2 pandemic situation has brought new challenges in the meat industry, as this sector has to maintain its operability to supply the meat and meat products demanded by the consumers. In this challenging period, the safety of the workers is as important as keeping the high demands for the safety of the meat and meat products along with consumer confidence. This paper aims to give an overview of the risks associated with the SARS-CoV-2 virus transmission between the workers in slaughterhouses and to evaluate the stability and infectivity in the working environment of these facilities. Considering the persistence of this virus on different surfaces and the environmental conditions affecting its stability (temperature, relative humidity, and natural light), in the study we proposed several short-, medium-, and long-term preventive measures for minimizing the potential threats of the actual pandemic.
Linkage Analysis between Finance and Environmental Protection Sectors in China: An Approach to Evaluating Green Finance
Authors: Li Libo , Wu Wenbing , Zhang Mingyu , Lin Lu
Published: March 2021

Given the growing awareness of sustainable development, the environmental protection industry has attracted much attention. Green finance has developed rapidly in policymaking and practices. This study provides a framework for evaluating green finance via linkage analysis based on input–output theory. Measurements on industrial linkages are calculated in China in two provinces from 2002 to 2018, which study the relationship between finance and environmental protection sectors. The results show that the environmental protection sector (EPS) in China has gradually developed from a sector with weak backward and strong forward linkages to a sector with strong backward and weak forward linkages from 2002 to 2015; however, in 2017 and 2018, the EPS returned to a sector with weak backward and strong forward linkages. At the provincial level, the EPS used to be a key sector with strong backward and forward linkages. The connection between the finance sector and the EPS rose first, then declined in the country and the Zhejiang province; Guangdong had a similar evolution in the former period, but it had a rising trend in the latest year. The findings provide insights for further promoting the support from the finance sector to the environmental protection activities.
Effects of Exercise Interventions on Weight, Body Mass Index, Lean Body Mass and Accumulated Visceral Fat in Overweight and Obese Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Lee Hyun Suk , Lee Junga
Published: March 2021

(1) Background: Exercise interventions for overweight and obese individuals help reduce accumulated visceral fat, which is an indicator of cardiometabolic risk, but the effectiveness of these interventions is controversial. The purpose of this meta-analysis was to investigate the effectiveness of exercise interventions in overweight and obese individuals in order to reduce weight, body mass index (BMI), and accumulated visceral fat, and increase lean body mass. (2) Methods: Databases were used to select eligible studies for this meta-analysis. Randomized controlled trials with control and experimental groups were included. The degrees of effectiveness of the exercise interventions were computed to assess the benefits on reducing weight, BMI, and accumulated visceral fat, and increasing lean body mass. (3) Results: Sixteen studies were included in this meta-analysis. Participation in exercise interventions reduced weight (d = −0.58 (95% confidence interval (CI), −0.84–−0.31; p < 0.001; k = 9)), BMI (d = −0.50 (95% CI, −0.78–−0.21; p < 0.001; k = 7)), and accumulated visceral fat (d = −1.08 (95% CI, −1.60–−0.57; p < 0.001; k = 5)), but did not significantly increase lean body mass (d = 0.26 (95% CI, −0.11–0.63; p = 0.17; k = 6)). The average exercise intervention for overweight and obese individuals was of moderate to vigorous intensity, 4 times per week, 50 min per session, and 22 weeks duration. (4) Conclusions: Participating in exercise interventions has favorable effects on weight, BMI, and accumulated visceral fat. Further studies considering different modalities, intensities, durations, and measurements of fatness need to be conducted.
The Influence of the Competences of the Professionals in Charge of Family Evidence-Based Programmes on Internalizing and Externalizing Symptoms in Adolescents
Authors: Orte Carmen , Sánchez-Prieto Lidia , Montaño Juan José , Pascual Belén
Published: March 2021

This study analyses the influence of trainers’ intrapersonal and group management competences on the effectiveness of the Universal Strengthening Families Program 11-14 (SFP 11-14). More specifically, it assesses the effect of these competences on internalizing and externalizing symptoms in adolescents. The analysed data is made up of ratings given by the 174 mothers participating in SFP 11-14. The results confirm the effectiveness of SFP 11-14 in reducing internalizing and externalizing symptoms in adolescents. Using linear regression models, evidence is provided of the influence of the trainers’ expertise, in terms of their competences, in improving internalizing symptoms in adolescents (through a reduction in levels of anxiety, depression, and somatization and in the global internalization scale). Emphasis is placed on how trainer competences can impact on the effectiveness of evidence-based programmes, stressing that this should be taken into account by the public authorities and other stakeholders in the assessment and design of family evidence-based programmes.
Geospatial User Feedback: How to Raise Users’ Voices and Collectively Build Knowledge at the Same Time
Authors: Zabala Alaitz , Masó Joan , Bastin Lucy , Giuliani Gregory , Pons Xavier
Published: March 2021

Geospatial data is used not only to contemplate reality but also, in combination with analytical tools, to generate new information that requires interpretation. In this process data users gain knowledge about the data and its limitations (the user side of data quality) as well as knowledge on the status and evolutions of the studied phenomena. Knowledge can be annotations on top of the data, responses to questions, a careful description of the processes applied, a piece of software code or scripts applied to the data, usage reports or a complete scientific paper. This paper proposes an extension of the current Open Geospatial Consortium standard for Geospatial User Feedback to include the required knowledge elements, and a practical implementation. The system can incrementally collect, store, and communicate knowledge elements created by users of the data and keep them linked to the original data by means of permanent data identifiers. The system implements a Web API to manage feedback items as a frontend to a database. The paper demonstrates how a JavaScript widget accessing this API as a client can be easily integrated into existing data catalogues, such as the ECOPotential web service or the GEOEssential data catalogue, to collectively collect and share knowledge.
TRAIL Mediates Neuronal Death in AUD: A Link between Neuroinflammation and Neurodegeneration
Authors: Qin Liya , Zou Jian , Barnett Alexandra , Vetreno Ryan P. , Crews Fulton T. , Coleman Leon G.
Published: March 2021

Although the cause of progressive neurodegeneration is often unclear, neuronal death can occur through several mechanisms. In conditions such as Alzheimer’s or alcohol use disorder (AUD), Toll-like receptor (TLR) induction is observed with neurodegeneration. However, links between TLR activation and neurodegeneration are lacking. We report a role of apoptotic neuronal death in AUD through TLR7-mediated induction of death receptor signaling. In postmortem human cortex, a two-fold increase in apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in neurons was found in AUD versus controls. This occurred with the increased expression of TLR7 and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) death receptors. Binge ethanol treatment in C57BL/6 mice increased TLR7 and induced neuronal apoptosis in cortical regions that was blocked by TLR7 antagonism. Mechanistic studies in primary organotypic brain slice culture (OBSC) found that the inhibition of TLR7 and its endogenous ligand let-7b blocked ethanol-induced neuronal cell death. Both IMQ and ethanol induced the expression of TRAIL and its death receptor. In addition, TRAIL-neutralizing monoclonal antibodies blocked both imiquimod (IMQ) and ethanol induced neuronal death. These findings implicate TRAIL as a mediator of neuronal apoptosis downstream of TLR7 activation. TLR7 and neuronal apoptosis are implicated in other neurodegenerative diseases, including Alzheimer’s disease. Therefore, TRAIL may represent a therapeutic target to slow neurodegeneration in multiple diseases.
Lipid Dynamics in Diisobutylene-Maleic Acid (DIBMA) Lipid Particles in Presence of Sensory Rhodopsin II
Authors: Voskoboynikova Natalia , Orekhov Philipp , Bozdaganyan Marine , Kodde Felix , Rademacher Malte , Schowe Maurice , Budke-Gieseking Annette , Brickwedde Britta , Psathaki Olympia-Ekaterini , Mulkidjanian Armen Y. , Cosentino Katia , Shaitan Konstantin V. , Steinhoff Heinz-Jürgen
Published: March 2021

Amphiphilic diisobutylene/maleic acid (DIBMA) copolymers extract lipid-encased membrane proteins from lipid bilayers in a detergent-free manner, yielding nanosized, discoidal DIBMA lipid particles (DIBMALPs). Depending on the DIBMA/lipid ratio, the size of DIBMALPs can be broadly varied which makes them suitable for the incorporation of proteins of different sizes. Here, we examine the influence of the DIBMALP sizes and the presence of protein on the dynamics of encased lipids. As shown by a set of biophysical methods, the stability of DIBMALPs remains unaffected at different DIBMA/lipid ratios. Coarse-grained molecular dynamics simulations confirm the formation of viable DIBMALPs with an overall size of up to 35 nm. Electron paramagnetic resonance spectroscopy of nitroxides located at the 5th, 12th or 16th carbon atom positions in phosphatidylcholine-based spin labels reveals that the dynamics of enclosed lipids are not altered by the DIBMALP size. The presence of the membrane protein sensory rhodopsin II from Natronomonas pharaonis (NpSRII) results in a slight increase in the lipid dynamics compared to empty DIBMALPs. The light-induced photocycle shows full functionality of DIBMALPs-embedded NpSRII and a significant effect of the protein-to-lipid ratio during preparation on the NpSRII dynamics. This study indicates a possible expansion of the applicability of the DIBMALP technology on studies of membrane protein–protein interaction and oligomerization in a constraining environment.
Potential Therapeutic Applications of Hydrogen in Chronic Inflammatory Diseases: Possible Inhibiting Role on Mitochondrial Stress
Authors: Hirano Shin-ichi , Ichikawa Yusuke , Sato Bunpei , Yamamoto Haru , Takefuji Yoshiyasu , Satoh Fumitake
Published: March 2021

Mitochondria are the largest source of reactive oxygen species (ROS) and are intracellular organelles that produce large amounts of the most potent hydroxyl radical (·OH). Molecular hydrogen (H2) can selectively eliminate ·OH generated inside of the mitochondria. Inflammation is induced by the release of proinflammatory cytokines produced by macrophages and neutrophils. However, an uncontrolled or exaggerated response often occurs, resulting in severe inflammation that can lead to acute or chronic inflammatory diseases. Recent studies have reported that ROS activate NLRP3 inflammasomes, and that this stimulation triggers the production of proinflammatory cytokines. It has been shown in literature that H2 can be based on the mechanisms that inhibit mitochondrial ROS. However, the ability for H2 to inhibit NLRP3 inflammasome activation via mitochondrial oxidation is poorly understood. In this review, we hypothesize a possible mechanism by which H2 inhibits mitochondrial oxidation. Medical applications of H2 may solve the problem of many chronic inflammation-based diseases, including coronavirus disease 2019 (COVID-19).
Comprehensive Analysis of Correlations in the Expression of miRNA Genes and Immune Checkpoint Genes in Bladder Cancer Cells
Authors: Stempor Przemysław A. , Avni Dror , Leibowitz Raya , Sidi Yechezkel , Stępień Maria , Dzieciątkowski Tomasz , Dobosz Paula
Published: March 2021

Personalised medicine is the future and hope for many patients, including those with cancers. Early detection, as well as rapid, well-selected treatment, are key factors leading to a good prognosis. MicroRNA mediated gene regulation is a promising area of development for new diagnostic and therapeutic methods, crucial for better prospects for patients. Bladder cancer is a frequent neoplasm, with high lethality and lacking modern, advanced therapeutic modalities, such as immunotherapy. MicroRNAs are involved in bladder cancer pathogenesis, proliferation, control and response to treatment, which we summarise in this perspective in response to lack of recent review publications in this field. We further performed a correlation-based analysis of microRNA and gene expression data in bladder cancer (BLCA) TCGA dataset. We identified 27 microRNAs hits with opposite expression profiles to genes involved in immune response in bladder cancer, and 24 microRNAs hits with similar expression profiles. We discuss previous studies linking the functions of these microRNAs to bladder cancer and assess if they are good candidates for personalised medicine therapeutics and diagnostics. The discussed functions include regulation of gene expression, interplay with transcription factors, response to treatment, apoptosis, cell proliferation and angiogenesis, initiation and development of cancer, genome instability and tumour-associated inflammatory reaction.
Exogenous 1′,4′-trans-Diol-ABA Induces Stress Tolerance by Affecting the Level of Gene Expression in Tobacco (Nicotiana tabacum L.)
Authors: Liu Teng , Li Cai-Xia , Zhong Juan , Shu Dan , Luo Di , Li Zhe-Min , Zhou Jin-Yan , Yang Jie , Tan Hong , Ma Xin-Rong
Published: March 2021

1′,4′-trans-diol-ABA is a key precursor of the biosynthesis of abscisic acid (ABA) biosynthesis in fungi. We successfully obtained the pure compound from a mutant of Botrytis cinerea and explored its function and possible mechanism on plants by spraying 2 mg/L 1′,4′-trans-diol-ABA on tobacco leaves. Our results showed that this compound enhanced the drought tolerance of tobacco seedlings. A comparative transcriptome analysis showed that a large number of genes responded to the compound, exhibiting 1523 genes that were differentially expressed at 12 h, which increased to 1993 at 24 h and 3074 at 48 h, respectively. The enrichment analysis demonstrated that the differentially expressed genes (DEGs) were primarily enriched in pathways related to hormones and resistance. The DEGs of transcription factors were generally up-regulated and included the bHLH, bZIP, ERF, MYB, NAC, WRKY and HSF families. Moreover, the levels of expression of PYL/PYR, PP2C, SnRK2, and ABF at the ABA signaling pathway responded positively to exogenous 1′,4′-trans-diol-ABA. Among them, seven ABF transcripts that were detected were significantly up-regulated. In addition, the genes involved in salicylic acid, ethylene and jasmonic acid pathways, reactive oxygen species scavenging system, and other resistance related genes were primarily induced by 1′,4′-trans-diol-ABA. These findings indicated that treatment with 1′,4′-trans-diol-ABA could improve tolerance to plant abiotic stress and potential biotic resistance by regulating gene expression, similar to the effects of exogenous ABA.
An Analysis of Differentially Expressed Coding and Long Non-Coding RNAs in Multiple Models of Skeletal Muscle Atrophy
Authors: Hitachi Keisuke , Nakatani Masashi , Kiyofuji Yuri , Inagaki Hidehito , Kurahashi Hiroki , Tsuchida Kunihiro
Published: March 2021

The loss of skeletal muscle mass (muscle atrophy or wasting) caused by aging, diseases, and injury decreases quality of life, survival rates, and healthy life expectancy in humans. Although long non-coding RNAs (lncRNAs) have been implicated in skeletal muscle formation and differentiation, their precise roles in muscle atrophy remain unclear. In this study, we used RNA-sequencing (RNA-Seq) to examine changes in the expression of lncRNAs in four muscle atrophy conditions (denervation, casting, fasting, and cancer cachexia) in mice. We successfully identified 33 annotated lncRNAs and 18 novel lncRNAs with common expression changes in all four muscle atrophy conditions. Furthermore, an analysis of lncRNA–mRNA correlations revealed that several lncRNAs affected small molecule biosynthetic processes during muscle atrophy. These results provide novel insights into the lncRNA-mediated regulatory mechanism underlying muscle atrophy and may be useful for the identification of promising therapeutic targets.
Expression of Interferons Lambda 3 and 4 Induces Identical Response in Human Liver Cell Lines Depending Exclusively on Canonical Signaling
Authors: Lunova Mariia , Kubovciak Jan , Smolková Barbora , Uzhytchak Mariia , Michalova Kyra , Dejneka Alexandr , Strnad Pavel , Lunov Oleg , Jirsa Milan
Published: March 2021

Lambda interferons mediate antiviral immunity by inducing interferon-stimulated genes (ISGs) in epithelial tissues. A common variant rs368234815TT/∆G creating functional gene from an IFNL4 pseudogene is associated with the expression of major ISGs in the liver but impaired clearance of hepatitis C. To explain this, we compared Halo-tagged and non-tagged IFNL3 and IFNL4 signaling in liver-derived cell lines. Transfection with non-tagged IFNL3, non-tagged IFNL4 and Halo-tagged IFNL4 led to a similar degree of JAK-STAT activation and ISG induction; however, the response to transfection with Halo-tagged IFNL3 was lower and delayed. Transfection with non-tagged IFNL3 or IFNL4 induced no transcriptome change in the cells lacking either IL10R2 or IFNLR1 receptor subunits. Cytosolic overexpression of signal peptide-lacking IFNL3 or IFNL4 in wild type cells did not interfere with JAK-STAT signaling triggered by interferons in the medium. Finally, expression profile changes induced by transfection with non-tagged IFNL3 and IFNL4 were highly similar. These data do not support the hypothesis about IFNL4-specific non-canonical signaling and point out that functional studies conducted with tagged interferons should be interpreted with caution.
MicroRNAs as Modulators of Oral Tumorigenesis—A Focused Review
Authors: Rishabh Kumar , Khadilkar Soham , Kumar Aviral , Kalra Ishu , Kumar Alan Prem , Kunnumakkara Ajaikumar B.
Published: March 2021

Oral cancers constitute the majority of head and neck tumors, with a relatively high incidence and poor survival rate in developing countries. While the five-year survival rates of the oral cancer patients have increased to 65%, the overall survival for advanced stages has been at 27% for the past ten years, emphasizing the necessity for further understanding the etiology of the disease, diagnosis, and formulating possible novel treatment regimens. MicroRNAs (miRNAs), a family of small non-coding RNA, have emerged as master modulators of gene expression in various cellular and biological process. Aberrant expression of these dynamic molecules has been associated with many human diseases, including oral cancers. The deregulated miRNAs have been shown to control various oncogenic processes, including sustaining proliferative signaling, evading growth suppressors, resisting cell death activating invasion and metastasis, and inducing angiogenesis. Hence, the aberrant expression of miRNAs associated with oral cancers, makes them potential candidates for the investigation of functional markers, which will aid in the differential diagnosis, prognosis, and development of novel therapeutic regimens. This review presents a holistic insight into our understanding of the role of miRNAs in regulating various hallmarks of oral tumorigenesis.
A Commonly Used Biocide 2-N-octyl-4-isothiazolin-3-oneInduces Blood–Brain Barrier Dysfunction via Cellular Thiol Modification and Mitochondrial Damage
Authors: Kim Donghyun , Kim Eun-Hye , Choi Sungbin , Lim Kyung-Min , Tie Lu , Majid Arshad , Bae Ok-Nam
Published: March 2021

Isothiazolinone (IT) biocides are potent antibacterial substances commonly used as preservatives or disinfectants, and 2-n-Octyl-4-isothiazolin-3-one (OIT; octhilinone) is a common IT biocide that is present in leather products, glue, paints, and cleaning products. Although humans are exposed to OIT through personal and industrial use, the potentially deleterious effects of OIT on human health are still unknown. To investigate the effects of OIT on the vascular system, which is continuously exposed to xenobiotics through systemic circulation, we treated brain endothelial cells with OIT. OIT treatment significantly activated caspase-3-mediated apoptosis and reduced the bioenergetic function of mitochondria in a bEnd.3 cell-based in vitro blood–brain barrier (BBB) model. Interestingly, OIT significantly altered the thiol redox status, as evidenced by reduced glutathione levels and protein S-nitrosylation. The endothelial barrier function of bEnd.3 cells was significantly impaired by OIT treatment. OIT affected mitochondrial dynamics through mitophagy and altered mitochondrial morphology in bEnd.3 cells. N-acetyl cysteine significantly reversed the effects of OIT on the metabolic capacity and endothelial function of bEnd.3 cells. Taken together, we demonstrated that the alteration of the thiol redox status and mitochondrial damage contributed to OIT-induced BBB dysfunction, and we hope that our findings will improve our understanding of the potential hazardous health effects of IT biocides.
A Simple Method for In-Depth Proteome Analysis of Mammalian Cell Culture Conditioned Media Containing Fetal Bovine Serum
Authors: Nakamura Ren , Nakajima Daisuke , Sato Hironori , Endo Yusuke , Ohara Osamu , Kawashima Yusuke
Published: March 2021

A conditioned medium of a cell culture is widely used for various biological applications and frequently analyzed to characterize the functional proteins responsible for observed biological functions. However, a large number of abundant proteins in fetal bovine serum (FBS), usually included in the conditioned medium of a mammalian cell culture medium, hampers in-depth proteomic analysis by liquid chromatography–tandem mass spectrometry (LC-MS/MS). For a deep proteomic analysis of a conditioned medium by LC-MS/MS, we developed a simple albumin depletion approach coupled with data-independent acquisition (DIA)-mode LC-MS/MS for the conditioned medium of mammalian cells in this study. The results showed that this approach enabled the detection of more than 3700 cell-derived proteins in the cell culture supernatant containing FBS. We further demonstrated the potency of this approach by analyzing proteins in the conditioned media of HeLa cells with and without tumor necrosis factor (TNF) stimulation: >40 differentially accumulated proteins, including four cytokines, upon TNF stimulation were identified in the culture media, which were hardly detected by conventional proteome approaches in the literature.
Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids
Authors: Romanowska Anita , Węgrzyn Katarzyna , Bury Katarzyna , Sikorska Emilia , Gnatek Aleksandra , Piwkowska Agnieszka , Konieczny Igor , Lesner Adam , Wysocka Magdalena
Published: March 2021

The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)n-O2Oc-NH2, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]8-O2Oc-NH2 and typical for large proteins.
Analysis of mir-9 Expression Pattern in Rat Retina during Postnatal Development
Authors: Pöstyéni Etelka , Kovács-Valasek Andrea , Urbán Péter , Czuni Lilla , Sétáló György , Fekete Csaba , Gabriel Robert
Published: March 2021

It is well established that miR-9 contributes to retinal neurogenesis. However, little is known about its presence and effects in the postnatal period. To expand our knowledge, miRNA-small RNA sequencing and in situ hybridization supported by RT-qPCR measurement were carried out. Mir-9 expression showed two peaks in the first three postnatal weeks in Wistar rats. The first peak was detected at postnatal Day 3 (P3) and the second at P10, then the expression gradually decreased until P21. Furthermore, we performed in silico prediction and established that miR-9 targets OneCut2 or synaptotagmin-17. Another two microRNAs (mir-135, mir-218) were found from databases which also target these proteins. They showed a similar tendency to mir-9; their lowest expression was at P7 and afterwards, they showed increase. We revealed that miR-9 is localized mainly in the inner retina. Labeling was observed in ganglion and amacrine cells. Additionally, horizontal cells were also marked. By dual miRNA-in situ hybridization/immunocytochemistry and qPCR, we revealed alterations in their temporal and spatial expression. Our results shed light on the significance of mir-9 regulation during the first three postnatal weeks in rat retina and suggest that miRNA could act on their targets in a stage-specific manner.
Heterogeneous Nuclear Ribonucleoprotein K Is Involved in the Estrogen-Signaling Pathway in Breast Cancer
Authors: Iwabuchi Erina , Miki Yasuhiro , Suzuki Takashi , Hirakawa Hisashi , Ishida Takanori , Sasano Hironobu
Published: March 2021

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) transcripts are abundant in estrogen receptor (ER)- or progesterone receptor (PR)-positive breast cancer. However, the biological functions of hnRNPK in the ER-mediated signaling pathway have remained largely unknown. Therefore, this study analyzes the functions of hnRNPK expression in the ER-mediated signaling pathway in breast cancer. We initially evaluated hnRNPK expression upon treatment with estradiol (E2) and ICI 182,780 in the ERα-positive breast carcinoma cell line MCF-7. The results revealed that E2 increased hnRNPK; however, hnRNPK expression was decreased with ICI 182,780 treatment, indicating estrogen dependency. We further evaluated the effects of hnRNPK knockdown in the ER-mediated signaling pathway in MCF-7 cells using small interfering RNAs. The results revealed that hnRNPK knockdown decreased ERα expression and ERα target gene pS2 by E2 treatment. As hnRNPK interacts with several other proteins, we explored the interaction between hnRNPK and ERα, which was demonstrated using immunoprecipitation and proximity ligation assay. Subsequently, we immunolocalized hnRNPK in patients with breast cancer, which revealed that hnRNPK immunoreactivity was significantly higher in ERα-positive carcinoma cells and significantly lower in Ki67-positive or proliferative carcinoma cells. These results indicated that hnRNPK directly interacted with ERα and was involved in the ER-mediated signaling pathway in breast carcinoma. Furthermore, hnRNPK expression could be an additional target of endocrine therapy in patients with ERα-positive breast cancer.
Red-Edge Excitation Shift Spectroscopy (REES): Application to Hidden Bound States of Ligands in Protein–Ligand Complexes
Authors: Kabir Md Lutful , Wang Feng , Clayton Andrew H. A.
Published: March 2021

Ligand-protein binding is responsible for the vast majority of bio-molecular functions. Most experimental techniques examine the most populated ligand-bound state. The determination of less populated, intermediate, and transient bound states is experimentally challenging. However, hidden bound states are also important because these can strongly influence ligand binding and unbinding processes. Here, we explored the use of a classical optical spectroscopic technique, red-edge excitation shift spectroscopy (REES) to determine the number, population, and energetics associated with ligand-bound states in protein–ligand complexes. We describe a statistical mechanical model of a two-level fluorescent ligand located amongst a finite number of discrete protein microstates. We relate the progressive emission red shift with red-edge excitation to thermodynamic parameters underlying the protein–ligand free energy landscape and to photo-physical parameters relating to the fluorescent ligand. We applied the theoretical model to published red-edge excitation shift data from small molecule inhibitor–kinase complexes. The derived thermodynamic parameters allowed dissection of the energetic contribution of intermediate bound states to inhibitor–kinase interactions.
NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR
Authors: Gwon Do Hyeong , Kim Song I. , Lee Seoung Hun , Noh Chan , Kim Yeojung , Yun Sangwon , Lee Won Hyung , Oh Jun Young , Kim Dong Woon , Hong Jinpyo , Lee Sun Yeul
Published: March 2021

Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (Het) mice. To study inflammatory pain, we injected 10 µL of 2% formalin into the right hind paws of mice and monitored pain behaviors, such as licking, lifting, and flinching, for 60 min. After the first 15 min (phase I), there were no significant differences in pain behaviors between wild-type (WT) and NFAT5-Het mice. However, from 15–60 min (phase II), NFAT5-Het mice displayed significantly fewer pain behaviors compared to WT mice. Further, the expression levels of inflammatory-pain-related factors, including c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated n-methyl-D-aspartate receptor subunit 2B (p-NR2B), were significantly elevated in the spinal dorsal neurons of formalin-treated WT mice but was not elevated in NFAT5-Het mice. Similarly, c-Fos, p-ERK, and p-NR2B levels were significantly higher in glutamate-treated PC12 neuronal cells but were not affected by Nfat5 silencing in glutamate-treated PC12 cells. Altogether, our findings suggest that NFAT5 deficiency may mitigate formalin-induced inflammatory pain by upregulating mammalian target of rapamycin (mTOR) expression and downregulating its downstream factors in spinal dorsal neurons. Therefore, NFAT5 is a potential therapeutic target for the treatment of inflammatory pain.
Thrombin–Fibrin(ogen) Interactions, Host Defense and Risk of Thrombosis
Authors: Hulshof Anne-Marije , Hemker H. Coenraad , Spronk Henri M. H. , Henskens Yvonne M. C. , ten Cate Hugo
Published: March 2021

Fibrinogen is a well-known risk factor for arterial and venous thrombosis. Its function is not restricted to clot formation, however, as it partakes in a complex interplay between thrombin, soluble plasma fibrinogen, and deposited fibrin matrices. Fibrinogen, like thrombin, participates predominantly in hemostasis to maintain vascular integrity, but executes some important pleiotropic effects: firstly, as observed in thrombin generation experiments, fibrin removes thrombin from free solution by adsorption. The adsorbed thrombin is protected from antithrombins, notably α2-macroglobulin, and remains physiologically active as it can activate factors V, VIII, and platelets. Secondly, immobilized fibrinogen or fibrin matrices activate monocytes/macrophages and neutrophils via Mac-1 interactions. Immobilized fibrin(ogen) thereby elicits a pro-inflammatory response with a reciprocal stimulating effect of the immune system on coagulation. In contrast, soluble fibrinogen prohibits recruitment of these immune cells. Thus, while fibrin matrices elicit a procoagulant response, both directly by protecting thrombin and indirectly through the immune system, high soluble fibrinogen levels might protect patients due to its immune diminutive function. The in vivo influence of the ‘protective’ plasma fibrinogen versus the ‘pro-thrombotic’ fibrin matrices on thrombosis should be explored in future research.
Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat
Authors: Wu Chung-Pu , Hung Cheng-Yu , Lusvarghi Sabrina , Chang Yen-Fu , Hsiao Sung-Han , Huang Yang-Hui , Hung Tai-Ho , Yu Jau-Song , Ambudkar Suresh. V.
Published: March 2021

Citarinostat (ACY-241) is a promising oral histone deacetylase 6 (HDAC6)-selective inhibitor currently in clinical trials for the treatment of multiple myeloma (MM) and non-small-cell lung cancer (NSCLC). However, the inevitable emergence of resistance to citarinostat may reduce its clinical effectiveness in cancer patients and limit its clinical usefulness in the future. In this study, we investigated the potential role of the multidrug efflux transporters ABCB1 and ABCG2, which are two of the most common mechanisms of acquired resistance to anticancer drugs, on the efficacy of citarinostat in human cancer cells. We discovered that the overexpression of ABCB1 or ABCG2 significantly reduced the sensitivity of human cancer cells to citarinostat. We demonstrated that the intracellular accumulation of citarinostat and its activity against HDAC6 were substantially reduced by the drug transport function of ABCB1 and ABCG2, which could be restored by treatment with an established inhibitor of ABCB1 or ABCG2, respectively. In conclusion, our results revealed a novel mechanism by which ABCB1 and ABCG2 actively transport citarinostat away from targeting HDAC6 in cancer cells. Our results suggest that the co-administration of citarinostat with a non-toxic modulator of ABCB1 and ABCG2 may optimize its therapeutic application in the clinic.
Phosphodiesterases Expression during Murine Cardiac Development
Authors: Carvalho Thays Maria da Conceição Silva , Cardarelli Silvia , Giorgi Mauro , Lenzi Andrea , Isidori Andrea M. , Naro Fabio
Published: March 2021

3′-5′ cyclic nucleotide phosphodiesterases (PDEs) are a large family of enzymes playing a fundamental role in the control of intracellular levels of cAMP and cGMP. Emerging evidence suggested an important role of phosphodiesterases in heart formation, but little is known about the expression of phosphodiesterases during cardiac development. In the present study, the pattern of expression and enzymatic activity of phosphodiesterases was investigated at different stages of heart formation. C57BL/6 mice were mated and embryos were collected from 14.5 to 18.5 days of development. Data obtained by qRT-PCR and Western blot analysis showed that seven different isoforms are expressed during heart development, and PDE1C, PDE2A, PDE4D, PDE5A and PDE8A are modulated from E14.5 to E18.5. In heart homogenates, the total cAMP and cGMP hydrolytic activity is constant at the evaluated times, and PDE4 accounts for the majority of the cAMP hydrolyzing ability and PDE2A accounts for cGMP hydrolysis. This study showed that a subset of PDEs is expressed in developing mice heart and some of them are modulated to maintain constant nucleotide phosphodiesterase activity in embryonic and fetal heart.