bluuebunny/crossref_metadata_2025 huggingface dataset:
How Virtual Reality Technology Has Changed Our Lives: An Overview of the Current and Potential Applications and Limitations
Authors: Hamad Ayah , Jia Bochen
Published: September 2022

Despite virtual reality (VR) being initially marketed toward gaming, there are many potential and existing VR applications in various sectors and fields, including education, training, simulations, and even in exercise and healthcare. Unfortunately, there is still a lack of general understanding of the strengths and limitations of VR as a technology in various application domains. Therefore, the aim of this literature review is to contribute to the library of literature concerning VR technology, its applications in everyday use, and some of its existing drawbacks. Key VR applications were discussed in terms of how they are currently utilized or can be utilized in the future, spanning fields such as medicine, engineering, education, and entertainment. The main benefits of VR are expressed through the text, followed by a discussion of some of the main limitations of current VR technologies and how they can be mitigated or improved. Overall, this literature review shows how virtual reality technology has the potential to be a greatly beneficial tool in a multitude of applications and a wide variety of fields. VR as a technology is still in its early stages, but more people are becoming interested in it and are optimistic about seeing what kind of changes VR can make in their everyday lives. With how rapidly modern society has adapted to personal computers and smartphones, VR has the opportunity to become the next big technological turning point that will eventually become commonplace in most households.
Understanding Work Addiction in Adult Children: The Effect of Addicted Parents and Work Motivation
Authors: Morkevičiūtė Modesta , Endriulaitienė Auksė
Published: September 2022

The aim of the study was to examine the mediating role that work motivation plays in the relationship between perceived work addiction of parents and their adult child’s work addiction. The sample was comprised of 537 participants working in different Lithuanian organizations that were selected on the basis of the convenience principle. Data were collected by means of online self-administered questionnaires. To test a mediation model, a structural equation modeling was performed. It was found that perceived work addiction of both mother and father was related to higher levels of work addiction of their adult child. The results also indicated that perceived work addiction of the father was related to increased work addiction in an adult child through higher levels of extrinsic motivation as a partial mediator. The indirect effect of perceived work addiction of the mother (via extrinsic motivation) was not significant. As was expected, the indirect relationship between work addiction in parents and their adult child via intrinsic motivation was not significant. This study demonstrates that integrating both family-related and motivational variables may provide relevant insights into the nature of and mechanisms underlying work addiction and that studies in this field deserve to be further developed in future research.
Comparison of Whole Salivary Cortisol and Interleukin 1-Beta Levels in Light Cigarette-Smokers and Users of Electronic Nicotine Delivery Systems before and after Non-Surgical Periodontal Therapy
Authors: Alhumaidan Abdulkareem A. , Al-Aali Khulud A. , Vohra Fahim , Javed Fawad , Abduljabbar Tariq
Published: September 2022

There are no studies that have compared whole salivary cortisol (CL) and interleukin 1-beta (IL-1β) levels in cigarette-smokers (CS) and electronic nicotine delivery systems (ENDS)-users before and after non-surgical periodontal therapy (NSPT). The aim was to compare whole salivary CL and IL-1β levels in light CS and ENDS users before and after non-surgical periodontal therapy (NSPT). Self-reported current CS, ENDS users, and non-smokers were included. A questionnaire was used to collect demographic data. All patients underwent NSPT. Periodontal parameters (probing depth (PD], gingival index (GI], clinical attachment loss (AL], plaque index (PI], and marginal bone loss (MBL]) and whole salivary CL and IL-1β were measured at baseline. At 3-months of follow-up, clinical parameters and whole salivary CL and IL-1β were re-assessed. p-values < 1% were arbitrated as statistically significant. Fifty-four individuals (18 CS, 18 ENDS users, and 18 non-smokers) were included. Clinical AL, MT, PD, PI, and MBL were similar in all groups at baseline. At 12-weeks of follow-up, PI (p < 0.01) and PD (p < 0.01) were high in CS and ENDS-users than non-smokers. Among non-smokers, there was a statistically significant correlation between whole salivary cortisol and IL-1β levels at 12-weeks’ follow-up (p < 0.001). There was no difference in whole salivary cortisol and IL-1β levels in CS and ENDS users at baseline and at 12-weeks follow-up. At 12-weeks of follow-up, there was a significant reduction in IL-1β (p < 0.01) and CL (p < 0.01) than baseline. In light CS and ENDS users without periodontal disease, clinical periodontal parameters and whole-salivary CL and Il-1β levels remain unchanged after NSPT.
Work-Related Injuries among Insured Construction Workers Presenting to a Swiss Adult Emergency Department: A Retrospective Study (2016–2020)
Authors: Dethlefsen Ralf , Orlik Luisa , Müller Martin , Exadaktylos Aristomenis K. , Scholz Stefan M. , Klukowska-Rötzler Jolanta , Ziaka Mairi
Published: September 2022

Occupational injuries are one of the main causes of Emergency Department visits and represent a substantial source of disability or even death. However, the published studies and reports on construction–occupational accidents in Switzerland are limited. We aimed to investigate the epidemiology of fatal and non-fatal injuries among construction workers older than 16 years of age over a 5-year period. Data were gathered from the emergency department (ED) of Bern University Hospital. A retrospective design was chosen to allow analysis of changes in construction accidents between 2016–2020. A total of 397 patients were enrolled. Compared to studies in other countries, we also showed that the upper extremity and falling from height is the most common injured body part and mechanism of injury. Furthermore, we were able to show that the most common age group representing was 26–35 years and the second common body part injured was the head, which is a difference from studies in other countries. Wound lacerations were the most common type of injury, followed by joint distortions. By stratifying according to the season, occupational injuries among construction workers were found to be significant higher during summer and autumn. As work-related injuries among construction workers are becoming more common, prevention strategies and safety instructions must be optimized.
Understanding the Farmland Rights Confirmation Policy from the Perspective of Farmers: Evidence from Jiangxi, China
Authors: Lu Lingying , Xu Guoliang , Li Zhiyuan , Wan Chunyan
Published: September 2022

Since the 1970s, although the Chinese central government has constructed farmland rights confirmation policy to stimulate the vitality of rural land elements, it is rare to discuss the effectiveness of the policy from the perspective of farmers. This paper applies the deep interview and questionnaire to present an analysis framework consisting of “policy implementation–input behavior in agricultural production–farmland transfer” and testifies the framework with the mediation model. The findings show that, in general, the farmland rights confirmation policy (FRCP) has a significant negative impact on leasing out farmland and a significant positive impact on leasing in farmland. In particular, for farmland leasing out, the mediating effects of agricultural capital input and agricultural time input account for 15.504% and 14.536% of the total effect, respectively. In addition, for leasing farmland in, these two mediating effects accordingly account for 13.798% and 12.155% of the total effect. It is worth noting that in the future, we should understand FRCP based on the consideration of farmers’ behavior in a given local context, while also focusing on policy implementation as well as policy design.
Analysis of Injury Patterns in Men’s Football between the English League and the Spanish League
Authors: Argibay-González Juan Carlos , Vázquez-Estévez Christopher , Gutiérrez-Santiago Alfonso , Paramés-González Adrián , Reguera-López-de-la-Osa Xoana , Prieto-Lage Iván
Published: September 2022

Background: Injuries in professional football lead to reduced team performance and large financial losses. The aim of this study was to analyse injuries in the two best team competitions in the world (LaLiga and Premier League), establishing similarities and differences, as well as determining injury causation patterns. Methods: A total of 277 on-field injuries requiring a substitution were analysed (142 in the Spanish league and 135 in the English league). The analysis was performed using traditional statistical tests (frequency analysis, chi-square test) with SPSS 25 and a T-Patterns sequence analysis with THEME 5.0. Results: In the Spanish league, there were a similar number of injuries in the first part of the season as in the second part of the season, while in the English league, they are more frequent in the first part of the season. In the Spanish league, injuries are more frequent in the first half of the match, while in the English league, they are more frequent in the second half. The type of player most frequently injured was the defender. Most of the injuries occurred without the presence of an opponent. The accumulated minutes during the season affect injuries of the muscular type. Conclusions: The most common type of injury in both leagues was a strain, followed by a sprain and a contusion. Although common injury patterns can be established between the two leagues, there are notable differences. One of the factors is determined by the English league calendar (many matches at Christmas). In Spain, there were more muscular injuries that were not caused by the opponent, while in England there were more tackling injuries. Age is a risk factor in the Spanish league. In this league, there is a moderately significant relationship between the number of injuries and the points won.
Correctional Officers’ Health Literacy and Practices for Pulmonary Tuberculosis Prevention in Prison
Authors: Rakpaitoon Suwida , Thanapop Sasithorn , Thanapop Chamnong
Published: September 2022

Tuberculosis (TB) prevention in prisons remains a problem that requires advocacy and partnership action. A correctional officer (CO) is responsible for enforcing the rules and maintaining routines at a prison and has the authority to support TB prevention under the limitations of health manpower in prisons. The objective of this cross-sectional study was to determine the health literacy (HL) and practices of TB prevention and their association among Thailand’s COs. A total of 208 COs participated using a random sampling method. A self-administered questionnaire on HL and TB prevention practices was used for data collection. Descriptive statistics, Pearson’s chi-square test, and binary logistic regression were used for the association analysis. The majority of the participants were male (71.2%), married (60.1%), had a bachelor’s degree (60.6%), and had never been trained in TB prevention (90.9%). In total, 63.0% had adequate HL, whereas 78.4% had good practices, and this corresponded with personal prevention (75.5%) and work prevention (74.6%). Significant associations were identified for education, and communication, decision-making, and self-management skills (p < 0.05). The probability (adjusted odds ratio [95% CI]) of good practices was higher among participants with adequate communication skills (7.92 [2.15–29.24]), adequate decision-making skills (6.00 [1.86–19.36]), bachelors’ degree or higher-level education (3.25 [1.12–9.39]), and adequate self-management skills (2.95 [1.08–8.11]). The study findings show that most of the COs have adequate HL which is associated with good practices in TB prevention. Prisons should support HL development among COs for partnership and sustainable TB prevention under the constraint of health personnel.
Experimental Methods of Investigating Airborne Indoor Virus-Transmissions Adapted to Several Ventilation Measures
Authors: Siebler Lukas , Calandri Maurizio , Rathje Torben , Stergiaropoulos Konstantinos
Published: September 2022

This study introduces a principle that unifies two experimental methods for evaluating airborne indoor virus-transmissions adapted to several ventilation measures. A first-time comparison of mechanical/natural ventilation and air purification with regard to infection risks is enabled. Effortful computational fluid dynamics demand detailed boundary conditions for accurate calculations of indoor airflows, which are often unknown. Hence, a suitable, simple and generalized experimental set up for identifying the spatial and temporal infection risk for different ventilation measures is more qualified even with unknown boundary conditions. A trace gas method is suitable for mechanical and natural ventilation with outdoor air exchange. For an accurate assessment of air purifiers based on filtration, a surrogate particle method is appropriate. The release of a controlled rate of either trace gas or particles simulates an infectious person releasing virus material. Surrounding substance concentration measurements identify the neighborhood exposure. One key aspect of the study is to prove that the requirement of concordant results of both methods is fulfilled. This is the only way to ensure that the comparison of different ventilation measures described above is reliable. Two examples (a two-person office and a classroom) show how practical both methods are and how the principle is applicable for different types and sizes of rooms.
Discharge Interventions for First Nations People with Injury or Chronic Conditions: A Protocol for a Systematic Review
Authors: Coombes Julieann , Holland Andrew J. A. , Hunter Kate , Bennett-Brook Keziah , Ryder Courtney , Finlay Summer M. , Orcher Phillip , Scarcella Mick , Briscoe Karl , Forbes Dale , Jacques Madeleine , Wilson Roland , Bourke Elizabeth , Kairuz Camila
Published: September 2022

Severe injury and chronic conditions require long-term management by multidisciplinary teams. Appropriate discharge planning ensures ongoing care to mitigate the long-term impact of injuries and chronic conditions. However, First Nations peoples in Australia face ongoing barriers to aftercare. This systematic review will locate and analyse global evidence of discharge interventions that have been implemented to improve aftercare and enhance health outcomes among First Nations people with an injury or chronic condition. A systematic search will be conducted using five databases, Google, and Google scholar. Global studies published in English will be included. We will analyse aftercare interventions implemented and the health outcomes associated. Two independent reviewers will screen and select studies and then extract and analyse the data. Quality appraisal of the included studies will be conducted using the Mixed Methods Appraisal Tool and the CONSIDER statement. The proposed study will analyse global evidence on discharge interventions that have been implemented for First Nations people with an injury or chronic conditions and their associated health outcomes. Our findings will guide healthcare quality improvement to ensure Aboriginal and Torres Strait Islander peoples have ongoing access to culturally safe aftercare services.
Periodontal Disease in Patients with Psoriasis: A Systematic Review
Authors: Nijakowski Kacper , Gruszczyński Dawid , Kolasińska Julia , Kopała Dariusz , Surdacka Anna
Published: September 2022

Psoriasis is a chronic, inflammatory, and recurrent skin disease. As with periodontitis, the development and progression of lesions depend on immunological, genetic, and environmental factors. This systematic review was designed to answer the question: “Is there a relationship between psoriasis and periodontal disease?”. Following the inclusion and exclusion criteria, sixteen studies were included in this systematic review (according to PRISMA statement guidelines). Based on the meta-analysis, psoriasis patients showed a more than two-fold increase in the odds of periodontal disease. Almost one-third of these patients suffered from periodontitis of varying severity. Despite the heterogeneity of the included studies, psoriasis is associated with a higher risk of periodontitis, and especially with advanced progression.
The Shopping Behavior of International Students in Poland during COVID-19 Pandemic
Authors: Szlachciuk Julita , Kulykovets Olena , Dębski Maciej , Krawczyk Adriana , Górska-Warsewicz Hanna
Published: September 2022

The purpose of this research is to analyze the shopping behavior of international students (Asian vs. European) studying in Poland. Participants were recruited from universities located in Warsaw between June and September 2020. A total of 806 questionnaires were collected, 87 of which were eliminated due to non-response. The research sample consisted of 719 people. We conducted an exploratory factor analysis and cluster analysis for the entire study population and separately for European and Asian students. In exploratory factor analysis, two factors were extracted for the entire population, while three factors each were extracted for the European and Asian student groups. In cluster analysis, we obtained four clusters each for the entire study population and the group of European and Asian students. Our study found that among Asian students, compared to European students, there was a greater change in shopping behavior during the COVID-19 pandemic, expressed by a greater preference for online shopping, greater purchases of fruits and vegetables, purchases of local products, and shorter shopping time.
The Effects of a Physical Activity, Nutrition, and Body Image Intervention on Girls in Intermediate Schools in Saudi Arabia
Authors: Ahmad Bahathig Abeer , Abu Saad Hazizi
Published: September 2022

Background: This cluster-randomized study aimed to evaluate the effects of an intervention focused on physical activity, nutrition, and body image perception among girls in intermediate schools in Saudi Arabia. A seminar was delivered to the mothers of the girls in the experimental group. The experimental group then attended six interactive sessions within 3 months featuring physical activity, nutrition, and body image perception, followed by a 3-month follow-up period. A total of 138 respondents (68 in the experimental group and 70 in the control group) completed the intervention. Each participant’s body mass index-for-age z-score and waist circumference were measured, and they completed a physical activity, sedentary behavior, and body image perception questionnaires before and after the intervention and at the follow-up. The intervention was evaluated using within- and between-groups generalized estimating equations. There were no significant changes in the respondents’ body mass index-for-age z-score or waist circumference (p > 0.05). However, immediate significant improvements were seen in physical activity, sedentary behavior, and body image satisfaction among the experimental group, and these improvements remained at follow-up (p < 0.001). These differences were more significant among the experimental group than among the control group. We found this intervention effective. Future studies can adapt this intervention for adolescent boys and extend its duration to improve the body mass index outcome.
Non-Safety and Safety Device Sharp Injuries—Risk of Incidents, SEDs Availability, Attitudes and Perceptions of Nurses According to Cross-Sectional Survey in Poland
Authors: Garus-Pakowska Anna , Górajski Mariusz , Sakowski Piotr
Published: September 2022

Sharp injuries are a serious issue among healthcare workers (HCWs). The aim of the study was to examine the frequency of sharps injuries among nurses (who have the most frequent contact with infectious material) when using devices with and without safety features, then to analyse the factors associated with such injuries and to compare the risk of injuries with safety engineered devices (SEDs) and non-safety engineered devices (non-SEDs). An online cross-sectional survey was completed between October 2021 and March 2022 by 280 nurses. The incidence of exposure to sharp injury during their professional life was 51.4%. The percentage of nurses experiencing a sharp injury in the year preceding the study was 29% and 9.6% for superficially and deep injury, respectively. Ampoules and conventional hollow-bore needles caused the most injuries (25.92% and 22.64% of nurses in the last year). Factors including sex (males), age and seniority (elderly), education (higher), work exhaustion and being left-handed were associated with the occurrence of conventional hollow-bore needle injuries. In the case of SEDs: age, seniority and right/left-handed were the most frequent risk factors associated with the occurrence of sharp injuries. SEDs injuries were much less frequent than non-SEDs. There was a significant difference between the risk of injuries with safety and non-safety needles, central cannulas and ampoules. Fisher’s exact test (p-value = 0.000) and positive Spearman’s rho statistics (0.2319, p-value = 0.0001) confirmed that in accredited hospitals, the availability of safety needles was higher. Almost half of the nurses (n = 115, 41.07%) stated that staff had little influence on the type of medical sharp instruments supplied. To reduce the risk of nurse injuries, access to medical devices with safe protection mechanisms should be ensured, the use of sharp instruments should be limited where possible, managers should consult nurses regarding the choice of safe devices, and training programs on the proper use of SEDs should be available.
Differences in the Course of Depression and Anxiety after COVID-19 Infection between Recovered Patients with and without a Psychiatric History: A Cross-Sectional Study
Authors: Hazumi Megumi , Usuda Kentaro , Okazaki Emi , Kataoka Mayumi , Nishi Daisuke
Published: September 2022

Background: This study aimed to examine the course of depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. A total of 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.
Editorial of Special Issue “Roles of Inflammasomes and Methyltransferases in Inflammation”
Authors: Yi Young-Su , Yun Miyong
Published: September 2022

Inflammation is the first line of defense against pathogens and cellular dangers [...]
PMMA-Based Nanocomposites for Odontology Applications: A State-of-the-Art
Authors: Díez-Pascual Ana M.
Published: September 2022

Polymethyl methacrylate (PMMA), a well-known polymer of the methacrylate family, is extensively used in biomedicine, particularly in odontological applications including artificial teeth, dentures and denture bases, obturators, provisional or permanent crowns, and so forth. The exceptional PMMA properties, including aesthetics, inexpensiveness, simple manipulation, low density, and adjustable mechanical properties, make it a perfect candidate in the field of dentistry. However, it presents some deficiencies, including weakness regarding hydrolytic degradation, poor fracture toughness, and a lack of antibacterial activity. To further enhance its properties and solve these drawbacks, different approaches can be performed, including the incorporation of nanofillers. In this regard, different types of metallic nanoparticles, metal oxide nanofillers, and carbon-based nanomaterials have been recently integrated into PMMA matrices with the aim to reduce water absorption and improve their performance, namely their thermal and flexural properties. In this review, recent studies regarding the development of PMMA-based nanocomposites for odontology applications are summarized and future perspectives are highlighted.
Relationship between Changes in Intestinal Microorganisms and Effect of High Temperature on the Growth and Development of Bombyx mori Larvae
Authors: Sun Xiaoning , Yuan Qian , Du Beibei , Jin Xinye , Huang Xiyun , Li Qiuying , Zhong Yueqiao , Pan Zhonghua , Xu Shiqing , Sima Yanghu
Published: September 2022

Temperature is an important environmental factor affecting the growth and development of silkworm (Bombyx mori). To analyze the effect of intestinal microbes on silkworm in response to a high-temperature environment, this study used a combination of high throughput sequencing and biochemical assays to detect silkworm intestinal microbes treated with high temperature for 72 h. The results show that high temperature affects the intestinal microbes of silkworm and that there are sex differences, specifically, females were more sensitive. The changes in the metabolism and transport ability of silkworm intestinal tissues under high temperature are related to the intestinal microbes. High temperatures may affect the intestinal microbes of silkworms, regulating the activity of related digestive enzymes and substance transport in the intestine, thereby affecting the silkworm’s digestion and absorption of nutrients, and ultimately affecting growth and development.
Progesterone Receptor Modulates Extraembryonic Mesoderm and Cardiac Progenitor Specification during Mouse Gastrulation
Authors: Drozd Anna Maria , Mariani Luca , Guo Xiaogang , Goitea Victor , Menezes Niels Alvaro , Ferretti Elisabetta
Published: September 2022

Progesterone treatment is commonly employed to promote and support pregnancy. While maternal tissues are the main progesterone targets in humans and mice, its receptor (PGR) is expressed in the murine embryo, questioning its function during embryonic development. Progesterone has been previously associated with murine blastocyst development. Whether it contributes to lineage specification is largely unknown. Gastrulation initiates lineage specification and generation of the progenitors contributing to all organs. Cells passing through the primitive streak (PS) will give rise to the mesoderm and endoderm. Cells emerging posteriorly will form the extraembryonic mesodermal tissues supporting embryonic growth. Cells arising anteriorly will contribute to the embryonic heart in two sets of distinct progenitors, first (FHF) and second heart field (SHF). We found that PGR is expressed in a posterior–anterior gradient in the PS of gastrulating embryos. We established in vitro differentiation systems inducing posterior (extraembryonic) and anterior (cardiac) mesoderm to unravel PGR function. We discovered that PGR specifically modulates extraembryonic and cardiac mesoderm. Overexpression experiments revealed that PGR safeguards cardiac differentiation, blocking premature SHF progenitor specification and sustaining the FHF progenitor pool. This role of PGR in heart development indicates that progesterone administration should be closely monitored in potential early-pregnancy patients undergoing infertility treatment.
Phenanthroindolizidine Alkaloids Isolated from Tylophora ovata as Potent Inhibitors of Inflammation, Spheroid Growth, and Invasion of Triple-Negative Breast Cancer
Authors: Reimche Irene , Yu Haiqian , Ariantari Ni Putu , Liu Zhen , Merkens Kay , Rotfuß Stella , Peter Karin , Jungwirth Ute , Bauer Nadine , Kiefer Friedemann , Neudörfl Jörg-Martin , Schmalz Hans-Günther , Proksch Peter , Teusch Nicole
Published: September 2022

Triple-negative breast cancer (TNBC), representing the most aggressive form of breast cancer with currently no targeted therapy available, is characterized by an inflammatory and hypoxic tumor microenvironment. To date, a broad spectrum of anti-tumor activities has been reported for phenanthroindolizidine alkaloids (PAs), however, their mode of action in TNBC remains elusive. Thus, we investigated six naturally occurring PAs extracted from the plant Tylophora ovata: O-methyltylophorinidine (1) and its five derivatives tylophorinidine (2), tylophoridicine E (3), 2-demethoxytylophorine (4), tylophoridicine D (5), and anhydrodehydrotylophorinidine (6). In comparison to natural (1) and for more-in depth studies, we also utilized a sample of synthetic O-methyltylophorinidine (1s). Our results indicate a remarkably effective blockade of nuclear factor kappa B (NFκB) within 2 h for compounds (1) and (1s) (IC50 = 17.1 ± 2.0 nM and 3.3 ± 0.2 nM) that is different from its effect on cell viability within 24 h (IC50 = 13.6 ± 0.4 nM and 4.2 ± 1 nM). Furthermore, NFκB inhibition data for the additional five analogues indicate a structure–activity relationship (SAR). Mechanistically, NFκB is significantly blocked through the stabilization of its inhibitor protein kappa B alpha (IκBα) under normoxic as well as hypoxic conditions. To better mimic the TNBC microenvironment in vitro, we established a 3D co-culture by combining the human TNBC cell line MDA-MB-231 with primary murine cancer-associated fibroblasts (CAF) and type I collagen. Compound (1) demonstrates superiority against the therapeutic gold standard paclitaxel by diminishing spheroid growth by 40% at 100 nM. The anti-proliferative effect of (1s) is distinct from paclitaxel in that it arrests the cell cycle at the G0/G1 state, thereby mediating a time-dependent delay in cell cycle progression. Furthermore, (1s) inhibited invasion of TNBC monoculture spheroids into a matrigel®-based environment at 10 nM. In conclusion, PAs serve as promising agents with presumably multiple target sites to combat inflammatory and hypoxia-driven cancer, such as TNBC, with a different mode of action than the currently applied chemotherapeutic drugs.
Response of Mycobacterium smegmatis to the Cytochrome bcc Inhibitor Q203
Authors: Chauhan Priyanka , van der Meulen Santhe Amber , Simões Caetano João Miguel , Goojani Hojjat Ghasemi , Botman Dennis , van Spanning Rob , Lill Holger , Bald Dirk
Published: September 2022

For the design of next-generation tuberculosis chemotherapy, insight into bacterial defence against drugs is required. Currently, targeting respiration has attracted strong attention for combatting drug-resistant mycobacteria. Q203 (telacebec), an inhibitor of the cytochrome bcc complex in the mycobacterial respiratory chain, is currently evaluated in phase-2 clinical trials. Q203 has bacteriostatic activity against M. tuberculosis, which can be converted to bactericidal activity by concurrently inhibiting an alternative branch of the mycobacterial respiratory chain, cytochrome bd. In contrast, non-tuberculous mycobacteria, such as Mycobacterium smegmatis, show only very little sensitivity to Q203. In this report, we investigated factors that M. smegmatis employs to adapt to Q203 in the presence or absence of a functional cytochrome bd, especially regarding its terminal oxidases. In the presence of a functional cytochrome bd, M. smegmatis responds to Q203 by increasing the expression of cytochrome bcc as well as of cytochrome bd, whereas a M. smegmatisbd-KO strain adapted to Q203 by increasing the expression of cytochrome bcc. Interestingly, single-cell studies revealed cell-to-cell variability in drug adaptation. We also investigated the role of a putative second cytochrome bd isoform postulated for M. smegmatis. Although this putative isoform showed differential expression in response to Q203 in the M. smegmatisbd-KO strain, it did not display functional features similar to the characterised cytochrome bd variant.
Different Inhibition of Nrf2 by Two Keap1 Isoforms α and β to Shape Malignant Behaviour of Human Hepatocellular Carcinoma
Authors: Chen Feilong , Xiao Mei , Feng Jing , Wufur Reziyamu , Liu Keli , Hu Shaofan , Zhang Yiguo
Published: September 2022

Nrf2 (nuclear factor E2-related factor 2, encoded by Nfe2l2) acts as a master transcriptional regulator in mediating antioxidant, detoxification, and cytoprotective responses against oxidative, electrophilic, and metabolic stress, but also plays a crucial role in cancer metabolism and multiple oncogenic pathways, whereas the redox sensor Keap1 functions as a predominant inhibitor of Nrf2 and, hence, changes in its expression abundance directly affect the Nrf2 stability and transcriptional activity. However, nuanced functional isoforms of Keap1 α and β have rarely been identified to date. Herein, we have established four distinct cell models stably expressing Keap1−/−, Keap1β(Keap1Δ1–31), Keap1-Restored, and Keap1α-Restored aiming to gain a better understanding of similarities and differences of two Keap1 isoforms between their distinct regulatory profiles. Our experimental evidence revealed that although Keap1 and its isoforms are still localized in the cytoplasmic compartments, they elicited differential inhibitory effects on Nrf2 and its target HO-1. Furthermore, transcriptome sequencing unraveled that they possess similar but different functions. Such functions were further determined by multiple experiments in vivo (i.e., subcutaneous tumour formation in nude mice) and in vitro (e.g., cell cloning, infection, migration, wound healing, cell cycle, apoptosis, CAT enzymatic activity, and intracellular GSH levels). Of note, the results obtained from tumourigenesis experiments in xenograft model mice were verified based on the prominent changes in the PTEN signaling to the PI3K-AKT-mTOR pathways, in addition to substantially aberrant expression patterns of those typical genes involved in the EMT (epithelial–mesenchymal transition), cell cycle, and apoptosis.
Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats
Authors: Tchekalarova Jana , Kortenska Lidia , Marinov Pencho , Ivanova Natasha
Published: September 2022

Prenatal stress (PNS) impairs the circadian rhythm of the sleep/wake cycle. The melatonin (MT) analogue Piromelatine (Pir) was designed for the treatment of insomnia. The present study aimed to explore effects of Pir on circadian rhythmicity, motor activity, and sleep structure in male and female rats with a history of prenatal stress (PNS). In addition, we elucidated the role of MT receptors and brain-derived neurotrophic factor (BDNF) to ascertain the underlying mechanism of the drug. Pregnant rats were exposed to different stressors from day seven until birth. Piromelatine (20 mg/kg/day/14 days) was administered to young adult offspring. Home-cage locomotion, electroencephalographic (EEG) and electromyographic (EMG) recordings were conducted for 24 h. Offspring treated with vehicle showed sex-and phase-dependent disturbed circadian rhythm of motor activity and sleep/wake cycle accompanied by elevated rapid eye movement (REM) pattern and theta power and diminished non-rapid eye movement (NREM) sleep and delta power. While Pir corrected the PNS-induced impaired sleep patterns, the MT receptor antagonist luzindol suppressed its effects in male and female offspring. In addition, Pir increased the BDNF expression in the hippocampus in male and female offspring with PNS. Our findings suggest that the beneficial effect of Pir on PNS-induced impairment of sleep/wake cycle circadian rhythm and sleep structure is exerted via activation of MT receptors and enhanced BDNF expression in the hippocampus in male and female offspring.
Golgi Phosphoprotein 3 Regulates the Physical Association of Glycolipid Glycosyltransferases
Authors: Ruggiero Fernando , Martínez-Koteski Natalia , Cavieres Viviana , Mardones Gonzalo , Fidelio Gerardo , Vilcaes Aldo , Daniotti Jose
Published: September 2022

Glycolipid glycosylation is an intricate process that mainly takes place in the Golgi by the complex interplay between glycosyltransferases. Several features such as the organization, stoichiometry and composition of these complexes may modify their sorting properties, sub-Golgi localization, enzymatic activity and in consequence, the pattern of glycosylation at the plasma membrane. In spite of the advance in our comprehension about physiological and pathological cellular states of glycosylation, the molecular basis underlying the metabolism of glycolipids and the players involved in this process remain not fully understood. In the present work, using biochemical and fluorescence microscopy approaches, we demonstrate the existence of a physical association between two ganglioside glycosyltransferases, namely, ST3Gal-II (GD1a synthase) and β3GalT-IV (GM1 synthase) with Golgi phosphoprotein 3 (GOLPH3) in mammalian cultured cells. After GOLPH3 knockdown, the localization of both enzymes was not affected, but the fomation of ST3Gal-II/β3GalT-IV complex was compromised and glycolipid expression pattern changed. Our results suggest a novel control mechanism of glycolipid expression through the regulation of the physical association between glycolipid glycosyltransferases mediated by GOLPH3.
State-of-the-Art Molecular Dynamics Simulation Studies of RNA-Dependent RNA Polymerase of SARS-CoV-2
Authors: Tanimoto Shoichi , Itoh Satoru G. , Okumura Hisashi
Published: September 2022

Molecular dynamics (MD) simulations are powerful theoretical methods that can reveal biomolecular properties, such as structure, fluctuations, and ligand binding, at the level of atomic detail. In this review article, recent MD simulation studies on these biomolecular properties of the RNA-dependent RNA polymerase (RdRp), which is a multidomain protein, of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are presented. Although the tertiary structures of RdRps in SARS-CoV-2 and SARS-CoV are almost identical, the RNA synthesis activity of RdRp of SARS-CoV is higher than SARS-CoV-2. Recent MD simulations observed a difference in the dynamic properties of the two RdRps, which may cause activity differences. RdRp is also a drug target for Coronavirus disease 2019 (COVID-19). Nucleotide analogs, such as remdesivir and favipiravir, are considered to be taken up by RdRp and inhibit RNA replication. Recent MD simulations revealed the recognition mechanism of RdRp for these drug molecules and adenosine triphosphate (ATP). The ligand-recognition ability of RdRp decreases in the order of remdesivir, favipiravir, and ATP. As a typical recognition process, it was found that several lysine residues of RdRp transfer these ligand molecules to the binding site such as a “bucket brigade.” This finding will contribute to understanding the mechanism of the efficient ligand recognition by RdRp. In addition, various simulation studies on the complexes of SARS-CoV-2 RdRp with several nucleotide analogs are reviewed, and the molecular mechanisms by which these compounds inhibit the function of RdRp are discussed. The simulation studies presented in this review will provide useful insights into how nucleotide analogs are recognized by RdRp and inhibit the RNA replication.
The Levels of Ghrelin, Glucagon, Visfatin and Glp-1 Are Decreased in the Peritoneal Fluid of Women with Endometriosis along with the Increased Expression of the CD10 Protease by the Macrophages
Authors: Krasnyi Aleksey M. , Sadekova Alsu A. , Smolnova Tatyana Y. , Chursin Vyacheslav V. , Buralkina Natalya A. , Chuprynin Vladimir D. , Yarotskaya Ekaterina , Pavlovich Stanislav V. , Sukhikh Gennadiy T.
Published: September 2022

The aim of this study was to evaluate the levels of ten energy metabolism factors: C-peptide, ghrelin, GIP, GLP-1, glucagon, insulin, leptin, PAI-1 (total), resistin, and visfatin, and to determine the expression of GLP1R receptors, CD10, CD26 proteases, and pro-inflammatory marker CD86 by macrophages in the peritoneal fluid (PF) in patients with endometriosis. The study included 54 women with endometriosis and a control group of 30 women with uterine myoma without signs of endometriosis. The levels of factors in PF were assessed by a multiplex method. Expression of GLP1R receptors, CD10, CD26 proteases, and CD86 by macrophages was evaluated using flow cytometry. It was found that in women with endometriosis, the concentrations of ghrelin, GLP-1, glucagon, and visfatin in PF were reduced (p = 0.007, p = 0.009, p = 0.002, p = 0.008, respectively). At the same time, there was a noted increase in the CD10 protease expression by peritoneal macrophages (p = 0.044). Correlation analysis showed a positive correlation of ghrelin and GLP-1 levels with CD86 macrophage expression (p = 0.044, p = 0.022, respectively) in the study group; a positive correlation was also found between the levels of GLP-1, glucagon, and visfatin with CD26 macrophage expression (p = 0.041, p = 0.048, p = 0.015, respectively) in PF. No correlations were found in the control group. These results indicate that a decrease in the levels of ghrelin, GLP-1, glucagon, and visfatin in PF may contribute to endometriosis development through their impact on the expression of pro-inflammatory markers of PF macrophages.
Effect of the TrFE Content on the Crystallization and SSA Thermal Fractionation of P(VDF-co-TrFE) Copolymers
Authors: María Nicolás , Le Goupil Florian , Cavallo Dario , Maiz Jon , Müller Alejandro J.
Published: September 2022

In this contribution, we study the effect of trifluoro ethylene (TrFE) comonomer content (samples with 80/20, 75/25, and 70/30 VDF/TrFE molar ratios were used) on the crystallization in P(VDF-co-TrFE) in comparison with a PVDF (Poly(vinylidene fluoride)) homopolymer. Employing Polarized Light Optical Microscopy (PLOM), the growth rates of spherulites or axialites were determined. Differential Scanning Calorimetry (DSC) was used to determine overall crystallization rates, self-nucleation, and Successive Self-nucleation and Annealing (SSA) thermal fractionation. The ferroelectric character of the samples was explored by polarization measurements. The results indicate that TrFE inclusion can limit the overall crystallization of the copolymer samples, especially for the ones with 20 and 25% TrFE. Self-nucleation measurements in PVDF indicate that the homopolymer can be self-nucleated, exhibiting the classic three Domains. However, the increased nucleation capacity in the copolymers provokes the absence of the self-nucleation Domain II. The PVDF displays a monomodal distribution of thermal fractions after SSA, but the P(VDF-co-TrFE) copolymers do not experience thermal fractionation, apparently due to TrFE incorporation in the PVDF crystals. Finally, the maximum and remnant polarization increases with increasing TrFE content up to a maximum of 25% TrFE content, after which it starts to decrease due to the lower dipole moment of the TrFE defect inclusion within the PVDF crystals.
Dual Inhibition of EGFR and IGF-1R Signaling Leads to Enhanced Antitumor Efficacy against Esophageal Squamous Cancer
Authors: Kang Jia , Guo Zanzan , Zhang Haoqi , Guo Rongqi , Zhu Xiaofei , Guo Xiaofang
Published: September 2022

Both the epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) have been implicated in the development of cancers, and the increased expression of both receptors has been observed in esophageal cancer. However, the tyrosine kinase inhibitors of both receptors have thus far failed to provide clinical benefits for esophageal cancer patients. Studies have confirmed the complicated crosstalks that exist between the EGFR and IGF-1R pathways. The EGFR and IGF-1R signals act as mutual compensation pathways, thereby conveying resistance to EGFR or IGF-1R inhibitors when used alone. This study evaluated the antitumor efficacy of the EGFR/HER2 inhibitors, gefitinib and lapatinib, in combination with the IGF-1R inhibitor, linsitinib, on the esophageal squamous cell carcinoma (ESCC). Gefitinib or lapatinib, in combination with linsitinib, synergistically inhibited the proliferation, migration, and invasion of ESCC cells, caused significant cell cycle arrest, and induced marked cell apoptosis. Their combination demonstrated stronger inhibition on the activation of EGFR, HER2, and IGF-1R as well as the downstream signaling molecules. In vivo, the addition of linsitinib to gefitinib or lapatinib also potentiated the inhibition effects on the growth of xenografts. Our results suggest the next clinical exploration of the combination of gefitinib or lapatinib with linsitinib in the treatment of ESCC patients.
A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis
Authors: Barbeau-Grégoire Maude , Otis Colombe , Cournoyer Antoine , Moreau Maxim , Lussier Bertrand , Troncy Eric
Published: September 2022

With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.