bluuebunny/crossref_metadata_2025 huggingface dataset:
Bibliometric Analysis of Literature on Physical Activity and COVID-19
Authors: Wattanapisit Apichai , Kotepui Manas , Wattanapisit Sanhapan , Crampton Noah
Published: June 2022

The coronavirus disease 2019 (COVID-19) pandemic induced a sudden surge in COVID-19 related publications. This bibliometric analysis aimed to analyze literature on physical activity and COVID-19 published in the PubMed database. The search terms ((physical activity [MeSH Terms] OR physical inactivity [MeSH Terms]) AND COVID-19 [MeSH Terms]) were applied to obtain publications from the inception of PubMed to February 2022. The analyses included the year of publication, type of publication, and origin of publication by country, region, and country income. The research areas were analyzed for research articles and systematic reviews. Of 1268 articles, 143 articles were excluded, and 1125 articles were analyzed. A total of 709 articles (63.02%) were published in 2021. A majority of publications were research articles (n = 678, 60.27%). The USA (n = 176, 15.64%), countries in the European Region (n = 496, 44.09%), and high-income countries (n = 861, 76.53%) were dominant publishing countries. Of 699 research articles and systematic reviews, surveillance and trends of physical activity were the main research area, followed by health outcomes, and correlates and determinants of physical activity. There is a wide gap in publication productivity in the field of physical activity and health during the pandemic among different countries’ economic statuses.
The Effect of Three-Year Swim Training on Cardio-Respiratory Fitness and Selected Somatic Features of Prepubertal Boys
Authors: Zarzeczny Ryszard , Kuberski Mariusz , Suliga Edyta
Published: June 2022

The data regarding somatic and physiological effects of sport-related physical activities in youth are limited. Moreover, whether exercise training is capable of increasing cardio-respiratory fitness remains a disputable issue. The study undertook to assess the effect of swimming training on cardio-respiratory fitness (CRF) and the development of physical traits in prepubertal boys, and to determine which of the traits is the best predictor of their CRF. Forty 10-year old prepubertal boys (10.5 ± 0.3 y) were divided into two groups (swimmers (SG), n = 20, and controls (CG), n = 20), which underwent anthropometric measurements and performed a 20 m shuttle run test (20 mSRT) semi-annually over a 3-year period. CRF indices (the number of 20 mSRT shuttles, maximal speed, and VO2max) were higher overall in the SG compared with the CG (p < 0.001). The values of the main physique variables increased faster in the CG, but the groups showed no differentiation of physical traits. In both groups, CRF indices were associated with the participants’ physical traits, the most strongly with the sum of four skinfold thicknesses in the SG and knee breadth in the CG. These results suggest that swimming training is a form of additional physical activity that improves prepubertal boys’ CRF but does not significantly affect their physical development. In using the 20 mSRT to assess the CRF of prepubertal boys, their physical activity level and age-related changes in body fatness need to be considered.
Episodic Future Thinking about Smoking-Related Illness: A Preliminary Investigation of Effects on Delay Discounting, Cigarette Craving, and Cigarette Demand
Authors: Ruhi-Williams Perisa , King Mary J. , Stein Jeffrey S. , Bickel Warren K.
Published: June 2022

Cigarette smokers show excessive delay discounting (devaluation of delayed rewards), which may contribute to tobacco use disorder. Episodic future thinking (EFT), or mental simulation of future events, has been shown to reduce both delay discounting and laboratory smoking behavior. Traditionally, EFT involves vividly imagining positive future events. In this preliminary investigation, we examined the effects of EFT specifically about smoking-related illness (SRI) on delay discounting, cigarette craving, and behavioral economic demand for cigarettes. In a 2 (episodic thinking) × 2 (smoking-related illness) factorial design, we randomly assigned smokers from Amazon Mechanical Turk to one of two EFT groups: EFT alone or EFT + SRI; or one of two episodic “recent” thinking (ERT) control groups: ERT alone or ERT + SRI. Both EFT groups generated and imagined positive future events, while both ERT groups imagined real events from the recent past. Both EFT + SRI and ERT + SRI groups imagined these events while also experiencing SRI symptoms. Participants then completed assessments of delay discounting, cigarette craving, and measures of cigarette demand. We observed significant main effects on delay discounting of both EFT (reduced discounting) and SRI (increased discounting), as well as significant main effects of both EFT and SRI on cigarette craving (in both cases, reduced craving). No significant main effect of EFT was observed on cigarette demand measures, although we observed a main effect of SRI on quantity of demand when cigarettes were free (Q0) (reduced demand). In all analyses, we observed no significant EFT × SRT interactions, indicating that these variables operate independently of one another. These methods may be adapted for use in clinical treatment to aid in smoking cessation interventions.
Rethinking Lockdown Policies in the Pre-Vaccine Era of COVID-19: A Configurational Perspective
Authors: Zhang Ziang , Liu Chao , Nunkoo Robin , Sunnassee Vivek A. , Chen Xiaoyan
Published: June 2022

The significance of lockdown policies for controlling the COVID-19 pandemic is widely recognized. However, most studies have focused on individual lockdown measures. The effectiveness of lockdown policy combinations has not been examined from a configurational perspective. This research applies fuzzy-set qualitative comparative analysis (fsQCA) to examine different lockdown policy combinations associated with high-epidemic situations in 84 countries. A high-epidemic situation can occur through three different “weak-confined” patterns of lockdown policy combinations. The findings demonstrate that a combination of lockdown policies is more successful than any single lockdown policy, whereas the absence of several key measures in policy combinations can lead to a high-epidemic situation. The importance of international travel controls can become obscured when they are the only measures adopted, and a high-epidemic situation can still arise where restrictions are placed on international travel but not on public transport or when workplaces are closed but schools remain open.
A Changing Home: A Cross-Sectional Study on Environmental Degradation, Resettlement and Psychological Distress in a Western German Coal-Mining Region
Authors: Krüger Theresa , Kraus Thomas , Kaifie Andrea
Published: June 2022

Unwelcome environmental changes can lead to psychological distress, known as “solastalgia”. In Germany, the open-pit mining of brown coal results in environmental changes as well as in the resettlement of adjacent villages. In this study, we investigated the risk of open-pit mining for solastalgia and psychological disorders (e.g., depression, generalized anxiety and somatization) in local communities. The current residents and resettlers from two German open-pit mines were surveyed concerning environmental stressors, place attachment, impacts and mental health status. In total, 620 people responded, including 181 resettlers, 114 people from villages threatened by resettlement and 325 people from non-threatened villages near an open-pit mine. All groups self-reported high levels of psychological distress, approximately ranging between 2–7.5 times above the population average. Respondents from resettlement-threatened villages showed the worst mental health status, with 52.7% indicating at least moderate somatization levels (score sum > 9), compared to 28% among resettlers. We observed a mean PHQ depression score of 7.9 (SD 5.9) for people from resettlement-threatened villages, 7.4 (SD 6.0) for people from not-threatened villages, compared to 5.0 (SD 6.5) for already resettled people (p < 0.001). In conclusion, the degradation and loss of the home environment caused by open-pit mining was associated with an increased prevalence of depressive, anxious and somatoform symptoms in local communities. This reveals a need for further in-depth research, targeted psychosocial support and improved policy frameworks, in favor of residents’ and resettlers’ mental health.
Attitudes of Nursing Staff in Hospitals towards Restraint Use: A Cross-Sectional Study
Authors: Thomann Silvia , Gleichner Gesche , Hahn Sabine , Zwakhalen Sandra
Published: June 2022

The attitude of nursing staff towards restraint use can be decisive for whether restraints are used. So far, nursing staff’s attitudes have been studied primarily in long-term and mental health care settings, while findings from somatic acute care hospital settings are largely lacking. Therefore, we aimed to investigate (a) the attitudes of hospital nursing staff towards restraint use, and (b) the construct validity and reliability of a measurement instrument for use in hospital settings that was developed and validated in long-term care settings (Maastricht Attitude Questionnaire (MAQ)). Using a cross-sectional design, the attitudes of 180 nursing staff towards restraint use were assessed. The data were analysed descriptively and by means of regression analysis and factor analysis. We found that nursing staff in hospitals have a neutral attitude towards restraint use and that the MAQ, with minor adaptations, can be used in hospital settings, although further testing is recommended. Neutral attitudes of nursing staff have also been observed in long-term and mental health care settings, where changing attitudes were found to be challenging. Interventions at the national level (e.g., legal regulations) and management level (e.g., providing alternatives and changing institutional culture) are suggested.
Well-Being and Stress of Children in Teaching by Digital Means during the COVID-19 Pandemic: A Case in Santarém, Brazilian Amazonia
Authors: Albarado Kaio Vinícius Paiva , Lauer-Leite Iani Dias , de Oliveira Carvalho Dennison Célio , Vieira Thiago Almeida
Published: June 2022

The COVID-19 pandemic has caused and is still causing many infections. An important change brought about by prevention actions was the closing of schools, and the adoption of teaching by digital means in private institutions. In this article, we aim to analyze the subjective well-being and stress of children aged 8 to 12 years in digital education during the COVID-19 pandemic in a city in the Brazilian Amazon. For data collection, we used the Children’s Global Life Satisfaction Scale, the Multidimensional Scale of Life Satisfaction for Children (MSLSC), and the Infantile Stress Scale, all via Google Forms. To analyze the data, we used descriptive statistics, correlation between variables and logistic regression. The Family domain obtained higher scores (4.54 ± 0.45). The Infantile Stress Scale showed that the children were in a normal phase, with some of them in an alert and even resistance phase. There was a strong positive correlation between the Family domain (r = 0.70; p-value < 0.05) and the Self domain (r = 0.70; p-value < 0.001). The higher the value of the predictor variable (Family domain), the lower the chances of a child belonging to the Resistance category. Therefore, the Family domain is an important component of children’s well-being, acting as a protective factor against child stress.
The Influence of SARS-CoV-2 Pandemic on TMJ Disorders, OSAS and BMI
Authors: Saccomanno Sabina , Saran Stefano , De Luca Martina , Mastrapasqua Rodolfo Francesco , Raffaelli Luca , Levrini Luca
Published: June 2022

The pandemic of the 21st century had a significant influence on the lives of the world population in a negative way. This situation determined a change of lifestyle; it caused the necessity of social isolation for a great number of people. In fact, people tended to avoid crowded environments, social events, to reduce medical checks and sports activities, favoring sedentary life because of fear of the virus. This social attitude brought a high level of stress that worsened many health conditions. This study has the aim of evaluating the possible influence of the pandemic on temporomandibular joint (TMJ) disorders, obstructive sleep apnea syndrome (OSAS) and body mass index (BMI). An anonymized survey, available in two languages (Italian and English), was given to 208 patients from different private dental practices. In this questionnaire, the patients shared experiences about their life during the pandemic. The article highlighted that during this health emergency, there was an increase in body weight in the considered sample. This brought a worsening of OSAS in 65% of patients with a previous diagnosis. Eventually, an increase in TMJ disorders and orofacial pain was reported.
Perceptions of Fertility Physicians Treating Women Undergoing IVF Using an Egg Donation
Authors: Ben-Kimhy Reut , Taubman–Ben-Ari Orit
Published: June 2022

In the course of their work, medical teams are routinely exposed to difficult and stressful situations. The few studies in the literature that have examined physicians’ perceptions and responses to such situations have focused primarily on the fields of emergency medicine and chronic and terminal illness. However, the field of fertility medicine can also evoke complex feelings among physicians. The present qualitative study examined the perceptions of fertility physicians treating women undergoing egg donation. Semi-structured in-depth interviews were conducted with 20 fertility physicians, and a categorical analysis was performed. The main category to emerge was the physicians’ perception of egg donation and its implications. Two prominent themes were identified within this category: doctor–patient communication surrounding egg donation and how the idea was presented to the patient; and doctors’ perception of the implications of egg donation, including maternal identity, the relationship between mother and infant, and the mother’s sense of the child’s identity. This is the first study to consider the response to fertility treatments, a contemporary and sensitive topic, from the perspective of the physicians. The findings can contribute to physicians’ understanding of themselves and can help to devise ways to assist them in managing their emotional responses to their work for the benefit of both themselves and their patients.
Assessment of the Body Composition and Bone Calcification of Students of Police Schools and Police Training Centers in Poland—A Cross-Sectional Study
Authors: Lepionka Tomasz , Anyżewska Anna , Maculewicz Ewelina , Klos Krzysztof , Lakomy Roman , Szarska Ewa , Tomczak Andrzej , Gaździńska Agata , Skuza Katarzyna , Bertrandt Jerzy
Published: June 2022

The 21st century is considered the age of malnutrition resulting in the unprecedented frequency of civilization diseases. Among these disorders, obesity is particularly distinguished and considered an epidemic-scale disease. For this reason, conducting studies on obesity and counteracting this phenomenon is essential. Research from recent years indicates a problem of excessive body weight among officers of uniformed services, who should be characterized by good health and fitness level due to the specificity of the work. As the problem of obesity affects every fourth Pole, research in uniformed services seems to be essential from health and national security perspectives. The presented study aimed to determine the elements of nutritional status in 289 students of Polish police schools and police training centers. Body composition was determined by bioelectrical impedance analysis, and bone calcification assessment was conducted by the DXA densitometric method. Based on BMI and body fat content, body weight disorders were found in 31.8% of all examined students. Densitometric test results showed changes in bone calcification of varying severity in 26.6% of the total number of respondents. The presence of obesity in students of police schools and training centers proves that the present nutrition model is energetically unbalanced, while the demonstrated disorders of bone calcification indicate an improper condition of mineral nutrition.
A Three-Dimensional Visualization and Optimization Method of Landslide Disaster Scenes Guided by Knowledge
Authors: Fu Lin , Zhu Jun , Lai Jianbo , Li Weilian , Dang Pei , Yin Lingzhi , Li Jialuo , Guo Yukun , You Jigang
Published: June 2022

The rapid acquisition of deposit volume information and dynamic modeling, as well as the visualization of disaster scenes, have great significance for the sharing of landslide information and the management of emergency rescue. However, existing methods have shortcomings, such as a long and costly deposit volume acquisition cycle, lack of knowledge and guidance, complex operations for scene modeling expression, and low scene rendering efficiency. Therefore, this paper focuses on the study of a three-dimensional visualization and optimization method for landslide disaster scenes guided by knowledge, and discusses key technologies such as the rapid acquisition of landslide deposit volume information based on three-dimensional reconstruction, the knowledge-guided dynamic modeling visualization of disaster scenes, and scene optimization considering visual significance. The prototype systems are developed and used in a case experiment and analysis. The experimental results show that the proposed method can quickly obtain the deposit volume, and the results are equivalent to ContextCapture, Metashape, and Pix4Dmapper software. The method realizes the dynamic visualization of the whole disaster process, provides rich information, achieves high readability, and improves the efficiency of scene rendering, with a stable average rendering frame rate of more than 80 frames/second.
Vulnerability Analysis of Geographical Railway Network under Geological Hazard in China
Authors: Yin Lingzhi , Zhu Jun , Li Wenshu , Wang Jinhong
Published: June 2022

As the passenger railway network is expanding and improving, the internal connections and interdependence in the network are rising. Once a sudden geological hazard occurs and damages the network structure, the train service is prone to large-scale halt or delay. A geographical railway network is modeled to analyze the spatial distribution characteristics of the railway network as well as its vulnerability under typical geological hazards, such as earthquakes, collapses, landslides and debris flows. First, this paper modeled the geographical railway network in China based on the complex network method and analyzed the spatial distribution characteristics of the railway network. Then, the data of geological hazards along the railway that occurred over the years were crawled through the Internet to construct the hazard database to analyze the time–space distribution characteristics. Finally, based on the data of geological hazards along the railway and results of the susceptibility to geological hazards, the vulnerability of the geographical railway network was evaluated. Among these geological hazards, the greatest impact on railway safety operation came from earthquakes (48%), followed by landslides (28%), debris flows (17%) and collapses (7%). About 30% of the lines of the geographical railway network were exposed in the susceptibility areas. The most vulnerable railway lines included Sichuan–Guizhou Railway, Chengdu–Kunming Railway and Chengdu–Guiyang high-speed Railway in Southwest China, Lanzhou–Urumqi Railway and Southern Xinjiang Railway in Northwest China, and Beijing–Harbin Railway and Harbin–Manzhouli Railway in Northeast China. Therefore, professional railway rescue materials should be arranged at key stations in the above sections, with a view to improving the capability to respond to sudden geological hazards.
EmergEventMine: End-to-End Chinese Emergency Event Extraction Using a Deep Adversarial Network
Authors: Yan Jianzhuo , Chen Lihong , Yu Yongchuan , Xu Hongxia , Gao Qingcai , Cao Kunpeng , Chen Jianhui
Published: June 2022

With the rapid development of the internet and social media, extracting emergency events from online news reports has become an urgent need for public safety. However, current studies on the text mining of emergency information mainly focus on text classification and event recognition, only obtaining a general and conceptual cognition about an emergency event, which cannot effectively support emergency risk warning, etc. Existing event extraction methods of other professional fields often depend on a domain-specific, well-designed syntactic dependency or external knowledge base, which can offer high accuracy in their professional fields, but their generalization ability is not good, and they are difficult to directly apply to the field of emergency. To address these problems, an end-to-end Chinese emergency event extraction model, called EmergEventMine, is proposed using a deep adversarial network. Considering the characteristics of Chinese emergency texts, including small-scale labelled corpora, relatively clearer syntactic structures, and concentrated argument distribution, this paper simplifies the event extraction with four subtasks as a two-stage task based on the goals of subtasks, and then develops a lightweight heterogeneous joint model based on deep neural networks for realizing end-to-end and few-shot Chinese emergency event extraction. Moreover, adversarial training is introduced into the joint model to alleviate the overfitting of the model on the small-scale labelled corpora. Experiments on the Chinese emergency corpus fully prove the effectiveness of the proposed model. Moreover, this model significantly outperforms other existing state-of-the-art event extraction models.
Special Issue “Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration”
Authors: Gutierrez-Merino Carlos , Mata Ana M.
Published: June 2022

Tissue degeneration is an event shared by many, if not all, age-related pathologies [...]
RAGE against the Machine: Can Increasing Our Understanding of RAGE Help Us to Battle SARS-CoV-2 Infection in Pregnancy?
Authors: Kurashima Courtney K. , Ng Po’okela K. , Kendal-Wright Claire E.
Published: June 2022

The receptor of advanced glycation end products (RAGE) is a receptor that is thought to be a key driver of inflammation in pregnancy, SARS-CoV-2, and also in the comorbidities that are known to aggravate these afflictions. In addition to this, vulnerable populations are particularly susceptible to the negative health outcomes when these afflictions are experienced in concert. RAGE binds a number of ligands produced by tissue damage and cellular stress, and its activation triggers the proinflammatory transcription factor Nuclear Factor Kappa B (NF-κB), with the subsequent generation of key proinflammatory cytokines. While this is important for fetal membrane weakening, RAGE is also activated at the end of pregnancy in the uterus, placenta, and cervix. The comorbidities of hypertension, cardiovascular disease, diabetes, and obesity are known to lead to poor pregnancy outcomes, and particularly in populations such as Native Hawaiians and Pacific Islanders. They have also been linked to RAGE activation when individuals are infected with SARS-CoV-2. Therefore, we propose that increasing our understanding of this receptor system will help us to understand how these various afflictions converge, how forms of RAGE could be used as a biomarker, and if its manipulation could be used to develop future therapeutic targets to help those at risk.
Electrical Stimulation Increases Axonal Growth from Dorsal Root Ganglia Co-Cultured with Schwann Cells in Highly Aligned PLA-PPy-Au Microfiber Substrates
Authors: Gisbert Roca Fernando , Serrano Requena Sara , Monleón Pradas Manuel , Martínez-Ramos Cristina
Published: June 2022

Nerve regeneration is a slow process that needs to be guided for distances greater than 5 mm. For this reason, different strategies are being studied to guide axonal growth and accelerate the axonal growth rate. In this study, we employ an electroconductive fibrillar substrate that is able to topographically guide axonal growth while accelerating the axonal growth rate when subjected to an exogenous electric field. Dorsal root ganglia were seeded in co-culture with Schwann cells on a substrate of polylactic acid microfibers coated with the electroconductive polymer polypyrrole, adding gold microfibers to increase its electrical conductivity. The substrate is capable of guiding axonal growth in a highly aligned manner and, when subjected to an electrical stimulation, an improvement in axonal growth is observed. As a result, an increase in the maximum length of the axons of 19.2% and an increase in the area occupied by the axons of 40% were obtained. In addition, an upregulation of the genes related to axon guidance, axogenesis, Schwann cells, proliferation and neurotrophins was observed for the electrically stimulated group. Therefore, our device is a good candidate for nerve regeneration therapies.
The Intersection of Non-Coding RNAs Contributes to Forest Trees’ Response to Abiotic Stress
Authors: Xiao Dandan , Chen Min , Yang Xiaoqian , Bao Hai , Yang Yuzhang , Wang Yanwei
Published: June 2022

Non-coding RNAs (ncRNAs) play essential roles in plants by modulating the expression of genes at the transcriptional or post-transcriptional level. In recent years, ncRNAs have been recognized as crucial regulators for growth and development in forest trees, and ncRNAs that respond to various abiotic stresses are now under intense study. In this review, we summarized recent advances in the understanding of abiotic stress-responsive microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in forest trees. Furthermore, we analyzed the intersection of miRNAs, and epigenetic modified ncRNAs of forest trees in response to abiotic stress. In particular, the abiotic stress-related lncRNA/circRNA–miRNA–mRNA regulatory network of forest trees was explored.
Sar1 Affects the Localization of Perilipin 2 to Lipid Droplets
Authors: Makiyama Tomohiko , Obama Takashi , Watanabe Yuichi , Itabe Hiroyuki
Published: June 2022

Lipid droplets (LDs) are intracellular organelles that are ubiquitous in many types of cells. The LD core consists of triacylglycerols (TGs) surrounded by a phospholipid monolayer and surface proteins such as perilipin 2 (PLIN2). Although TGs accumulate in the phospholipid bilayer of the endoplasmic reticulum (ER) and subsequently nascent LDs buds from ER, the mechanism by which LD proteins are transported to LD particles is not fully understood. Sar1 is a GTPase known as a regulator of coat protein complex Ⅱ (COPⅡ) vesicle budding, and its role in LD formation was investigated in this study. HuH7 human hepatoma cells were infected with adenoviral particles containing genes coding GFP fused with wild-type Sar1 (Sar1 WT) or a GTPase mutant form (Sar1 H79G). When HuH7 cells were treated with oleic acid, Sar1 WT formed a ring-like structure around the LDs. The transient expression of Sar1 did not significantly alter the levels of TG and PLIN2 in the cells. However, the localization of PLIN2 to the LDs decreased in the cells expressing Sar1 H79G. Furthermore, the effects of Sar1 on PLIN2 localization to the LDs were verified by the suppression of endogenous Sar1 using the short hairpin RNA technique. In conclusion, it was found that Sar1 has some roles in the intracellular distribution of PLIN2 to LDs in liver cells.
Structural and Molecular Kinetic Features of Activities of DNA Polymerases
Authors: Kuznetsova Aleksandra A. , Fedorova Olga S. , Kuznetsov Nikita A.
Published: June 2022

DNA polymerases catalyze DNA synthesis during the replication, repair, and recombination of DNA. Based on phylogenetic analysis and primary protein sequences, DNA polymerases have been categorized into seven families: A, B, C, D, X, Y, and RT. This review presents generalized data on the catalytic mechanism of action of DNA polymerases. The structural features of different DNA polymerase families are described in detail. The discussion highlights the kinetics and conformational dynamics of DNA polymerases from all known polymerase families during DNA synthesis.
5-Fluorouracil Treatment of CT26 Colon Cancer Is Compromised by Combined Therapy with IMMODIN
Authors: Demeckova Vlasta , Mudronova Dagmar , Gancarcikova Sona , Kubatka Peter , Kajo Karol , Kassayova Monika , Bojkova Bianka , Adamkov Marian , Solár Peter
Published: June 2022

Due to the physiological complexity of the tumour, a single drug therapeutic strategy may not be sufficient for effective treatment. Emerging evidence suggests that combination strategies may be important to achieve more efficient tumour responses. Different immunomodulators are frequently tested to reverse the situation for the purpose of improving immune response and minimizing chemotherapy side effects. Immodin (IM) represents an attractive alternative to complement chemotherapy, which can be used to enhance the immune system after disturbances resulting from the side effects of chemotherapy. In the presented study, a model of CT26 tumor-bearing mice was used to investigate the effect of single IM or its combination with 5-fluorouracil (5-FU) on colon cancer cells. Our results highlight that the beneficial role of IM claimed in previous studies cannot be generalised to all chemotherapeutic drugs, as 5-FU toxicity was not increased. On the contrary, the chemotherapeutic anti-cancer efficacy of 5-FU was greatly compromised when combined with IM. Indeed, the combined treatment was significantly less effective regarding the tumour growth and animal survival, most probably due to the increased number of tumour-associated macrophages, and increased 5-FU cytotoxic effect related to kidneys and the liver.
How to Restore Oxidative Balance That Was Disrupted by SARS-CoV-2 Infection
Authors: Kiełbowski Kajetan , Herian Mariola , Pawlik Andrzej
Published: June 2022

Coronavirus 2019 disease (COVID-19) is caused by different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December of 2019. COVID-19 pathogenesis is complex and involves a dysregulated renin angiotensin system. Severe courses of the disease are associated with a dysregulated immunological response known as cytokine storm. Many scientists have demonstrated that SARS-CoV-2 impacts oxidative homeostasis and stimulates the production of reactive oxygen species (ROS). In addition, the virus inhibits glutathione (GSH) and nuclear factor erythroid 2-related factor 2 (NRF2)—a major antioxidant which induces expression of protective proteins and prevents ROS damage. Furthermore, the virus stimulates NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes which play a significant role in inducing a cytokine storm. A variety of agents with antioxidant properties have shown beneficial effects in experimental and clinical studies of COVID-19. This review aims to present mechanisms of oxidative stress induced by SARS-CoV-2 and to discuss whether antioxidative drugs can counteract detrimental outcomes of a cytokine storm.
Lowering n-6/n-3 Ratio as an Important Dietary Intervention to Prevent LPS-Inducible Dyslipidemia and Hepatic Abnormalities in ob/ob Mice
Authors: Park Seohyun , Lee Jae-Joon , Lee Jisu , Lee Jennifer K. , Byun Jaemin , Kim Inyong , Ha Jung-Heun
Published: June 2022

Obesity is closely associated with low-grade chronic and systemic inflammation and dyslipidemia, and the consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) may modulate obesity-related disorders, such as inflammation and dyslipidemia. An emerging research question is to understand the dietary intervention strategy that is more important regarding n-3 PUFA consumption: (1) a lower ratio of n-6/n-3 PUFAs or (2) a higher amount of n-3 PUFAs consumption. To understand the desirable dietary intervention method of n-3 PUFAs consumption, we replaced lard from the experimental diets with either perilla oil (PO) or corn oil (CO) to have identical n-3 amounts in the experimental diets. PO had a lower n-6/n-3 ratio, whereas CO contained higher amounts of PUFAs; it inherently contained relatively lower n-3 but higher n-6 PUFAs than PO. After the 12-week dietary intervention in ob/ob mice, dyslipidemia was observed in the normal chow and CO-fed ob/ob mice; however, PO feeding increased the high density lipoprotein-cholesterol (HDL-C) level; further, not only did the HDL-C level increase, the low density lipoprotein-cholesterol (LDL-C) and triglyceride (TG) levels also decreased significantly after lipopolysaccharide (LPS) injection. Consequently, extra TG accumulated in the liver and white adipose tissue (WAT) of normal chow- or CO-fed ob/ob mice after LPS injection; however, PO consumption decreased serum TG accumulation in the liver and WAT. PUFAs replacement attenuated systemic inflammation induced by LPS injection by increasing anti-inflammatory cytokines but inhibiting pro-inflammatory cytokine production in the serum and WAT. PO further decreased hepatic inflammation and fibrosis in comparison with the ND and CO. Hepatic functional biomarkers (aspartate aminotransferase (AST) and alanine transaminase (ALT) levels) were also remarkably decreased in the PO group. In LPS-challenged ob/ob mice, PO and CO decreased adipocyte size and adipokine secretion, with a reduction in phosphorylation of MAPKs compared to the ND group. In addition, LPS-inducible endoplasmic reticulum (ER) and oxidative stress decreased with consumption of PUFAs. Taken together, PUFAs from PO and CO play a role in regulating obesity-related disorders. Moreover, PO, which possesses a lower ratio of n-6/n-3 PUFAs, remarkably alleviated metabolic dysfunction in LPS-induced ob/ob mice. Therefore, an interventional trial considering the ratio of n-6/n-3 PUFAs may be desirable for modulating metabolic complications, such as inflammatory responses and ER stress in the circulation, liver, and/or WAT.
Dealing with Macrophage Plasticity to Address Therapeutic Challenges in Head and Neck Cancers
Authors: Furgiuele Sonia , Descamps Géraldine , Cascarano Lorena , Boucq Ambre , Dubois Christine , Journe Fabrice , Saussez Sven
Published: June 2022

The head and neck tumor microenvironment (TME) is highly infiltrated with macrophages. More specifically, tumor-associated macrophages (TAM/M2-like) are one of the most critical components associated with poor overall survival in head and neck cancers (HNC). Two extreme states of macrophage phenotypes are described as conducting pro-inflammatory/anti-tumoral (M1) or anti-inflammatory/pro-tumoral (M2) activities. Moreover, specific metabolic pathways as well as oxidative stress responses are tightly associated with their phenotypes and functions. Hence, due to their plasticity, targeting M2 macrophages to repolarize in the M1 phenotype would be a promising cancer treatment. In this context, we evaluated macrophage infiltration in 60 HNC patients and demonstrated the high infiltration of CD68+ cells that were mainly related to CD163+ M2 macrophages. We then optimized a polarization protocol from THP1 monocytes, validated by specific gene and protein expression levels. In addition, specific actors of glutamine pathway and oxidative stress were quantified to indicate the use of glutaminolysis by M2 and the production of reactive oxygen species by M1. Finally, we evaluated and confirmed the plasticity of our model using M1 activators to repolarize M2 in M1. Overall, our study provides a complete reversible polarization protocol allowing us to further evaluate various reprogramming effectors targeting glutaminolysis and/or oxidative stress in macrophages.
Serum-Free Cultures: Could They Be a Future Direction to Improve Neuronal Differentiation of Mesenchymal Stromal Cells?
Authors: Schepici Giovanni , Gugliandolo Agnese , Mazzon Emanuela
Published: June 2022

Mesenchymal stem/stromal cells (MSCs) are undifferentiated cells with multilinear potential, known for their immunomodulatory and regenerative properties. Although the scientific community is working to improve their application, concerns limit their use to repair tissues following neurological damage. One of these obstacles is represented by the use of culture media supplemented with fetal bovine serum (FBS), which, due to its xenogenic nature and the risk of contamination, has increased scientific, ethical and safety problems. Therefore, the use of serum-free media could improve MSC culture methods, avoiding infectious and immunogenic transmission problems as well as MSC bioprocesses, without the use of animal components. The purpose of our review is to provide an overview of experimental studies that demonstrate that serum-free cultures, along with the supplementation of growth factors or chemicals, can lead to a more defined and controlled environment, enhancing the proliferation and neuronal differentiation of MSCs.
The Combined Diffusion and Adsorption Concept for Prediction of Nanoparticles Transport through Dermal Layers Based on Experiments in Membranes
Authors: Błaszczyk Mariola M. , Sęk Jerzy , Przybysz Łukasz
Published: June 2022

The non-invasive introduction of active substances into the human body is a top challenge for researchers in medicine, pharmacology, and cosmetology. Development of nanotechnology and possibilities of creating more and more complex drug carriers on a nanoscale give a more realistic prospect of meeting this challenge. However, in the absence of sufficient knowledge of the mechanisms of such systems’ transport through the human skin structure, it is necessary to look deeper into these issues. There are several models describing nanoparticles transport through the skin, but they are mainly based on diffusion process analysis. In this work, a model was proposed to predict nanoparticles transport through the skin, based on the combined diffusion and adsorption concept. This approach was based on experimental studies of silver and copper nanoparticles’ diffusion process through different filtration membrane layers. Dependence of the degree of adsorption on the surface parameter was described using modified Langmuir equation. Then, these considerations were related to the structure of the stratum corneum, which made it possible to predict the changes in the mass of penetrating nanoparticles as a function of transport path length. A discussion of the presented model, depending on such parameters as nanoparticle size, skin cell thickness, or viscosity of the “intercellular cement”, was also performed.
Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression
Authors: Dupas Thomas , Persello Antoine , Blangy-Letheule Angélique , Denis Manon , Erraud Angélique , Aillerie Virginie , Leroux Aurélia A. , Rivière Matthieu , Lebreton Jacques , Tessier Arnaud , Rozec Bertrand , Lauzier Benjamin
Published: June 2022

The young population, which is particularly at risk of sepsis, is, paradoxically, rarely studied. Acute stimulation of O-GlcNAcylation, a post-translational modification involved in metabolic regulation, cell survival and stress response, is beneficial in young rats with sepsis. Considering that sepsis impacts the gene expression profile and that O-GlcNAcylation is a regulator of transcription, the aims of this study are to (i) unveil beneficial mechanisms of O-GlcNAcylation and (ii) decipher the relationship between O-GlcNAcylation and transcription during sepsis. Endotoxemic challenge was induced in 28-day-old male rats using a lipopolysaccharide injection (E. coli O111:B4, 20 mg·kg−1) and compared to control rats (NaCl 0.9%). One hour after, rats were assigned to no therapy or fluidotherapy (NaCl 0.9%, 10 mL.kg−1) ± NButGT (10 mg·kg−1) to stimulate O-GlcNAc levels. Cardiac O-GlcNAcylation levels were evaluated via Western blot and gene transcription using 3′ SRP analysis. Lipopolysaccharide injection favorizes inflammatory state with the overexpression of genes involved in the NF-κB, JAK/STAT and MAPK pathways. NButGT treatment increased cardiac O-GlcNAcylation levels (p < 0.05). Yet, the mRNA expression was not impacted two hours after fluidotherapy or NButGT treatment. In conclusion, O-GlcNAc stimulation-induced beneficial effects are not dependent on the gene expression profile at the early phase of sepsis.
Correction: Kim et al. Correlative Light and Electron Microscopy Using Frozen Section Obtained Using Cryo-Ultramicrotomy. Int. J. Mol. Sci. 2021, 22, 4273
Authors: Kim Hong-Lim , Riew Tae-Ryong , Park Jieun , Lee Youngchun , Kim In-Beom
Published: June 2022

The authors wish to make a correction to this paper [...]
May Staphylococcus lugdunensis Be an Etiological Factor of Chronic Maxillary Sinuses Infection?
Authors: Kosecka-Strojek Maja , Wolska-Gębarzewska Mariola , Podbielska-Kubera Adrianna , Samet Alfred , Krawczyk Beata , Międzobrodzki Jacek , Michalik Michał
Published: June 2022

Staphylococcus lugdunensis is an opportunistic pathogen found in the healthy human skin microbiome bacterial community that is able to cause infections of diverse localization, manifestation, and course, including laryngological infections, such as necrotizing sinusitis. Chronic maxillary sinusitis is a disease present in up to one third of European and American populations, and its etiology is not fully described. Within this study, we aimed to characterize 18 S. lugdunensis strains recovered from maxillary sinuses and evaluate them as etiological agents of chronic disease. We performed MLST analysis, the complex analysis of both phenotypic and genetic virulence factors, antibiotic susceptibility profiles, and biofilm formation assay for the detection of biofilm-associated genes. Altogether, S. lugdunensis strains were clustered into eight different STs, and we demonstrated several virulence factors associated with the chronic disease. All tested strains were able to produce biofilm in vitro with numerous strains with a very strong ability, and overall, they were mostly susceptible to antibiotics, although we found resistance to fosfomycin, erythromycin, and clindamycin in several strains. We believe that further in-depth analysis of S. lugdunensis strains from different niches, including the nasal one, should be performed in the future in order to reduce infection rate and broaden the knowledge about this opportunistic pathogen that is gaining attention.
Cross-Talk between the Cytokine IL-37 and Thyroid Hormones in Modulating Chronic Inflammation Associated with Target Organ Damage in Age-Related Metabolic and Vascular Conditions
Authors: Majnarić Ljiljana Trtica , Bosnić Zvonimir , Štefanić Mario , Wittlinger Thomas
Published: June 2022

Chronic inflammation is considered to be the main mechanism contributing to the development of age-related metabolic and vascular conditions. The phases of chronic inflammation that mediate the progression of target organ damage in these conditions are poorly known, however. In particular, there is a paucity of data on the link between chronic inflammation and metabolic disorders. Based on some of our own results and recent developments in our understanding of age-related inflammation as a whole-body response, we discuss the hypothesis that cross-talk between the cytokine IL-37 and thyroid hormones could be the key regulatory mechanism that justifies the metabolic effects of chronic tissue-related inflammation. The cytokine IL-37 is emerging as a strong natural suppressor of the chronic innate immune response. The effect of this cytokine has been identified in reversing metabolic costs of chronic inflammation. Thyroid hormones are known to regulate energy metabolism. There is a close link between thyroid function and inflammation in elderly individuals. Nonlinear associations between IL-37 and thyroid hormones, considered within the wider clinical context, can improve our understanding of the phases of chronic inflammation that are associated with target organ damage in age-related metabolic and vascular conditions.
Photoswitchable Fluorescent Proteins: Mechanisms on Ultrafast Timescales
Authors: Tang Longteng , Fang Chong
Published: June 2022

The advancement of super-resolution imaging (SRI) relies on fluorescent proteins with novel photochromic properties. Using light, the reversibly switchable fluorescent proteins (RSFPs) can be converted between bright and dark states for many photocycles and their emergence has inspired the invention of advanced SRI techniques. The general photoswitching mechanism involves the chromophore cis-trans isomerization and proton transfer for negative and positive RSFPs and hydration–dehydration for decoupled RSFPs. However, a detailed understanding of these processes on ultrafast timescales (femtosecond to millisecond) is lacking, which fundamentally hinders the further development of RSFPs. In this review, we summarize the current progress of utilizing various ultrafast electronic and vibrational spectroscopies, and time-resolved crystallography in investigating the on/off photoswitching pathways of RSFPs. We show that significant insights have been gained for some well-studied proteins, but the real-time “action” details regarding the bidirectional cis-trans isomerization, proton transfer, and intermediate states remain unclear for most systems, and many other relevant proteins have not been studied yet. We expect this review to lay the foundation and inspire more ultrafast studies on existing and future engineered RSFPs. The gained mechanistic insights will accelerate the rational development of RSFPs with enhanced two-way switching rate and efficiency, better photostability, higher brightness, and redder emission colors.
The Role of Glucocorticoid Receptor in the Pathophysiology of Pituitary Corticotroph Adenomas
Authors: Regazzo Daniela , Mondin Alessandro , Scaroni Carla , Occhi Gianluca , Barbot Mattia
Published: June 2022

Adrenocorticotropic Hormone (ACTH)-secreting pituitary adenomas are rare tumors characterized by autonomous ACTH secretion with a consequent increase in circulating cortisol levels. The resulting clinical picture is called Cushing’s disease (CD), a severe condition burdened with high morbidity and mortality. Apart from increased cortisol levels, CD patients exhibit a partial resistance to the negative glucocorticoid (GC) feedback, which is of paramount clinical utility, as the lack of suppression after dexamethasone administration is one of the mainstays for the differential diagnosis of CD. Since the glucocorticoid receptor (GR) is the main regulator of negative feedback of the hypothalamic–pituitary–adrenal axis in normal conditions, its implication in the pathophysiology of ACTH-secreting pituitary tumors is highly plausible. In this paper, we review GR function and structure and the mechanisms of GC resistance in ACTH-secreting pituitary tumors and assess the effects of the available medical therapies targeting GR on tumor growth.