bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Non-Pharmacological Treatments for Fibromyalgia Functional and Well-Being Status: The Role of Literacy
Authors: Amzolini Anca Maria , Neagoe Carmen Daniela , Avramescu Taina Elena , Mitrea Adina , Traistaru Rodica , Micu Elena Simona , Ianoşi Simona Laura , Matei Daniela
Published: September 2024

Background/Objectives: Fibromyalgia (FM) affects up to 5% of the global population and is a leading cause of significant social and economic consequences. Higher health literacy leads to better understanding of treatment plans, improved self-care, and adherence to recommendations, enhancing overall quality of life. This study aims to determine whether different aspects of the disease are influenced by patients’ education level and literacy when applying the same therapy and to assess how patients’ perceptions of therapy outcomes vary over time based on their educational level. Methods: This study involved 140 fibromyalgia (FM) patients diagnosed using the 2016 ACR criteria, with 128 completing the study. Participants attended three visits over 28 weeks and were stratified into four groups based on educational level: Group 1—secondary school or less; Group 2—high school graduates; Group 3—college graduates; Group 4—university graduates. Patients were assigned to groups (n = 32, 32, 30, and 34, respectively) after the initial evaluation (T0). The treatment was assessed (T1) and followed up three months later (T2) to evaluate changes in functional status and quality of life. All patients underwent the same rehabilitation program, cognitive therapy, and kinesiotherapy. Results: Significant differences in disease impact on the patient’s life (FIQ total score) were observed between groups from the initial evaluation (p = 0.000). The overall FIQ score was notably affected by non-pharmacological therapy in patients with higher education. These differences continued to be significant even three months after the treatment ended (p = 0.000). Functional limitations were evident from the start (p = 0.000) and improved significantly post-treatment in patients with higher education (p = 0.000). However, subjective evaluations of disease impact (assessed by the first item of FIQ) did not consistently align with objective findings (hand grip strength). Functional limitations did not significantly differ in subjective evaluations (F1Q1) across educational levels (p = 0.045), and inverse correlations were noted between functional status and SF-12 well-being components. Conclusions: This study underscores that higher education enhances fibromyalgia management and functional outcomes, particularly when combined with non-pharmacological therapies. However, subjective perceptions may not always align with objective improvements, indicating that factors beyond education, such as personal and external influences, also impact disease management. Thus, improving health literacy through educational interventions could further benefit FM patients’ quality of life.
ChatGPT as a Digital Assistant for Archaeology: Insights from the Smart Anomaly Detection Assistant Development
Authors: Ciccone Gabriele
Published: September 2024

The introduction of generative AI has the potential to radically transform various fields of research, including archaeology. This study explores the potential of generative AI, specifically ChatGPT, in developing a computer application for analyzing aerial and satellite images to detect archaeological anomalies. The main focus was not on developing the application itself but on evaluating ChatGPT’s effectiveness as an IT assistant for humanistic researchers. Starting with a simple prompt to analyze a multispectral orthophoto, the application was developed through successive iterations, improved through continuous interactions with ChatGPT. Various technical and methodological challenges were addressed, leading to the creation of a functional application with multiple features, including various analysis methods and tools. This process demonstrated how the use of large language models (LLMs) can break down the barriers between humanities and computer science disciplines, enabling researchers without programming skills to develop complex applications in a short time.
Effect of Pre-Harvest Intermittent UV-B Exposure on Growth and Secondary Metabolites in Achyranthes japonica Nakai Microgreens in a Vertical Farm
Authors: Kim Ye Lin , Yeom Moon-Sun , Sim Han-Sol , Lee Ga Oun , Kang In-Je , Yang Gyu-Sik , Yun Jae Gil , Son Ki-Ho
Published: September 2024

Achyranthes japonica Nakai (AJN) is a medicinal plant known to be beneficial for the joints. Since it takes at least two years from sowing to harvesting in an open field, new AJN cultivation strategies are needed to shorten the production period and improve quality. In this study, high-quality AJN is produced as microgreens in a vertical farm using a commercial ginseng soil mix (Myeongpum-Insamsangto, Shinsung Mineral Co., Ltd., Goesan, Republic of Korea) and controlled environmental conditions. The cultivation conditions included a temperature of 23 ± 2 °C, relative humidity of 50 ± 10%, and a photosynthetic photon flux density of 170 ± 15 µmol·m−2·s−1. Pre-harvest intermittent UV-B exposure, with an intensity of 1.0 ± 0.3 W/m−2, was applied for one day before harvest to evaluate its effects, using controlled environmental conditions in the vertical farm. Ultraviolet-B (UV-B) irradiation increases secondary metabolite levels in plants; however, the effect of UV-B on 20-hydroxyecdysone (20E), an indicator of AJN, is unclear. Therefore, we aimed to investigate whether UV-B treatment of AJN microgreens affected growth and secondary metabolites. The treatment group was set to 12 h of continuous UV-B treatment during the day, two 6 h UV-B treatments, and four 3 h UV-B treatments to confirm the effectiveness of regular and intermittent treatment and recovery. Short-term UV-B treatment before harvesting increased phenols, flavonoids, antioxidant capacity, and 20E levels without affecting AJN biomass. The intermittent 6 h UV-B irradiation with a 6 h recovery time stimulated 20E content by approximately 1.4 times compared to the control. These study findings indicate that short-term UV-B treatment before harvesting, an appropriate recovery time, and intermittent UV-B exposure are more effective at increasing 20E content than continuous treatment. This approach provides a promising strategy for improving the nutritional and health benefits of AJN microgreens in vertical farming systems.
Psychometric Properties of the PLAYself in a Cohort of Secondary School Student-Athletes
Authors: Lininger Monica R. , Root Hayley J.
Published: September 2024

Background: Physical literacy is the motivation, confidence, physical competence, knowledge, and understanding, enabling individuals to value and take responsibility for engagement in physical activities for life. While tools exist to measure physical literacy in most populations, the psychometric properties of the Physical Literacy Assessment for Youth (PLAY) tool in an older adolescent age group are currently unknown. The purpose of this work was to determine the psychometric properties of the PLAY tool, specifically the PLAYself, in an older adolescent age group (~14–18 years). Methods: One hundred and fifty-one secondary school in-season student-athletes completed the PLAYself, with construct validity assessed using an Exploratory Factor Analysis (EFA). Results: Results from the EFA yielded a 7-factor model across the three subsections (environment, physical literacy self-description, relative rankings of literacies) of the PLAYself, all with acceptable levels of internal consistency. Conclusions: The PLAYself produced acceptable estimates for construct validity and reliability, making it a useful tool for measuring physical literacy in secondary school student-athletes.
The Adoption of a “Diseased Identity” in Traditional 12-Step Groups: Exploring the Implications of These Processes for Individuals and Practitioners in Health and Social Care Services
Authors: McGovern William , Addison Michelle , McGovern Ruth
Published: September 2024

Self-help groups are increasingly utilised by communities of interest and shared experience, services, and government departments as platforms for supporting and improving health and social care outcomes for drug and alcohol users. Traditional 12-step self-help groups like Narcotics Anonymous and Alcoholics Anonymous (NA and AA) are worldwide organisations and each have their own programme of change, language, criteria for membership, processes for problem resolution, and self-transformation. Within these types of groups, members are openly encouraged to identify with and adopt an (diseased) identity that is consistently invoked to work on the self. In the self-help recovery literature, it is widely recognised that individuals can benefit by thinking about themselves as “diseased” and then acting and behaving in a manner which is congruent with their reframed “identity”. Less is known about the processes involved in this and social-, psychological-, and health-related implications for individuals in drug- and alcohol-specific self-help groups. A thematic analysis of data from (n-36) in-depth qualitative interviews with long-term (6 months–10 years) self-help users identified four themes associated with the adoption of a diseased identity and self-help group processes: (1) normalising the disease and illness; (2) identifying as diseased; (3) living as a diseased individual; and (4) one addict helping another addict. The results of this research should not be interpretated as a critique of the 12-step approach or groups. Instead, it should be recognised that whilst improvements to individual wellbeing are reported, identifying as diseased can exacerbate negative self-perceptions that individuals hold about themselves, their character, capabilities, and ability. Being diseased, accepting disease, and identifying as diseased also has the potential to inhibit their engagement with wider social networks and professional services outside of their own fellowship or group. We conclude this paper by exploring the implications of a “diseased identity” and self-help processes for individuals who access self-help groups, and health and social care practitioners who support self-help users as they engage with services and self-help groups.
Dietary Nutritional Supplements Are Associated with the Deterioration of Hepatic Fibrosis in Women and Individuals without Underlying Disease
Authors: Cha Minsu , Lee Sangheun , Han Kijun
Published: September 2024

Despite the growing societal interest in the health benefits of dietary nutritional supplements, their safety and efficacy remain unclear. We aimed to investigate the correlation between hepatic fibrosis and the consumption of dietary nutritional supplements. This study utilized data from the Korea National Health and Nutrition Examination Survey spanning the period from 2014 to 2022. Significant fibrosis was defined as a fibrosis index based on four factors (FIB-4) ≥1.45 and an aspartate aminotransferase-to-platelet ratio index (APRI) ≥0.30. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated. In a study involving 30,639 participants (supplement consumers [n = 17,772] and non-consumers [n = 12,867]), dietary nutritional supplement consumption was associated with alanine aminotransferase (ALT) elevation and increased hepatic fibrosis biomarkers (APRI and FIB-4). Dietary nutritional supplement consumption was independently linked to ALT elevation (AOR, 1.11; 95% CI, 1.04–1.18), FIB-4 (AOR, 1.07; 95% CI, 1.00–1.15), and APRI (AOR, 1.14; 95% CI, 1.07–1.21). This association was particularly significant in women and subgroups of people who were not diabetic or hypertriglyceridemic. In our comprehensive analysis, the consumption of dietary nutritional supplements was possibly associated with hepatic fibrosis, particularly in specific subgroups. Given the limitations of this study, these findings are not considered definitive conclusions; however, they serve as valuable preliminary data for future research.
Assessment of the Mental Health of Police Officers: A Systematic Review of Specific Instruments
Authors: Teles Davi Oliveira , Oliveira Raquel Alves de , Parnaíba Anna Luísa de Oliveira , Rios Mariana Araújo , Machado Melissa Bezerra , Aquino Priscila de Souza , Menezes Purdenciana Ribeiro de , Ribeiro Samila Gomes , Soares Paula Renata Amorim Lessa , Biazus Dalcin Camila , Pinheiro Ana Karina Bezerra
Published: September 2024

Objective: The objective was to identify validated instruments from the literature that assess the mental health of police officers. Methods: This is a systematic review of validated instruments used to assess the mental health of police officers. Searches were conducted in the MEDLINE, Web of Science, Scopus, Embase, CINAHL/EBSCO, and Virtual Health Library databases. This review follows the JBI Manual for Systematic Reviews and the PRISMA statement. The methodological quality of the articles and the risk of bias were assessed. Results: A total of 1530 studies were identified across the six databases, with 158 studies read in full by the authors after excluding duplicates and those that did not meet the inclusion criteria. The final 29 studies were analyzed for methodological quality and risk of bias using the AXIS and SFS-D tools. Conclusion: This review identified 27 self-administered validated instruments useful for assessing various mental health outcomes in police officers, with the most frequently used being the Police Stress Questionnaire. These findings may help guide security force administration, occupational health professionals, and mental health researchers in selecting and implementing psychometrically reliable instruments for screening the mental health of police officers.
The Challenges for EU User Testing Policies for Patient Information Leaflets
Authors: Pelizzari Nicola
Published: September 2024

Patient information leaflets (PILs) are essential tools in healthcare, providing crucial information about medication use. In the European Union, the European Medicines Agency (EMA) oversees the regulation and standardisation of PILs to ensure their readability and accessibility. However, challenges persist in ensuring these documents are comprehensible and user-friendly. This study employs a qualitative analytical approach, reviewing existing literature and regulatory documents to identify gaps in the EU user testing policies for PILs. It focuses on the diversity of participant samples, the independence of the testing process, and the robustness of user testing protocols. Findings indicate that current user testing practices often lack diversity and may be biased when pharmaceutical companies conduct their own tests. Additionally, there is a lack of user testing protocols for translated PILs, potentially compromising their accuracy and cultural relevance. To improve the efficacy of PILs, it is essential to include diverse and representative samples in user testing, mandate independent third-party evaluations, implement protocols for user testing on translated PILs, and ensure continuous updates to guidelines based on the latest best practices in health communication. These measures will enhance patient safety and understanding of medication information.
Life after Lockdown: An Exploratory Qualitative Study of Behaviors and Impacts of Avoiding COVID-19 in Individuals at High Risk of Severe COVID-19 and Their Caregivers
Authors: Maia Tiago , Yokota Renata , Arnetorp Sofie , Smith Joanne , Rae-Garwood Gail , Settergren Gabriella , Eckerd Marie , Williams Paul
Published: September 2024

This exploratory qualitative study involved semi-structured interviews with adults and caregivers of adults at high risk of severe COVID-19, addressing current COVID-19 avoidance and protective behaviors and how these behaviors impacted their lives. Results were interpreted in a separate think tank session. Insights were developed into a conceptual model of COVID-19 avoidance and protective behaviors and the associated impacts on health-related quality of life and overall functioning. Data were interpreted using a hybrid inductive and deductive thematic analysis. Twelve high-risk individuals and two caregivers were interviewed across four focus groups (April–July 2022). Major behavioral themes included physical distancing, physical and medical protection, quality of support services and networks, and information to make decisions. Major impacts included family, social, and emotional functioning; work and finances; and healthcare access. The final conceptual model comprised 13 behaviors to avoid COVID-19 categorized within four themes, and 13 impacts within five themes. Individuals at high risk of severe COVID-19 and their caregivers continue practicing COVID-19 avoidance behaviors post-lockdown and feel left behind by the general population. Our conceptual model may be used to inform health authorities and other governing bodies’ decisions in executing strategies aimed at improving these individuals’ lives.
SGIR-Tree: Integrating R-Tree Spatial Indexing as Subgraphs in Graph Database Management Systems
Authors: Kim Juyoung , Hong Seoyoung , Jeong Seungchan , Park Seula , Yu Kiyun
Published: September 2024

Efficient spatial query processing in Graph Database Management Systems (GDBMSs) has become increasingly important owing to the prevalence of spatial graph data. However, current GDBMSs lack effective spatial indexing, causing performance issues with complex spatial graph queries. This study proposes a spatial index called Subgraph Integrated R-Tree (SGIR-Tree) for efficient spatial query processing in GDBMSs. The SGIR-Tree integrates the hierarchical R-Tree structure with the graph structure of GDBMSs by converting R-Tree elements into graph components like nodes and edges. The Minimum Bounding Rectangle (MBR) information of spatial objects and R-Tree nodes is stored as properties of these graph elements, and the leaf nodes are directly connected to the spatial nodes. This approach combines the efficiency of spatial indexing with the flexibility of graph databases, thereby allowing spatial query results to be directly utilized in graph traversal. Experiments using OpenStreetMap datasets demonstrate that the SGIR-Tree outperforms the previous approaches in terms of query overhead and index overhead. The results are expected to improve spatial graph data processing in various fields, including location-based service and urban planning, significantly advancing spatial data management in GDBMSs.
Improved Road Extraction Models through Semi-Supervised Learning with ACCT
Authors: Yu Hao , Du Shihong , Tan Zhenshan , Zhang Xiuyuan , Li Zhijiang
Published: September 2024

Improving the performance and reducing the training cost of road extraction models in the absence of samples is important for updating road maps. Despite the success of recent road extraction models on standard datasets, they often fail to perform when applied to new datasets or real-world scenarios where labeled samples are not available. In this paper, our focus diverges from the typical quest to pinpoint the optimal road extraction model or evaluate generalization prowess across models. Instead, we propose a method called Asymmetric Consistent Co-Training (ACCT) to train existing road extraction models faster and make them perform better in new scenarios lacking samples. ACCT uses two models with different structures and a supervision module to enhance accuracy through mutual learning. Labeled and unlabeled images are processed by both models to generate road maps from different perspectives. The supervision module ensures consistency between predictions by computing losses based on labeling status. ACCT iteratively adjusts parameters using unlabeled data, improving generalization. Empirical evaluations show that ACCT improves IoU by 2.79% to 10.26% using only 1/8 of the labeled data compared to fully supervised methods. It also reduces parameters by over 49% compared to state-of-the-art semi-supervised methods while maintaining similar accuracy. These results highlight the potential of leveraging large amounts of unlabeled data to enhance road extraction models as data acquisition technology advances.
Systematic Modeling of Risk-Associated Copy Number Alterations in Cancer
Authors: Guardado Alejandra , Aguirre-Gamboa Raúl , Treviño Victor
Published: September 2024

The determination of the cancer prognosis is paramount for patients and medical personnel so that they can devise treatment strategies. Transcriptional-based signatures and subtypes derived from cancer biopsy material have been used in clinical practice for several cancer types to aid in setting the patient prognosis and forming treatment strategies. Other genomic features in cancer biopsies, such as copy number alterations (CNAs), have been underused in clinical practice, and yet they represent a complementary source of molecular information that can add detail to the prognosis, which is supported by recent work in breast, ovarian, and lung cancers. Here, through a systematic strategy, we explored the prognostic power of CNAs in 37 cancer types. In this analysis, we defined two modes of informative features, deep and soft, depending on the number of alleles gained or lost. These informative modes were grouped by amplifications or deletions to form four single-data prognostic models. Finally, the single-data models were summed or combined to generate four additional multidata prognostic models. First, we show that the modes of features are cancer-type dependent, where deep alterations generate better models. Nevertheless, some cancers require soft alterations to generate a feasible model due to the lack of significant deep alterations. Then, we show that the models generated by summing coefficients from amplifications and deletions appear to be more practical for many but not all cancer types. We show that the CNA-derived risk group is independent of other clinical factors. Furthermore, overall, we show that CNA-derived models can define clinically relevant risk groups in 33 of the 37 (90%) cancer types analyzed. Our study highlights the use of CNAs as biomarkers that are potentially clinically relevant to survival in cancer patients.
Effects of Alkalinity Stress on Amino Acid Metabolism Profiles and Oxidative-Stress-Mediated Apoptosis/Ferroptosis in Hybrid Sturgeon (Huso dauricus ♀ × Acipenser schrenckii ♂) Livers
Authors: Zhai Cunhua , Liu Xiafei , Li Yutao , Wang Ruoyu , Lv Weihua , Ma Bo , Cao Dingchen , Zhang Ying
Published: September 2024

Alkaline water is toxic to cultured aquatic animals that frequently live in pH-neutral freshwater. Overfishing and habitat destruction have contributed to the decline in the wild sturgeon population; consequently, the domestic hybrid sturgeon has become an increasingly important commercial species in China. Hybrid sturgeons are widely cultured in alkaline water, but little is known about the effects of alkalinity stress on hybrid sturgeon liver tissues. We exposed hybrid sturgeons to four alkaline concentrations (3.14 ± 0.02 mmol/L, 7.57 ± 0.08 mmol/L, 11.78 ± 0.24 mmol/L and 15.46 ± 0.48 mmol/L). Histopathology, biochemical index assessment, gene expression level detection and metabolomics analysis were used to investigate the negative effects on liver functions following exposure to NaHCO3. Livers exposed to alkaline stress exhibited severe tissue injury and clear apoptotic characteristics. With increased exposure concentrations, the hepatic superoxide dismutase, catalase, glutathione peroxidase and alkaline phosphatase activities significantly decreased in a dose-dependent manner. NaHCO3 exposure up-regulated the transcriptional levels of apoptosis/ferroptosis-related genes in livers. Similarly, the expression trends of interleukin-1β and heat shock protein genes also increased in high-alkalinity environments. However, the expression levels of complement protein 3 significantly decreased (p < 0.05). Hepatic untargeted metabolomics revealed the alteration conditions of various metabolites associated with the antioxidant response, the ferroptosis process and amino acid metabolism (such as beta-alanine metabolism; alanine, aspartate and glutamate metabolism; and glycine, serine and threonine metabolism). These data provided evidence that NaHCO3 impaired immune functions and the integrity of hybrid sturgeon liver tissues by mediating oxidative-stress-mediated apoptosis and ferroptosis. Our results shed light on the breeding welfare of domestic hybrid sturgeons and promote the economic development of fisheries in China.
Postnatal Allergic Inhalation Induces Glial Inflammation in the Olfactory Bulb and Leads to Autism-Like Traits in Mice
Authors: Tanaka Eizo , Yamasaki Ryo , Saitoh Ban-yu , Abdelhadi Amina , Nagata Satoshi , Yoshidomi Sato , Inoue Yuka , Matsumoto Koichiro , Kira Jun-ichi , Isobe Noriko
Published: September 2024

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. To explore its pathophysiology, we investigated the association between neonatal allergic exposure and behavioral changes. Adult female C57BL/6J mice were immunized with adjuvant (aluminum hydroxide) or ovalbumin emulsified with adjuvant. After immunization, the mice were mated, and offspring were born at full term. The postnatal dams and infants were then simultaneously exposed to an allergen (ovalbumin) or vehicle via inhalation. After weaning, behavioral testing and histopathological analyses were conducted on male offspring. Compared with the vehicle-exposed offspring, the ovalbumin-exposed offspring had decreased sociability and increased repetitive behavior, thus representing an ASD-like phenotype in mice. Moreover, histopathological analyses revealed that the ovalbumin-exposed mice had increased astroglial, microglial, and eosinophilic infiltration in the olfactory bulb, as well as increased eosinophils in the nasal mucosa. The ovalbumin-exposed mice also had decreased dendritic spine density and a lower proportion of mature spines, suggesting the impairment of stimulus-induced synaptogenesis. In conclusion, postnatal allergic exposure induced an ASD-like phenotype, as well as allergic rhinitis, which was followed by glial inflammation in the olfactory bulb parenchyma.
A Proteogenomic Approach to Unveiling the Complex Biology of the Microbiome
Authors: Pavelescu Luciana Alexandra , Profir Monica , Enache Robert Mihai , Roşu Oana Alexandra , Creţoiu Sanda Maria , Gaspar Bogdan Severus
Published: September 2024

The complex biology of the microbiome was elucidated once the genomics era began. The proteogenomic approach analyzes and integrates genetic makeup (genomics) and microbial communities′ expressed proteins (proteomics). Therefore, researchers gained insights into gene expression, protein functions, and metabolic pathways, understanding microbial dynamics and behavior, interactions with host cells, and responses to environmental stimuli. In this context, our work aims to bring together data regarding the application of genomics, proteomics, and bioinformatics in microbiome research and to provide new perspectives for applying microbiota modulation in clinical practice with maximum efficiency. This review also synthesizes data from the literature, shedding light on the potential biomarkers and therapeutic targets for various diseases influenced by the microbiome.
Characterization of Endothelial Cell Subclusters in Localized Scleroderma Skin with Single-Cell RNA Sequencing Identifies NOTCH Signaling Pathway
Authors: Hutchins Theresa , Sanyal Anwesha , Esencan Deren , Lafyatis Robert , Jacobe Heidi , Torok Kathryn S.
Published: September 2024

Localized scleroderma (LS) is an autoimmune disease characterized by inflammation and fibrosis, leading to severe cutaneous manifestations such as skin hardening, tightness, discoloration, and other textural changes that may result in disability. While LS shares similar histopathologic features and immune-fibroblast interactions with systemic sclerosis (SSc), its molecular mechanisms remain understudied. Endothelial cells (EC) are known to play a crucial role in SSc but have not been investigated in LS. Single-cell RNA sequencing (scRNA-seq) now allows for detailed examination of this cell type in the primary organ of interest for scleroderma, the skin. In this study, we analyzed skin-isolated cells from 27 LS patients (pediatric and adult) and 17 healthy controls using scRNA-seq. Given the known role of EC damage as an initial event in SSc and the histologic and clinical skin similarities to LS, we focused primarily on endothelial cells. Our analysis identified eight endothelial subclusters within the dataset, encompassing both disease and healthy samples. Interaction analysis revealed that signaling from diseased endothelial cells was predicted to promote fibrosis through SELE interaction with FGFBP1 and other target genes. We also observed high levels of JAG in arterial endothelial cells and NOTCH in capillary endothelial cells, indicating the activation of a signaling pathway potentially responsible for epidermal abnormalities and contributing to LS pathogenesis. In summary, our scRNA-seq analysis identified potential disease-propagating endothelial cell clusters with upregulated pathways in LS skin, highlighting their importance in disease progression.
Hyperbaric Treatment Stimulates Chaperone-Mediated Macroautophagy and Autophagy in the Liver Cells of Healthy Female Rats
Authors: Pedrycz Agnieszka , Kozakiewicz Mariusz , Rahnama Mansur , Kos Marek , Grywalska Ewelina , Bracha Marietta , Grzywacz Anna , Bojar Iwona
Published: September 2024

The role of autophagy goes far beyond the elimination of damaged cellular components and the quality control of proteins. It also cleanses cells from inclusions, including pathogenic viruses, and provides energy-forming components. The liver, which is an organ with increased metabolism, is made up of cells that are particularly vulnerable to damage. Therefore, detoxification of liver cells in the process of autophagy has become a very important issue clinically. The aim of this study was an immunohistochemical evaluation of proteins activated in rat liver cells at different stages of hyperbaric autophagy. The rats used for the study were randomly divided into six equivalent groups—three control groups and three experimental groups. Animals from the experimental groups were subjected to hyperbaric treatment in a hyperbaric chamber, with a pressure of 1.6 ATA for 120 min. They breathed atmospheric air. Rats were decapitated within 5 or 10 days after removal from the chamber. Immunohistochemical reactions with beclin 1, LC3B, RAB7, and HSC73 proteins were carried out on preparations made from liver slices. A three-step labeled streptavidin–biotin detection method of paraffin blocks (LSAB three-step) was used for immunohistochemical research. The results were evaluated using computer programs for morphometric analysis of microscopic images by calculating the mean surface areas occupied by a positive immunohistochemical reaction in individual groups for all antibodies tested. Increased closure of substrates in the autophagosome (beclin 1) induced late endosome transport and accelerated autophagosome maturation process (RAB7). Furthermore, a larger number of autophagosomes (LC3B) was observed in liver cells immediately after the cessation of hyperbaric activity; however, this decreased after 5 days. During this time, chaperone-mediated autophagy (HSC73) was observed on a larger scale. This means that increased macroautophagy induced by hyperbaric treatment weakens with time that has elapsed since the cessation of high pressure, whereas similarly induced chaperone-mediated autophagy intensifies over time.
Structural Basis for Long Residence Time c-Src Antagonist: Insights from Molecular Dynamics Simulations
Authors: Zhong Haiyang , Zhang Zhengshuo , Chen Mengdan , Chen Yue , Yang Can , Xue Yunsheng , Xu Pei , Liu Hongli
Published: September 2024

c-Src is involved in multiple signaling pathways and serves as a critical target in various cancers. Growing evidence suggests that prolonging a drug’s residence time (RT) can enhance its efficacy and selectivity. Thus, the development of c-Src antagonists with longer residence time could potentially improve therapeutic outcomes. In this study, we employed molecular dynamics simulations to explore the binding modes and dissociation processes of c-Src with antagonists characterized by either long or short RTs. Our results reveal that the long RT compound DAS-DFGO-I (DFGO) occupies an allosteric site, forming hydrogen bonds with residues E310 and D404 and engaging in hydrophobic interactions with residues such as L322 and V377. These interactions significantly contribute to the long RT of DFGO. However, the hydrogen bonds between the amide group of DFGO and residues E310 and D404 are unstable. Substituting the amide group with a sulfonamide yielded a new compound, DFOGS, which exhibited more stable hydrogen bonds with E310 and D404, thereby increasing its binding stability with c-Src. These results provide theoretical guidance for the rational design of long residence time c-Src inhibitors to improve selectivity and efficacy.
Hypoxia Pathways in Parkinson’s Disease: From Pathogenesis to Therapeutic Targets
Authors: Gao Yuanyuan , Zhang Jiarui , Tang Tuoxian , Liu Zhenjiang
Published: September 2024

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body’s oxygen at rest. Oxygen deprivation to the brain can lead to loss of consciousness within seconds and death within minutes. Recent studies have identified regions of the brain with spontaneous episodic hypoxia, referred to as “hypoxic pockets”. Hypoxia can also result from impaired blood flow due to conditions such as heart disease, blood clots, stroke, or hemorrhage, as well as from reduced oxygen intake or excessive oxygen consumption caused by factors like low ambient oxygen, pulmonary diseases, infections, inflammation, and cancer. Severe hypoxia in the brain can manifest symptoms similar to Parkinson’s disease (PD), including cerebral edema, mood disturbances, and cognitive impairments. Additionally, the development of PD appears to be closely associated with hypoxia and hypoxic pathways. This review seeks to investigate the molecular interactions between hypoxia and PD, emphasizing the pathological role of hypoxic pathways in PD and exploring their potential as therapeutic targets.
Cholesterol and Cholesterol-Lowering Medications in COVID-19—An Unresolved Matter
Authors: Grewal Thomas , Nguyen Mai Khanh Linh , Buechler Christa
Published: September 2024

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 2019 (COVID-19), a disease with very heterogeneous symptoms. Dyslipidaemia is prevalent in at least 20% of Europeans, and dyslipidaemia before SARS-CoV-2 infection increases the risk for severe COVID-19 and mortality by 139%. Many reports described reduced serum cholesterol levels in virus-infected patients, in particular in those with severe disease. The liver is the major organ for lipid homeostasis and hepatic dysfunction appears to occur in one in five patients infected with SARS-CoV-2. Thus, SARS-CoV-2 infection, COVID-19 disease severity and liver injury may be related to impaired cholesterol homeostasis. These observations prompted efforts to assess the therapeutic opportunities of cholesterol-lowering medications to reduce COVID-19 severity. The majority of studies implicate statins to have beneficial effects on disease severity and outcome in COVID-19. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have also shown potential to protect against COVID-19. This review describes the relationship between systemic cholesterol levels, liver injury and COVID-19 disease severity. The potential effects of statins and PCSK9 in COVID-19 are summarised. Finally, the relationship between cholesterol and lung function, the first organ to be affected by SARS-CoV-2, is described.
A Protocol for the Isolation of Oval Cells without Preconditioning
Authors: Olivera-Salazar Rocío , Sánchez Aránzazu , Herrera Blanca , García-Sáez Juan , Vega-Clemente Luz , Villarejo Campos Pedro , García-Olmo Damián , García-Arranz Mariano
Published: September 2024

Oval cells (OCs) is the name of hepatic progenitor cells (HPCs) in rodents. They are a small population of cells in the liver with the remarkable ability to proliferate and regenerate hepatocytes and cholangiocytes in response to acute liver damage. Isolating OCs generally requires a pretreatment with special diets, chemicals, and/or surgery to induce hepatic damage and OC proliferation in mice. Unfortunately, these pretreatments are not only painful for the mice but also increase the cost of the assays, and the effects on the different organs as well as on various liver cells are still unclear. Therefore, the search for a protocol to obtain OCs without prior liver damage is mandatory. In our study, we present a protocol to isolate murine OCs from healthy liver (HL-OCs) and compare them with OCs isolated from mice pretreated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC-OCs). Our results demonstrated that cells derived from untreated mice exhibited similar behavior to those from treated mice in terms of surface marker expression, proliferation, and differentiation capacity. Therefore, given the impracticability of isolating human cells with prior hepatotoxic treatment, our model holds promise for enabling the isolation of progenitor cells from human tissue in the future. This advancement could prove invaluable for translational medicine in the understanding and treatment of liver diseases.
Investigation of the Pharmacodynamic Components of Gastrodia elata Blume for Treatment of Type 2 Diabetes Mellitus through HPLC, Bioactivity, Network Pharmacology and Molecular Docking
Authors: Yang Xiu , Li Lilang , Yan Yanfang , Hu Xuehao , Li Qiji , Li Liangqun , Wang Yu , Tao Xian , Yang Lishou , Peng Mei , Yang Juan , Yang Xiaosheng , Gao Ming
Published: September 2024

The occurrence of type 2 diabetes mellitus (T2DM), a worldwide chronic disease, is mainly caused by insufficient insulin production and places a huge burden on the health system. Gastrodia elata Blume (GE), a food of medicine–food homology, has been reported to have the ability to inhibit glycosidase activity, indicating its potential in the treatment of diabetes. However, the main pharmacological components of GE for the treatment of T2DM have not been fully clarified. Therefore, this study aims to clarify the pharmacological components changes of GE with different drying methods and the treatment of T2DM using HPLC, network pharmacology, molecular docking and experimental evaluations. The results showed that the GE samples processed by the steam-lyophilized method possessed the highest total content of the six marker components and the strongest antioxidant and α-glucosidase inhibitory abilities. Meanwhile, the six marker compounds had a total of 238 T2DM-related gene targets. Notably, these active compounds have good affinity for key gene targets associated with T2DM signaling pathways. In conclusion, this study revealed that different drying methods of GE affect the content of its major active compounds, antioxidant capacity, α-glucosidase inhibitory capacity and potential pharmacological effects on T2DM, indicating that it is a potential treatment of T2DM.
Serum Vitamin D3 as a Potential Biomarker for Neuronal Damage in Smoldering Multiple Sclerosis
Authors: Niedziela Natalia , Nowak-Kiczmer Maria , Malciene Lina , Stasiołek Mariusz , Niedziela Jacek T. , Czuba Zenon P. , Lis Martyna , Sowa Agata , Adamczyk-Sowa Monika
Published: September 2024

Permanent inflammatory demyelinating and neurodegenerative processes lead to neurological disability in patients with multiple sclerosis (MS). The anti-inflammatory properties of vitamin D3 (VitD) are well established, but its role in neurodegeneration is still uncertain. The usefulness of the serum concentration of VitD as a potential biomarker in evaluating brain injury in terms of recently known smoldering MS was under consideration. Methods: We assessed the concentrations of the parameters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) of relapsing-remitting (RRMS, n = 123) and progressive MS (PMS, n = 88) patients in the group with normal levels of VitD (VitDn) and in the VitD deficiency group (VitDd). The levels of NF-H and UCHL1 were higher in the group of VitDd compared to VitDn. The higher serum levels of VitD were correlated with lower concentrations of GFAP, NF-H and S100B in the CSF of the whole group of MS patients and in women with MS as opposed to the levels of UCHL1. In men, there were noted negative correlations between the levels of serum VitD and GFAP and NF-H in CSF but not between VitD and S100B and UCHL1. The negative correlations were observed between VitD and the selected parameters of brain injury in MS patients, in women as well as in men. The concentrations of serum VitD together with selected parameters of brain injury in CSF seem to be promising biomarkers of neurodegeneration processes in smoldering MS.
SARS-CoV-2-Specific T-Cell as a Potent Therapeutic Strategy against Immune Evasion of Emerging COVID-19 Variants
Authors: Im Keon-Il , Kim Nayoun , Lee Junseok , Oh Ui-Hyeon , Lee Hye-Won , Lee Dong-Gun , Min Gi-June , Lee Raeseok , Lee Jinah , Kim Seungtaek , Cho Seok-Goo
Published: September 2024

Despite advances in vaccination and therapies for coronavirus disease, challenges remain due to reduced antibody longevity and the emergence of virulent variants like Omicron (BA.1) and its subvariants (BA.1.1, BA.2, BA.3, and BA.5). This study explored the potential of adoptive immunotherapy and harnessing the protective abilities using virus-specific T cells (VSTs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VSTs were generated by stimulating donor-derived peripheral blood mononuclear cells with spike, nucleocapsid, and membrane protein peptide mixtures. Phenotypic characterization, including T-cell receptor (TCR) vβ and pentamer analyses, was performed on the ex vivo-expanded cells. We infected human leukocyte antigen (HLA)-partially matched human Calu-3 cells with various authentic SARS-CoV-2 strains in a Biosafety Level 3 facility and co-cultured them with VSTs. VSTs exhibited a diverse TCR vβ repertoire, confirming their ability to target a broad range of SARS-CoV-2 antigens from both the ancestral and mutant strains, including Omicron BA.1 and BA.5. These ex vivo-expanded cells exhibited robust cytotoxicity and low alloreactivity against HLA-partially matched SARS-CoV-2-infected cells. Their cytotoxic effects were consistent across variants, targeting conserved spike and nucleocapsid epitopes. Our findings suggest that third-party partial HLA-matching VSTs could counter immune-escape mechanisms posed by emerging variants of concern.
NLRP3 Inflammasome in the Pathogenesis of Miscarriages
Authors: Omeljaniuk Wioleta Justyna , Garley Marzena , Pryczynicz Anna , Motyka Joanna , Charkiewicz Angelika Edyta , Milewska Elżbieta , Laudański Piotr , Miltyk Wojciech
Published: September 2024

Despite significant advances in prenatal medicine, spontaneous miscarriage remains one of the most common and serious pregnancy complications, affecting an increasing number of women. Since many aspects of the pathogenesis of spontaneous miscarriage remain unexplained, the aim of this study has been to assess the involvement of the NLRP3 inflammasome as a potential causative factor. The concentrations of NLRP3, IL-1β, IL-18, and cytochrome C in the serum of patients after miscarriage were measured by means of the immunoenzymatic method. In the placental tissue, the expression of NLRP3, IL-1β, IL-18, and Caspase-1 as well as that of the classical apoptosis biomarkers Fas, FasL, Bcl-2, and Ca was evaluated by means of immunohistochemistry techniques. Additionally, in whole blood, the concentrations of elements crucial for pregnancy progression, such as Ca, K, Mg, and Na, were examined by means of the ICP-OES method. Significantly higher concentrations of NLRP3 and IL-18 were demonstrated in the serum of patients with miscarriage as compared to the control group. In the placental tissue samples, a higher expression of IL-1β, IL-18, and Caspase-1 proteins was noted in women who had experienced miscarriage as compared to the control group. At the same time, a significantly lower expression of FasL and Bcl-2 proteins as well as Ca deposits was observed in women after miscarriage as compared to those with a normal pregnancy outcome. Significantly lower concentrations of Ca and K were recorded in the blood of patients with spontaneous miscarriage as compared to pregnant women. The analysis of the results x indicated a greater involvement of the inflammasome in women with spontaneous miscarriage associated with oxidative–antioxidative imbalance than in the case of miscarriage related to NET formation. Our research has provided evidence for the involvement of the inflammasome in the process of spontaneous miscarriage and identifies a new direction for diagnostics that includes NLRP3 as a preventive element in prenatal care, particularly in light of the steadily declining number of pregnancies and the increasing number of reproductive failures.
Expanding Role of Interleukin-1 Family Cytokines in Acute Ischemic Stroke
Authors: Matys Paulina , Mirończuk Anna , Starosz Aleksandra , Grubczak Kamil , Kochanowicz Jan , Kułakowska Alina , Kapica-Topczewska Katarzyna
Published: September 2024

Ischemic stroke (IS) is a critical medical condition that results in significant neurological deficits and tissue damage, affecting millions worldwide. Currently, there is a significant lack of reliable tools for assessing and predicting IS outcomes. The inflammatory response following IS may exacerbate tissue injury or provide neuroprotection. This review sought to summarize current knowledge on the IL-1 family’s involvement in IS, which includes pro-inflammatory molecules, such as IL-1α, IL-1β, IL-18, and IL-36, as well as anti-inflammatory molecules, like IL-1Ra, IL-33, IL-36A, IL-37, and IL-38. The balance between these opposing inflammatory processes may serve as a biomarker for determining patient outcomes and recovery paths. Treatments targeting these cytokines or their receptors show promise, but more comprehensive research is essential to clarify their precise roles in IS development and progression.
Review of Antimicrobial Properties of Titanium Dioxide Nanoparticles
Authors: Serov Dmitriy A. , Gritsaeva Ann V. , Yanbaev Fatikh M. , Simakin Alexander V. , Gudkov Sergey V.
Published: September 2024

There is a growing interest in the utilization of metal oxide nanoparticles as antimicrobial agents. This review will focus on titanium dioxide nanoparticles (TiO2 NPs), which have been demonstrated to exhibit high antimicrobial activity against bacteria and fungi, chemical stability, low toxicity to eukaryotic cells, and therefore high biocompatibility. Despite the extensive research conducted in this field, there is currently no consensus on how to enhance the antimicrobial efficacy of TiO2 NPs. The aim of this review is to evaluate the influence of various factors, including particle size, shape, composition, and synthesis parameters, as well as microbial type, on the antibacterial activity of TiO2 NPs against bacteria and fungi. Furthermore, the review offers a comprehensive overview of the methodologies employed in the synthesis and characterization of TiO2 NPs. The antimicrobial activity of TiO2 exhibits a weak dependence on the microorganism species. A tendency towards increased antibacterial activity is observed with decreasing TiO2 NP size. The dependence on the shape and composition is more pronounced. The most pronounced antimicrobial potential is exhibited by amorphous NPs and NPs doped with inorganic compounds. This review may be of interest to specialists in biology, medicine, chemistry, and other related fields.