bluuebunny/crossref_metadata_2025 huggingface dataset:
Downward Intergenerational Support and Well-Being in Older Chinese Adults
Authors: Liu Xin , Bai Shuying
Published: October 2024

Life satisfaction, as an important indicator of subjective well-being, is crucial for older adults. This study aims to examine the effects of downward intergenerational financial and practical support on life satisfaction among older adults in China, while exploring the mediating role of self-esteem and the potential differences across gender. Data were collected from 507 older adults aged 60 and above in China. The findings indicate that both financial and practical support provided by older adults positively predict their life satisfaction. Mediation analysis reveals that self-esteem partially mediates the relationship between downward intergenerational support and life satisfaction. This suggests that helping their children enhances older adults’ sense of self-worth, which in turn improves their overall well-being. Gender differences were also observed: financial support had a stronger impact on life satisfaction for men, while practical support was more significant for women. These results highlight the influence of traditional gender roles and cultural expectations on the dynamics of intergenerational support in contemporary Chinese families.
Effects of Abscisic Acid on the Physiological and Biochemical Responses of Saccharina japonica Under High-Temperature Stress
Authors: Cui Jiexin , Dai Yinru , Lai Yichang , Tan Yenzhen , Liu Tao
Published: October 2024

Saccharina japonica is one of the most productive aquatic plants in the world, widely used in food, feed, medicine, and other industries. Predominantly inhabiting temperate marine environments in mid- to high-latitude regions of the Northern Hemisphere, the growth of S. japonica is significantly limited by high-temperature stress. Abscisic acid (ABA) plays an important role in plant growth and development and stress responses. However, the role of ABA on high-temperature stress tolerance in S. japonica still needs to be further elucidated. Here, we found that exogenous ABA significantly alleviated disease and decay in S. japonica under high-temperature stress while also increasing the relative growth rate, chlorophyll fluorescence parameters, photosynthetic pigment, and osmotic substance content. Meanwhile, exogenous ABA enhanced the activity of protective enzymes and up-regulated the transcript levels of antioxidant-related genes, thereby reducing oxidative damage. Most importantly, we observed a significant increase in ABA content and the transcript levels of key genes involved in ABA synthesis in S. japonica under high-temperature stress, which were further amplified by the addition of exogenous ABA. In conclusion, this study provides evidence that ABA can moderate the detrimental effects of high-temperature stress and provides a theoretical basis for the screening of S. japonica germplasm resources and the cultivation of new stress-resistant varieties.
Peroxymonosulfate Activation by Rice-Husk-Derived Biochar (RBC) for the Degradation of Sulfamethoxazole: The Key Role of Hydroxyl Groups
Authors: Liu Tong , Li Chen-Xuan , Chen Xing , Chen Yihan , Cui Kangping , Wei Qiang
Published: October 2024

In this work, rice-husk-derived biochar (RBC) was synthesized by using simple one-step pyrolysis strategies and served as catalysts to activate peroxymonosulfate (PMS) for degrading sulfamethoxazole (SMX). When the annealing temperature (T) = 800 °C, RBC800 exhibits the typical hardwood structure with several micropores and mesoporous. Furthermore, RBC800 obtains more defect sites than RBC600, RBC700, and RBC900. In the RBC800/PMS system, the removal rate of the SMX reached 92.0% under optimal conditions. The kinetic reaction rate constant (kobs) of the RBC800/PMS system was 0.009 min−1, which was about 1.50, 1.28, and 4.50 times that of the RBC600/PMS (kobs = 0.006 min−1), RBC700/PMS (kobs = 0.007 min−1), and RBC900/PMS (kobs = 0.002 min−1) systems, respectively. In the RBC800/PMS system, sulfate radical (SO4•−) is the main active species. Compared with other active sites, the hydroxyl group (C-OH) on the surface of RBC800 interacts more strongly with PMS, which is more likely to promote the stretching of the O-O bond of the PMS, thus breaking into the activated state and significantly reducing the activation energy required for reaction. The degradation intermediates of SMX were speculated, and the toxicity analysis was conducted. Generally, this work reveals in depth the interaction between reactive sites of biochar-based catalysts and PMS at the molecular level.
Human Salivary Microbiota Diversity According to Ethnicity, Sex, TRPV1 Variants and Sensitivity to Capsaicin
Authors: Vinerbi Elena , Morini Gabriella , Picozzi Claudia , Tofanelli Sergio
Published: October 2024

The salivary microbiota of Italian and sub-Saharan African individuals was investigated using Nanopore sequencing technology (ONT: Oxford Nanopore Technologies). We detected variations in community composition in relation to endogenous (ethnicity, sex, and diplotypic variants of the TRPV1 gene) and exogenous (sensitivity to capsaicin) factors. The results showed that Prevotella, Haemophilus, Neisseria, Streptococcus, Veillonella, and Rothia are the most abundant genera, in accordance with the literature. However, alpha diversity and frequency spectra differed significantly between DNA pools. The microbiota in African, male TRPV1 bb/ab diplotype and capsaicin low-sensitive DNA pools was more diverse than Italian, female TRPV1 aa diplotype and capsaicin high-sensitive DNA pools. Relative abundance differed at the phylum, genus, and species level.
The Deposition of Hydroxyapatite Particles Within an Organic Matrix on the Surface of Poly(lactic acid)
Authors: Dopierała Katarzyna , Krok Emilia , Stachowska Ewa , Nowak-Grzebyta Jagoda , Walczak Krzysztof , Andrzejewski Jacek , Prochaska Krystyna
Published: October 2024

Hydroxyapatite (HAP) is a well-established material in biomedical applications, especially for bone tissue regeneration, dental implants, and drug delivery systems. Recent research emphasizes enhancing the biocompatibility and osteoconductivity of orthopedic implants using HAP. This study explores the potential of combining HAP with a lipid matrix to improve the surface properties and biocompatibility of poly(lactic acid) (PLA)-based, 3D-printed, resorbable bone implants. We utilized the Langmuir–Blodgett method to deposit HAP within a dihexadecyl phosphate (DHP) matrix onto PLA substrates. This study demonstrates that DHP and HAP form stable monolayers at the air/water interface with HAP particles distributed within a homogeneous lipid matrix. The presence of HAP and the resulting changes in surface free energy (SFE) are hypothesized to enhance the biocompatibility of PLA implants. Our findings indicate that films composed of DHP + HAP 5:1 are particularly effective in altering PLA surface characteristics, potentially improving osteointegration, and reducing microbial adherence. Overall, this work highlights that surface modification of PLA with HAP and lipid matrices is the first step towards new, promising, and cost-effective strategies for developing advanced biomaterials for bone regeneration.
Recent Advances in Artificial Intelligence to Improve Immunotherapy and the Use of Digital Twins to Identify Prognosis of Patients with Solid Tumors
Authors: D’Orsi Laura , Capasso Biagio , Lamacchia Giuseppe , Pizzichini Paolo , Ferranti Sergio , Liverani Andrea , Fontana Costantino , Panunzi Simona , De Gaetano Andrea , Lo Presti Elena
Published: October 2024

To date, the public health system has been impacted by the increasing costs of many diagnostic and therapeutic pathways due to limited resources. At the same time, we are constantly seeking to improve these paths through approaches aimed at personalized medicine. To achieve the required levels of diagnostic and therapeutic precision, it is necessary to integrate data from different sources and simulation platforms. Today, artificial intelligence (AI), machine learning (ML), and predictive computer models are more efficient at guiding decisions regarding better therapies and medical procedures. The evolution of these multiparametric and multimodal systems has led to the creation of digital twins (DTs). The goal of our review is to summarize AI applications in discovering new immunotherapies and developing predictive models for more precise immunotherapeutic decision-making. The findings from this literature review highlight that DTs, particularly predictive mathematical models, will be pivotal in advancing healthcare outcomes. Over time, DTs will indeed bring the benefits of diagnostic precision and personalized treatment to a broader spectrum of patients.
Special Issue: “Gut Microbiota and Nutrition in Human Health”
Authors: Park Sunmin
Published: October 2024

The microbiome is a singular term for a vast array of life forms that live symbiotically within the bodies of human and animal hosts, forming commensal, parasitic, or mutualistic relationships [...]
Expression of Reversion-Inducing Cysteine-Rich Protein with Kazal Motifs (RECK) Gene and Its Regulation by miR200b in Ovarian Endometriosis
Authors: Gozdz Agata , Maksym Radosław B. , Ścieżyńska Aneta , Götte Martin , Kieda Claudine , Włodarski Paweł K. , Malejczyk Jacek
Published: October 2024

Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient’s fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with RECK mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify RECK as a direct target of miR200b. The described effect of miR200b on RECK, together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis.
Occludin Is Essential to Maintain Normal Alveolar Barrier Integrity and Its Protective Role During ARDS Progression
Authors: Lin Xin , Bai Haiqing , Barravecchia Michael , Norman Rosemary , Schiralli Lester Gillian M. , Kottmann R. Matthew , Leonard Antony , Rahman Arshad , Young Jennifer L. , Dean David A.
Published: October 2024

Acute respiratory distress syndrome (ARDS) is a severe lung condition without targeted therapy that is characterized by the disruption of epithelial and endothelial barriers. The role of the tight junction protein occludin in the pathogenesis of this disease is unknown, although it has previously been deemed redundant in some tissues. The aim of the present study is to determine whether occludin is required for lung function by controlling alveolar barrier integrity in mouse models. Immunofluorescence staining of lungs from ARDS patients revealed a significant decrease in occludin expression compared to controls. Gene delivery of shRNA against occludin in the mouse lung reduced occludin levels and induced lung injury, as assessed by wet-to-dry-ratio, histology, and cellularity and protein content of bronchial alveolar lavage fluid. Conversely, gene delivery of an occludin-expressing plasmid increased occludin expression and dampened endotoxin-induced lung injury. In primary rat alveolar epithelial cells, occludin levels were positively correlated with barrier integrity, as well as membrane localization of claudin-18, another tight junction protein. Collectively, our data demonstrate that occludin plays a significant role in alveolar barrier function and that targeting occludin may provide a new therapeutic approach for ARDS.
Pathological Alterations in Heart Mitochondria in a Rat Model of Isoprenaline-Induced Myocardial Injury and Their Correction with Water-Soluble Taxifolin
Authors: Belosludtseva Natalia V. , Uryupina Tatyana A. , Pavlik Lyubov L. , Mikheeva Irina B. , Talanov Eugeny Yu. , Venediktova Natalya I. , Serov Dmitriy A. , Stepanov Mikhail R. , Ananyan Mikhail A. , Mironova Galina D.
Published: October 2024

Mitochondrial damage and associated oxidative stress are considered to be major contributory factors in cardiac pathology. One of the most potent naturally occurring antioxidants is taxifolin, especially in its water-soluble form. Herein, the effect of a 14-day course of the peroral application of the water-soluble taxifolin (aqTAX, 15 mg/kg of body weight) on the progression of ultrastructural and functional disorders in mitochondria and the heart’s electrical activity in a rat model of myocardial injury induced with isoprenaline (ISO, 150 mg/kg/day for two consecutive days, subcut) was studied. The delayed ISO-induced myocardial damage was accompanied by an increase in the duration of RR and QT intervals, and long-term application of aqTAX partially restored the disturbed intraventricular conduction. It was shown that the injections of ISO lead to profound ultrastructural alterations of myofibrils and mitochondria in cardiomyocytes in the left ventricle myocardium, including the impairment of the ordered arrangement of mitochondria between myofibrils as well as a decrease in the size and the number of these organelles per unit area. In addition, a reduction in the protein level of the subunits of the respiratory chain complexes I-V and the activity of the antioxidant enzymes catalase, glutathione peroxidase, and Mn-SOD in mitochondria was observed. The application of aqTAX caused an increase in the efficiency of oxidation phosphorylation and a partial restoration of the morphometric parameters of mitochondria in the heart tissue of animals with the experimental pathology. These beneficial effects of aqTAX are associated with the inhibition of lipid peroxidation and the normalization of the enzymatic activities of glutathione peroxidase and Mn-SOD in rat cardiac mitochondria, which may reduce the oxidative damage to the organelles. Taken together, these data allow one to consider this compound as a promising cardioprotector in the complex therapy of heart failure.
Impact of Nordihydroguaiaretic Acid on Proliferation, Energy Metabolism, and Chemosensitization in Non-Small-Cell Lung Cancer (NSCLC) Cell Lines
Authors: Chipón Carina , Riffo Paula , Ojeda Loreto , Salas Mónica , Burgos Rafael A. , Ehrenfeld Pamela , López-Muñoz Rodrigo , Zambrano Angara
Published: October 2024

Lung cancer (LC) is the leading cause of cancer death worldwide. LC can be classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), with the last subtype accounting for approximately 85% of all diagnosed lung cancer cases. Despite the existence of different types of treatment for this disease, the development of resistance to therapies and tumor recurrence in patients have maintained the need to find new therapeutic options to combat this pathology, where natural products stand out as an attractive source for this search. Nordihydroguaiaretic acid (NDGA) is the main metabolite extracted from the Larrea tridentata plant and has been shown to have different biological activities, including anticancer activity. In this study, H1975, H1299, and A549 cell lines were treated with NDGA, and its effect on cell viability, proliferation, and metabolism was evaluated using a resazurin reduction assay, incorporation of BrdU, and ki-67 gene expression and glucose uptake measurement, respectively. In addition, the combination of NDGA with clinical chemotherapeutics was investigated using an MTT assay and Combenefit software (version 2.02). The results showed that NDGA decreases the viability and proliferation of NSCLC cells and differentially modulates the expression of genes associated with different metabolic pathways. For example, the LDH gene expression decreased in all cell lines analyzed. However, GLUT3 gene expression increased after 24 h of treatment. The expression of the HIF-1 gene decreased early in the H1299 and A549 cell lines. In addition, the combination of NDGA with three chemotherapeutics (carboplatin, gemcitabine, and taxol) shows a synergic pattern in the decrease of cell viability on the H1299 cell line. In summary, this research provides new evidence about the role of NDGA in lung cancer. Interestingly, using NDGA to enhance the anticancer activity of antitumoral drugs could be an improved therapeutic resource against lung cancer.
Dopamine in Sports: A Narrative Review on the Genetic and Epigenetic Factors Shaping Personality and Athletic Performance
Authors: Humińska-Lisowska Kinga
Published: October 2024

This narrative review examines the relationship between dopamine-related genetic polymorphisms, personality traits, and athletic success. Advances in sports genetics have identified specific single nucleotide polymorphisms (SNPs) in dopamine-related genes linked to personality traits crucial for athletic performance, such as motivation, cognitive function, and emotional resilience. This review clarifies how genetic variations can influence athletic predisposition through dopaminergic pathways and environmental interactions. Key findings reveal associations between specific SNPs and enhanced performance in various sports. For example, polymorphisms such as COMT Val158Met rs4680 and BDNF Val66Met rs6265 are associated with traits that could benefit performance, such as increased focus, stress resilience and conscientiousness, especially in martial arts. DRD3 rs167771 is associated with higher agreeableness, benefiting teamwork in sports like football. This synthesis underscores the multidimensional role of genetics in shaping athletic ability and advocates for integrating genetic profiling into personalized training to optimize performance and well-being. However, research gaps remain, including the need for standardized training protocols and exploring gene–environment interactions in diverse populations. Future studies should focus on how genetic and epigenetic factors can inform tailored interventions to enhance both physical and psychological aspects of athletic performance. By bridging genetics, personality psychology, and exercise science, this review paves the way for innovative training and performance optimization strategies.
Pan-Chloroplast Genomes Reveal the Accession-Specific Marker for Gastrodia elata f. glauca
Authors: Li Jiaxue , Pan Daichuan , Wang Junfei , Zeng Xu , Guo Shunxing
Published: October 2024

Gastrodia elata rhizomes have been applied as traditional medicinal materials for thousands of years. In China, G. elata f. elata (red flower and stem, Ge), G. elata f. viridis (green, Gv), and G. elata f. glauca (black, Gg) represent the primary cultivars in artificial cultivation. Although the annual output of G. elata amounts to 150,000 tons, only 20% is Gg. The long production period, low yield, and high quality of Gg led to its extremely high market prices. However, an effective method to identify this crude drug based solely on its morphological or chemical characteristics is lacking. In this study, the complete chloroplast genomes of three G. elata variants were sequenced using the Illumina HiSeq 2500 platform. Another 21 chloroplast genomes from Gastrodia species, which have published in previous reports, were combined and analyzed together. Our results showed that larger genomic sizes, fewer long tandem repeats, and more simple sequence repeats were the major features of the Gg chloroplast genomes. Phylogenetic analysis showed that the Gg samples were separately clustered in a subclade. Moreover, an accession-specific marker was successfully developed and validated for distinguishing additional rhizome samples. Our study provides investigations of the taxonomic relationships of Gastrodia species. The molecular marker will be useful for differentiating Gastrodia products on the market.
ALKBH5 Reduces BMP15 mRNA Stability and Regulates Bovine Puberty Initiation Through an m6A-Dependent Pathway
Authors: Yang Xiaorui , Wang Ziming , Chen Yue , Ding He , Fang Yi , Ma Xin , Liu Hongyu , Guo Jing , Zhao Jing , Wang Jun , Lu Wenfa
Published: October 2024

The timing of puberty significantly influences subsequent reproductive performance in cattle. N6-methyladenosine (m6A) is a key epigenetic modification involved in the regulation of pubertal onset. However, limited research has investigated alterations in m6A methylation within the hypothalamic–pituitary–ovarian (HPO) axis during the onset of puberty. In this study, combined analysis of methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-seq) is used to describe the overall modification pattern of m6A in the HPO axis, while GSEA, KEGG, and GO analyses are used to describe the enrichment pathways of differentially expressed genes and differentially methylated genes. The m6A modifications of the differential genes KL, IGSF10, PAPPA2, and BMP15 and the pathways of cell adhesion molecules (CAMs), TGF-β, cell cycle, and steroid hormone synthesis may play roles in regulating the function of the HPO axis tissue during pubertal transition. Notably, BMP15′s m6A modification depends on the action of the demethylase ALKBH5, which is recognized by the reader protein YTHDF2, promoting bovine granulosa cell proliferation, steroid production, and estrogen secretion. This study reveals for the first time the modification mechanism of BMP15 m6A during the initiation of bovine puberty, which will provide useful information for improving the reproductive efficiency of Chinese beef cattle.
Myeloproliferative Neoplasm-like Mutations of Calreticulin Induce Phenotypes Associated with Calreticulin Dysfunction in C. elegans
Authors: Guijarro-Hernández Ana , Hurtado Cristina , Urizar-Compains Estibaliz , Ezcurra Begoña , Galiana-Sáenz Alberto , Baquero Enrique , Cabello Juan , Vizmanos José Luis
Published: October 2024

In previous research, we created a C. elegans model with homozygous mutations in calreticulin similar to those found in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), two myeloproliferative neoplasms (MPNs). This model, lacking JAK orthologs, enabled us to examine the transcriptomic effects caused by mutant calreticulin without the influence of JAK/STAT activation, the primary pathogenic mechanism associated with calreticulin mutations known to date. Most of the gene expression changes observed seemed to be due to a partial loss of protein function, with the alteration of the extracellular matrix being particularly notable. In this study, our aim was to determine whether this model exhibited any phenotype related to these transcriptomic alterations. The results demonstrate that these strains exhibit multiple phenotypes related to the alteration of the extracellular matrix, fat levels, and fertility, which could be a possible consequence of a partial loss of calreticulin function. These phenotypes resemble some of the clinical and molecular characteristics described in patients with MPNs, but they had never before been linked to a loss of protein function in humans. Thus, these results collectively suggest that CALR mutations could have significant effects on MPNs due to loss of protein function. Delving deeper into these effects to develop innovative therapies for these patients offers considerable potential and interest, given that targeted therapies for these patients have not yielded very promising results so far.
Post Mortem Molecular Biomarkers of Asphyxia: A Literature Review
Authors: Sacco Matteo Antonio , Aquila Isabella
Published: October 2024

Asphyxia is a critical condition characterized by inadequate oxygen supply to the body. Post mortem diagnostics of asphyxia present significant challenges in forensic pathology, particularly when there are equivocal signs during autopsy or uncertain circumstantial data. The identification of biochemical biomarkers that indicate asphyxia has emerged as a promising area of research, as these markers can provide vital insights into the physiological changes occurring at the cellular level during asphyxiation. We performed a review of the scientific literature on the search engines Pubmed and Scopus in order to assess the state of the art on this topic. The aim of this study is to analyze which are the most promising markers and methods in the post mortem diagnosis of asphyxia. The literature review highlighted the great potential that molecular investigations can have in the analysis of this type of death, especially considering that hypoxia determines strong biochemical alterations in response to cellular stress. These changes are marked by specific biochemical alterations, which can be detected through various advanced technologies and methodologies, including mass spectrometry, immunohistochemistry, and metabolomic profiling. The review evidenced a combination of markers that can be used for diagnostic purposes in various cases, including mechanical asphyxia, carbon monoxide (CO) poisoning, perinatal asphyxia, and drowning analysis. However, we highlight that, to date, there are still no standard protocols for forensic biochemistry in asphyxia. By scrutinizing the reliability of identified biomarkers and their potential to reshape forensic investigative practices, this research aims to elucidate the critical role that post mortem biochemical analysis can play in diagnosing asphyxia, ultimately contributing to a more nuanced understanding of death-related scenarios and the development of standardized protocols in forensic examinations.
The Mechanism of the Nucleus Accumbens–Ventral Pallidum Pathway Mediated by Drug Withdrawal-Induced High-Seeking Motivation in Cocaine Addiction
Authors: Tan Jiayan , Meng Yiming , Du Wenjie , Jin Lingtong , Liang Jing , Shen Fang
Published: October 2024

The reinforcement of drug-seeking motivation following drug withdrawal is recognized as a significant factor contributing to relapse. The ventral pallidum (VP) plays a crucial role in encoding and translating motivational aspects of reward. However, current research lacks a clear understanding of how the VP mediates drug-seeking motivation and the feedback modulation between the VP and the nucleus accumbens (NAc) following drug withdrawal. Therefore, utilizing a rat model of cocaine self-administration, we investigated the circuitry mechanisms underlying drug-seeking behavior post-drug withdrawal involving the NAc-VP pathway. Initially, we observed a significant enhancement in drug-seeking behavior 14 days after cocaine withdrawal. Subsequently, we identified the feedback mechanism through which the NAc-VP regulates this behavior. Immunofluorescence results indicated an increase in c-Fos expression levels in the ventral pallidum ventromedial (VPvm) and ventrolateral ventral pallidum (VPvl) following drug withdrawal. Calcium fiber photometry further elucidated that during the expression of high motivational drug-seeking behavior, there was a specific enhancement in VPvm neuronal activity, and retrograde tracing techniques suggested a weakened transmission function in the NAc-VPm pathway. Additionally, chemical genetic techniques demonstrated that inhibiting the activity of the NAc-VP pathway could increase the motivational level of drug-seeking behavior. These findings indicate that the reduced inhibitory function of the NAc-VP pathway following prolonged cocaine withdrawal forms the basis for heightened reactivity in VPvm neurons, thus regulating the expression of high motivational behavior triggered by drug-related cues. Our study results suggest that maintaining normal NAc-VP pathway functionality may decrease drug-seeking motivation post long-term drug withdrawal, offering new insights for interventions targeting relapse.
Amifostine and Melatonin Prevent Acute Salivary Gland Dysfunction 10 Days After Radiation Through Anti-Ferroptosis and Anti-Ferritinophagy Effects
Authors: Kim Ji-Min , Kim Dong-Hyun , Kim Won-Taek , Shin Sung-Chan , Cheon Yong-il , Park Gi-Cheol , Lee Hyoun-Wook , Lee Byung-Joo
Published: October 2024

Irradiation of the head and neck inevitably leads to decreased salivary gland function. It is postulated that radiation generates excessive reactive oxygen species (ROS) and reduces salivary gland function by ferroptosis, a new cell death mechanism; however, research in this area is currently lacking. In this study, we investigated the effects of amifostine and melatonin on acute salivary gland dysfunction and ferroptosis. Thirty-two Sprague Dawley rats were divided into four groups: control, radiation, radiation + amifostine, and radiation + melatonin. ROS; iron levels; glutathione peroxidase 4; 4-hydroxynonenal; various cytokines; and fibrosis and salivary gland functional markers were measured. Western blotting was used to detect ferritinophagy. After irradiation, we observed an increase in iron levels, ROS generation, oxidized glutathione, lipid peroxidation, fibrosis, and salivary gland dysfunction and a decrease in glutathione peroxidase 4 in salivary gland tissue. Treatment with amifostine or melatonin decreased the ferroptotic response and improved acute salivary gland function 10 days after radiation. The increase in iron levels associated with ferritinophagy was reduced after treatment with amifostine or melatonin. Our results demonstrate that radiation-induced acute salivary gland dysfunction is associated with ferroptosis and ferritinophagy. Amifostine and melatonin inhibit radiation-induced ferroptosis and ferritinophagy in the salivary gland and prevent acute salivary gland dysfunction 10 days after radiation.
Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters
Authors: Petrillo Sara , Perna Alessia , Quatrana Andrea , Silvestri Gabriella , Bertini Enrico , Piemonte Fiorella , Santoro Massimo
Published: October 2024

Friedreich ataxia (FRDA) is the most common inherited ataxia, primarily impacting the nervous system and the heart. It is characterized by GAA repeat expansion in the FXN gene, leading to reduced mitochondrial frataxin levels. Previously, we described a family displaying two expanded GAA alleles, not only in the proband affected by late-onset FRDA but also in the younger asymptomatic sister. The molecular characterization of the expanded repeats showed that the affected sister carried two canonical uninterrupted GAA expended repeats, whereas the asymptomatic sister had a compound heterozygous for a canonical GAA repeat and an expanded GAAGGA motif. Therefore, we decided to perform RNA sequencing (RNA-seq) on fibroblasts from both sisters in order to understand whether some genes and/or pathways might be differently involved in the occurrence of FRDA clinical manifestation. The transcriptomic analysis revealed 398 differentially expressed genes. Notably, TLR4, IL20RB, and SLITRK5 were up-regulated, while TCF21 and GRIN2A were down-regulated, as validated by qRT-PCR. Gene ontology (GO) enrichment and network analysis highlighted significant involvement in immune response and neuronal functions. Our results, in particular, suggest that TLR4 may contribute to inflammation in FRDA, while IL20RB, SLITRK5, TCF21, and GRIN2A dysregulation may play roles in the disease pathogenesis. This study introduces new perspectives on the inflammatory and developmental aspects in FRDA, offering potential targets for therapeutic intervention.
Amelioration of Systemic Amyloidosis by Blocking IL-17A and Not by IL-17F, and Arteriosclerosis by Blocking Both IL-17A and IL-17F in an Inflammatory Skin Mouse Model
Authors: Nakanishi Takehisa , Iida Shohei , Ichishi Masako , Kondo Makoto , Nishimura Mai , Ichikawa Ayaka , Matsushima Yoshiaki , Iwakura Yoichiro , Watanabe Masatoshi , Yamanaka Keiichi
Published: October 2024

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients’ quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine’s impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ.
Transcriptome Sequencing-Based Screening of Key Melatonin-Related Genes in Ischemic Stroke
Authors: Li Tianzhi , Li Hongyan , Zhang Sijie , Wang Yihan , He Jinshan , Kang Jingsong
Published: October 2024

Ischemic stroke (IS) is a complex syndrome of neurological deficits due to stenosis or occlusion of the carotid and vertebral arteries for which there is still no effective treatment. Melatonin, a hormone secreted by the pineal gland, has multiple biological effects, such as antioxidant and anti-inflammatory properties, circadian rhythm regulation, and tissue regeneration, demonstrating potential applications in the treatment of IS. The aim of this study was to investigate key melatonin-regulated genes associated with IS using transcriptome sequencing and bioinformatics analyses and to explore their potential mechanisms of action in the disease process. We obtained gene expression data related to ischemic stroke (IS) from the Gene Expression Omnibus (GEO) database and identified candidate genes using machine learning algorithms. We then assessed the predictive power of these genes using PPI network analysis and diagnostic models. Finally, a series of enrichment analyses identified four key genes: ADM, PTGS2, MMP9, and VCAN. In addition, we determined the mRNA levels of these four key genes in an IS rat model using qPCR and found that all of these genes were significantly upregulated in the IS model compared to the control group, which is consistent with the results of previous analyses. Meanwhile, these genes have biological functions such as regulating vascular tone, participating in the inflammatory response, influencing tissue remodeling, and regulating cell adhesion and proliferation, playing key roles in the pathogenesis of IS. Therefore, we suggest that these four key genes may serve as prospective biomarkers for IS and help predict the risk of developing IS. In conclusion, this study elucidates for the first time the potential role of melatonin in the pathogenesis of IS and lays the foundation for in-depth studies on the functions of these key genes in the pathophysiology of IS and their potential applications in clinical diagnosis and treatment.
Optimisation, Synthesis, and Characterisation of ZnO Nanoparticles Using Leonotis ocymifolia (L. ocymifolia) Leaf Extracts for Antibacterial and Photodegradation Applications
Authors: Mutukwa Dorcas , Taziwa Raymond Tichaona , Tichapondwa Shepherd Masimba , Khotseng Lindiwe
Published: October 2024

This work presents a green synthesis route, which utilises extracts from an indigenous plant in South Africa, eastern and southern Africa that is understudied and underutilised, for preparing zinc oxide nanoparticles (ZnO NPs). This study involved optimisation of the green synthesis method using Leonotis ocymifolia (L.O.) extracts and performing comparative studies on the effects of using different zinc (Zn) salt precursors; zinc sulphate heptahydrate (Z001) and zinc acetate dihydrate (Z002) to synthesise the ZnO NPs. The comparative studies also compared the L.O-mediated ZnO NPs and chemical-mediated ZnO NPs (Z003). The as-prepared ZnO NPs were tested for their effectiveness in the photodegradation of methylene blue (MB) dye. Furthermore, antibacterial studies were conducted using the agar well diffusion method on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. The structural, morphological, and optical characteristics of the synthesised ZnO NPs were analysed using XRD, FTIR, SEM, EDS, DRS, and BET techniques. The XRD results indicated that the L.O-mediated ZnO NPs had smaller crystallite sizes (18.24–19.32 nm) than their chemically synthesised counterparts (21.50 nm). FTIR confirmed the presence of biomolecules on the surface of the L.O-mediated NPs, and DRS analysis revealed bandgap energies between 3.07 and 3.18 eV. The EDS results confirmed the chemical composition of the synthesised ZnO NPs, which were made up of Zn and O atoms. Photocatalytic studies demonstrated that the L.O-mediated ZnO NPs (Z001) exhibited a superior degradation efficiency of the MB dye (89.81%) compared to chemically synthesised ZnO NPs (56.13%) under ultraviolet (UV) light for 240 min. Antibacterial tests showed that L.O-mediated ZnO NPs were more effective against S. aureus than E. coli. The enhanced photocatalytic and antibacterial properties of L.O-mediated ZnO NPs highlight their potential for environmental remediation and antimicrobial applications, thus supporting sustainable development goals.
Organic-Inorganic Biocompatible Coatings for Temporary and Permanent Metal Implants
Authors: Parfenova Lyudmila V. , Galimshina Zulfiya R. , Parfenov Evgeny V.
Published: October 2024

The general trend of increasing life expectancy will consistently drive the demand for orthopedic prostheses. In addition to the elderly, the younger population is also in urgent need of orthopedic devices, as bone fractures are a relatively common injury type; it is important to treat the patient quickly, painlessly, and eliminate further health complications. In the field of traumatology and orthopedics, metals and their alloys are currently the most commonly used materials. In this context, numerous scientists are engaged in the search for new implant materials and coatings. Among the various coating techniques, plasma electrolytic oxidation (PEO) (or micro-arc oxidation—MAO) occupy a distinct position. This method offers a cost-effective and environmentally friendly approach to modification of metal surfaces. PEO can effectively form porous, corrosion-resistant, and bioactive coatings on light alloys. The porous oxide surface structure welcomes organic molecules that can significantly enhance the corrosion resistance of the implant and improve the biological response of the body. The review considers the most crucial aspects of new combined PEO-organic coatings on metal implants, in terms of their potential for implantation, corrosion resistance, and biological activity in vitro and in vivo.
A Comprehensive Review of Thyroid Eye Disease Pathogenesis: From Immune Dysregulations to Novel Diagnostic and Therapeutic Approaches
Authors: Kulbay Merve , Tanya Stuti M. , Tuli Nicolas , Dahoud Jade , Dahoud Andrea , Alsaleh Fares , Arthurs Bryan , El-Hadad Christian
Published: October 2024

Thyroid eye disease is a complex inflammatory disorder of the orbit that has gained tremendous interest over the past years, and numerous scientific efforts have been deployed to elucidate its pathophysiology for novel drug development. Our manuscript will delve into the molecular dysregulations involved in the pathogenesis of thyroid eye disease that led to its clinical manifestations. Abnormalities within the apoptotic pathway, inflammatory cascade, and autoimmune regulatory systems will be covered. We will further discuss the challenges involved in its diagnosis and management and provide a summary of the current diagnostic tools (i.e., molecular biomarkers, diagnostic scores) from the perspective of clinicians. Finally, our comprehensive literature review will provide a thorough summary of most recent preclinical and clinical studies around the topic of thyroid eye disease, with an emphasis on the manuscripts published within the last five years. We believe our manuscript will bring novelty within the field by bridging the fundamental sciences with the clinical aspect of this disease. This review will be a great tool for clinicians in better understanding the pathogenesis of thyroid eye disease while providing an outlook on future perspectives (i.e., liquid biopsies, artificial intelligence).
Safety of Zein Nanoparticles on Human Innate Immunity and Inflammation
Authors: Corteggio Annunziata , Heinzl Tommaso , Boraschi Diana , Voci Silvia , Gagliardi Agnese , Cosco Donato , Italiani Paola
Published: October 2024

In recent years, natural polymers have attracted great interest for the development of release systems for vaccine formulations and drug delivery. Zein, a hydrophobic proline-rich protein mixture obtained from maize, is one of the most widely used polymers, very promising for applications in tissue engineering and the parenteral delivery of bioactive agents. Still, we have a limited understanding of the interaction between zein particles and the human immune system, in particular innate immunity/inflammation, which is the first line of defense of our body. Assessing the immune safety of nanoparticles is of central importance for ensuring that nano-formulations for medical use do not cause adverse effects on human health. Here, we evaluated the capacity of zein nanoparticles to induce/modulate the innate/inflammatory response, the development of innate memory, and the macrophage polarization by using reliable in vitro systems based on human primary monocytes and monocyte-derived macrophages. We observed that zein nanoparticles do not influence any of these aspects of the innate immune/inflammatory response, suggesting its safety and its potential efficiency as a nanocarrier for drug or antigen delivery.
A New Easy-to-Perform Flow Cytometry Assay for Determining Bacterial- and Viral-Infection-Induced Polymorphonuclear Neutrophil and Monocyte Membrane Marker Modulation in Febrile Patients
Authors: La Sorda Marilena , De Lorenzis Desy , Battaglia Alessandra , Fiori Barbara , Graffeo Rosalia , Santangelo Rosaria , D’Inzeo Tiziana , De Pascale Gennaro , Schinzari Giovanni , Pedone Romina Rose , Rossi Ernesto , Sanguinetti Maurizio , Sali Michela , Fattorossi Andrea
Published: October 2024

We developed a flow cytometry (FC) assay enabling the rapid and accurate identification of bacterial and viral infections using whole blood samples. The streamlined flow cytometry assay is designed to be user-friendly, making it accessible even for operators with limited experience in FC techniques. The key components of the assay focus on the expression levels of specific surface markers—CD64 on polymorphonuclear neutrophils (PMN) as a marker for bacterial infection, and CD169 on monocytes (MO) for viral infection. The strong performance indicated by an area under the receiver operating characteristic (ROC) curve of 0.94 for both PMN CD64 positive predictive value (PPV) 97.96% and negative predictive value (NPV) 76.67%, and MO CD169 PPV 82.6% and NPV 86.9%, highlight the assay’s robustness in differentiating between bacterial and viral infections accurately. The FC assay includes the assessment of immune system status through HLA-DR and IL-1R2 modulation in MO, providing a useful insight into the patients’ immune response. The significant increase in the frequency of MO exhibiting reduced HLA-DR expression and elevated IL-1R2 levels in infected patients (compared to healthy controls) underscores the potential of these markers as indicators of infection severity. Although the overall correlation between HLA-DR and IL-1R2 expression levels was not significant across all patients, there was a trend in patients with more severe disease suggesting that these markers may have the potential to assist in stratifying patient risk. The present FC assay has the potential to become routine in the clinical microbiology laboratory community and to be helpful in guiding clinical decision making.
ATPase Valosin-Containing Protein (VCP) Is Involved During the Replication and Egress of Sialodacryoadenitis Virus (SDAV) in Neurons
Authors: Bartak Michalina , Krahel Weronika D. , Chodkowski Marcin , Grel Hubert , Walczak Jarosław , Pallepati Adithya , Komorowski Michał , Cymerys Joanna
Published: October 2024

Sialodacryoadenitis virus (SDAV) has been identified as the etiological agent responsible for the respiratory system and salivary gland infections in rats. The existing literature on SDAV infections is insufficient to address the topic adequately, particularly in relation to the central nervous system. In order to ascertain how SDAV gains access to neuronal cells and subsequently exits, our attention was focused on the small molecule valosin-containing protein (VCP), which is an ATPase. VCP is acknowledged for its function in the ubiquitin-mediated proteasomal degradation of proteins, including those of viral origin. To ascertain the potential influence of VCP on SDAV replication and egress, high-content screening was employed to determine the viral titer and protein content. Western blot analysis was employed to ascertain the relative expression of VCP. Real-time imaging of SDAV-infected cells and confocal imaging for qualitative morphological analysis were conducted. The Eeyarestatin I (EerI) inhibitor was employed to disrupt VCP involvement in the endoplasmic reticulum-associated protein degradation pathway (ERAD) in both pre- and post-incubation systems, with concentrations of 5 μM/mL and 25 μM/mL, respectively. We demonstrated for the first time that SDAV productively replicates in cultured primary neurons. VCP expression is markedly elevated during SDAV infection. The application of 5 μM/mL EerI in the post-treatment system yielded a statistically significant inhibition of the SDAV yield. It is likely that this modulates the efficacy of virion assembly by arresting viral proteins in the submembrane area.