bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Separations of Organic Acidic or Basic Enantiomeric Mixtures—A Protocol Suggestion
Authors: Pálovics Emese , Madarász János , Pokol György , Fogassy Elemér , Bánhegyi Dorottya Fruzsina
Published: January 2023

In this review, we aim to present new concepts for the revisited separation of enantiomers from racemic compounds and a protocol worth to be followed in designing the preparation of pure enantiomers. We have taken into account not only the influence of the properties (eutectic composition) and characteristics of the reactants (racemic compound, resolving agent), but also the behavior of the resulting diastereomers and the different conditions (e.g., crystallization time, solvents used, solvate-forming compounds, achiral additives, etc.). The examples discussed are resolutions developed by our research team, through which we will try to illustrate the impact of all these considerations, presenting the methodological investigations interpreting recent discoveries and observations. Some special solid-state analytical and structural investigations assisting us in the elucidation and invention design of the resolution processes of some active pharmaceutical ingredients, such as Tetramisole, tofisopam, and Amlodipine, are also shown.
Integration of Electrical Signals and Phytohormones in the Control of Systemic Response
Authors: Ladeynova Maria , Kuznetsova Darya , Mudrilov Maxim , Vodeneev Vladimir
Published: January 2023

Plants are constantly exposed to environmental stresses. Local stimuli sensed by one part of a plant are translated into long-distance signals that can influence the activities in distant tissues. Changes in levels of phytohormones in distant parts of the plant occur in response to various local stimuli. The regulation of hormone levels can be mediated by long-distance electrical signals, which are also induced by local stimulation. We consider the crosstalk between electrical signals and phytohormones and identify interaction points, as well as provide insights into the integration nodes that involve changes in pH, Ca2+ and ROS levels. This review also provides an overview of our current knowledge of how electrical signals and hormones work together to induce a systemic response.
Creation of Two-Line Fragrant Glutinous Hybrid Rice by Editing the Wx and OsBADH2 Genes via the CRISPR/Cas9 System
Authors: Tian Yahong , Zhou Yin , Gao Guanjun , Zhang Qinglu , Li Yanhua , Lou Guangming , He Yuqing
Published: January 2023

Global food security has benefited from the development and promotion of the two-line hybrid rice system. Excellent eating quality determines the market competitiveness of hybrid rice varieties based on achieving the fundamental requirements of high yield and good adaptability. Developing sterile and restorer lines with improved quality for two-line hybrid breeding by editing quality genes with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 is an efficient and practical alternative to the lengthy and laborious process of conventional breeding to improve rice quality. We edited Wx and OsBADH2 using CRISPR/Cas9 technology to produce both homozygous male sterile mutant lines and homozygous restorer mutant lines with Cas9-free. These mutants have a much lower amylose content while having a significantly higher 2-acetyl-1-pyrroline aroma content. Based on this, a fragrant glutinous hybrid rice was developed without too much effect on most agronomic traits. This study demonstrates the use of CRISPR/Cas9 in creating two-line fragrant glutinous hybrid rice by editing the components of the male sterile and the restorative lines.
The Role of SOX Transcription Factors in Ageing and Age-Related Diseases
Authors: Stevanovic Milena , Lazic Andrijana , Schwirtlich Marija , Stanisavljevic Ninkovic Danijela
Published: January 2023

The quest for eternal youth and immortality is as old as humankind. Ageing is an inevitable physiological process accompanied by many functional declines that are driving factors for age-related diseases. Stem cell exhaustion is one of the major hallmarks of ageing. The SOX transcription factors play well-known roles in self-renewal and differentiation of both embryonic and adult stem cells. As a consequence of ageing, the repertoire of adult stem cells present in various organs steadily declines, and their dysfunction/death could lead to reduced regenerative potential and development of age-related diseases. Thus, restoring the function of aged stem cells, inducing their regenerative potential, and slowing down the ageing process are critical for improving the health span and, consequently, the lifespan of humans. Reprograming factors, including SOX family members, emerge as crucial players in rejuvenation. This review focuses on the roles of SOX transcription factors in stem cell exhaustion and age-related diseases, including neurodegenerative diseases, visual deterioration, chronic obstructive pulmonary disease, osteoporosis, and age-related cancers. A better understanding of the molecular mechanisms of ageing and the roles of SOX transcription factors in this process could open new avenues for developing novel strategies that will delay ageing and prevent age-related diseases.
Oxidative Stress and Air Pollution: Its Impact on Chronic Respiratory Diseases
Authors: Sierra-Vargas Martha Patricia , Montero-Vargas Josaphat Miguel , Debray-García Yazmín , Vizuet-de-Rueda Juan Carlos , Loaeza-Román Alejandra , Terán Luis M.
Published: January 2023

Redox regulation participates in the control of various aspects of metabolism. Reactive oxygen and nitrogen species participate in many reactions under physiological conditions. When these species overcome the antioxidant defense system, a distressed status emerges, increasing biomolecular damage and leading to functional alterations. Air pollution is one of the exogenous sources of reactive oxygen and nitrogen species. Ambient airborne particulate matter (PM) is important because of its complex composition, which includes transition metals and organic compounds. Once in contact with the lungs’ epithelium, PM components initiate the synthesis of inflammatory mediators, macrophage activation, modulation of gene expression, and the activation of transcription factors, which are all related to the physiopathology of chronic respiratory diseases, including cancer. Even though the pathophysiological pathways that give rise to the development of distress and biological damage are not fully understood, scientific evidence indicates that redox-dependent signaling pathways are involved. This article presents an overview of the redox interaction of air pollution inside the human body and the courses related to chronic respiratory diseases.
Blockers of Skeletal Muscle Nav1.4 Channels: From Therapy of Myotonic Syndrome to Molecular Determinants of Pharmacological Action and Back
Authors: De Bellis Michela , Boccanegra Brigida , Cerchiara Alessandro Giovanni , Imbrici Paola , De Luca Annamaria
Published: January 2023

The voltage-gated sodium channels represent an important target for drug discovery since a large number of physiological processes are regulated by these channels. In several excitability disorders, including epilepsy, cardiac arrhythmias, chronic pain, and non-dystrophic myotonia, blockers of voltage-gated sodium channels are clinically used. Myotonia is a skeletal muscle condition characterized by the over-excitability of the sarcolemma, resulting in delayed relaxation after contraction and muscle stiffness. The therapeutic management of this disorder relies on mexiletine and other sodium channel blockers, which are not selective for the Nav1.4 skeletal muscle sodium channel isoform. Hence, the importance of deepening the knowledge of molecular requirements for developing more potent and use-dependent drugs acting on Nav1.4. Here, we review the available treatment options for non-dystrophic myotonia and the structure–activity relationship studies performed in our laboratory with a focus on new compounds with potential antimyotonic activity.
Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway
Authors: Hu Wei , Hu Yaorui , Pei Yao , Li Rongrong , Xu Fuyi , Chi Xiaodong , Mi Jia , Bergquist Jonas , Lu Lu , Zhang Luping , Yang Chunhua
Published: January 2023

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinβ6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.
Enhanced Tumor Uptake and Retention of Cyanine Dye–Albumin Complex for Tumor-Targeted Imaging and Phototherapy
Authors: Jo Gayoung , Kim Eun Jeong , Hyun Hoon
Published: January 2023

Heptamethine cyanine dyes are widely used for in vivo near-infrared (NIR) fluorescence imaging and NIR laser-induced cancer phototherapy due to their good optical properties. Since most of heptamethine cyanine dyes available commercially are highly hydrophobic, they can usually be used for in vivo applications after formation of complexes with blood plasma proteins, especially serum albumin, to increase aqueous solubility. The complex formation between cyanine dyes and albumin improves the chemical stability and optical property of the hydrophobic cyanine dyes, which is the bottom of their practical use. In this study, the complexes between three different heptamethine cyanine dyes, namely clinically available indocyanine green (ICG), commercially available IR-786 and zwitterionic ZW800-Cl, and bovine serum albumin (BSA), were prepared to explore the effect of cyanine dyes on their tumor uptake and retention. Among the three complexes, IR-786©BSA exhibited increased tumor accumulation with prolonged tumor retention, compared to other complexes. Moreover, IR-786 bound to BSA played an important role in tumor growth suppression due to its cytotoxicity. To achieve complete tumor ablation, the tumor targeted by IR-786©BSA was further exposed to 808 nm laser irradiation for effective photothermal cancer treatment.
The Role of B Cell and T Cell Glycosylation in Systemic Lupus Erythematosus
Authors: Ramos-Martínez Ivan , Ramos-Martínez Edgar , Cerbón Marco , Pérez-Torres Armando , Pérez-Campos Mayoral Laura , Hernández-Huerta María Teresa , Martínez-Cruz Margarito , Pérez-Santiago Alma Dolores , Sánchez-Medina Marco Antonio , García-Montalvo Iván Antonio , Zenteno Edgar , Matias-Cervantes Carlos Alberto , Ojeda-Meixueiro Víctor , Pérez-Campos Eduardo
Published: January 2023

Glycosylation is a post-translational modification that affects the stability, structure, antigenicity and charge of proteins. In the immune system, glycosylation is involved in the regulation of ligand–receptor interactions, such as in B-cell and T-cell activating receptors. Alterations in glycosylation have been described in several autoimmune diseases, such as systemic lupus erythematosus (SLE), in which alterations have been found mainly in the glycosylation of B lymphocytes, T lymphocytes and immunoglobulins. In immunoglobulin G of lupus patients, a decrease in galactosylation, sialylation, and nucleotide fucose, as well as an increase in the N-acetylglucosamine bisector, are observed. These changes in glycoisolation affect the interactions of immunoglobulins with Fc receptors and are associated with pericarditis, proteinuria, nephritis, and the presence of antinuclear antibodies. In T cells, alterations have been described in the glycosylation of receptors involved in activation, such as the T cell receptor; these changes affect the affinity with their ligands and modulate the binding to endogenous lectins such as galectins. In T cells from lupus patients, a decrease in galectin 1 binding is observed, which could favor activation and reduce apoptosis. Furthermore, these alterations in glycosylation correlate with disease activity and clinical manifestations, and thus have potential use as biomarkers. In this review, we summarize findings on glycosylation alterations in SLE and how they relate to immune system defects and their clinical manifestations.
Protein-Coding Region Derived Small RNA in Exosomes from Influenza A Virus–Infected Cells
Authors: Kwasnik Malgorzata , Socha Wojciech , Czech Bartosz , Wasiak Magdalena , Rola Jerzy , Rozek Wojciech
Published: January 2023

Exosomes may function as multifactorial mediators of cell-to-cell communication, playing crucial roles in both physiological and pathological processes. Exosomes released from virus-infected cells may contain RNA and proteins facilitating infection spread. The purpose of our study was to analyze how the small RNA content of exosomes is affected by infection with the influenza A virus (IAV). Exosomes were isolated by ultracentrifugation after hemadsorption of virions and their small RNA content was identified using high-throughput sequencing. As compared to mock-infected controls, 856 RNA transcripts were significantly differentially expressed in exosomes from IAV-infected cells, including fragments of 458 protein-coding (pcRNA), 336 small, 28 long intergenic non-coding RNA transcripts, and 33 pseudogene transcripts. Upregulated pcRNA species corresponded mainly to proteins associated with translation and antiviral response, and the most upregulated among them were RSAD2, CCDC141 and IFIT2. Downregulated pcRNA species corresponded to proteins associated with the cell cycle and DNA packaging. Analysis of differentially expressed pseudogenes showed that in most cases, an increase in the transcription level of pseudogenes was correlated with an increase in their parental genes. Although the role of exosome RNA in IAV infection remains undefined, the biological processes identified based on the corresponding proteins may indicate the roles of some of its parts in IAV replication.
Fluoroplast Doped by Ag2O Nanoparticles as New Repairing Non-Cytotoxic Antibacterial Coating for Meat Industry
Authors: Gudkov Sergey V. , Li Ruibin , Serov Dmitriy A. , Burmistrov Dmitriy E. , Baimler Ilya V. , Baryshev Alexey S. , Simakin Alexander V. , Uvarov Oleg V. , Astashev Maxim E. , Nefedova Natalia B. , Smolentsev Sergey Y. , Onegov Andrey V. , Sevostyanov Mikhail A. , Kolmakov Alexey G. , Kaplan Mikhail A. , Drozdov Andrey , Tolordava Eteri R. , Semenova Anastasia A. , Lisitsyn Andrey B. , Lednev Vasily N.
Published: January 2023

Foodborne infections are an important global health problem due to their high prevalence and potential for severe complications. Bacterial contamination of meat during processing at the enterprise can be a source of foodborne infections. Polymeric coatings with antibacterial properties can be applied to prevent bacterial contamination. A composite coating based on fluoroplast and Ag2O NPs can serve as such a coating. In present study, we, for the first time, created a composite coating based on fluoroplast and Ag2O NPs. Using laser ablation in water, we obtained spherical Ag2O NPs with an average size of 45 nm and a ζ-potential of −32 mV. The resulting Ag2O NPs at concentrations of 0.001–0.1% were transferred into acetone and mixed with a fluoroplast-based varnish. The developed coating made it possible to completely eliminate damage to a Teflon cutting board. The fluoroplast/Ag2O NP coating was free of defects and inhomogeneities at the nano level. The fluoroplast/Ag2O NP composite increased the production of ROS (H2O2, OH radical), 8-oxogualnine in DNA in vitro, and long-lived active forms of proteins. The effect depended on the mass fraction of the added Ag2O NPs. The 0.01–0.1% fluoroplast/NP Ag2O coating exhibited excellent bacteriostatic and bactericidal properties against both Gram-positive and Gram-negative bacteria but did not affect the viability of eukaryotic cells. The developed PTFE/NP Ag2O 0.01–0.1% coating can be used to protect cutting boards from bacterial contamination in the meat processing industry.
Genome-Wide Association Studies of Seven Root Traits in Soybean (Glycine max L.) Landraces
Authors: Kim Seong-Hoon , Tayade Rupesh , Kang Byeong-Hee , Hahn Bum-Soo , Ha Bo-Keun , Kim Yoon-Ha
Published: January 2023

Soybean [Glycine max (L.) Merr.], an important oilseed crop, is a low-cost source of protein and oil. In Southeast Asia and Africa, soybeans are widely cultivated for use as traditional food and feed and industrial purposes. Given the ongoing changes in global climate, developing crops that are resistant to climatic extremes and produce viable yields under predicted climatic conditions will be essential in the coming decades. To develop such crops, it will be necessary to gain a thorough understanding of the genetic basis of agronomic and plant root traits. As plant roots generally lie beneath the soil surface, detailed observations and phenotyping throughout plant development present several challenges, and thus the associated traits have tended to be ignored in genomics studies. In this study, we phenotyped 357 soybean landraces at the early vegetative (V2) growth stages and used a 180 K single-nucleotide polymorphism (SNP) soybean array in a genome-wide association study (GWAS) conducted to determine the phenotypic relationships among root traits, elucidate the genetic bases, and identify significant SNPs associated with root trait-controlling genomic regions/loci. A total of 112 significant SNP loci/regions were detected for seven root traits, and we identified 55 putative candidate genes considered to be the most promising. Our findings in this study indicate that a combined approach based on SNP array and GWAS analyses can be applied to unravel the genetic basis of complex root traits in soybean, and may provide an alternative high-resolution marker strategy to traditional bi-parental mapping. In addition, the identified SNPs, candidate genes, and diverse variations in the root traits of soybean landraces will serve as a valuable basis for further application in genetic studies and the breeding of climate-resilient soybeans characterized by improved root traits.
Choroid Plexus Aquaporins in CSF Homeostasis and the Glymphatic System: Their Relevance for Alzheimer’s Disease
Authors: Municio Cristina , Carrero Laura , Antequera Desireé , Carro Eva
Published: January 2023

The glymphatic system, a fluid-clearance pathway involved in brain waste clearance, is known to be impaired in neurological disorders, including Alzheimer’s disease (AD). For this reason, it is important to understand the specific mechanisms and factors controlling glymphatic function. This pathway enables the flow of cerebrospinal fluid (CSF) into the brain and subsequently the brain interstitium, supported by aquaporins (AQPs). Continuous CSF transport through the brain parenchyma is critical for the effective transport and drainage of waste solutes, such as toxic proteins, through the glymphatic system. However, a balance between CSF production and secretion from the choroid plexus, through AQP regulation, is also needed. Thus, any condition that affects CSF homeostasis will also interfere with effective waste removal through the clearance glymphatic pathway and the subsequent processes of neurodegeneration. In this review, we highlight the role of AQPs in the choroid plexus in the modulation of CSF homeostasis and, consequently, the glymphatic clearance pathway, with a special focus on AD.
Microglial Activation and Priming in Alzheimer’s Disease: State of the Art and Future Perspectives
Authors: Bivona Giulia , Iemmolo Matilda , Agnello Luisa , Lo Sasso Bruna , Gambino Caterina Maria , Giglio Rosaria Vincenza , Scazzone Concetta , Ghersi Giulio , Ciaccio Marcello
Published: January 2023

Alzheimer’s Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid β (Aβ) and protein Tau aggregates are disease hallmarks and key players in AD pathogenesis. However, it has been hypothesized that microglia can contribute to AD pathophysiology, as well. Microglia are CNS-resident immune cells belonging to the myeloid lineage of the innate arm of immunity. Under physiological conditions, microglia are in constant motion in order to carry on their housekeeping function, and they maintain an anti-inflammatory, quiescent state, with low expression of cytokines and no phagocytic activity. Upon various stimuli (debris, ATP, misfolded proteins, aggregates and pathogens), microglia acquire a phagocytic function and overexpress cytokine gene modules. This process is generally regarded as microglia activation and implies that the production of pro-inflammatory cytokines is counterbalanced by the synthesis and the release of anti-inflammatory molecules. This mechanism avoids excessive inflammatory response and inappropriate microglial activation, which causes tissue damage and brain homeostasis impairment. Once the pathogenic stimulus has been cleared, activated microglia return to the naïve, anti-inflammatory state. Upon repeated stimuli (as in the case of Aβ deposition in the early stage of AD), activated microglia shift toward a less protective, neurotoxic phenotype, known as “primed” microglia. The main characteristic of primed microglia is their lower capability to turn back toward the naïve, anti-inflammatory state, which makes these cells prone to chronic activation and favours chronic inflammation in the brain. Primed microglia have impaired defence capacity against injury and detrimental effects on the brain microenvironment. Additionally, priming has been associated with AD onset and progression and can represent a promising target for AD treatment strategies. Many factors (genetics, environmental factors, baseline inflammatory status of microglia, ageing) generate an aberrantly activated phenotype that undergoes priming easier and earlier than normally activated microglia do. Novel, promising targets for therapeutic strategies for AD have been sought in the field of microglia activation and, importantly, among those factors influencing the baseline status of these cells. The CX3CL1 pathway could be a valuable target treatment approach in AD, although preliminary findings from the studies in this field are controversial. The current review aims to summarize state of the art on the role of microglia dysfunction in AD pathogenesis and proposes biochemical pathways with possible targets for AD treatment.
Concentration-Dependent Efficacy of Recombinant Human Bone Morphogenetic Protein-2 Using a HA/β-TCP Hydrogel Carrier in a Mini-Pig Vertebral Oblique Lateral Interbody Fusion Model
Authors: Lee Hye-Yeong , Kang Ji-In , Lee Hye-Lan , Hwang Gwang-Yong , Kim Keung-Nyun , Ha Yoon
Published: January 2023

Bone morphogenetic protein-2 (BMP-2) is used in the treatment of degenerative spinal disease and vertebral fractures, spine fusion, dental surgery, and facial surgery. However, high doses are associated with side effects such as inflammation and osteophytes. In this study, we performed spinal fusion surgery on mini-pigs using BMP-2 and a HA/β-TCP hydrogel carrier, and evaluated the degree of fusion and osteophyte growth according to time and dosage. Increasing the dose of BMP-2 led to a significantly higher fusion rate than was observed in the control group, and there was no significant difference between the 8-week and 16-week samples. We also found that the HA + β-TCP hydrogel combination helped maintain the rate of BMP-2 release. In conclusion, the BMP-2-loaded HA/β-TCP hydrogel carrier used in this study overcame the drawback of potentially causing side effects when used at high concentrations by enabling the sustained release of BMP-2. This method is also highly efficient, since it provides mineral matter to accelerate the fusion rate of the spine and improve bone quality.
Development of a Duplex LAMP Assay with Probe-Based Readout for Simultaneous Real-Time Detection of Schistosoma mansoni and Strongyloides spp. -A Laboratory Approach to Point-Of-Care
Authors: Crego-Vicente Beatriz , Fernández-Soto Pedro , García-Bernalt Diego Juan , Febrer-Sendra Begoña , Muro Antonio
Published: January 2023

Loop-mediated isothermal amplification (LAMP) is the most popular technology for point-of-care testing applications due its rapid, sensitive and specific detection with simple instrumentation compared to PCR-based methods. Many systems for reading the results of LAMP amplifications exist, including real-time fluorescence detection using fluorophore-labelled probes attached to oligonucleotide sequences complementary to the target nucleic acid. This methodology allows the simultaneous detection of multiple targets (multiplexing) in one LAMP assay. A method for multiplexing LAMP is the amplification by release of quenching (DARQ) technique by using a 5′-quencher modified LAMP primer annealed to 3′-fluorophore-labelled acting as detection oligonucleotide. The main application of multiplex LAMP is the rapid and accurate diagnosis of infectious diseases, allowing differentiation of co-infecting pathogens in a single reaction. Schistosomiasis, caused among other species by Schistosoma mansoni and strongyloidiasis, caused by Strongyloides stercoralis, are the most common helminth-parasite infections worldwide with overlapping distribution areas and high possibility of coinfections in the human population. It would be of great interest to develop a duplex LAMP to detect both pathogens in the same reaction. In this study, we investigate the use of our two previously developed and well-stablished LAMP assays for S. mansoni and Strongyloides spp. DNA detection in a new duplex real-time eight-primer system based on a modified DARQ probe method that can be performed in a portable isothermal fluorimeter with minimal laboratory resources. We also applied a strategy to stabilize the duplexed DARQ-LAMP mixtures at room temperature for use as ready-to-use formats facilitating analysis in field settings as point-of-care diagnostics for schistosomiasis and strongyloidiasis.
Myelin Basic Protein in Oligodendrocyte-Derived Extracellular Vesicles as a Diagnostic and Prognostic Biomarker in Multiple Sclerosis: A Pilot Study
Authors: Agliardi Cristina , Guerini Franca Rosa , Zanzottera Milena , Bolognesi Elisabetta , Picciolini Silvia , Caputo Domenico , Rovaris Marco , Pasanisi Maria Barbara , Clerici Mario
Published: January 2023

Approximately 15% of multiple sclerosis (MS) patients develop a progressive form of disease from onset; this condition (primary progressive-PP) MS is difficult to diagnose and treat, and is associated with a poor prognosis. Extracellular vesicles (EVs) of brain origin isolated from blood and their protein cargoes could function as a biomarker of pathological conditions. We verified whether MBP and MOG content in oligodendrocytes-derived EVs (ODEVs) could be biomarkers of MS and could help in the differential diagnosis of clinical MS phenotypes. A total of 136 individuals (7 clinically isolated syndrome (CIS), 18 PPMS, 49 relapsing remitting (RRMS)) and 70 matched healthy controls (HC) were enrolled. ODEVs were enriched from serum by immune-capture with anti-MOG antibody; MBP and MOG protein cargoes were measured by ELISA. MBP concentration in ODEVs was significantly increased in CIS (p < 0.001), RRMS (p < 0.001) and PPMS (p < 0.001) compared to HC and was correlated with disease severity measured by EDSS and MSSS. Notably, MBP concentration in ODEVs was also significantly augmented in PPMS compared to RRMS (p = 0.004) and CIS (p = 0.03). Logistic regression and ROC analyses confirmed these results. A minimally invasive blood test measuring the concentration of MBP in ODEVs is a promising tool that could facilitate MS diagnosis.
Neutrophils in Dendritic Cell-Based Cancer Vaccination: The Potential Roles of Neutrophil Extracellular Trap Formation
Authors: Chan Lily , Wood Geoffrey A. , Wootton Sarah K. , Bridle Byram W. , Karimi Khalil
Published: January 2023

Neutrophils have conflicting roles in the context of cancers, where they have been associated with contributing to both anti-tumor and pro-tumor responses. Their functional heterogenicity is plastic and can be manipulated by environmental stimuli, which has fueled an area of research investigating therapeutic strategies targeting neutrophils. Dendritic cell (DC)-based cancer vaccination is an immunotherapy that has exhibited clinical promise but has shown limited clinical efficacy. Enhancing our understanding of the communications occurring during DC cancer vaccination can uncover opportunities for enhancing the DC vaccine platform. There have been observed communications between neutrophils and DCs during natural immune responses. However, their crosstalk has been poorly studied in the context of DC vaccination. Here, we review the dual functionality of neutrophils in the context of cancers, describe the crosstalk between neutrophils and DCs during immune responses, and discuss their implications in DC cancer vaccination. This discussion will focus on how neutrophil extracellular traps can influence immune responses in the tumor microenvironment and what roles they may play in promoting or hindering DC vaccine-induced anti-tumor efficacy.
Dental Pulp Inflammation Initiates the Occurrence of Mast Cells Expressing the α1 and β1 Subunits of Soluble Guanylyl Cyclase
Authors: Korkmaz Yüksel , Plomann Markus , Puladi Behrus , Demirbas Aysegül , Bloch Wilhelm , Deschner James
Published: January 2023

The binding of nitric oxide (NO) to heme in the β1 subunit of soluble guanylyl cyclase (sGC) activates both the heterodimeric α1β1 and α2β1 isoforms of the enzyme, leading to the increased production of cGMP from GTP. In cultured human mast cells, exogenous NO is able to inhibit mast cell degranulation via NO-cGMP signaling. However, under inflammatory oxidative or nitrosative stress, sGC becomes insensitive to NO. The occurrence of mast cells in healthy and inflamed human tissues and the in vivo expression of the α1 and β1 subunits of sGC in human mast cells during inflammation remain largely unresolved and were investigated here. Using peroxidase and double immunohistochemical incubations, no mast cells were found in healthy dental pulp, whereas the inflammation of dental pulp initiated the occurrence of several mast cells expressing the α1 and β1 subunits of sGC. Since inflammation-induced oxidative and nitrosative stress oxidizes Fe2+ to Fe3+ in the β1 subunit of sGC, leading to the desensitization of sGC to NO, we hypothesize that the NO- and heme-independent pharmacological activation of sGC in mast cells may be considered as a regulatory strategy for mast cell functions in inflamed human dental pulp.
Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine
Authors: Hori Ikuma , Harashima Hideyoshi , Yamada Yuma
Published: January 2023

Delivering drugs to mitochondria, the main source of energy in neurons, can be a useful therapeutic strategy for the treatment of neurodegenerative diseases. Berberine (BBR), an isoquinoline alkaloid, acts on mitochondria and is involved in mechanisms associated with the normalization and regulation of intracellular metabolism. Therefore, BBR has attracted considerable interest as a possible therapeutic drug for neurodegenerative diseases. While BBR has been reported to act on mitochondria, there are few reports on the efficient delivery of BBR into mitochondria. This paper reports on the mitochondrial delivery of BBR using a lipid nanoparticle (LNP), a “MITO-Porter” that targets mitochondria, and its pharmacological action in Neuro2a cells, a model neuroblastoma. A MITO-Porter containing encapsulated BBR (MITO-Porter (BBR)) was prepared. Treatment with MITO-Porter (BBR) increased the amount of BBR that accumulated in mitochondria compared with a treatment with naked BBR. Treatment with MITO-Porter (BBR) resulted in increased ATP production in Neuro2a cells, which are important for maintaining life phenomena, compared with treatment with naked BBR. Treatment with MITO-Porter (BBR) also increased the level of expression of mitochondrial ubiquitin ligase (MITOL), which is involved in mitochondrial quality control. Our findings indicate that increasing the accumulation of BBR into mitochondria is important for inducing enhanced pharmacological actions. The use of this system has the potential for being important in terms of the regulation of the metabolic mechanism of mitochondria in nerve cells.
GPR30 Alleviates Pressure Overload-Induced Myocardial Hypertrophy in Ovariectomized Mice by Regulating Autophagy
Authors: Zhang Shuaishuai , Ma Jipeng , Wang Xiaowu , Zhao Diancai , Zhang Jinglong , Jiang Liqing , Duan Weixun , Wang Xiaoya , Hong Ziwei , Li Zilin , Liu Jincheng
Published: January 2023

The incidence of heart failure mainly resulting from cardiac hypertrophy and fibrosis increases sharply in post-menopausal women compared with men at the same age, which indicates a cardioprotective role of estrogen. Previous studies in our group have shown that the novel estrogen receptor G Protein Coupled Receptor 30 (GPR30) could attenuate myocardial fibrosis caused by ischemic heart disease. However, the role of GPR30 in myocardial hypertrophy in ovariectomized mice has not been investigated yet. In this study, female mice with bilateral ovariectomy or sham surgery underwent transverse aortic constriction (TAC) surgery. After 8 weeks, mice in the OVX + TAC group exhibited more severe myocardial hypertrophy and fibrosis than mice in the TAC group. G1, the specific agonist of GPR30, could attenuate myocardial hypertrophy and fibrosis of mice in the OVX + TAC group. Furthermore, the expression of LC3II was significantly higher in the OVX + TAC group than in the OVX + TAC + G1 group, which indicates that autophagy might play an important role in this process. An in vitro study showed that G1 alleviated AngiotensionII (AngII)-induced hypertrophy and reduced the autophagy level of H9c2 cells, as revealed by LC3II expression and tandem mRFP-GFP-LC3 fluorescence analysis. Additionally, Western blot results showed that the AKT/mTOR pathway was inhibited in the AngII group, whereas it was restored in the AngII + G1 group. To further verify the mechanism, PI3K inhibitor LY294002 or autophagy activator rapamycin was added in the AngII + G1 group, and the antihypertrophy effect of G1 on H9c2 cells was blocked by LY294002 or rapamycin. In summary, our results demonstrate that G1 can attenuate cardiac hypertrophy and fibrosis and improve the cardiac function of mice in the OVX + TAC group through AKT/mTOR mediated inhibition of autophagy. Thus, this study demonstrates a potential option for the drug treatment of pressure overload-induced cardiac hypertrophy in postmenopausal women.
The Mechanism of Two Benzaldehydes from Aspergillus terreus C23-3 Improve Neuroinflammatory and Neuronal Damage to Delay the Progression of Alzheimer’s Disease
Authors: Chen Minqi , Liang Jinyue , Liu Yi , Liu Yayue , Zhou Chunxia , Hong Pengzhi , Zhang Yi , Qian Zhong-Ji
Published: January 2023

Alzheimer’s disease (AD), a neurodegenerative disease, is the most common cause of dementia in humans worldwide. Although more in-depth research has been carried out on AD, the therapeutic effect of AD is not as expected, and natural active substances are increasingly sought after by scientists. In the present study, we evaluated two benzaldehydes from a coral-derived Aspergillus terreus strain C23-3, their anti-neuroinflammatory activity in microglia (BV-2), and their neuroprotective activity and mechanisms in hippocampal neuronal cells (HT-22). These include the protein expression of iNOS, COX-2, MAPKs pathways, Tau protein-related pathways, caspases family-related signaling pathways. They also include the levels of TNF-α, IL-6, IL-18 and ROS, as well as the level of mitochondrial oxidative stress and neuronal cell apoptosis. The results showed that both benzaldehydes were effective in reducing the secretion of various inflammatory mediators, as well as pro-inflammatory factors. Among these, benzaldehyde 2 inhibited mitochondrial oxidative stress and blocked neuronal cell apoptosis through Tau protein-related pathways and caspases family-related signaling pathways, thereby inhibiting β-amyloid (Aβ)-induced neurological damage. This study reveals that benzaldehyde 2 has potential as a therapeutic agent for Alzheimer’s disease, and offers a new approach to the high-value use of marine natural products.
Overexpression of Liriodenron WOX5 in Arabidopsis Leads to Ectopic Flower Formation and Altered Root Morphology
Authors: Wang Dandan , Ma Xiaoxiao , Hao Zhaodong , Long Xiaofei , Shi Jisen , Chen Jinhui
Published: January 2023

Roots are essential for plant growth, and studies on root-related genes, exemplified by WUSCHEL-RELATED HOMEOBOX5 (WOX5), have mainly concentrated on model organisms with less emphasis on the function of these genes in woody plants. Here, we report that overexpression of the WOX5 gene from Liriodendron hybrid (LhWOX5) in Arabidopsis leads to significant morphological changes in both the aerial and subterranean organs. In the Arabidopsis aerial parts, overexpression of LhWOX5 results in the production of ectopic floral meristems and leaves, possibly via the ectopic activation of CLV3 and LFY. In addition, in the Arabidopsis root, overexpression of LhWOX5 alters root apical meristem morphology, leading to a curled and shortened primary root. Importantly, these abnormal phenotypes in the aerial and subterranean organs caused by constitutive ectopic expression of LhWOX5 mimic the observed phenotypes when overexpressing AtWUS and AtWOX5 in Arabidopsis, respectively. Taken together, we propose that the LhWOX5 gene, originating from the Magnoliaceae plant Liriodendron, is a functional homolog of the AtWUS gene from Arabidopsis, while showing the highest degree of sequence similarity with its ortholog, AtWOX5. Our study provides insight into the potential role of LhWOX5 in the development of both the shoot and root.
Molecular Mechanism and Agricultural Application of the NifA–NifL System for Nitrogen Fixation
Authors: Zhang Wenyao , Chen Yihang , Huang Keyang , Wang Feng , Mei Ziqing
Published: January 2023

Nitrogen–fixing bacteria execute biological nitrogen fixation through nitrogenase, converting inert dinitrogen (N2) in the atmosphere into bioavailable nitrogen. Elaborating the molecular mechanisms of orderly and efficient biological nitrogen fixation and applying them to agricultural production can alleviate the “nitrogen problem”. Azotobacter vinelandii is a well–established model bacterium for studying nitrogen fixation, utilizing nitrogenase encoded by the nif gene cluster to fix nitrogen. In Azotobacter vinelandii, the NifA–NifL system fine–tunes the nif gene cluster transcription by sensing the redox signals and energy status, then modulating nitrogen fixation. In this manuscript, we investigate the transcriptional regulation mechanism of the nif gene in autogenous nitrogen–fixing bacteria. We discuss how autogenous nitrogen fixation can better be integrated into agriculture, providing preliminary comprehensive data for the study of autogenous nitrogen–fixing regulation.
Effects of Different Surface Treatments of Woven Glass Fibers on Mechanical Properties of an Acrylic Denture Base Material
Authors: Schauperl Zdravko , Ivanković Luka , Bauer Leonard , Šolić Sanja , Ivanković Marica
Published: January 2023

Silanized glass fibers are popular reinforcements of acrylic denture base materials. To increase the number of surface hydroxyl groups and to improve interfacial adhesion between the matrix and reinforcements, acid or base treatments of glass fibers are commonly performed before the silanization. However, limited data are available on the effect of these treatments on the mechanical properties of acrylic matrix composite materials used for denture base applications. In this work, before the silanization of a woven glass fiber fabric (GF) with 3-(trimethoxysilyl) propyl methacrylate, activation pretreatments using HCl and NH4OH aqueous solutions have been performed. To characterize the glass surface, FTIR spectroscopy was used. Specimens of cured acrylic denture base resin and composites were divided into five groups: (1) cured acrylic denture base resin-control group; (2) composite with non-silanized GF; (3) composite with silanized GF; (4) composite with NH4OH activated and silanized GF; (5) composite with HCl activated and silanized GF. The flexural and impact properties of specimens were evaluated by means of three-point-bending tests and Charpy impact testing, respectively. The residual reactivity of the samples was analyzed using differential scanning calorimetry. The results of mechanical testing showed that acid and base pretreatments of the glass fabric had a positive effect on the flexural modulus of prepared composites but a negative effect on their impact strength. Possible interfacial adhesion mechanisms and the diffusion control of isothermal cure reactions due to vitrification have been discussed.
Understanding the Role of Oxidative Stress, Neuroinflammation and Abnormal Myelination in Excessive Aggression Associated with Depression: Recent Input from Mechanistic Studies
Authors: Gorlova Anna , Svirin Evgeniy , Pavlov Dmitrii , Cespuglio Raymond , Proshin Andrey , Schroeter Careen A. , Lesch Klaus-Peter , Strekalova Tatyana
Published: January 2023

Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities are known to contribute significantly to the accompanying functional impairment and the global burden of disease. Progress in the development of targeted treatments of excessive aggression and accompanying symptoms has been limited, and there exists a major unmet need to develop more efficacious treatments for depressed patients. Due to the complex nature and the clinical heterogeneity of MDD and the lack of precise knowledge regarding its pathophysiology, effective management is challenging. Nonetheless, the aetiology and pathophysiology of MDD has been the subject of extensive research and there is a vast body of the latest literature that points to new mechanisms for this disorder. Here, we overview the key mechanisms, which include neuroinflammation, oxidative stress, insulin receptor signalling and abnormal myelination. We discuss the hypotheses that have been proposed to unify these processes, as many of these pathways are integrated for the neurobiology of MDD. We also describe the current translational approaches in modelling depression, including the recent advances in stress models of MDD, and emerging novel therapies, including novel approaches to management of excessive aggression, such as anti-diabetic drugs, antioxidant treatment and herbal compositions.
Synaptic Activity Regulates Mitochondrial Iron Metabolism to Enhance Neuronal Bioenergetics
Authors: Tena-Morraja Paula , Riqué-Pujol Guillem , Müller-Sánchez Claudia , Reina Manuel , Martínez-Estrada Ofelia M. , Soriano Francesc X.
Published: January 2023

Synaptic activity is the main energy-consuming process in the central nervous system. We are beginning to understand how energy is supplied and used during synaptic activity by neurons. However, the long-term metabolic adaptations associated with a previous episode of synaptic activity are not well understood. Herein, we show that an episode of synaptic activity increases mitochondrial bioenergetics beyond the duration of the synaptic activity by transcriptionally inducing the expression of iron metabolism genes with the consequent enhancement of cellular and mitochondrial iron uptake. Iron is a necessary component of the electron transport chain complexes, and its chelation or knockdown of mitochondrial iron transporter Mfrn1 blocks the activity-mediated bioenergetics boost. We found that Mfrn1 expression is regulated by the well-known regulator of synaptic plasticity CREB, suggesting the coordinated expression of synaptic plasticity programs with those required to meet the associated increase in energetic demands.
Enzymatic Methods for Mutation Detection in Cancer Samples and Liquid Biopsies
Authors: Darbeheshti Farzaneh , Makrigiorgos G. Mike
Published: January 2023

Low-level tumor somatic DNA mutations in tissue and liquid biopsies obtained from cancer patients can have profound implications for development of metastasis, prognosis, choice of treatment, follow-up, or early cancer detection. Unless detected, such low-frequency DNA alterations can misinform patient management decisions or become missed opportunities for personalized medicine. Next-generation sequencing technologies and digital-PCR can resolve low-level mutations but require access to specialized instrumentation, time, and resources. Enzymatic-based approaches to detection of low-level mutations provide a simple, straightforward, and affordable alternative to enrich and detect such alterations and is broadly available to low-resource laboratory settings. This review summarizes the traditional uses of enzymatic mutation detection and describes the latest exciting developments, potential, and applications with specific reference to the field of liquid biopsy in cancer.
Fibrin-Rhamnogalacturonan I Composite Gel for Therapeutic Enzyme Delivery to Intestinal Tumors
Authors: Faizullin Dzhigangir , Valiullina Yuliya , Salnikov Vadim , Zelenikhin Pavel , Zuev Yuriy , Ilinskaya Olga
Published: January 2023

Therapy of colorectal cancer with protein drugs, including targeted therapy using monoclonal antibodies, requires the preservation of the drug’s structure and activity in the gastrointestinal tract or bloodstream. Here, we confirmed experimentally the fundamental possibility of creating composite protein–polysaccharide hydrogels based on non-degrading rhamnogalacturonan I (RG) and fibrin as a delivery vehicle for antitumor RNase binase. The method is based on enzymatic polymerization of fibrin in the presence of RG with the inclusion of liposomes, containing an encapsulated enzyme drug, into the gel network. The proposed method for fabricating a gel matrix does not require the use of cytotoxic chemical cross-linking agents and divalent cations, and contains completely biocompatible and biodegradable components. The process proceeds under physiological conditions, excluding the effect of high temperatures, organic solvents and ultrasound on protein components. Immobilization of therapeutic enzyme binase in the carrier matrix by encapsulating it in liposomes made from uncharged lipid made it possible to achieve its prolonged release with preservation of activity for a long time. The release time of binase from the composite carrier can be regulated by variation of the fibrin and RG concentration.