bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockchain and NFTs in the Cultural Heritage Domain: A Review of Current Research Topics
Authors: Stublić Helena , Bilogrivić Matea , Zlodi Goran
Published: April 2023

In the last few years, blockchain technology and NFTs have been the subject of much research in different sectors ranging from informatics, to medicine, to economics. Although it is most often associated with cryptocurrencies, due to its features of immutability and durability, this technology has found its place in various fields, including GLAM institutions. This article will review the literature from 2017 to 2022 dealing with blockchain and NFTs in the heritage sector. Topics covered, proposed models, and projects will be highlighted. Archives are currently leading the research into the use of blockchain technology and have already developed models such as TrustChain. However, libraries, museums, and galleries are also beginning to show an interest in the new technology and its potential benefits. Therefore, we also approached the GLAM sector as a whole, to emphasize the importance of the joint development on the advancement of shared approaches and protocols in utilizing blockchain technology to enhance the trustworthy management and preservation of digital resources. This is particularly important because GLAM institutions care for a shared heritage and serve a common audience. In the second part of the article we will discuss the proposed uses of the technology and highlight still unexplored topics that should be elaborated in further research. The aim of this paper is to make a synthesis of previous research and bring the potential of blockchain technology and NFTs closer to experts in the heritage field, given that they are still quite unknown.
Known Glass Compositions in Iron Age Europe—Current Synthesis and Emerging Questions
Authors: Lončarić Valentina , Costa Mafalda
Published: April 2023

Ancient glass has been extensively studied from a technological and raw material provenance perspective since the middle of the 20th century. With the rising applications of analytical techniques in the field of Heritage Studies, the last two decades saw an exponential increase in publications on ancient and historical glass technology from around the globe. Given the amount of works on glass chemical composition, it is surprising to note that the long-held production model for Iron Age glasses found in Europe has only recently been challenged by the publication of uncharacteristic glass compositions. Traditionally, LBA glass industries based on plant-ash fluxes/HMG (Egypt and the Levant) and mixed-alkali fluxes/LMHK (Italy) are thought to be supplanted by natron-fluxed/LMG production operating in Egypt and the Levant since around the 9th century BCE. Recently, however, arguments have been put forth for a more diversified network of glassmaking traditions, including small-scale autonomous European workshops. This article reviews the current state of research into Iron Age (1st millennium BCE) glasses in Europe by examining the available published data on glass compositions to critically assess some practical and theoretical issues stemming from this heterogenous field of research. Key questions are addressed, and future lanes of research are proposed.
Using High-Density SNP Array to Investigate Genetic Relationships and Structure of Apple Germplasm in Bosnia and Herzegovina
Authors: Konjić Almira , Kurtović Mirsad , Grahić Jasmin , Pojskić Naris , Kalajdžić Abdurahim , Gaši Fuad
Published: April 2023

Apple accessions, currently maintained within the two main ex situ collections in Bosnia and Herzegovina (B&H), have previously been genotyped using microsatellite markers. The obtained molecular data provided insight into mislabeled accessions and redundancies, as well as the overall genetic structure of the germplasm. The available dataset enabled the creation of a core collection consisting of 52 accessions. The reliability and usefulness of microsatellites has made this low-density marker system a norm in studies on apple germplasm. However, the increased access to medium- and high-density SNP arrays, developed specifically for apples, has opened new avenues of research into apple genetic resources. In this study, 45 apple genotypes consisting of 33 diploid core collection accessions from B&H and 12 international reference cultivars were genotyped using an Axiom® Apple 480 K SNP array in order to examine their genetic relationships, population structure and diversity, as well as to compare the obtained results with those calculated on previously reported SSR profiles. The SNPs displayed a better ability to differentiate apple accessions based on their origin, as well as to cluster them according to their pedigree. Calculating identity by descent revealed 16 pairings with first-degree relationships and uncovered the introgression of ‘Delicious’ and ‘Golden Delicious’ into the core collection.
Regeneration of Transgenic Ficus lyrata via Indirect Somatic Embryogenesis and Isolation of Variants for Development of New Cultivars
Authors: Fan Shufang , Jian Dawei , Chen Jianjun , Chen Longqing
Published: April 2023

Ficus lyrata is a popular ornamental foliage plant with unique violin- or guitar-shaped green leaves. In our previous study, a grapevine gene VvMybA1 was introduced into F. lyrata via Agrobacterium-mediated transformation, which resulted in the availability of purple-leaved plants. Since VvMybA1 is a transcription factor, the regeneration of transgenic purple-leaved plants might potentially produce variants with multicolored leaves. The objective of this study was to establish a method for regenerating purple-leaved F. lyrata and determine if variants with different coloration or variegation could be isolated from regenerated populations. Leaf explants derived from a completely purple-leaved transgenic plant were cultured on Murashige and Skoog (MS) basal medium supplemented with different concentrations of 6-benzyladenine (BA) and α-naphthalene acetic acid (NAA). Callogenesis occurred in leaf explants, and a subculture of callus-borne explants on the same medium resulted in callus proliferation and the occurrence of somatic embryos. Somatic embryos were more effectively induced from callus pieces cultured on MS medium supplemented with 8.88 μM of BA and 0.27 μM of NAA. More than 30 embryos were induced per callus piece, and the embryos matured and converted to plantlets. MS medium supplemented with 4.92 μM of indolyl-3-butanoic acid (IBA) greatly improved root development. Plantlets were transplanted into soilless substrate and grown in a shaded greenhouse for morphological evaluation. Nine variants with different degrees of coloration and variegation were isolated from the regenerated populations. Our results suggest that the regeneration of transgenic plants that harbor a transcription factor, such as VvMybA1, could be an additional way of isolating novel variants for the development of new cultivars of ornamental plants.
The Founder: Dispositional Greed, Showbiz, and the Commercial Determinants of Health
Authors: Logan Alan C. , D’Adamo Christopher R. , Prescott Susan L.
Published: April 2023

Marketing unhealthy products by multinational corporations has caused considerable harm to individual health, collective wellbeing, and environmental sustainability. This is a growing threat to all societies and a significant contributor to the rising global burden of non-communicable diseases and early mortality. While there is growing consideration of the commercial determinants of health, this is largely focused on the methods by which unhealthy products are marketed and disseminated, including efforts to manipulate policy. Little attention has been paid to the underlying psychological traits and worldviews that are driving corporate greed. Here, we consider the role of “dispositional greed” in the commercial determinants of health with a focus on the historical attitudes and culture in the ultra-processed food industry—exemplified by “The Founder” of the McDonald’s franchise. We argue that greed and associated psychological constructs, such as social dominance orientation and collective narcissism, permeate the commercial determinants of health at a collective level. This includes how a culture of greed within organizations, and individual dispositional greed, can magnify and cluster at scale, perpetuated by social dominance orientation. We also consider the ways in which “showbiz” marketing specifically targets marginalized populations and vulnerable groups, including children—in ways that are justified, or even celebrated despite clear links to non-communicable diseases and increased mortality. Finally, we consider how greed and exploitative mindsets mirror cultural values and priorities, with trends for increasing collective narcissism at scale, recognizing that many of these attitudes are cultivated in early life. A healthier future will depend on navigating a path that balances material prosperity with physical and spiritual wellbeing. This will require cultural change that places higher value on kindness, reciprocity, and mutualistic values especially in early life, for more equitable flourishing.
Early Warning Systems for Emerging Profiles of Antimicrobial Resistance in Italy: A National Survey
Authors: Iera Jessica , Seghieri Chiara , Tavoschi Lara , Isonne Claudia , Baccolini Valentina , Petrone Daniele , Agodi Antonella , Barchitta Martina , Arnoldo Luca , Creti Roberta , Forni Silvia , Raglio Annibale , Ricchizzi Enrico , Bandini Lorenzo , Grossi Adriano , D’Ancona Fortunato
Published: April 2023

Antimicrobial resistance (AMR) national surveillance systems in Italy lack alert systems for timely detection of emerging profiles of AMR with potential relevance to public health. Furthermore, the existence of early warning systems (EWS) at subnational level is unclear. This study aims at mapping and characterizing EWS for microbiological threats available at regional level in Italy, focusing on emerging AMR, and at outlining potential barriers and facilitators to their development/implementation. To this end, a three-section, web-based survey was developed and administered to all Italian regional AMR representatives from June to August 2022. Twenty out of twenty-one regions and autonomous provinces (95.2%) responded to the survey. Among these, nine (45%) reported the implementation of EWS for microbiological threats at regional level, three (15%) reported that EWS are in the process of being developed, and eight (40%) reported that EWS are not currently available. EWS characteristics varied widely among the identified systems concerning both AMR profiles reported and data flow: the microorganisms most frequently included were extensively drug-resistant (XDR) Enterobacterales, with the lack of a dedicated regional IT platform reported in most cases. The results of this study depict a highly heterogeneous scenario and suggest that more efforts aimed at strengthening national AMR surveillance systems are needed.
Interaction of Crime Risk across Crime Types in Hotspot Areas
Authors: Zhang Hong , Gao Yongping , Yao Dizhao , Zhang Jie
Published: April 2023

Repeat and near-repeat victimization are important concepts in the study of crime. The incidence of repeat offenses within a single type of crime has been confirmed. However, the study of the circumstances existing across crime types requires further investigation. This article investigates whether the phenomenon of near-repeat crime exists in different types of crime by studying the spread of crime risk within different crime types. Taking Suzhou City as the research area, a DBSCAN-based algorithm is proposed, which can detect a large number of important and stable hotspots through the multi-density self-adaptation of algorithm parameters. Pearson correlation is used to analyze the risk correlation between different types of crime. In different crime hotspots, the types of crime and the spread of crime risk among different types is also different. After a crime occurs, identifying the risk can aid crime prevention.
Anti-Glucotoxicity Effect of Phytoconstituents via Inhibiting MGO-AGEs Formation and Breaking MGO-AGEs
Authors: Yadav Neera , Palkhede Jyoti Dnyaneshwar , Kim Sun-Yeou
Published: April 2023

The therapeutic benefits of phytochemicals in the treatment of various illnesses and disorders are well documented. They show significant promise for the discovery and creation of novel medications for treating a variety of human diseases. Numerous phytoconstituents have shown antibiotic, antioxidant, and wound-healing effects in the conventional system. Traditional medicines based on alkaloids, phenolics, tannins, saponins, terpenes, steroids, flavonoids, glycosides, and phytosterols have been in use for a long time and are crucial as alternative treatments. These phytochemical elements are crucial for scavenging free radicals, capturing reactive carbonyl species, changing protein glycation sites, inactivating carbohydrate hydrolases, fighting pathological conditions, and accelerating the healing of wounds. In this review, 221 research papers have been reviewed. This research sought to provide an update on the types and methods of formation of methylglyoxal-advanced glycation end products (MGO-AGEs) and molecular pathways induced by AGEs during the progression of the chronic complications of diabetes and associated diseases as well as to discuss the role of phytoconstituents in MGO scavenging and AGEs breaking. The development and commercialization of functional foods using these natural compounds can provide potential health benefits.
Molecular Integrative Analysis of the Inhibitory Effects of Dipeptides on Amyloid β Peptide 1–42 Polymerization
Authors: Yuan Nan , Ye Lianmeng , Sun Yan , Wu Hao , Xiao Zhengpan , Fu Wanmeng , Chen Zuqian , Pei Yechun , Min Yi , Wang Dayong
Published: April 2023

The major pathological feature of Alzheimer’s disease (AD) is the aggregation of amyloid β peptide (Aβ) in the brain. Inhibition of Aβ42 aggregation may prevent the advancement of AD. This study employed molecular dynamics, molecular docking, electron microscopy, circular dichroism, staining of aggregated Aβ with ThT, cell viability, and flow cytometry for the detection of reactive oxygen species (ROS) and apoptosis. Aβ42 polymerizes into fibrils due to hydrophobic interactions to minimize free energy, adopting a β-strand structure and forming three hydrophobic areas. Eight dipeptides were screened by molecular docking from a structural database of 20 L-α-amino acids, and the docking was validated by molecular dynamics (MD) analysis of binding stability and interaction potential energy. Among the dipeptides, arginine dipeptide (RR) inhibited Aβ42 aggregation the most. The ThT assay and EM revealed that RR reduced Aβ42 aggregation, whereas the circular dichroism spectroscopy analysis showed a 62.8% decrease in β-sheet conformation and a 39.3% increase in random coiling of Aβ42 in the presence of RR. RR also significantly reduced the toxicity of Aβ42 secreted by SH-SY5Y cells, including cell death, ROS production, and apoptosis. The formation of three hydrophobic regions and polymerization of Aβ42 reduced the Gibbs free energy, and RR was the most effective dipeptide at interfering with polymerization.
Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us
Authors: Sandrelli Federica , Bisaglia Marco
Published: April 2023

Amyotrophic lateral sclerosis (ALS) is an adult-onset disease which causes the progressive degeneration of cortical and spinal motoneurons, leading to death a few years after the first symptom onset. ALS is mainly a sporadic disorder, and its causative mechanisms are mostly unclear. About 5–10% of cases have a genetic inheritance, and the study of ALS-associated genes has been fundamental in defining the pathological pathways likely also involved in the sporadic forms of the disease. Mutations affecting the DJ-1 gene appear to explain a subset of familial ALS forms. DJ-1 is involved in multiple molecular mechanisms, acting primarily as a protective agent against oxidative stress. Here, we focus on the involvement of DJ-1 in interconnected cellular functions related to mitochondrial homeostasis, reactive oxygen species (ROS) levels, energy metabolism, and hypoxia response, in both physiological and pathological conditions. We discuss the possibility that impairments in one of these pathways may affect the others, contributing to a pathological background in which additional environmental or genetic factors may act in favor of the onset and/or progression of ALS. These pathways may represent potential therapeutic targets to reduce the likelihood of developing ALS and/or slow disease progression.
Cyclic Stretch-Induced Mechanical Stress Applied at 1 Hz Frequency Can Alter the Metastatic Potential Properties of SAOS-2 Osteosarcoma Cells
Authors: Alloisio Giulia , Rodriguez David Becerril , Luce Marco , Ciaccio Chiara , Marini Stefano , Cricenti Antonio , Gioia Magda
Published: April 2023

Recently, there has been an increasing focus on cellular morphology and mechanical behavior in order to gain a better understanding of the modulation of cell malignancy. This study used uniaxial-stretching technology to select a mechanical regimen able to elevate SAOS-2 cell migration, which is crucial in osteosarcoma cell pathology. Using confocal and atomic force microscopy, we demonstrated that a 24 h 0.5% cyclic elongation applied at 1 Hz induces morphological changes in cells. Following mechanical stimulation, the cell area enlarged, developing a more elongated shape, which disrupted the initial nuclear-to-cytoplasm ratio. The peripheral cell surface also increased its roughness. Cell-based biochemical assays and real-time PCR quantification showed that these morphologically induced changes are unrelated to the osteoblastic differentiative grade. Interestingly, two essential cell-motility properties in the modulation of the metastatic process changed following the 24 h 1 Hz mechanical stimulation. These were cell adhesion and cell migration, which, in fact, were dampened and enhanced, respectively. Notably, our results showed that the stretch-induced up-regulation of cell motility occurs through a mechanism that does not depend on matrix metalloproteinase (MMP) activity, while the inhibition of ion–stretch channels could counteract it. Overall, our results suggest that further research on mechanobiology could represent an alternative approach for the identification of novel molecular targets of osteosarcoma cell malignancy.
Exercise and Doxorubicin Modify Markers of Iron Overload and Cardiolipin Deficiency in Cardiac Mitochondria
Authors: Montalvo Ryan N. , Boeno Franccesco P. , Dowllah Imtiaz M. , Moritz Cesar E. Jacintho , Nguyen Branden L. , Doerr Vivian , Bomkamp Matthew P. , Smuder Ashley J.
Published: April 2023

Doxorubicin (DOX) is a chemotherapeutic agent highly effective at limiting cancer progression. Despite the efficacy of this anticancer drug, the clinical use of DOX is limited due to cardiotoxicity. The cardiac mitochondria are implicated as the primary target of DOX, resulting in inactivation of electron transport system complexes, oxidative stress, and iron overload. However, it is established that the cardiac mitochondrial subpopulations reveal differential responses to DOX exposure, with subsarcolemmal (SS) mitochondria demonstrating redox imbalance and the intermyofibrillar (IMF) mitochondria showing reduced respiration. In this regard, exercise training is an effective intervention to prevent DOX-induced cardiac dysfunction. Although it is clear that exercise confers mitochondrial protection, it is currently unknown if exercise training mitigates DOX cardiac mitochondrial toxicity by promoting beneficial adaptations to both the SS and IMF mitochondria. To test this, SS and IMF mitochondria were isolated from sedentary and exercise-preconditioned female Sprague Dawley rats exposed to acute DOX treatment. Our findings reveal a greater effect of exercise preconditioning on redox balance and iron handling in the SS mitochondria of DOX-treated rats compared to IMF, with rescue of cardiolipin synthase 1 expression in both subpopulations. These results demonstrate that exercise preconditioning improves mitochondrial homeostasis when combined with DOX treatment, and that the SS mitochondria display greater protection compared to the IMF mitochondria. These data provide important insights into the molecular mechanisms that are in part responsible for exercise-induced protection against DOX toxicity.
Embryonic Stem Cells Can Generate Oral Epithelia under Matrix Instruction
Authors: Das Ridhima , Harper Lisa , Kitajima Kayoko , Osman Tarig Al-Hadi , Cimpan Mihaela Roxana , Johannssen Anne Chr. , Suliman Salwa , Mackenzie Ian C. , Costea Daniela-Elena
Published: April 2023

We aimed to investigate whether molecular clues from the extracellular matrix (ECM) can induce oral epithelial differentiation of pluripotent stem cells. Mouse embryonic stem cells (ESC) of the feeder-independent cell line E14 were used as a model for pluripotent stem cells. They were first grown in 2D on various matrices in media containing vitamin C and without leukemia inhibitory factor (LIF). Matrices investigated were gelatin, laminin, and extracellular matrices (ECM) synthesized by primary normal oral fibroblasts and keratinocytes in culture. Differentiation into epithelial lineages was assessed by light microscopy, immunocytochemistry, and flow cytometry for cytokeratins and stem cell markers. ESC grown in 2D on various matrices were afterwards grown in 3D organotypic cultures with or without oral fibroblasts in the collagen matrix and examined histologically and by immunohistochemistry for epithelial (keratin pairs 1/10 and 4/13 to distinguish epidermal from oral epithelia and keratins 8,18,19 to phenotype simple epithelia) and mesenchymal (vimentin) phenotypes. ECM synthesized by either oral fibroblasts or keratinocytes was able to induce, in 2D cultures, the expression of cytokeratins of the stratified epithelial phenotype. When grown in 3D, all ESC developed into two morphologically distinct cell populations on collagen gels: (i) epithelial-like cells organized in islands with occasional cyst- or duct-like structures and (ii) spindle-shaped cells suggestive of mesenchymal differentiation. The 3D culture on oral fibroblast-populated collagen matrices was necessary for further differentiation into oral epithelia. Only ESC initially grown on 2D keratinocyte or fibroblast-synthesized matrices reached full epithelial maturation. In conclusion, ESC can generate oral epithelia under matrix instruction.
Fibrates Affect Levels of Phosphorylated p38 in Intestinal Cells in a Differentiation-Dependent Manner
Authors: Cizkova Katerina , Tauber Zdenek
Published: April 2023

Fibrates are widely used hypolipidaemic agents that act as ligands of the peroxisome proliferator-activated receptor α (PPARα). p38 is a protein kinase that is mainly activated by environmental and genotoxic stress. We investigated the effect of the PPARα activators fenofibrate and WY-14643 and the PPARα inhibitor GW6471 on the levels of activated p38 (p-p38) in the colorectal cancer cell lines HT-29 and Caco2 in relation to their differentiation status. Fibrates increased p-p38 in undifferentiated HT-29 cells, whereas in other cases p-p38 expression was decreased. HT-29 cells showed p-p38 predominantly in the cytoplasm, whereas Caco2 cells showed higher nuclear positivity. The effect of fibrates may depend on the differentiation status of the cell, as differentiated HT-29 and undifferentiated Caco2 cells share similar characteristics in terms of villin, CYP2J2, and soluble epoxide hydrolase (sEH) expression. In human colorectal carcinoma, higher levels of p-p38 were detected in the cytoplasm, whereas in normal colonic surface epithelium, p-p38 showed nuclear positivity. The decrease in p-p38 positivity was associated with a decrease in sEH, consistent with in vitro results. In conclusion, fibrates affect the level of p-p38, but its exact role in the process of carcinogenesis remains unclear and further research is needed in this area.
Zebrafish as an Innovative Tool for Epilepsy Modeling: State of the Art and Potential Future Directions
Authors: D’Amora Marta , Galgani Alessandro , Marchese Maria , Tantussi Francesco , Faraguna Ugo , De Angelis Francesco , Giorgi Filippo Sean
Published: April 2023

This article discusses the potential of Zebrafish (ZF) (Danio Rerio), as a model for epilepsy research. Epilepsy is a neurological disorder affecting both children and adults, and many aspects of this disease are still poorly understood. In vivo and in vitro models derived from rodents are the most widely used for studying both epilepsy pathophysiology and novel drug treatments. However, researchers have recently obtained several valuable insights into these two fields of investigation by studying ZF. Despite the relatively simple brain structure of these animals, researchers can collect large amounts of data in a much shorter period and at lower costs compared to classical rodent models. This is particularly useful when a large number of candidate antiseizure drugs need to be screened, and ethical issues are minimized. In ZF, seizures have been induced through a variety of chemoconvulsants, primarily pentylenetetrazol (PTZ), kainic acid (KA), and pilocarpine. Furthermore, ZF can be easily genetically modified to test specific aspects of monogenic forms of human epilepsy, as well as to discover potential convulsive phenotypes in monogenic mutants. The article reports on the state-of-the-art and potential new fields of application of ZF research, including its potential role in revealing epileptogenic mechanisms, rather than merely assessing iatrogenic acute seizure modulation.
Immunomodulatory Effects of the Pea Defensin Psd1 in the Caco-2/Immune Cells Co-Culture upon Candida albicans Infection
Authors: Bogdanov Ivan V. , Fateeva Serafima I. , Voropaev Alexander D. , Ovchinnikova Tatiana V. , Finkina Ekaterina I.
Published: April 2023

Candidiasis is one of the most common fungal diseases that can pose a threat to life in immunodeficient individuals, particularly in its disseminated form. Not only fungal invasion but also fatal infection-related inflammation are common causes of systemic candidiasis. In this study, we investigated in vitro immunomodulatory properties of the antifungal pea defensin Psd1 upon Candida albicans infection. Using the real-time PCR, we showed that Psd1 inhibited the antimicrobial peptide HBD-2 and pro-inflammatory cytokines IL-1 and IL-8 downregulation at mRNA level in epithelium cells caused by C. albicans infection. By using the Caco-2/immune cells co-culture upon C. albicans infection and the multiplex xMAP assay, we demonstrated that this pathogenic fungus induced a pronounced host defense response; however, the cytokine responses were different in the presence of dendritic cells or monocytes. We revealed that Psd1 at a low concentration (2 µM) had a pronounced immunomodulatory effect on the Caco-2/immune cells co-culture upon fungal infection. Thus, we hypothesized that the pea defensin Psd1 might be an effective agent in the treatment of candidiasis not only due to its antifungal activity, but also owing to its ability to modulate a protective immune response upon infection.
Structure-Based GC Investigation Sheds New Light on ITS2 Evolution in Corydalis Species
Authors: Xian Qing , Wang Suyin , Liu Yanyan , Kan Shenglong , Zhang Wei
Published: April 2023

Guanine and cytosine (GC) content is a fundamental component of genetic diversity and essential for phylogenetic analyses. However, the GC content of the ribosomal internal transcribed spacer 2 (ITS2) remains unknown, despite the fact that ITS2 is a widely used phylogenetic marker. Here, the ITS2 was high-throughput sequenced from 29 Corydalis species, and their GC contents were comparatively investigated in the context of ITS2’s characteristic secondary structure and concerted evolution. Our results showed that the GC contents of ITS2 were 131% higher than those of their adjacent 5.8S regions, suggesting that ITS2 underwent GC-biased evolution. These GCs were distributed in a heterogeneous manner in the ITS2 secondary structure, with the paired regions being 130% larger than the unpaired regions, indicating that GC is chosen for thermodynamic stability. In addition, species with homogeneous ITS2 sequences were always GC-rich, supporting GC-biased gene conversion (gBGC), which occurred with ITS2’s concerted evolution. The RNA substitution model inferred also showed a GC preference among base pair transformations, which again supports gBGC. Overall, structurally based GC investigation reveals that ITS2 evolves under structural stability and gBGC selection, significantly increasing its GC content.
Role of Coxsackievirus B3-Induced Immune Responses in the Transition from Myocarditis to Dilated Cardiomyopathy and Heart Failure
Authors: Yip Fione , Lai Brian , Yang Decheng
Published: April 2023

Dilated cardiomyopathy (DCM) is a cardiac disease marked by the stretching and thinning of the heart muscle and impaired left ventricular contractile function. While most patients do not develop significant cardiac diseases from myocarditis, disparate immune responses can affect pathological outcomes, including DCM progression. These altered immune responses, which may be caused by genetic variance, can prolong cytotoxicity, induce direct cleavage of host protein, or encourage atypical wound healing responses that result in tissue scarring and impaired mechanical and electrical heart function. However, it is unclear which alterations within host immune profiles are crucial to dictating the outcomes of myocarditis. Coxsackievirus B3 (CVB3) is a well-studied virus that has been identified as a causal agent of myocarditis in various models, along with other viruses such as adenovirus, parvovirus B19, and SARS-CoV-2. This paper takes CVB3 as a pathogenic example to review the recent advances in understanding virus-induced immune responses and differential gene expression that regulates iron, lipid, and glucose metabolic remodeling, the severity of cardiac tissue damage, and the development of DCM and heart failure.
Special Issue “Application Progress and Insights of Nanoporous Materials”
Authors: Eurov Daniil , Kurdyukov Dmitry
Published: April 2023

Application Progress and Insights of Nanoporous Materials is an open Special Issue in International Journal of Molecular Sciences, which aims to publish original research and review papers concerning fundamental and applied aspects of nanoporous materials of various composition and morphology, investigation of their properties and underlying mechanisms for fabrication of porous media with the desired characteristics [...]
PPARδ Agonist GW501516 Suppresses the TGF-β-Induced Profibrotic Response of Human Bronchial Fibroblasts from Asthmatic Patients
Authors: Paw Milena , Wnuk Dawid , Madeja Zbigniew , Michalik Marta
Published: April 2023

The airway wall remodeling observed in asthma is associated with subepithelial fibrosis and enhanced activation of human bronchial fibroblasts (HBFs) in the fibroblast to myofibroblast transition (FMT), induced mainly by transforming growth factor-β (TGF-β). The relationships between asthma severity, obesity, and hyperlipidemia suggest the involvement of peroxisome proliferator-activated receptors (PPARs) in the remodeling of asthmatic bronchi. In this study, we investigated the effect of PPARδ ligands (GW501516 as an agonist, and GSK0660 as an antagonist) on the FMT potential of HBFs derived from asthmatic patients cultured in vitro. This report shows, for the first time, the inhibitory effect of a PPARδ agonist on the number of myofibroblasts and the expression of myofibroblast-related markers—α-smooth muscle actin, collagen 1, tenascin C, and connexin 43—in asthma-related TGF-β-treated HBF populations. We suggest that actin cytoskeleton reorganization and Smad2 transcriptional activity altered by GW501516 lead to the attenuation of the FMT in HBF populations derived from asthmatics. In conclusion, our data demonstrate that a PPARδ agonist stimulates antifibrotic effects in an in vitro model of bronchial subepithelial fibrosis. This suggests its potential role in the development of a possible novel therapeutic approach for the treatment of subepithelial fibrosis during asthma.
Retrospective Case-Control Study Genes Related to Bone Metabolism That Justify the Condition of Periodontal Disease and Failure of Dental Implants in Patients with down Syndrome
Authors: Baus-Domínguez María , Gómez-Díaz Raquel , Torres-Lagares Daniel , Gutiérrez-Pérez Jose-Luis , Machuca-Portillo Guillermo , Serrera-Figallo María-Ángeles
Published: April 2023

Down syndrome patients show success rates in dental implants much lower than those observed in the general population. This retrospective case-control study aimed to identify possible genes that are related to the regulation of inflammatory responses and bone metabolism related to periimplantitis and implant loss, as well as genes related to bone quality. This process involved using the functional analysis of the gene expression software Transcriptome Analysis Console (TAC version 4.0 Applied BiosystemsTM, Thermo Fisher Scientific, Waltham, MA, USA) and a search for possible candidate genes involved. The focus was placed on the 93 genes related to periodontitis, periimplantitis, bone loss, implant loss, and genes related to bone quality and regulators underlying the establishment and maintenance of osseointegration. Five genes showed statistically significant results (p < 0.05) in our comparison. Four of them, IL1B (p = 0.023), IL1RN (p = 0.048), BGLAP (p = 0.0372) and PTK2 (p = 0.0075) were down-regulated in the periodontal disease and implant rejection group, and only one was overexpressed: FOXO1A (p = 0.0552). The genes with statistically significant alterations described in this article determine that the group of Down syndrome patients with periodontal disease and implant failure is a group of patients genetically susceptible to suffering from both conditions together.
Effect of Ethanol-Induced Methyl Donors Consumption on the State of Hypomethylation in Cervical Cancer
Authors: Han Xiao , Fang Fang , Cui Weiwei , Liu Ya , Liu Yuxin
Published: April 2023

Cervical cancer causes malignant tumors in females and threatens the physical and mental health of women. Current research shows that persistent infection of high-risk HPV is the main cause of cervical cancer. However, not all cervical cancer is caused by HPV infection, which may also be related to other factors, such as nutritional status and lifestyle. This study focuses on the effect of alcohol consumption on the methylation status of cervical cancer from the perspective of methyl donors. We established a mouse tumor-bearing model with cervical cancer SiHa cells, and at the same time, we cultured SiHa cells in vitro. Different concentrations of ethanol were administered to the model mice and SiHa cells. Then, we detected the levels of the methyl-donor folate and methionine and their metabolite homocysteine levels in mice serum, tumor tissues, and SiHa cells. Furthermore, we determined the expression of the members of the DNA methyltransferase family (DNMT1, DNMT3a, and DNMT3b) in tumor tissue by immunohistochemistry. qRT-PCR and Western blotting analysis were used to detect the mRNA and protein levels of members of the DNA methyltransferase family in cervical cancer SiHa cells. Our results show that the levels of the methyl donor (folate and methionine) decreased with the increase of ethanol concentration (p < 0.05), and the homocysteine level increased significantly (p < 0.05). In SiHa cells, the mRNA and protein levels of the DNMT family members and their receptors were significantly higher than those in the control group (p < 0.05). Collectively, these results suggest that ethanol could influence DNMT expression by inducing methyl donor consumption, thereby causing cervical cancer cells to exhibit genome-wide hypomethylation.
Advances in the Anti-Tumor Activity of Biflavonoids in Selaginella
Authors: Ren Mengdie , Li Sihui , Gao Qiong , Qiao Lei , Cao Qianping , Yang Ze , Chen Chaoqiang , Jiang Yongmei , Wang Gang , Fu Shaobin
Published: April 2023

Despite the many strategies employed to slow the spread of cancer, the development of new anti-tumor drugs and the minimization of side effects have been major research hotspots in the anti-tumor field. Natural drugs are a huge treasure trove of drug development, and they have been widely used in the clinic as anti-tumor drugs. Selaginella species in the family Selaginellaceae are widely distributed worldwide, and they have been well-documented in clinical practice for the prevention and treatment of cancer. Biflavonoids are the main active ingredients in Selaginella, and they have good biological and anti-tumor activities, which warrant extensive research. The promise of biflavonoids from Selaginella (SFB) in the field of cancer therapy is being realized thanks to new research that offers insights into the multi-targeting therapeutic mechanisms and key signaling pathways. The pharmacological effects of SFB against various cancers in vitro and in vivo are reviewed in this review. In addition, the types and characteristics of biflavonoid structures are described in detail; we also provide a brief summary of the efforts to develop drug delivery systems or combinations to enhance the bioavailability of SFB monomers. In conclusion, SFB species have great potential to be developed as adjuvant or even primary therapeutic agents for cancer, with promising applications.
Viral Vector-Based Gene Therapy
Authors: Li Xuedan , Le Yang , Zhang Zhegang , Nian Xuanxuan , Liu Bo , Yang Xiaoming
Published: April 2023

Gene therapy is a technique involving the modification of an individual’s genes for treating a particular disease. The key to effective gene therapy is an efficient carrier delivery system. Viral vectors that have been artificially modified to lose their pathogenicity are used widely as a delivery system, with the key advantages of their natural high transduction efficiency and stable expression. With decades of development, viral vector-based gene therapies have achieved promising clinical outcomes. Currently, the three key vector strategies are based on adeno-associated viruses, adenoviruses, and lentiviruses. However, certain challenges, such as immunotoxicity and “off-target”, continue to exist. In the present review, the above three viral vectors are discussed along with their respective therapeutic applications. In addition, the major translational challenges encountered in viral vector-based gene therapies are summarized, and the possible strategies to address these challenges are also discussed.
Transcriptomics and Phenotypic Analysis of gpr56 Knockout in Zebrafish
Authors: Sun Luning , Yang Boyu , Peng Zheng , Yang Tianle , Qin Bin , Ao Jieyu , Yang Yanqun , Wang Jingling , Zheng Lan , Xie Huaping
Published: April 2023

The adhesion G-protein-coupled receptor is a seven-transmembrane receptor protein with a complex structure. Impaired GPR56 has been found to cause developmental damage to the human brain, resulting in intellectual disability and motor dysfunction. To date, studies on gpr56 deficiency in zebrafish have been limited to the nervous system, and there have been no reports of its systemic effects on juvenile fish at developmental stages. In order to explore the function of gpr56 in zebrafish, the CRISPR/Cas9 gene-editing system was used to construct a gpr56-knockout zebrafish. Subsequently, the differentially expressed genes (DEGs) at the transcriptional level between the 3 days post fertilization (dpf) homozygotes of the gpr56 mutation and the wildtype zebrafish were analyzed via RNA-seq. The results of the clustering analysis, quantitative PCR (qPCR), and in situ hybridization demonstrated that the expression of innate immunity-related genes in the mutant was disordered, and multiple genes encoding digestive enzymes of the pancreatic exocrine glands were significantly downregulated in the mutant. Motor ability tests demonstrated that the gpr56−/− zebrafish were more active, and this change was more pronounced in the presence of cold and additional stimuli. In conclusion, our results revealed the effect of gpr56 deletion on the gene expression of juvenile zebrafish and found that the gpr56 mutant was extremely active, providing an important clue for studying the mechanism of gpr56 in the development of juvenile zebrafish.
The Oligostilbene Gnetin H Is a Novel Glycolysis Inhibitor That Regulates Thioredoxin Interacting Protein Expression and Synergizes with OXPHOS Inhibitor in Cancer Cells
Authors: Singh Shivendra , De Carlo Flavia , Ibrahim Mohamed A. , Penfornis Patrice , Mouton Alan J. , Tripathi Siddharth K. , Agarwal Ameeta K. , Eastham Linda , Pasco David S. , Balachandran Premalatha , Claudio Pier Paolo
Published: April 2023

Since aerobic glycolysis was first observed in tumors almost a century ago by Otto Warburg, the field of cancer cell metabolism has sparked the interest of scientists around the world as it might offer new avenues of treatment for malignant cells. Our current study claims the discovery of gnetin H (GH) as a novel glycolysis inhibitor that can decrease metabolic activity and lactic acid synthesis and displays a strong cytostatic effect in melanoma and glioblastoma cells. Compared to most of the other glycolysis inhibitors used in combination with the complex-1 mitochondrial inhibitor phenformin (Phen), GH more potently inhibited cell growth. RNA-Seq with the T98G glioblastoma cell line treated with GH showed more than an 80-fold reduction in thioredoxin interacting protein (TXNIP) expression, indicating that GH has a direct effect on regulating a key gene involved in the homeostasis of cellular glucose. GH in combination with phenformin also substantially enhances the levels of p-AMPK, a marker of metabolic catastrophe. These findings suggest that the concurrent use of the glycolytic inhibitor GH with a complex-1 mitochondrial inhibitor could be used as a powerful tool for inducing metabolic catastrophe in cancer cells and reducing their growth.
Puerarin Alleviates H2O2-Induced Oxidative Stress and Blood–Milk Barrier Impairment in Dairy Cows
Authors: Lyu Chenchen , Yuan Bao , Meng Yu , Cong Shuai , Che Haoyu , Ji Xingyu , Wang Haoqi , Chen Chengzhen , Li Xinwei , Jiang Hao , Zhang Jiabao
Published: April 2023

During the perinatal period, the bovine mammary epithelial cells of dairy cows exhibit vigorous metabolism and produce large amounts of reactive oxygen species (ROS). The resulting redox balance disruption leads to oxidative stress, one of the main causes of mastitis. Puerarin (PUE) is a natural flavonoid in the root of PUE that has attracted extensive attention as a potential antioxidant. This study first investigated whether PUE could reduce oxidative damage and mastitis induced by hydrogen peroxide (H2O2) in bovine mammary epithelial cells in vitro and elucidated the molecular mechanism. In vitro, BMECs (Bovine mammary epithelial cells) were divided into four treatment groups: Control group (no treatment), H2O2 group (H2O2 stimulation), PUE + H2O2 group (H2O2 stimulation before PUE rescue) and PUE group (positive control). The growth of BMECs in each group was observed, and oxidative stress-related indices were detected. Fluorescence quantitative PCR (qRT–PCR) was used to detect the expression of tightly linked genes, antioxidant genes, and inflammatory factors. The expression of p65 protein was detected by Western blot. In vivo, twenty cows with an average age of 5 years having given birth three times were divided into the normal dairy cow group, normal dairy cow group fed PUE, mastitis dairy cow group fed PUE, and mastitis dairy cow group fed PUE (n = 5). The contents of TNF-α, IL-6, and IL-1β in milk and serum were detected. In BMECs, the results showed that the PUE treatment increased the activities of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC); ROS and malondialdehyde (MDA) levels were reduced. Thus, PUE alleviated H2O2-induced oxidative stress in vitro. In addition, the PUE treatment eliminated the inhibition of H2O2 on the expression of oxidation genes and tight junction genes, and the enrichment degree of NRF-2, HO-1, xCT, and tight junctions (claudin4, occludin, ZO-1 and symplekin) increased. The PUE treatment also inhibited the expression of NF-κB-associated inflammatory factors (IL-6 and IL-8) and the chemokine CCL5 in H2O2-induced BMECs. In vivo experiments also confirmed that feeding PUE can reduce the expression of inflammatory factors in the milk and serum of lactating dairy cows. In conclusion, PUE can effectively reduce the oxidative stress of bovine mammary epithelial cells, enhance the tight junctions between cells, and play an anti-inflammatory role. This study provides a theoretical basis for PUE prevention and treatment of mastitis and oxidative stress. The use of PUE should be considered as a feed additive in future dairy farming.
Cancer Stem Cells and Prostate Cancer: A Narrative Review
Authors: Al Salhi Yazan , Sequi Manfredi Bruno , Valenzi Fabio Maria , Fuschi Andrea , Martoccia Alessia , Suraci Paolo Pietro , Carbone Antonio , Tema Giorgia , Lombardo Riccardo , Cicione Antonio , Pastore Antonio Luigi , De Nunzio Cosimo
Published: April 2023

Cancer stem cells (CSCs) are a small and elusive subpopulation of self-renewing cancer cells with the remarkable ability to initiate, propagate, and spread malignant disease. In the past years, several authors have focused on the possible role of CSCs in PCa development and progression. PCa CSCs typically originate from a luminal prostate cell. Three main pathways are involved in the CSC development, including the Wnt, Sonic Hedgehog, and Notch signaling pathways. Studies have observed an important role for epithelial mesenchymal transition in this process as well as for some specific miRNA. These studies led to the development of studies targeting these specific pathways to improve the management of PCa development and progression. CSCs in prostate cancer represent an actual and promising field of research.
Frontier on Alzheimer’s Disease
Authors: Cervellati Carlo , Zuliani Giovanni
Published: April 2023

Although substantial progress has been made in the last two decades, there are still important unfilled gaps in the understanding of the pathomechanism of Alzheimer’s disease (AD) [...]