bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Horse and Donkey Meat to Enhance the Quality of the Traditional Meat Product (Kaddid): Analysis of Physico-Chemical Traits
Authors: Aroua Mohamed , Fehri Nour Elhouda , Ben Said Samia , Quattrone Alda , Agradi Stella , Brecchia Gabriele , Balzaretti Claudia Maria , Mahouachi Mokhtar , Castrica Marta
Published: September 2024

The aim of this study was to evaluate the use of horse and donkey meat in the production of kaddid—a traditional dish typically not made with these meats—from a physical and chemical perspective. The results showed that both meats exhibit similar water retention during cooking, contributing to comparable tenderness and juiciness, with no significant differences in pH values, indicating similar quality (p > 0.05). However, their amino acid profiles differ: horse meat contains lower levels of glutamate (p < 0.05), methionine (p < 0.01), isoleucine (p < 0.05), and leucine (p < 0.05), but higher levels of proline (p < 0.05), histidine (p < 0.01), and lysine (p < 0.001) compared to donkey meat. Both meats provide essential amino acids. Horse meat is richer in saturated and monounsaturated fatty acids (32.44% and 39.58%, respectively), while donkey meat has a higher content of polyunsaturated fatty acids (31.51%), with a more favorable PUFA/SFA ratio, suggesting better cardiovascular health benefits. In terms of dried meat, donkey kaddid has a higher protein (17.45 g/100 g) and lower fat content (2.1 g/100 g) compared to horse kaddid (16.7 g/100 g, and 3.5 g/100 g, respectively) (p < 0.05). These findings inform consumer choices and production practices, promoting the use of horse and donkey meat for kaddid production.
Pulsed Light Treatment Effect on Color, Oxidative Stability, and Listeria monocytogenes Population of Sliced Mortadella
Authors: Fracari Priscila Rossato , Massia Ana Guimarães , Laroque Denise Adamoli , Santos Bibiana Alves dos , Cichoski Alexandre José , Carciofi Bruno Augusto Mattar , Campagnol Paulo Cezar Bastianello
Published: September 2024

This study evaluated the effects of high-intensity pulsed light (PL) on sliced mortadella, assessing how the parameters pulse width (1260 to 2520 µs) and number of pulses (one to three) influence color, oxidative stability, and Listeria monocytogenes population. The different PL parameters generated a fluence ranging from 2.64 to 6.57 J/cm2 and irradiance ranging from 1046.9 to 1738.8 W/cm2. The PL slightly increased the temperature and pH of the samples, and this elevation was well correlated to the higher number of pulses and higher fluence. The color parameter a* was reduced while b* values increased after PL application, with these effects being more significant in treatments with a higher number of pulses and higher fluence. The highest values of TBARS were found in treatments with higher fluence (5.28 and 6.57 J/cm2), which were characterized by the attribute “oxidized color” in sensory evaluation. The different PL conditions reduced the count of L. monocytogenes by up to 1.44 Log CFU/cm2. The treatment with a pulse width of 1260 µs, two pulses, fluence of 4.38 J/cm2, and irradiance of 1738.3 W/cm2 achieved the same efficacy in pathogen reduction as the treatments with higher fluence. Moreover, these PL conditions had a minimal impact on the color and oxidative stability of mortadella, demonstrating an effective balance between microbiological safety and quality preservation.
Using Carbon Dioxide for Subsea Long-Duration Energy Storage
Authors: Cutajar Charise , Sant Tonio , Briffa Luke Jurgen
Published: September 2024

This paper investigates the operating benefits and limitations of utilizing carbon dioxide in hydro-pneumatic energy storage systems, a form of compressed gas energy storage technology, when the systems are deployed offshore. Allowing the carbon dioxide to transition into a two-phase fluid will improve the storage density for long-duration energy storage. A preliminary comparative study between an air-based and a carbon dioxide-based subsea hydro-pneumatic energy storage system is first presented. The analysis is based on thermodynamic calculations assuming ideal isothermal conditions to quantify the potential augmentation in energy storage capacity for a given volume of pressure containment when operating with carbon dioxide in lieu of air. This is followed by a transient thermal analysis of the carbon dioxide-based hydro-pneumatic energy storage system, taking into account the real scenario of a finite thermal resistance for heat exchange between the gas and the surrounding seawater. Results from numerical modelling revealed that the energy storage capacity of a carbon dioxide-based subsea hydro-pneumatic energy storage system operating under ideal isothermal conditions can be theoretically increased by a factor of 2.17 compared to an identical air-based solution. The numerical modelling revealed that, under real conditions under which transient effects resulting from a finite thermal resistance are accounted for, the achievable factor is lower, depending on the charging and discharging time, the initial temperature, and whether a polyethene liner for corrosion prevention is considered or not.
IL-10 A-Allele as a Biomarker for Periodontitis Severity in Bulgarian Patients
Authors: Pashova-Tasseva Zdravka , Dosseva-Panova Velitchka , Mlachkova Antoaneta , Savov Alexey , Tosheva Ekaterina
Published: September 2024

Background: Periodontitis is a complex disease, and bacterial factors play a crucial role in its initiation. The contributions of genetic and epigenetic factors to the pathogenesis of periodontal disease are increasingly recognized. Single-nucleotide polymorphisms (SNPs) in various molecules, including cytokines, are of particular interest due to their established involvement in numerous diseases. This study investigates the influence of SNPs in the IL-10 gene at positions −592 (rs1800872) C>A and −1082 (rs1800896) T>C (also referred to as 1082A>G) on the severity of periodontitis in a cohort of Bulgarian patients. Methods: In the recent study, both clinical and paraclinical methodologies were employed to comprehensively assess the periodontal status of the participants. The genotypic characterization of IL-10 polymorphisms was performed by PCR RFLP analysis. Statistical analyses, including principal component analysis (PCA), were executed utilizing IBM SPSS Statistics Version 21. Results: We have established a statistically significant association between the presence of at least one A-allele in the patients’ genotype and the incidence of severe periodontitis (p = 0.047). Conclusions: IL-10 single-nucleotide polymorphisms (SNPs) could be effectively considered as biomarkers for the severity of periodontitis.
Editorial for the Special Issue “Satellite DNA Genomics”
Authors: Garrido-Ramos Manuel A. , Plohl Miroslav , Šatović-Vukšić Eva
Published: September 2024

A significant portion of eukaryotic genomes consists of non-coding repetitive DNA sequences arranged in tandem arrays, known as satellite DNA (satDNA) [...]
Association of SCN1A Polymorphisms rs3812718 and rs2298771 with Epilepsy
Authors: Katsarou Martha-Spyridoula , Siatouni Anna , Tsikrika Danae , Kokkiou Elena , Stefanatou Maria , Verentzioti Anastasia , Alexoudi Athanasia , Gatzonis Stylianos , Drakoulis Nikolaos , Papasavva Maria
Published: September 2024

Background/Objectives: Epilepsy is a brain disease with both environmental and genetic inputs. Ion channel dysfunction seems to be of great significance for abnormal neuronal behavior during epileptic seizures. Within neurons, the voltage-gated sodium channels are crucial proteins contributing to the initiation and propagation of action potentials. The voltage-gated sodium channel α subunit 1 (SCN1A) gene encodes for the α subunit of a voltage-gated ion channel. The aim of the study was to investigate the relation of two common SCN1A variants, i.e., rs3812718 and rs2298771, with distinct epileptic phenotypes in a South-Eastern European population. Methods: DNA was extracted from 214 unrelated participants with focal onset, focal to bilateral tonic–clonic, or generalized onset epileptic seizures and genotyped using real-time PCR (LightSNiP assays) followed by melting curve analysis. Statistical analysis of the results was performed using IBM SPSS Statistics software (version 29.0 for Windows). Results: Genotype frequency distribution analysis indicated an association for the A-allele-containing genotypes of both rs3812718 and rs2298771 polymorphisms of SCN1A with generalized onset seizures and focal to bilateral tonic–clonic seizures versus focal onset seizures. Conclusions: Consequently, the study provides evidence that supports a potential association of the investigated SCN1A polymorphisms with distinct seizure subtype susceptibility in South-Eastern Europeans.
Probabilistic Seismic Hazard Assessment of Lisbon (Portugal)
Authors: Gögen Büşra , Karimzadeh Shaghayegh , Lourenço Paulo
Published: September 2024

The 1755 Lisbon earthquake holds significant historical importance in Portuguese history. The subsequent tsunami resulted in extensive destruction and damage, affecting not only Lisbon but also other regions of Portugal, Spain, and North Africa. This significant and hazardous event led to an increase in awareness about earthquake and tsunami risks, not only within Portugal but throughout Europe. This heightened awareness facilitated advancements in scientific developments, including design codes, standards, and earthquake engineering. However, recent studies focusing on hazard assessment for Lisbon are limited. For this reason, this paper aims to present a comprehensive probabilistic seismic hazard analysis (PSHA) for the Lisbon metropolitan area. The first stage of PSHA involves defining applicable and active seismic source models (area and line sources) within the study area. Subsequently, historical and instrumental earthquake records are collected to build a homogenized earthquake catalog, utilizing both global and local earthquake databases. Following this, the completeness level of the earthquake catalog is tested. By incorporating suitable ground motion models to the region and local soil characteristics, seismic hazard maps for various return periods and hazard curves in terms of peak ground acceleration (PGA) are developed. The findings based on the area source model agree with existing literature, indicating PGA values ranging from 0.3 g to 0.9 g, 0.2 g to 0.7 g, 0.2 g to 0.5 g, and 0.1 g to 0.3 g for return periods of 2475, 975, 475, and 50 years, respectively.
Effectiveness of Mindfulness-Based Interventions with Respect to Psychological and Biomedical Outcomes in Young People with Type 1 Diabetes: A Systematic Review
Authors: Gutiérrez-Domingo Tamara , Farhane-Medina Naima Z. , Villaécija Joaquín , Vivas Sebastián , Tabernero Carmen , Castillo-Mayén Rosario , Luque Bárbara
Published: September 2024

Background: Type 1 diabetes is a chronic disease especially affecting young people. Mindfulness-based psychological interventions might reduce emotional symptoms post-diagnosis, but the evidence is limited. Objectives: This systematic review aimed to evaluate the effectiveness of mindfulness interventions on psychological well-being and biomedical variables in young people with type 1 diabetes. Methods: A systematic review of trials was conducted that involved a bibliographic search in electronic databases (Web of Science, MEDLINE, SciELO, Scopus, PsycINFO, and Cochrane Library) considering studies published between 2013 and 2024. Results: A total of 434 records were identified, of which 252 underwent selection according to title and abstract, leaving 32 that were evaluated for eligibility and 7 included in this review. From Google Scholar, six more studies were identified and evaluated, and two were selected. Finally, nine studies were subjected to full reading and a detailed analysis of the inclusion criteria. A total of 66.6% of the studies were evaluated as having a methodological quality of moderate or optimal, but the samples analysed tended to be small, and only two articles carried out short-term follow-up evaluations. Conclusions: Mindfulness-based interventions, upon reviewing the preliminary results, may be posited as a viable strategy to enhance psychological (anxiety, diabetes distress, perceived stress, depression, self-efficacy, psychological well-being, and quality of life) and biomedical outcomes (glycaemic control, blood glucose levels, and diastolic blood pressure) for type 1 diabetes in young people. Although promising, further research is required to improve the quality, methodology, and design of studies.
Association of Tai Chi and Square Dance with Cognitive Function in Chinese Older Adults
Authors: Zhao Xiaoguang , Liu Dongxue , Wang Jin
Published: September 2024

Objective: This study explores the association of Tai Chi and square dance with cognitive function and compares the effects of the two fitness programs on cognitive function in Chinese older adults. Methods: A total of 1732 older people (aged 60 years and over) met the inclusion criteria from the 2018 Chinese Longitudinal Healthy Longevity Survey. Based on the frequency of participating in Tai Chi and square dance, older adults were divided into three groups: a Tai Chi group (n = 234), a square dance group (n = 345), and a control group (n = 1153). Cognitive function was measured using a modified Mini-Mental State Examination (MMSE). Participation in Tai Chi or square dance was investigated by asking the subjects to report how often they participated in the fitness programs. Results: Older adults in both the Tai Chi group and the square dance group had higher scores in all MMSE items, including orientation, registration, attention and calculation, recall, and language, compared to those in the control group. But there were no significant differences in any MMSE items between the Tai Chi group and the square dance group. Multiple regression analysis showed that participating in Tai Chi or square dance, age, educational level, and sex can predict cognitive function in older people. Conclusion: Our findings suggest that participating in Tai Chi and square dance are associated with better cognitive function, and Tai Chi and square dance have similar effects on cognitive function in the Chinese older population.
Triacontanol Reverses Abscisic Acid Effects on Stomatal Regulation in Solanum lycopersicum L. under Drought Stress Conditions
Authors: Bravo-Díaz María Asunción , Ramos-Zambrano Emilia , Juárez-Yáñez Tomás Ernesto , Perea-Flores María de Jesús , Martínez-Ayala Alma Leticia
Published: September 2024

When applied under abiotic stress conditions, triacontanol (TRIA) is effective in regulating the physicochemical processes in plants through mechanisms of defence such as abscisic acid (ABA) signalling. However, TRIA’s role in relation to ABA and stomatal opening is unclear. Therefore, the objective of this study was to evaluate the effects of TRIA and ABA and their combinations on different variables related to stomatal regulation in Solanum lycopersicum, which is subjected to drought stress, and on the leaf epidermis. The negative effects of stress and responses triggered by ABA were reversed in plants treated with TRIA. TRIA increased stomatal conductance and photosynthetic activity in the early hours, and it was determined that TRIA produced larger stomata than did the other treatments. Moreover, the chloroplasts of plants treated with TRIA were significantly smaller and more numerous than those of the control, which could improve CO2 diffusion efficiency and may be related to the regulation of stomatal opening and photosynthesis. Finally, the abaxial epidermis tests reaffirmed the inhibitory effects of TRIA on ABA on stomatal opening. These results confirm the important role of TRIA in regulating various processes in plants and processes triggered by ABA, such as those related to stomatal regulation.
Aerial Root Growth and Development Mechanism of Flowering Cherry ‘Gotenba zakura’ (Prunus incisa) and Its Relationship with Waterlogging Tolerance
Authors: Feng Xiaoxuan , Lyu Tong , Lyu Yingmin
Published: September 2024

Flowering cherry is a renowned ornamental woody plant valued for its landscape applications and economic benefits in gardens. However, waterlogging during the rainy season in some areas causes death and heavy losses. Fortunately, we have found that the flowering cherry ‘Gotenba zakura’ (Prunus incisa Thunberg) is capable of generating aerial roots when subjected to heavy rains and prolonged floods. In this study, we conducted an associated analysis to explore the core regulating network of the aerial root growth mechanism in flowering cherry ‘Gotenba zakura’ by combining phenotypic observations, physiological assays, and transcriptome comparisons across five distinct stages. Through the analysis of the heatmap of DEGs (Differentially Expressed Genes) and the gene co-expression network (GCN), we identified genes that may play critical roles under waterlogging stress. The gene network indicates that aerial roots enhance waterlogging tolerance through ROS degradation, endogenous hormone induction, and energy production. This discovery provides a solid foundation for understanding the waterlogging tolerance of flowering cherry and offers molecular evidence for selecting promising rootstocks for breeding, aimed at improving waterlogging tolerance through grafting.
A Case of Yellow Nail Syndrome Complicated with Pulmonary Infection Due to Nocardia cyriacigeorgica
Authors: Li Qiuyu , Zheng Jiajia , Zhang Qiuyue , Liang Ying , Zhu Hong , Sun Yongchang
Published: September 2024

Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by nail bed changes, pulmonary involvement, and lymphatic drainage disorders. Pulmonary involvement usually manifests as bronchiectasis, bronchiolitis, and pleural effusion. There are few studies on yellow nail syndrome combined with opportunistic infection. Here, we report a case of clinically diagnosed YNS combined with Nocardia cyriacigeorgica infection and the course of treatment used, which can provide some useful information for clinicians to better understand this rare illness.
Geometric Characterization of the Mateur Plain in Northern Tunisia Using Vertical Electrical Sounding and Remote Sensing Techniques
Authors: Issaoui Wissal , Nasr Imen , Alexakis Dimitrios , Bejaoui Wafa , Ibraheem Ismael , Ezzine Ahmed , Ben Othman Dhouha , Inoubli Mohamed
Published: September 2024

The Mateur aquifer system in Northern Tunisia was examined using data from 19 water boreholes, 69 vertical electrical sounding (VES) stations, and a Sentinel-2 satellite image. Available boreholes and their corresponding logs were compared to define precisely the multi-layer aquifer system, including the Quaternary and Campanian aquifers of the Mateur plain. Quantitative interpretation and qualitative evaluation of VES data were conducted to define the geometry of these reservoirs. These interpretations were enhanced by remote sensing imagery processing, which enabled the identification of the Mateur plain’s superficial lineaments. Based on well log information, the lithological columns show that the Quaternary series in the Ras El Ain region contains a layer of clayey, pebbly, and gravelly limestone. Additionally, in the Oued El Tine area, a clayey lithological unit has been identified as a multi-layer aquifer. The study area, exhibiting apparent resistivity values ranging between 20 and 170 Ohm·m, appears to be rich in groundwater resources. The correlation between the lithological columns and the interpreted VES data, presented as geoelectrical cross-sections, revealed variations in depth (8–106 m), thickness (10 to 55 m), and resistivity (20–98 Ohm·m) of a coarse unit corresponding to the Mateur aquifer. Twenty-three superficial lineaments were extracted from the Sentinel-2 image. Their common superposition indicated that both of them are in a good coincidence; these could be the result of normal faults, creating an aquifer system divided into raised and sunken blocks.
Comparative Study of the Antioxidant Activity of the Conformers of C-tetra(4-methoxyphenyl)calix[4]resorcinarene
Authors: Maldonado-Sanabria Laura Angélica , Rodriguez-Saavedra Ivette Nicole , Reyes-Peña Ingrid Valentina , Castillo-Aguirre Alver , Maldonado Mauricio , Crespo Almudena , Esteso Miguel A.
Published: September 2024

C-tetra(4-methoxyphenyl)calix[4]resorcinarene was synthesized by hydrochloric acid-catalysed cyclocondensation of resorcinol and 4-methoxybenzaldehyde. Under these conditions, the reaction produces a conformational mixture of crown and chair structural conformers, which were separated and characterized by chromatographic and spectroscopic techniques. The antioxidant activity of both conformers was measured by using the DPPH assay, through which it was observed that the chair conformer showed greater antioxidant activity (IC50 = 47.46 ppm) than the crown conformer (IC50 = 78.46 ppm). Additionally, it was observed that the mixture of both conformers presented lower antioxidant activity than either conformer in isolation. The results found suggest that the chair conformer has efficient antioxidant activity that makes it a potential target for further research.
Transcriptome Profiling of Phenylalanine-Treated Human Neuronal Model: Spotlight on Neurite Impairment and Synaptic Connectivity
Authors: Stankovic Sara , Lazic Andrijana , Parezanovic Marina , Stevanovic Milena , Pavlovic Sonja , Stojiljkovic Maja , Klaassen Kristel
Published: September 2024

Phenylketonuria (PKU) is the most common inherited disorder of amino acid metabolism, characterized by high levels of phenylalanine (Phe) in the blood and brain, leading to cognitive impairment without treatment. Nevertheless, Phe-mediated brain dysfunction is not fully understood. The objective of this study was to address gene expression alterations due to excessive Phe exposure in the human neuronal model and provide molecular advances in PKU pathophysiology. Hence, we performed NT2/D1 differentiation in culture, and, for the first time, we used Phe-treated NT2-derived neurons (NT2/N) as a novel model for Phe-mediated neuronal impairment. NT2/N were treated with 1.25 mM, 2.5 mM, 5 mM, 10 mM, and 30 mM Phe and subjected to whole-mRNA short-read sequencing. Differentially expressed genes (DEGs) were analyzed and enrichment analysis was performed. Under three different Phe concentrations (2.5 mM, 5 mM, and 10 mM), DEGs pointed to the PREX1, LRP4, CDC42BPG, GPR50, PRMT8, RASGRF2, and CDH6 genes, placing them in the context of PKU for the first time. Enriched processes included dendrite and axon impairment, synaptic transmission, and membrane assembly. In contrast to these groups, the 30 mM Phe treatment group clearly represented the neurotoxicity of Phe, exhibiting enrichment in apoptotic pathways. In conclusion, we established NT2/N as a novel model for Phe-mediated neuronal dysfunction and outlined the Phe-induced gene expression changes resulting in neurite impairment and altered synaptic connectivity.
Correction: Tang et al. Integrated Multi-Omics Analysis Reveals Mountain-Cultivated Ginseng Ameliorates Cold-Stimulated Steroid-Resistant Asthma by Regulating Interactions among Microbiota, Genes, and Metabolites. Int. J. Mol. Sci. 2024, 25, 9110
Authors: Tang Daohao , Wang Chao , Liu Hanlin , Wu Junzhe , Tan Luying , Liu Sihan , Lv Haoming , Wang Cuizhu , Wang Fang , Liu Jinping
Published: September 2024

In the original publication [...]
Circulating microRNAs in Carotid Atherosclerosis: Complex Interplay and Possible Associations with Atherothrombotic Stroke
Authors: Tanashyan Marine M. , Shabalina Alla A. , Annushkin Vladislav A. , Mazur Andrey S. , Kuznetsova Polina I. , Raskurazhev Anton A.
Published: September 2024

Atherosclerosis is a chronic inflammatory disorder which remains the main cause of cardiovascular morbidity and mortality, with carotid atherosclerosis (CA) being a major cause of ischemic stroke. Epigenetic regulation plays a significant role in CA progression and stroke, yet the impact of circulating microRNA expression, associated with atherogenesis, has not been clearly defined. We included 81 patients with moderate–severe CA (mean age 67 ± 7 years, 53% male), 42% of whom had prior ipsilateral ischemic stroke (i.e., were symptomatic). A total of 24 miRs were identified and their plasma expression levels were measured. We observed that several microRNAs were up-regulated in stroke survivors, namely miR-200c-3p (30.6 vs. 29.7, p = 0.047), miR-106b-3p (31.01 vs. 30.25, p = 0.004), and miR-494-5p (39 vs. 33, p < 0.001), while others (miR183-3p [25.5 vs. 28.6, p < 0.001], miR-126-5p [35.6 vs. 37.1, p = 0.03], and miR-216-3p [12.34 vs. 16.2, p < 0.001]) had lower plasma levels in symptomatic patients. In a multivariable logistic regression model for symptomatic CA, the only miRs showing statistical significance were miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p. Cluster analysis demonstrated differential miR expression in CA patients depending on their stroke status. Epigenetic modulation, represented as complex interplay between circulating miRs of different atherogenic potential, may play a significant role in CA development and progression. In our study, we show possible candidates for future research regarding CA and stroke.
Modulation of the Cardiovascular Risk in Type 1 Diabetic Rats by Endurance Training in Combination with the Prebiotic Xylooligosaccharide
Authors: Choneva Mariya , Delchev Slavi , Hrischev Petar , Dimov Ivica , Boyanov Krasimir , Dimitrov Iliyan , Gerginska Fanka , Georgieva Katerina , Bacelova Mariana , Bivolarska Anelia
Published: September 2024

Diabetic cardiomyopathy is a major etiological factor in heart failure in diabetic patients, characterized by mitochondrial oxidative metabolism dysfunction, myocardial fibrosis, and marked glycogen elevation. The aim of the present study is to evaluate the effect of endurance training and prebiotic xylooligosaccharide (XOS) on the activity of key oxidative enzymes, myocardial collagen, and glycogen distribution as well as some serum biochemical risk markers in streptozotocin-induced type 1 diabetic rats. Male Wistar rats (n = 36) were divided into four diabetic groups (n = 9): sedentary diabetic rats on a normal diet (SDN), trained diabetic rats on a normal diet (TDN), trained diabetic rats on a normal diet with an XOS supplement (TD-XOS), and sedentary diabetic rats with an XOS supplement (SD-XOS). The results show that aerobic training managed to increase the enzyme activity of respiratory Complex I and II and the lactate dehydrogenase in the cardiomyocytes of the diabetic rats. Furthermore, the combination of exercise and XOS significantly decreased the collagen and glycogen content. No significant effects on blood pressure, heart rate or markers of inflammation were detected. These results demonstrate the beneficial effects of exercise, alone or in combination with XOS, on the cardiac mitochondrial enzymology and histopathology of diabetic rats.
Systematic Identification and Characterization of O-Methyltransferase Gene Family Members Involved in Flavonoid Biosynthesis in Chrysanthemum indicum L.
Authors: Zhang Man , Wang Tao , Guo Qiaosheng , Su Yong , Yang Feng
Published: September 2024

Chrysanthemum indicum L. capitulum is an enriched source of flavonoids with broad-ranging biological activities, mainly due to their anti-inflammatory, anti-cancer, immune regulation, anti-microbial activity, hepatoprotective, and neuroprotective effects. The O-methylation of various secondary metabolites has previously been demonstrated to be mainly catalyzed by S-adenosyl-L-methionine-dependent O-methyltransferase (OMT) proteins encoded by the OMT gene family. However, limited comprehensive study was published on the OMT gene family, especially the CCoAOMT subfamily, involved in the O-methylation of flavonoids in Chrysanthemum. Here, we analyzed the spatiotemporal expression patterns of C. indicum OMT genes in leaf and flower at different developmental stages. Transcriptome sequencing and qRT-PCR analysis showed that COMTs were mainly highly expressed in capitulum, especially in full bloom, while CCoAOMTs were mainly highly expressed in leaves. Correlation analysis of OMT gene expression and flavonoids accumulation revealed that four OMTs (CHR00029120, CHR00029783, CHR00077404, and CHR00078333) were putatively involved in most methylated flavonoids biosynthesis in the capitulum. Furthermore, we identified a true CCoAOMT enzyme, CiCCoAOMT1, and found that it catalyzed O-methylation of quercetin and luteolin at the 3′-OH position. In summary, this work provides an important theoretical basis for further research on the biological functions of OMTs in C. indicum.
Molecular Therapeutics for Diabetic Kidney Disease: An Update
Authors: Guo Man , He Fangfang , Zhang Chun
Published: September 2024

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus (DM). With the increasing prevalence of DM worldwide, the incidence of DKD remains high. If DKD is not well controlled, it can develop into chronic kidney disease or end-stage renal disease (ESRD), which places considerable economic pressure on society. Traditional therapies, including glycemic control, blood pressure control, blood lipid control, the use of renin–angiotensin system blockers and novel drugs, such as sodium–glucose cotransporter 2 inhibitors, mineralocorticoid receptor inhibitors and glucagon-like peptide-1 receptor agonists, have been used in DKD patients. Although the above treatment strategies can delay the progression of DKD, most DKD patients still ultimately progress to ESRD. Therefore, new and multimodal treatment methods need to be explored. In recent years, researchers have continuously developed new treatment methods and targets to delay the progression of DKD, including miRNA therapy, stem cell therapy, gene therapy, gut microbiota-targeted therapy and lifestyle intervention. These new molecular therapy methods constitute opportunities to better understand and treat DKD. In this review, we summarize the progress of molecular therapeutics for DKD, leading to new treatment strategies.
Strongly ROS-Correlated, Time-Dependent, and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation
Authors: Alfei Silvana , Zuccari Guendalina , Athanassopoulos Constantinos M. , Domenicotti Cinzia , Marengo Barbara
Published: September 2024

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior.
Parvovirus B19 Infection Is Associated with the Formation of Neutrophil Extracellular Traps and Thrombosis: A Possible Linkage of the VP1 Unique Region
Authors: Tzang Bor-Show , Chin Hao-Yang , Tzang Chih-Chen , Chuang Pei-Hua , Chen Der-Yuan , Hsu Tsai-Ching
Published: September 2024

Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis.
Converging Pathways between Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) and Diabetes in Children
Authors: Faienza Maria Felicia , Farella Ilaria , Khalil Mohamad , Portincasa Piero
Published: September 2024

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM, where each condition influences and exacerbates the progression of the other. This review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment into the diagnostic arsenal for children showing insufficient glycemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.
Special Issue: “Rational Design and Synthesis of Bioactive Molecules”
Authors: Kostova Irena
Published: September 2024

The rational design of novel bioactive molecules is a critical but challenging task in drug discovery [...]
Effect of Sodium-Glucose Co-Transporter 2 Inhibitors Combined with Metformin on Pancreatic Cancer Cell Lines
Authors: Cristovão André , Andrade Nelson , Martel Fátima , Silva Cláudia
Published: September 2024

Pancreatic cancer (PC) is the ninth-leading cause of cancer-related deaths worldwide. Diabetic patients have an increased risk and mortality rates for PC. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and metformin (Met) are widely used anti-diabetic medications. Both Met and SGLT2 inhibitors have anticancer properties in PC, but nothing is known concerning their combined effect. So, we investigated the in vitro effect of SGLT2 inhibitors combined with Met. Canagliflozin and dapagliflozin possessed cytotoxic, antiproliferative, and pro-apoptotic properties in the tested PC cell lines. In PANC-1 cells, the antimigratory and pro-apoptotic effects were enhanced when dapagliflozin was combined with Met, and G1 cell cycle arrest was enhanced when dapagliflozin or canagliflozin was combined with Met. In AsPC-1 cells, the cytotoxic effect and the G1 cell cycle arrest were enhanced when canagliflozin and dapagliflozin, respectively, were combined with Met. Only the cytotoxic effects of SGLT2 inhibitors, but not the combination treatments, involved PI3K and JNK-dependent pathways in AsPC-1 cells. In conclusion, combination treatments increased the anticancer effects in a cell type-dependent way in the two investigated cell lines. Additionally, the cytotoxic effect of SGLT2 inhibitors was dependent on the PI3K and JNK pathways in AsPC-1 cells, but Met appears to act via a distinct mechanism.
Mitochondrial Aconitase and Its Contribution to the Pathogenesis of Neurodegenerative Diseases
Authors: Padalko Volodymyr , Posnik Filip , Adamczyk Malgorzata
Published: September 2024

This survey reviews modern ideas on the structure and functions of mitochondrial and cytosolic aconitase isoenzymes in eukaryotes. Cumulative experimental evidence about mitochondrial aconitases (Aco2) as one of the main targets of reactive oxygen and nitrogen species is generalized. The important role of Aco2 in maintenance of homeostasis of the intracellular iron pool and maintenance of the mitochondrial DNA is discussed. The role of Aco2 in the pathogenesis of some neurodegenerative diseases is highlighted. Inactivation or dysfunction of Aco2 as well as mutations found in the ACO2 gene appear to be significant factors in the development and promotion of various types of neurodegenerative diseases. A restoration of efficient mitochondrial functioning as a source of energy for the cell by targeting Aco2 seems to be one of the promising therapeutic directions to minimize progressive neurodegenerative disorders.
Optimization of Basophil Activation Test in the Diagnosis and Qualification for Allergen-Specific Immunotherapy in Children with Respiratory Allergy to the House Dust Mite Dermatophagoides pteronyssinus
Authors: Spiewak Radoslaw , Gregorius Aleksandra , Ostrowski Grzegorz , Czarnobilska Ewa
Published: September 2024

The aim of this study was to optimize a basophil activation test in the detection of allergy to the house dust mite Dermatophagoides pteronyssinus in children with allergic respiratory diseases. This study involved 32 cases, 13 girls and 19 boys aged 4–17 years, with perennial asthma or allergic rhinitis caused by D. pteronyssinus. The control group consisted of 13 girls and 19 boys aged 4–17 years with seasonal allergic asthma or rhinitis provoked by Timothy or birch pollen. House dust mite (HDM) allergy was excluded in the controls based on their medical history, skin prick test (SPT) results and sIgE determination. In all patients, a basophil activation test (BAT) was performed with five dilutions of D. pteronyssinus allergen (the dilution series ranged from 22.5 to 0.00225 ng/mL). The results were analyzed by using the receiver operating characteristics (ROC) to determine the optimal allergen concentrations, outcome measures and cut-off points that would differentiate most accurately between HDM-allergic and non-allergic patients. As a “gold standard”, criteria for allergen-specific immunotherapy with D. pteronyssinus or respective pollens were applied by an experienced pediatric allergist following the guidelines of the European Academy of Allergy and Clinical Immunology. The highest diagnostic efficiency was yielded by the protocol assuming a cut-off value of 9.76% activated basophils after activation with a single allergen concentration of 2.25 ng/mL (sensitivity 90.6%, specificity 100%). This protocol yielded 3 (4.7%) misclassifications, all false negative, when compared with the “gold standard”. There was a strong correlation with the BAT results at 22.5, 2.25 and 0.225 ng/mL (respectively r = 0.90 and r = 0.78, p < 0.001), as well as between the BAT at 2.25 ng/mL and SPT (r = 0.82, p < 0.001) and between the SPT and sIgE levels (r = 0.78, p < 0.001). High cross-reactivity between D. pteronyssinus and D. farinae was confirmed based on the BAT at 22.5 ng/mL (r = 0.82, p < 0.001). In conclusion, the BAT showed very good concordance with the result of a meticulous process of decision-making that combined validated allergy tests (SPT, sIgE) with expert guidelines, specialist knowledge and experience. Facing the risk of the incorrect qualification of patients for costly, long-lasting and potentially risky allergen-specific immunotherapy, the inclusion of a basophil activation test into diagnostic process seems fully justified.
1-L Transcription in Prion Diseases
Authors: Nahalka Jozef
Published: September 2024

Understanding the pathogenesis and mechanisms of prion diseases can significantly expand our knowledge in the field of neurodegenerative diseases. Prion biology is increasingly recognized as being relevant to the pathophysiology of Alzheimer’s disease and Parkinson’s disease, both of which affect millions of people each year. This bioinformatics study used a theoretical protein-RNA recognition code (1-L transcription) to reveal the post-transcriptional regulation of the prion protein (PrPC). The principle for this method is directly elucidated on PrPC, in which an octa-repeat can be 1-L transcribed into a GGA triplet repeat RNA aptamer known to reduce the misfolding of normal PrPC into abnormal PrPSc. The identified genes/proteins are associated with mitochondria, cancer, COVID-19 and ER-stress, and approximately half are directly or indirectly associated with prion diseases. For example, the octa-repeat supports CD44, and regions of the brain with astrocytic prion accumulation also display high levels of CD44.
Immune Mechanisms and Biomarkers in Systemic Lupus Erythematosus
Authors: Parodis Ioannis , Sjöwall Christopher
Published: September 2024

The immense heterogeneity of the chronic, inflammatory, autoimmune disease systemic lupus erythematosus (SLE), both with regard to immunological aberrancies and clinical manifestations, poses diagnostic difficulties and challenges in the management of patients [...]
Navigating the Intersection of Glycemic Control and Fertility: A Network Perspective
Authors: Di Carlo Carlo , Cimini Costanza , Belda-Perez Ramses , Valbonetti Luca , Bernabò Nicola , Barboni Barbara
Published: September 2024

The rising incidence of metabolic diseases is linked to elevated blood glucose levels, contributing to conditions such as diabetes and promoting the accumulation of advanced glycation end products (AGEs). AGEs, formed by non-enzymatic reactions between sugars and proteins, build up in tissues and are implicated in various diseases. This article explores the relationship between glycemic control and AGE accumulation, focusing on fertility implications. A computational model using network theory was developed, featuring a molecular database and a network with 145 nodes and 262 links, categorized as a Barabasi–Albert scale-free network. Three main subsets of nodes emerged, centered on glycemic control, fertility, and immunity, with AGEs playing a critical role. The transient receptor potential vanilloid 1 (TRPV1), a receptor expressed in several tissues including sperm, was identified as a key hub, suggesting that the modulation of TRPV1 in sperm by AGEs may influence fertility. Additionally, a novel link between glycemic control and immunity was found, indicating that immune cells may play a role in endocytosing specific AGEs. This discovery underscores the complex interplay between glycemic control and immune function, with significant implications for metabolic, immune health, and fertility.
CD4+ Effective Memory T Cell Markers GBP2 and LAG3 Are Risk Factors for PTB and COVID-19 Infection: A Study Integrating Single-Cell Expression Quantitative Trait Locus and Mendelian Randomization Analyses
Authors: Zhu Liangyu , Wu Hanxin , Peng Li , Huang Xun , Yang Rui , Ma Weijie , Zhong Lei , Li Bingxue , Song Jieqin , Luo Suyi , Gao Li , Wu Xinya , Ma Weijiang , Bao Fukai , Liu Aihua
Published: September 2024

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4+ Effective Memory T Cell (CD4+ TEM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4+ TEM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10−15) and LAG3 (rs67706382, p = 6.16× 10−16). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4+ TEM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4+ TEM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find.