bluuebunny/crossref_metadata_2025 huggingface dataset:
Models of Aviation Noise Impact in the Context of Operation Decrease at Tan Son Nhat Airport
Authors: Nguyen Tran Thi Hong Nhung , Trieu Bach Lien , Nguyen Thu Lan , Morinaga Makoto , Hiraguri Yasuhiro , Morihara Takashi , Sasazawa Yosiaki , Nguyen Tri Quang Hung , Yano Takashi
Published: April 2023

Air traffic bans in response to the spread of the coronavirus have changed the sound situation of urban areas around airports. This study aimed to investigate the effect of this unprecedented event on the community response to noise before and after the international flight operation at Tan Son Nhat Airport (TSN) in March 2020. The “before” survey was conducted in August 2019, and the two “after” surveys were conducted in June and September 2020. Structural equation models (SEMs) for noise annoyance and insomnia were developed by linking the questionnaire items of the social surveys. The first effort aimed to achieve a common model of noise annoyance and insomnia, corresponding to the situation before and after the change, respectively. Approximately, 1200 responses were obtained from surveys conducted in 12 residential areas around TSN in 2019 and 2020. The average daily flight numbers observed in August 2019 during the two surveys conducted in 2020 were 728, 413, and 299, respectively. The sound pressure levels of the 12 sites around TSN decreased from 45–81 dB (mean = 64, SD = 9.8) in 2019 to 41–76 dB (mean = 60, SD = 9.8) and 41–73 dB (mean = 59, SD = 9.3) in June and September 2020, respectively. The SEM indicated that the residents’ health was related to increased annoyance and insomnia.
“Why Am I Even Here If I Can’t Save the Patients?”: The Frontline Healthcare Workers’ Experience of Burnout during COVID-19 Pandemic in Mthatha, South Africa
Authors: Fathuse Noluyolo , Hlongwana Khumbulani W. , Ginindza Themba G.
Published: April 2023

Introduction: Globally, the high prevalence of burnout in healthcare workers (HCWs) is of the utmost concern. Burnout is a state of emotional exhaustion, depersonalization and a decreased sense of personal accomplishment. While the 2019 Coronavirus (COVID-19) exacerbated the burnout prevalence among HCWs, limited studies have explored this phenomenon using qualitative methodologies in the Eastern Cape Province and South Africa generally. This study explored how frontline healthcare workers experienced burnout during the COVID-19 pandemic in Mthatha Regional Hospital. Methods: Ten face-to-face in-depth interviews were conducted with non-specialized medical doctors and nurses who directly cared for COVID-19-infected patients during the pandemic in Mthatha Regional Hospital (MRH). In-depth interviews were digitally recorded and transcribed verbatim. Data were managed through NVIVO 12 software before being thematically analyzed using Colaizzi’s analysis method. Results: Four main themes emerged from the analysis. These themes were burnout manifestation (emotional strain, detachment and irritability, uncertainty-induced fear, and anxiety, physical exhaustion, yet, low job accomplishment, dread and professional responsibility), precursors of burnout (occupational exposure to high mortality, staff shortages, elongated high patient volume and workload, disease uncertainties and consistent feeling of grief), alleviating factors of burnout (time off work, psychologist intervention, periods of low infection rate and additional staff), and the last theme was every cloud has a silver lining (improved infection prevention and control (IPC) measures, learning to be more empathetic, the passion remains and confidence grows). Conclusion: The COVID-19 pandemic brought about a rapid change in the work environment of healthcare workers who are the backbone of efficient healthcare services, thereby rendering them vulnerable to increased burnout risks. This study provides strategic information for policymakers and managers on developing and strengthening welfare policies to promote and protect frontline health workers’ well-being and work functioning.
Effect of Aerobic Exercise Training on Sleep and Core Temperature in Middle-Aged Women with Chronic Insomnia: A Randomized Controlled Trial
Authors: Baron Pauline , Hermand Éric , Bourlois Valentin , Pezé Thierry , Aron Christophe , Lombard Remi , Hurdiel Rémy
Published: April 2023

Background: Exercise represents a viable non-pharmacological intervention to help treating insomnia but the interaction mechanisms between sleep and physical activity still remain poorly understood. The aim of this study was to investigate the effect of a aerobic exercise training intervention on sleep and core temperature. Methods: Twenty-four adult women suffering from insomnia participated in this study. They were randomized into an exercise group and a control group. Aerobic exercise training consisted in moderate to vigorous aerobic exercise training for 12 weeks. Outcome measures included both subjective (Insomnia Severity Index, ISI) and objective (actigraphy recordings) sleep quality assessments, and core body temperature continuously recorded for a minimum 24 h. Results: The exercise group showed a decrease in ISI (p < 0.001) and in various objective sleep parameters. The core temperature batyphase value was lowered (p = 0.037) whereas its amplitude was larger (p = 0.002). We also found a tight correlation between the evolution of insomnia and the evolution of mean night-time core temperature and batyphase values. Conclusions: A moderate to vigorous aerobic exercise program appears to be an effective non-drug therapy for improving sleep in women with insomnia. In addition, exercise programs should aim to increase core body temperature during practice to induce sleep-promoting adaptations and rebound.
Validation and Psychometric Properties of the Tobacco Urge Management Scale (TUMS)
Authors: Chin Samantha M. , Lepore Stephen J. , Collins Bradley N. , Dumenci Levent , Rincon Maria A.
Published: April 2023

Background: During quit attempts, smokers must overcome smoking urges triggered by environmental cues and nicotine withdrawal symptoms. This study investigates the psychometric properties of the 12-item Tobacco Urge Management Scale (TUMS), a new measure of smoking urge management behaviors. Methods: We analyzed secondary data (n = 327) from a behavioral smoking cessation intervention trial, Kids Safe and Smokefree (KiSS). Results: Confirmatory factor analysis of the TUMS indicated that a one-factor model and a correlated two-factor model had similar model fit indices, and a Chi-square difference test supported the one-factor model. Further study of the parsimonious one-factor scale provided evidence of reliability and construct validity. Known group validity was evidenced by significantly higher TUMS scores in the KiSS intervention arm receiving urge management skills training than in the control arm (p < 0.001). Concurrent validity was evidenced by TUMS’s inverse association with cigarettes smoked per day and positive associations with nonsmoking days, 7-day abstinence, and self-efficacy to control smoking behaviors (p’s < 0.05). Conclusion: The TUMS is a reliable, valid measure of smoking urge management behaviors. The measure can support theory-driven research on smoking-specific coping mechanisms, inform clinical practice by identifying coping strategies that might be under-utilized in treatment-seeking smokers, and function as a measure of treatment adherence in cessation trials that target urge management behaviors.
Paternal Leave Entitlement and Workplace Culture: A Key Challenge to Paternal Mental Health
Authors: Gheyoh Ndzi Ernestine , Holmes Amy
Published: April 2023

Paternal mental health continues to be a health concern in the UK. Paternal leave entitlement and workplace cultures have failed to support fathers in navigating the complexity of fatherhood, which has an impact on fathers’ wellbeing. Interviewing twenty fathers in the York area, this study seeks to explore the impact of parental leave entitlements and workplace cultures on fathers’ mental health. The findings demonstrate that the influence of gendered norms and hegemonic masculinity perceptions are ingrained in the current leave entitlement and workplace cultures. While fathers are entitled to take leave, the leave is significantly insufficient to allow them to forge a meaningful bond with a newborn or adapt to the change in routine brought about by the birth of a baby. Furthermore, workplace cultures fail to recognise the responsibilities that come with fatherhood and provide insufficient support for fathers. The COVID-19 lockdown presented fathers with a unique opportunity to be available and take on more family responsibilities. Fathers felt they did not have to navigate gendered and hegemonic perceptions to spend more time with the family. This paper challenges structural and cultural barriers that prevent fathers from taking leave and impacting negatively on fathers’ mental health. The paper suggests a review of the current paternal leave entitlement and cultural change in the workplace.
Spatiotemporal Evolution Analysis of the Chinese Railway Network Structure Based on Self-Organizing Maps
Authors: Yin Lingzhi , Wang Yafei
Published: April 2023

Delving into the spatiotemporal evolution of the railway network in different periods can provide guidance and reference for the planning and layout of the railway network. However, most of the existing studies tended to model the railway data separately and compare the network indices of adjacent periods based on the railway data of different periods, thus failing to integrate the railway network in different periods into a unified framework for evolution analysis. Therefore, this paper used the railway data from 2008, 2010, 2015, and 2019, and analyzed the spatiotemporal integration of the railway network evolution based on the complex network theory and the self-organizing maps (SOM) method. Firstly, this study constructed the geographical railway network in the four years and probed into how the network feature indices changed. Then, it used the SOM method to capture the spatiotemporal integration of the railway network evolution in multi-time series. Finally, it clustered the change trajectory of each city node and unveiled the relationship between the evolution of city nodes and the hierarchy of urban systems. The results show that from 2008 to 2019, the railway network feature indices showed an upward trend and that the expansion pattern of the railway network could be divided into the core–peripheral pattern, belt expansion pattern, strings of beads pattern, and multi-center network pattern. The evolution of the change trajectory of the city nodes was highly related to the hierarchical structure of the urban system. This study helps to understand the evolution process of the railway network in China, and provides decision-making reference for improving and optimizing China’s railway network.
Aging of the Arterial System
Authors: Castelli Roberto , Gidaro Antonio , Casu Gavino , Merella Pierluigi , Profili Nicia I. , Donadoni Mattia , Maioli Margherita , Delitala Alessandro P.
Published: April 2023

Aging of the vascular system is associated with deep changes of the structural proprieties of the arterial wall. Arterial hypertension, diabetes mellitus, and chronic kidney disease are the major determinants for the loss of elasticity and reduced compliance of vascular wall. Arterial stiffness is a key parameter for assessing the elasticity of the arterial wall and can be easily evaluated with non-invasive methods, such as pulse wave velocity. Early assessment of vessel stiffness is critical because its alteration can precede clinical manifestation of cardiovascular disease. Although there is no specific pharmacological target for arterial stiffness, the treatment of its risk factors helps to improve the elasticity of the arterial wall.
Efflux Pumps and Different Genetic Contexts of tet(X4) Contribute to High Tigecycline Resistance in Escherichia fergusonii from Pigs
Authors: Wang Junlin , Wan Xiulin , Meng Hecheng , Olsen Rikke Heidemann , Chen Xun , Li Lili
Published: April 2023

Tigecycline is a last-resort antibiotic for the treatment of infections caused by multidrug-resistant bacteria. The emergence of plasmid-mediated tigecycline resistance genes is posing a serious threat to food safety and human health and has attracted worldwide attention. In this study, we characterized six tigecycline-resistant Escherichia fergusonii strains from porcine nasal swab samples collected from 50 swine farms in China. All the E. fergusonii isolates were highly resistant to tigecycline with minimal inhibitory concentration (MIC) values of 16–32 mg/L, and all contained the tet(X4) gene. In addition, 13–19 multiple resistance genes were identified in these isolates, revealed by whole-genome sequencing analysis. The tet(X4) gene was identified as being located in two different genetic structures, hp-abh-tet(X4)-ISCR2 in five isolates and hp-abh-tet(X4)-ΔISCR2-ISEc57-IS26 in one isolate. The role of efflux pumps in tigecycline resistance was evaluated by using inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The MIC values of tigecycline showed a 2- to 4-fold reduction in the presence of CCCP, indicating the involvement of active efflux pumps in tigecycline resistance in E. fergusonii. The tet(X4) gene was found to be transferable to Escherichia coli J53 by conjugation and resulted in the acquisition of tigcycline resistances in the transconjugants. Whole-genome multilocus sequence typing (wgMLST) and phylogenetic analysis showed a close relationship of five isolates originating from different pig farms, suggesting the transmission of tet(X4)-positive E. fergusonii between farms. In conclusion, our findings suggest that E. fergusonii strains in pigs are reservoirs of a transferable tet(X4) gene and provide insights into the tigecycline resistance mechanism as well as the diversity and complexity of the genetic context of tet(X4) in E. fergusonii.
Collagen-Derived Dipeptides and Amino Acids Have Immunomodulatory Effects in M1-Differentiated RAW264.7 Cells and PBMC
Authors: Tominaga Takaki , Huang Jiapeng , Wang Shuo , Noguchi Miwa , Tong Yishan , Asano-Oritani Momoko , Suzuki Katsuhiko
Published: April 2023

A number of food components, such as polyphenols and phytonutrients, have immunomodulatory effects. Collagen has various bioactivities, such as antioxidative effects, the promotion of wound healing, and relieving symptoms of bone/joint disease. Collagen is digested into dipeptides and amino acids in the gastrointestinal tract and subsequently absorbed. However, the difference in immunomodulatory effects between collagen-derived dipeptides and amino acids is unknown. To investigate such differences, we incubated M1 macrophages or peripheral blood mononuclear cells (PBMC) with collagen-derived dipeptides (hydroxyproline-glycine (Hyp-Gly) and proline-hydroxyproline (Pro-Hyp)) and amino acids (proline (Pro), hydroxyproline (Hyp), and glycine (Gly)). We first investigated the dose dependency of Hyp-Gly on cytokine secretion. Hyp-Gly modulates cytokine secretion from M1 macrophages at 100 µM, but not at 10 µM and 1 µM. We then compared immunomodulatory effects between dipeptides and mixtures of amino acids on M1 macrophages and PBMC. There was, however, no difference in cytokine secretion between dipeptides and their respective amino acids. We conclude that collagen-derived dipeptides and amino acids have immunomodulatory effects on M1-differentiated RAW264.7 cells and PBMC and that there is no difference in the immunomodulatory effects between dipeptides and amino acids.
A New One-Tube Reaction Assay for the Universal Determination of Sweet Cherry (Prunus avium L.) Self-(In)Compatible MGST- and S-Alleles Using Capillary Fragment Analysis
Authors: Čmejlová Jana , Paprštein František , Suran Pavol , Zelený Lubor , Čmejla Radek
Published: April 2023

The sweet cherry plant (Prunus avium L.) is primarily self-incompatible, with so-called S-alleles responsible for the inability of flowers to be pollinated not only by their own pollen grains but also by pollen from other cherries having the same S-alleles. This characteristic has wide-ranging impacts on commercial growing, harvesting, and breeding. However, mutations in S-alleles as well as changes in the expression of M locus-encoded glutathione-S-transferase (MGST) can lead to complete or partial self-compatibility, simplifying orchard management and reducing possible crop losses. Knowledge of S-alleles is important for growers and breeders, but current determination methods are challenging, requiring several PCR runs. Here we present a system for the identification of multiple S-alleles and MGST promoter variants in one-tube PCR, with subsequent fragment analysis on a capillary genetic analyzer. The assay was shown to unequivocally determine three MGST alleles, 14 self-incompatible S-alleles, and all three known self-compatible S-alleles (S3′, S4′, S5′) in 55 combinations tested, and thus it is especially suitable for routine S-allele diagnostics and molecular marker-assisted breeding for self-compatible sweet cherries. In addition, we identified a previously unknown S-allele in the ’Techlovicka´ genotype (S54) and a new variant of the MGST promoter with an 8-bp deletion in the ´Kronio´ cultivar.
Anti-Inflammatory and Antimicrobial Properties of Thyme Oil and Its Main Constituents
Authors: Vassiliou Evros , Awoleye Oreoluwa , Davis Amanda , Mishra Sasmita
Published: April 2023

Thyme oil (TO) is derived from the flowers of various plants belonging to the genus Thymus. It has been used as a therapeutic agent since ancient times. Thymus comprises numerous molecular species exhibiting diverse therapeutic properties that are dependent on their biologically active concentrations in the extracted oil. It is therefore not surprising that oils extracted from different thyme plants present different therapeutic properties. Furthermore, the phenophase of the same plant species has been shown to yield different anti-inflammatory properties. Given the proven efficacy of TO and the diversity of its constituents, a better understanding of the interactions of the various components is warranted. The aim of this review is to gather the latest research findings regarding TO and its components with respect to their immunomodulatory properties. An optimization of the various components has the potential to yield more effective thyme formulations with increased potency.
MemophenolTM Prevents Amyloid-β Deposition and Attenuates Inflammation and Oxidative Stress in the Brain of an Alzheimer’s Disease Rat
Authors: Impellizzeri Daniela , Tomasello Mario , Cordaro Marika , D’Amico Ramona , Fusco Roberta , Abdelhameed Ali S. , Wenzel Uwe , Siracusa Rosalba , Calabrese Vittorio , Cuzzocrea Salvatore , Di Paola Rosanna
Published: April 2023

Alzheimer’s disease (AD) is the most common cause of dementia, and its prevalence rises with age. Inflammation and altered antioxidant systems play essential roles in the genesis of neurodegenerative diseases. In this work, we looked at the effects of MemophenolTM, a compound rich in polyphenols derived from French grape (Vitis vinifera L.) and wild North American blueberry (Vaccinium angustifolium A.) extracts, in a rat model of AD. Methods: For 60 days, the animals were administered with AlCl3 (100 mg/kg, orally) and D-galactose (60 mg/kg, intraperitoneally), while from day 30, MemophenolTM (15 mg/kg) was supplied orally for 30 consecutive days. AlCl3 accumulates mainly in the hippocampus, the main part of the brain involved in memory and learning. Behavioral tests were performed the day before the sacrifice when brains were collected for analysis. Results: MemophenolTM decreased behavioral alterations and hippocampus neuronal degeneration. It also lowered phosphorylated Tau (p-Tau) levels, amyloid precursor protein (APP) overexpression, and β-amyloid (Aβ) buildup. Furthermore, MemophenolTM reduced the pro-oxidative and pro-inflammatory hippocampus changes caused by AD. Our finding, relevant to AD pathogenesis and therapeutics, suggests that MemophenolTM, by modulating oxidative and inflammatory pathways and by regulating cellular brain stress response mechanisms, protects against the behavioral and histopathological changes associated with AD.
The Transfer of the Hepatocyte Growth Factor Gene by Macrophages Ameliorates the Progression of Peritoneal Fibrosis in Mice
Authors: Obata Yoko , Abe Katsushige , Miyazaki Masanobu , Koji Takehiko , Tabata Yasuhiko , Nishino Tomoya
Published: April 2023

Growing evidence indicates that hepatocyte growth factor (HGF) possesses potent antifibrotic activity. Furthermore, macrophages migrate to inflamed sites and have been linked to the progression of fibrosis. In this study, we utilized macrophages as vehicles to express and deliver the HGF gene and investigated whether macrophages carrying the HGF expression vector (HGF-M) could suppress peritoneal fibrosis development in mice. We obtained macrophages from the peritoneal cavity of mice stimulated with 3% thioglycollate and used cationized gelatin microspheres (CGMs) to produce HGF expression vector-gelatin complexes. Macrophages phagocytosed these CGMs, and gene transfer into macrophages was confirmed in vitro. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG) for three weeks; seven days after the first CG injection, HGF-M was administered intravenously. Transplantation of HGF-M significantly suppressed submesothelial thickening and reduced type III collagen expression. Moreover, in the HGF-M-treated group, the number of α-smooth muscle actin- and TGF-β-positive cells were significantly lower in the peritoneum, and ultrafiltration was preserved. Our results indicated that the transplantation of HGF-M prevented the progression of peritoneal fibrosis and indicated that this novel gene therapy using macrophages may have potential for treating peritoneal fibrosis.
The oDGal Mouse: A Novel, Physiologically Relevant Rodent Model of Sporadic Alzheimer’s Disease
Authors: Chadwick Wayne , Maudsley Stuart , Hull William , Havolli Enes , Boshoff Eugene , Hill Mark D. W. , Goetghebeur Pascal J. D. , Harrison David C. , Nizami Sohaib , Bedford David C. , Coope Gareth , Real Katia , Thiemermann Christoph , Maycox Peter , Carlton Mark , Cole Sarah L.
Published: April 2023

Sporadic Alzheimer’s disease (sAD) represents a serious and growing worldwide economic and healthcare burden. Almost 95% of current AD patients are associated with sAD as opposed to patients presenting with well-characterized genetic mutations that lead to AD predisposition, i.e., familial AD (fAD). Presently, the use of transgenic (Tg) animals overexpressing human versions of these causative fAD genes represents the dominant research model for AD therapeutic development. As significant differences in etiology exist between sAD and fAD, it is perhaps more appropriate to develop novel, more sAD-reminiscent experimental models that would expedite the discovery of effective therapies for the majority of AD patients. Here we present the oDGal mouse model, a novel model of sAD that displays a range of AD-like pathologies as well as multiple cognitive deficits reminiscent of AD symptomology. Hippocampal cognitive impairment and pathology were delayed with N-acetyl-cysteine (NaC) treatment, which strongly suggests that reactive oxygen species (ROS) are the drivers of downstream pathologies such as elevated amyloid beta and hyperphosphorylated tau. These features demonstrate a desired pathophenotype that distinguishes our model from current transgenic rodent AD models. A preclinical model that presents a phenotype of non-genetic AD-like pathologies and cognitive deficits would benefit the sAD field, particularly when translating therapeutics from the preclinical to the clinical phase.
Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression
Authors: Sestokaite Agne , Gedvilaite Vaida , Cicenas Saulius , Sabaliauskaite Rasa , Jarmalaite Sonata
Published: April 2023

Non-small cell cancer (NSCLC) has been identified with a great variation of mutations that can be surveyed during disease progression. The aim of the study was to identify and monitor lung cancer-specific mutations incidence in cell-free DNA as well as overall plasma cell-free DNA load by means of targeted next-generation sequencing. Sequencing libraries were prepared from cell-free DNA (cfDNA) isolated from 72 plasma samples of 41 patients using the Oncomine Lung cfDNA panel covering hot spot regions of 11 genes. Sequencing was performed with the Ion Torrent™ Ion S5™ system. Four genes were detected with highest mutation incidence: KRAS (43.9% of all cases), followed by ALK (36.6%), TP53 (31.7%), and PIK3CA (29.3%). Seven patients had co-occurring KRAS + TP53 (6/41, 14.6%) or KRAS + PIK3CA (7/41, 17.1%) mutations. Moreover, the mutational status of TP53 as well an overall cell-free DNA load were confirmed to be predictors of poor progression-free survival (HR = 2.5 [0.8–7.7]; p = 0.029 and HR = 2.3 [0.9–5.5]; p = 0.029, respectively) in NSCLC patients. In addition, TP53 mutation status significantly predicts shorter overall survival (HR = 3.4 [1.2–9.7]; p < 0.001). We demonstrated that TP53 mutation incidence as well as a cell-free DNA load can be used as biomarkers for NSCLC monitoring and can help to detect the disease progression prior to radiological confirmation of the status.
Inhibitory Synaptic Influences on Developmental Motor Disorders
Authors: Fogarty Matthew J.
Published: April 2023

During development, GABA and glycine play major trophic and synaptic roles in the establishment of the neuromotor system. In this review, we summarise the formation, function and maturation of GABAergic and glycinergic synapses within neuromotor circuits during development. We take special care to discuss the differences in limb and respiratory neuromotor control. We then investigate the influences that GABAergic and glycinergic neurotransmission has on two major developmental neuromotor disorders: Rett syndrome and spastic cerebral palsy. We present these two syndromes in order to contrast the approaches to disease mechanism and therapy. While both conditions have motor dysfunctions at their core, one condition Rett syndrome, despite having myriad symptoms, has scientists focused on the breathing abnormalities and their alleviation—to great clinical advances. By contrast, cerebral palsy remains a scientific quagmire or poor definitions, no widely adopted model and a lack of therapeutic focus. We conclude that the sheer abundance of diversity of inhibitory neurotransmitter targets should provide hope for intractable conditions, particularly those that exhibit broad spectra of dysfunction—such as spastic cerebral palsy and Rett syndrome.
A Compilation of the Diverse miRNA Functions in Caenorhabditis elegans and Drosophila melanogaster Development
Authors: Quesnelle Daniel C. , Bendena William G. , Chin-Sang Ian D.
Published: April 2023

MicroRNAs are critical regulators of post-transcriptional gene expression in a wide range of taxa, including invertebrates, mammals, and plants. Since their discovery in the nematode, Caenorhabditis elegans, miRNA research has exploded, and they are being identified in almost every facet of development. Invertebrate model organisms, particularly C. elegans, and Drosophila melanogaster, are ideal systems for studying miRNA function, and the roles of many miRNAs are known in these animals. In this review, we compiled the functions of many of the miRNAs that are involved in the development of these invertebrate model species. We examine how gene regulation by miRNAs shapes both embryonic and larval development and show that, although many different aspects of development are regulated, several trends are apparent in the nature of their regulation.
Improved Wound Healing and Skin Regeneration Ability of 3,2′-Dihydroxyflavone-Treated Mesenchymal Stem Cell-Derived Extracellular Vesicles
Authors: Kim Sehee , Shin Yeokyung , Choi Yujin , Lim Kyung-Min , Jeong Yeojin , Dayem Ahmed Abdal , Lee Yoonjoo , An Jongyub , Song Kwonwoo , Jang Soo Bin , Cho Ssang-Goo
Published: April 2023

Flavonoids enhance the self-renewal and differentiation potential of mesenchymal stem cells (MSCs) and have therapeutic activities, including regenerative, anti-oxidative, and anti-inflammatory effects. Recent studies have revealed that MSC-derived extracellular vesicles (MSC-EVs) have therapeutic effects on tissue regeneration and inflammation. To facilitate further research on the therapeutic potential of MSC-EVs derived from flavonoid-treated MSCs, we surveyed the production of EVs and their therapeutic applications in wound regeneration. MSCs treated with flavonoids enhanced EV production twofold compared with naïve MSCs. EVs produced by MSCs treated with flavonoids (Fla-EVs) displayed significant anti-inflammatory and wound-healing effects in vitro. The wound-healing capacity of EVs was mediated by the upregulation of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. Interestingly, the protein level of p-ERK under inhibition of MEK signals was maintained in Fla-EV-treated fibroblasts, suggesting that Fla-EVs have a higher therapeutic potential than naïve MSC-EVs (Cont-EVs) in wound healing. Moreover, the in vivo wound closure effect of the Fla-EVs showed significant improvement compared with that of the flavonoid-only treatment group and the Cont-EVs. This study provides a strategy for the efficient production of EVs with superior therapeutic potential using flavonoids.
Interactions between Guidance Cues and Neuronal Activity: Therapeutic Insights from Mouse Models
Authors: Tomar Maitri , Beros Jamie , Meloni Bruno , Rodger Jennifer
Published: April 2023

Topographic mapping of neural circuits is fundamental in shaping the structural and functional organization of brain regions. This developmentally important process is crucial not only for the representation of different sensory inputs but also for their integration. Disruption of topographic organization has been associated with several neurodevelopmental disorders. The aim of this review is to highlight the mechanisms involved in creating and refining such well-defined maps in the brain with a focus on the Eph and ephrin families of axon guidance cues. We first describe the transgenic models where ephrin-A expression has been manipulated to understand the role of these guidance cues in defining topography in various sensory systems. We further describe the behavioral consequences of lacking ephrin-A guidance cues in these animal models. These studies have given us unexpected insight into how neuronal activity is equally important in refining neural circuits in different brain regions. We conclude the review by discussing studies that have used treatments such as repetitive transcranial magnetic stimulation (rTMS) to manipulate activity in the brain to compensate for the lack of guidance cues in ephrin-knockout animal models. We describe how rTMS could have therapeutic relevance in neurodevelopmental disorders with disrupted brain organization.
The Acute Effects and Mechanism of Ketamine on Nicotine-Induced Neurogenic Relaxation of the Corpus Cavernosum in Mice
Authors: Li Ming-Wei , Chao Tze-Chen , Lim Li-Yi , Chang Hsi-Hsien , Yang Stephen Shei-Dei
Published: April 2023

The present study aimed to investigate the acute effects and the mechanism of ketamine on nicotine-induced relaxation of the corpus cavernosum (CC) in mice. This study measured the intra-cavernosal pressure (ICP) of male C57BL/6 mice and the CC muscle activities using an organ bath wire myograph. Various drugs were used to investigate the mechanism of ketamine on nicotine-induced relaxation. Direct ketamine injection into the major pelvic ganglion (MPG) inhibited MPG-induced increases in ICP. D-serine/L-glutamate-induced relaxation of the CC was inhibited by MK-801 (N-methyl-D-aspartate (NMDA) receptor inhibitor), and nicotine-induced relaxation was enhanced by D-serine/L-glutamate. NMDA had no effect on CC relaxation. Nicotine-induced relaxation of the CC was suppressed by mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist), lidocaine, guanethidine (an adrenergic neuronal blocker), Nw-nitro-L-arginine (a non-selective nitric oxide synthase inhibitor), MK-801, and ketamine. This relaxation was almost completely inhibited in CC strips pretreated with 6-hydroxydopamine (a neurotoxic synthetic organic compound). Ketamine inhibited cavernosal nerve neurotransmission via direct action on the ganglion and impaired nicotine-induced CC relaxation. The relaxation of the CC was dependent on the interaction of the sympathetic and parasympathetic nerves, which may be mediated by the NMDA receptor.
Sulforaphane and Its Protective Role in Prostate Cancer: A Mechanistic Approach
Authors: Mordecai James , Ullah Saleem , Ahmad Irshad
Published: April 2023

The increasing incidence of prostate cancer worldwide has spurred research into novel therapeutics for its treatment and prevention. Sulforaphane, derived from broccoli and other members of the Brassica genus, is a phytochemical shown to have anticancer properties. Numerous studies have shown that sulforaphane prevents the development and progression of prostatic tumors. This review evaluates the most recent published reports on prevention of the progression of prostate cancer by sulforaphane in vitro, in vivo and in clinical settings. A detailed description of the proposed mechanisms of action of sulforaphane on prostatic cells is provided. Furthermore, we discuss the challenges, limitations and future prospects of using sulforaphane as a therapeutic agent in treatment of prostate cancer.
Molecular Research on Amyloidosis
Authors: Nakamura Kazufumi
Published: April 2023

Amyloidosis is a large group of diseases that are caused by the deposition of insoluble amyloid fibrils formed by misfolded soluble proteins in organs or tissues [...]
Purple Sweet Potato Powder Containing Anthocyanin Mitigates High-Fat-Diet-Induced Dry Eye Disease
Authors: Chiang Ming-Cheng , Liu Ying-Chung , Chen Bo-Yi , Wu Dai-Lin , Wu Chia-Lian , Cheng Chun-Wen , Chang Wen-Lung , Lee Huei-Jane
Published: April 2023

Purple sweet potato (PSP) powder with anthocyanins possesses the ability to reduce oxidative stress and inflammation. Studies have presumed a positive correlation between body fat and dry eye disease (DED) in adults. The regulation of oxidative stress and inflammation has been proposed as the mechanism underlying DED. This study developed an animal model of high fat diet (HFD)-induced DED. We added 5% PSP powder to the HFD to evaluate the effects and underlying mechanisms in mitigating HFD-induced DED. A statin drug, atorvastatin, was also added to the diet separately to assess its effect. The HFD altered the structure of lacrimal gland (LG) tissue, reduced LG secretory function, and eliminated the expression of proteins related to DED development, including α-smooth muscle actin and aquaporin-5. Although PSP treatment could not significantly reduce body weight or body fat, it ameliorated the effects of DED by preserving LG secretory function, preventing ocular surface erosion, and preserving LG structure. PSP treatment increased superoxide dismutase levels but reduced hypoxia-inducible factor 1-α levels, indicating that PSP treatment reduced oxidative stress. PSP treatment increased ATP-binding cassette transporter 1 and acetyl-CoA carboxylase 1 levels in LG tissue, signifying that PSP treatment regulated lipid homeostasis maintenance to reduce the effects of DED. In conclusion, PSP treatment ameliorated the effects of HFD-induced DED through the regulation of oxidative stress and lipid homeostasis in the LG.
Rapid and Robust Multi-Phenotypic Assay System for ALS Using Human iPS Cells with Mutations in Causative Genes
Authors: Kondo Tosho , Ebinuma Ihori , Tanaka Hirotaka , Nishikawa Yukitoshi , Komiya Takaki , Ishikawa Mitsuru , Okano Hideyuki
Published: April 2023

Amyotrophic lateral sclerosis (ALS) is a major life-threatening disease caused by motor neuron degeneration. More effective treatments through drug discovery are urgently needed. Here, we established an effective high-throughput screening system using induced pluripotent stem cells (iPSCs). Using a Tet-On-dependent transcription factor expression system carried on the PiggyBac vector, motor neurons were efficiently and rapidly generated from iPSCs by a single-step induction method. Induced iPSC transcripts displayed characteristics similar to those of spinal cord neurons. iPSC-generated motor neurons carried a mutation in fused in sarcoma (FUS) and superoxide dismutase 1 (SOD1) genes and had abnormal protein accumulation corresponding to each mutation. Calcium imaging and multiple electrode array (MEA) recordings demonstrated that ALS neurons were abnormally hyperexcitable. Noticeably, protein accumulation and hyperexcitability were ameliorated by treatment with rapamycin (mTOR inhibitor) and retigabine (Kv7 channel activator), respectively. Furthermore, rapamycin suppressed ALS neuronal death and hyperexcitability, suggesting that protein aggregate clearance through the activation of autophagy effectively normalized activity and improved neuronal survival. Our culture system reproduced several ALS phenotypes, including protein accumulation, hyperexcitability, and neuronal death. This rapid and robust phenotypic screening system will likely facilitate the discovery of novel ALS therapeutics and stratified and personalized medicine for sporadic motor neuron diseases.
Transcriptome, Biochemical and Phenotypic Analysis of the Effects of a Precision Engineered Biostimulant for Inducing Salinity Stress Tolerance in Tomato
Authors: Ikuyinminu Elomofe , Goñi Oscar , Łangowski Łukasz , O’Connell Shane
Published: April 2023

Salinity stress is a major problem affecting plant growth and crop productivity. While plant biostimulants have been reported to be an effective solution to tackle salinity stress in different crops, the key genes and metabolic pathways involved in these tolerance processes remain unclear. This study focused on integrating phenotypic, physiological, biochemical and transcriptome data obtained from different tissues of Solanum lycopersicum L. plants (cv. Micro-Tom) subjected to a saline irrigation water program for 61 days (EC: 5.8 dS/m) and treated with a combination of protein hydrolysate and Ascophyllum nodosum-derived biostimulant, namely PSI-475. The biostimulant application was associated with the maintenance of higher K+/Na+ ratios in both young leaf and root tissue and the overexpression of transporter genes related to ion homeostasis (e.g., NHX4, HKT1;2). A more efficient osmotic adjustment was characterized by a significant increase in relative water content (RWC), which most likely was associated with osmolyte accumulation and upregulation of genes related to aquaporins (e.g., PIP2.1, TIP2.1). A higher content of photosynthetic pigments (+19.8% to +27.5%), increased expression of genes involved in photosynthetic efficiency and chlorophyll biosynthesis (e.g., LHC, PORC) and enhanced primary carbon and nitrogen metabolic mechanisms were observed, leading to a higher fruit yield and fruit number (47.5% and 32.5%, respectively). Overall, it can be concluded that the precision engineered PSI-475 biostimulant can provide long-term protective effects on salinity stressed tomato plants through a well-defined mode of action in different plant tissues.
Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms
Authors: Zhang Ping , Wang Guoyun
Published: April 2023

Endometriosis is an estrogen-dependent disease characterized by the growth of endometrial-like tissue outside the uterus. Progestins are currently the most commonly used treatment for endometriosis because of their excellent therapeutic effects and limited side effects. However, progestins have been unsuccessful in some symptomatic patients. The inability of the endometrium to respond properly to progesterone is known as progesterone resistance. An increasing body of evidence suggests the loss of progesterone signaling and the existence of progesterone resistance in endometriosis. The mechanisms of progesterone resistance have received considerable scholarly attention in recent years. Abnormal PGR signaling, chronic inflammation, aberrant gene expression, epigenetic alterations, and environmental toxins are considered potential molecular causes of progesterone resistance in endometriosis. The general objective of this review was to summarize the evidence and mechanisms of progesterone resistance. A deeper understanding of how these mechanisms contribute to progesterone resistance may help develop a novel therapeutic regimen for women with endometriosis by reversing progesterone resistance.
The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function
Authors: Pinto Francisco M. , Odriozola Ainize , Candenas Luz , Subirán Nerea
Published: April 2023

During the last seventy years, studies on mammalian sperm cells have demonstrated the essential role of capacitation, hyperactivation and the acrosome reaction in the acquisition of fertilization ability. These studies revealed the important biochemical and physiological changes that sperm undergo in their travel throughout the female genital tract, including changes in membrane fluidity, the activation of soluble adenylate cyclase, increases in intracellular pH and Ca2+ and the development of motility. Sperm are highly polarized cells, with a resting membrane potential of about −40 mV, which must rapidly adapt to the ionic changes occurring through the sperm membrane. This review summarizes the current knowledge about the relationship between variations in the sperm potential membrane, including depolarization and hyperpolarization, and their correlation with changes in sperm motility and capacitation to further lead to the acrosome reaction, a calcium-dependent exocytosis process. We also review the functionality of different ion channels that are present in spermatozoa in order to understand their association with human infertility.
Convolutional Neural Networks Analysis Reveals Three Possible Sources of Bronze Age Writings between Greece and India
Authors: Daggumati Shruti , Revesz Peter Z.
Published: April 2023

This paper analyzes the relationships among eight ancient scripts from between Greece and India. We used convolutional neural networks combined with support vector machines to give a numerical rating of the similarity between pairs of signs (one sign from each of two different scripts). Two scripts that had a one-to-one matching of their signs were determined to be related. The result of the analysis is the finding of the following three groups, which are listed in chronological order: (1) Sumerian pictograms, the Indus Valley script, and the proto-Elamite script; (2) Cretan hieroglyphs and Linear B; and (3) the Phoenician, Greek, and Brahmi alphabets. Based on their geographic locations and times of appearance, Group (1) may originate from Mesopotamia in the early Bronze Age, Group (2) may originate from Europe in the middle Bronze Age, and Group (3) may originate from the Sinai Peninsula in the late Bronze Age.
FedUA: An Uncertainty-Aware Distillation-Based Federated Learning Scheme for Image Classification
Authors: Lee Shao-Ming , Wu Ja-Ling
Published: April 2023

Recently, federated learning (FL) has gradually become an important research topic in machine learning and information theory. FL emphasizes that clients jointly engage in solving learning tasks. In addition to data security issues, fundamental challenges in this type of learning include the imbalance and non-IID among clients’ data and the unreliable connections between devices due to limited communication bandwidths. The above issues are intractable to FL. This study starts from the uncertainty analysis of deep neural networks (DNNs) to evaluate the effectiveness of FL, and proposes a new architecture for model aggregation. Our scheme improves FL’s performance by applying knowledge distillation and the DNN’s uncertainty quantification methods. A series of experiments on the image classification task confirms that our proposed model aggregation scheme can effectively solve the problem of non-IID data, especially when affordable transmission costs are limited.
Deleterious Effects of Cymbopogon nardus (L.) Essential Oil on Life Cycle and Midgut of the Natural Predator Ceraeochrysa claveri (Navás, 1911) (Neuroptera: Chrysopidae)
Authors: Caballero-Gallardo Karina , Scudeler Elton Luiz , Carvalho dos Santos Daniela , Stashenko Elena E. , Olivero-Verbel Jesus
Published: April 2023

Cymbopogon nardus (citronella) essential oil (EO) has been widely used in the cosmetic and food industry due to its repellent and fumigant properties. The aim of this study was to evaluate its effects on the life cycle and midgut morphology of the natural predator Ceraeochrysa claveri. Larvae were fed on sugarcane borer eggs (Diatraea saccharalis) pretreated with citronella EO solutions (1–100 µg/mL in methanol, 5 s) or solvent and air-dried at room temperature for 30 min. Larval and pupal stage duration, the percentage of emergence of the insect, and malformed insects were recorded. One day after adults emerged from their cocoons, adult insects were used to obtain their midgut and analyzed using light microscopy. The chemical composition of C. nardus EO revealed that citronellal (25.3%), citronellol (17.9%), geraniol (11.6%), elemol (6.5%), δ-cadinone (3.6%), and germacrene D (3.4%) were the predominant compounds. Exposure to the EO produced a significant change in development duration for third instar and prepupa of the insect. The observed alterations in the lifecycle included prepupae with no cocoon formation, dead pupa inside the cocoon, and malformed adults. Several injuries in the midgut epithelium of exposed adults were registered, such as detachment of columnar cells leaving only swollen regenerative cells fixed on the basement membrane, and the formation of epithelial folds. In summary, these data suggest that C. nardus oil has adverse effects on the life cycle and midgut morphology of a beneficial predator.