bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the Health and Environmental Health Literacy of Professionals: Evaluating the Effect of a Virtual Intervention on Phthalate Environmental Health Literacy
Authors: Tomsho Kathryn S. , Quinn Marlee R. , Wang Zifan , Preston Emma V. , Adamkiewicz Gary , Joseph Naima T. , Wylie Blair J. , James-Todd Tamarra
Published: November 2024

The American College of Obstetricians and Gynecologists provided updated guidance in 2021, recommending that reproductive health professionals should include discussion of environmental exposures with their patients. However, environmental health is seldom included in medical training, with endocrine-disrupting chemicals, such as phthalates—linked to adverse pregnancy outcomes—being among the least discussed. We developed a one-hour virtual educational intervention to train reproductive health professionals on the routes of phthalate exposure, potential associated health impacts, and suggestions on how to discuss exposure reduction with patients. The intervention was designed to include perspectives from patients, scientists, and clinicians. Using a pre/post/post design, we evaluated the impact of the intervention on reproductive health professionals’ phthalate-related reproductive health literacy via a validated environmental health literacy (EHL) scale, their confidence in discussing phthalates, and the frequency of discussions about phthalates with patients. All materials, including the study questionnaires and intervention materials, were administered virtually to reproductive health professionals (n = 203) currently seeing patients working in the United States. After completing the intervention, reproductive health professionals’ average EHL increased (pre-course: 22.3, post-course: 23.7, 2 months post-course: 24.0), as did their confidence in discussing phthalates with their patients (pre-course: 1% (2/203) reported being quite confident, post-course: 64% (131/203) reported being quite confident, and 2 months post course: 86% (174/203) reported being quite confident). Additionally, the reported frequency of discussions about phthalates with patients rose substantially (pre-course: 0% (0/203) reported usually discussing phthalates with patients, and 2 months post-course: 86% (175/203) reported usually discussing phthalates with patients): In line with the recommendations of the American College of Obstetricians and Gynecologists, this online phthalate educational intervention tool increased EHL among reproductive health professionals and shifted clinical care to include discussion about phthalates, a reproductive toxicant.
Outdoor Pollution Comparison Between Bucharest and Its Outskirts Using Mobile Laboratory
Authors: Popescu Razvan Stefan , Popescu Lelia Letitia , Catalina Tiberiu
Published: November 2024

This study presents a modern mobile laboratory to monitor outdoor air quality in Bucharest, Romania, with a focus on pollutants associated with transportation. Particulate matter (PM2.5, PM10), carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2), nitrogen oxides (NO, NO2), and BTEX compounds (benzene, toluene, ethylbenzene, and xylenes) were among the significant pollutants that were examined in the lab. Meteorological variables such wind direction and speed, temperature, humidity, and solar radiation were also routinely observed in order to assess their influence on pollution levels. The study looked at two locations—a bustling city road in Bucharest and a remote community 40 kmawayin Snagov—under a range of weather conditions, including sunny, rainy, warm, and chilly days. The findings showed that the primary source of pollution in the urban area, which had significantly higher pollution levels than the rural site, was transportation. Particularly in the city, alarming concentrations of harmful particulate matter and carcinogens like benzene were found, underscoring the need for continuous air quality monitoring. The weather has a major impact on the dispersal of contaminants. Because of washout effects, rainy days decreased airborne pollutants, but sunny days showed higher pollution deposition. This study highlights the importance of outdoor air quality monitoring, particularly in urban environments, where traffic and weather have a significant impact on pollution levels. These findings provide crucial data that policymakers can utilize to implement targeted pollution control measures that protect human health.
Exploring Brazilian Immigrant Mothers’ Beliefs and Practices Regarding Their Preschool Children’s Oral Health: A Qualitative Study Conducted in the United States
Authors: Nogueira Denise Lima , Miranda Fontenele Maria Gabriela , Bento Adriana , Cohen Steven A. , Greaney Mary L. , Lindsay Ana Cristina
Published: November 2024

Parents’ beliefs and practices significantly shape young children’s oral health (OH), particularly during preschool years when these habits are being established. Immigrant parents often face challenges in promoting OH due to cultural, financial, and logistical barriers. This qualitative study explored OH beliefs, practices, and barriers among Brazilian immigrant mothers in the United States (U.S.). Semi-structured interviews, guided by the Health Belief Model (HBM), were conducted with mothers of children aged 2–5 years. Thematic analysis, also guided by the HBM, revealed four key themes: (1) beliefs about children’s OH; (2) awareness of the parent’s role in fostering early OH behaviors; (3) identification of risk and protective factors affecting children’s OH; and (4) perceived barriers to maintaining children’s optimal OH. Mothers emphasized the importance of proper oral hygiene, regular dental check-ups, and balanced diets for promoting children’s OH. Despite recognizing their role in supporting oral hygiene routines and care, mothers noted barriers such as limited access to care, linguistic barriers, and difficulty adopting and maintaining healthy OH practices due to work and family demands. Notably, 96.6% (n = 28) of the mothers scored low on the SASH scale (SASH < 2.99), reflecting low acculturation levels, which may further contribute to these challenges. Study findings highlight the critical role of parental beliefs and practices in shaping early OH behaviors and the unique challenges faced by Brazilian immigrant mothers. Culturally relevant public health interventions, including tailored education and improved access to affordable dental care, are essential for enhancing OH outcomes in young children from these families.
Social Location and Decision-Making Among Women Living with HIV in the Southern United States: An Intersectional Approach
Authors: Caiola Courtney , Choufani Marianne R. , André Juliette , Sommer Sadie B. , Schoemann Alexander M. , Bass Sarah B. , Barroso Julie
Published: November 2024

HIV care engagement and antiretroviral therapy (ART) adherence interventions aimed at decreasing viral suppression disparities for women living with HIV (WLWH) in the Southern United States (i.e., the South) are few and seldom consider diverse social locations. These refer broadly and dynamically to contextual factors and the position people occupy in a social hierarchy based on intersecting systems of oppression and social determinants of health like gender, race/ethnic, and class inequities; geographic location; and HIV-related stigma. Using an intersectional approach, we conducted in-depth interviews and used a phased approach to directed content analysis to describe women’s perceptions of their social location and how it impacts their decision-making about HIV care engagement and ART adherence. Participants were recruited to participate from a broad geographic area and represented the diverse social locations occupied by WLWH in the South. Findings from 40 in-depth interviews include descriptions of how geographic context impacts HIV care engagement and medication adherence through access to care, quality of care, and the place-based context of day-to-day experiences of living with HIV. Participants spoke of multilevel power relationships based on their gender and racial identities, and how social determinants and intersecting identities occur simultaneously and vary as a function of one another to impact health and HIV care decision-making. The findings offer a nuanced understanding of how WLWH perceive their contextually specific social locations and make critical decisions about their HIV care engagement and medication adherence.
Improving Child and Adolescent Mental Health: A Bibliometric Analysis of Related Intervention Studies
Authors: Chen Gaoran , Chen Wenqi , Qi Shaojie , Shek Daniel T. L.
Published: November 2024

In response to the increase in adolescent mental health problems, related intervention research has flourished. This study examined 2258 mental health intervention studies captured by the Web of Science, focusing on their distribution, interdisciplinary collaboration, and emerging trends, using bibliometric analysis. Our findings revealed a rise in studies and enhanced collaboration across disciplines, with studies from the United States, Australia, and the United Kingdom showing high academic output, intellectual impact, and strong scientific partnerships. However, there is a noticeable Western-centrism in the research. Identifying current trends and key areas of focus offers valuable insights for future practices in child and adolescent mental health.
Food Acquisition Locations and Food Groups Acquired According to Levels of Food Insecurity in Brazil
Authors: de Oliveira Roberta Teixeira , Castro Junior Paulo César Pereira de , Suéte Matos Yoko Ametista Carvalho , Ferreira Aline Alves , Salles-Costa Rosana
Published: November 2024

Food insecurity (FI) is a persistent issue in Brazil, with significant disparities existing across the country’s macroregions. This study investigated the food acquisition locations and types of foods purchased at different levels of FI, utilizing data from 57,920 households in the 2017–2018 Brazilian Household Budget Survey. Food acquisition locations were grouped into supermarkets, small markets, street fairs/fruit and vegetable stores/public markets, and others. Foods were categorized into 12 groups: rice, beans, vegetables, fruits, red meats, fish, poultry, eggs, milk and dairy products, bread, cookies, and sugary drinks. Supermarkets are the primary source of food in Brazil. However, in the North and Northeast regions, small markets are more frequently used across all levels of FI. Nationally, most food groups are predominantly purchased at supermarkets. Nevertheless, households experiencing moderate or severe FI rely more on small markets for essential items such as rice, beans, and proteins, as well as ultraprocessed foods. These findings highlight the need for public policies that improve food access for vulnerable populations and address regional inequalities. Enhancing access and ensuring food security across different regions is essential to promoting equitable and healthy diets throughout the country.
Restricted Daily Exposure of Environmental Enrichment: Bridging the Practical Gap from Animal Studies to Human Application
Authors: Nik Ramli Nik Nasihah , Kamarul Sahrin Nurin Amalia , Nasarudin Siti Nur Atiqah Zulaikah , Hashim Mohamad Hisham , Abdul Mutalib Maisarah , Mohamad Alwi Muhammad Najib , Abd Rashed Aswir , Ramasamy Rajesh
Published: November 2024

Daily restricted environmental enrichment (REE) refers to limited, structured periods of enrichment aimed at improving both physical and cognitive well-being in animals and humans. This review explores the significance of REE, focusing on studies that investigate 2 and 3 h daily enrichment protocols. Through an analysis of 21 key studies, this paper highlights how even brief periods of REE can lead to substantial improvements in brain plasticity, cognitive function, and stress resilience. The review tracks the evolution of environmental enrichment from early research on enriched environments in animals to modern applications in human rehabilitation, particularly for stroke recovery and mental health treatment. While the traditional approach to environmental enrichment often involves continuous exposure, recent research suggests that restricted daily enrichment can yield comparable benefits, offering a practical, scalable solution for clinical settings. This review underscores the importance of adapting REE for individual needs and developing flexible, home-based programs for broader application.
Machine Learning Integration with Single-Cell Transcriptome Sequencing Datasets Reveals the Impact of Tumor-Associated Neutrophils on the Immune Microenvironment and Immunotherapy Outcomes in Gastric Cancer
Authors: Zhang Jingcheng , Zhang Mingsi , Lou Jiaheng , Wu Linyue , Zhang Shuo , Liu Xiaojuan , Ke Yani , Zhao Sicheng , Song Zhiyuan , Bai Xing , Cai Yan , Jiang Tao , Zhang Guangji
Published: November 2024

The characteristics of neutrophils play a crucial role in defining the tumor inflammatory environment. However, the function of tumor-associated neutrophils (TANs) in tumor immunity and their response to immune checkpoint inhibitors (ICIs) remains incompletely understood. By analyzing single-cell RNA sequencing data from over 600,000 cells in gastric cancer (GSE163558 and GSE183904), colorectal cancer (GSE205506), and lung cancer (GSE207422), we identified neutrophil subsets in primary gastric cancer that are associated with the treatment response to ICIs. Specifically, we focused on neutrophils with high expression of CD44 (CD44_NEU), which are abundant during tumor progression and exert significant influence on the gastric cancer immune microenvironment. Machine learning analysis revealed 22 core genes associated with CD44_NEU, impacting inflammation, proliferation, migration, and oxidative stress. In addition, multiple immunofluorescence staining and gastric cancer spatial transcriptome data (GSE203612) showed a correlation between CD44_NEU and T-cell infiltration in gastric cancer tissues. A risk score model derived from seven essential genes (AQP9, BASP1, BCL2A1, PLEK, PDE4B, PROK2, and ACSL1) showed better predictive capability for patient survival compared to clinical features alone, and integrating these scores with clinical variables resulted in a prognostic nomogram. Overall, this study highlights the heterogeneity of TANs, particularly the CD44_NEU critical influence on immunotherapy outcomes, paving the way for personalized treatment strategies.
Comparative Metabolic Defense Responses of Three Tree Species to the Supplemental Feeding Behavior of Anoplophora glabripennis
Authors: Qi Ruohan , Pei Jiahe , Zhou Quan , Hao Keyu , Tian Yi , Ren Lili , Luo Youqing
Published: November 2024

Elaeagnus angustifolia L. can attract adult Asian longhorned beetle (ALB), Anoplophora glabripennis (Motschulsky), and kill their offspring by gum secretion in oviposition scars. This plant has the potential to be used as a dead-end trap tree for ALB management. However, there is a limited understanding of the attraction ability and biochemical defense response of E. angustifolia to ALB. In this study, we conducted host selection experiments with ALB and then performed physiological and biochemical assays on twigs from different tree species before and after ALB feeding. We analyzed the differential metabolites using the liquid chromatograph–mass spectrometer method. The results showed that ALB’s feeding preference was E. angustifolia > P.× xiaohei var. gansuensis > P. alba var. pyramidalis. After ALB feeding, the content of soluble sugars, soluble proteins, flavonoids, and tannins decreased significantly in all species. In three comparison groups, a total of 492 differential metabolites were identified (E. angustifolia:195, P.× xiaohei var. gansuensis:255, P. alba var. pyramidalis:244). Differential metabolites were divided into overlapping and specific metabolites for analysis. The overlapping differential metabolites 7-isojasmonic acid, zerumbone, and salicin in the twigs of three tree species showed upregulation after ALB feeding. The specific metabolites silibinin, catechin, and geniposide, in E. angustifolia, significantly increased after being damaged. Differential metabolites enriched in KEGG pathways indicated that ALB feeding activated tyrosine metabolism and the biosynthesis of phenylpropanoids in three tree species, with a particularly high enrichment of differential metabolites in the flavonoid biosynthesis pathway in E. angustifolia. This study provides the metabolic defense strategies of different tree species against ALB feeding and proposes candidate metabolites that can serve as metabolic biomarkers, potentially offering valuable insights into using E. angustifolia as a control measure against ALB.
Advancements in Mesenchymal Stem Cell-Based Therapy for Enhancing Arteriovenous Fistula Patency
Authors: Baranwal Gaurav , Mukhtar Haseeb , Kane Jamie , Lemieux Alaura , Misra Sanjay
Published: November 2024

Chronic kidney disease (CKD) affects more than 10% of the world’s population. Hemodialysis, along with peritoneal dialysis and renal transplant, is one of the renal replacement therapies offered to patients with CKD/end-stage renal disease (ESRD). To proceed with hemodialysis, vascular access is required. The two means of long-term access are arteriovenous fistula (AVF) and arteriovenous graft (AVG). Multiple therapies have been created to help the long-term patency of AVFs. These therapies are needed as 40% of AVFs fail within the first year and additional intervention is required. Much of the existing research has focused on biomarkers, immune cells, hypoxia, and cell-based therapies. Regeneration therapy using mesenchymal stem cells seeks to investigate other ways that we can treat AVF failure. Mesenchymal stem cells are harvested as two main types, fetal and adult. Fetal cells are harvested at different times in fetal gestation and from multiple sources, placental blood, Whartons jelly, and amniotic stem cell fluid. Taken together, this review summarizes the different preclinical/clinical studies conducted using different types of MSCs towards vascular regenerative medicine and further highlights its potential to be a suitable alternative approach to enhance AVF patency.
In Vitro and In Vivo Translational Insights into the Intraoperative Use of Antiseptics and Lavage Solutions Against Microorganisms Causing Orthopedic Infections
Authors: Dudek Bartłomiej , Brożyna Malwina , Karoluk Michał , Frankiewicz Mariusz , Migdał Paweł , Szustakiewicz Konrad , Matys Tomasz , Wiater Adrian , Junka Adam
Published: November 2024

The growing antibiotic resistance of microorganisms causing postoperative infections following orthopedic surgeries underscores the urgent need for localized antiseptic and lavage delivery systems to enhance infection control. This study evaluates the in vitro effectiveness of antiseptic and lavage solutions—including polyhexanide, povidone–iodine, low-concentrated hypochlorite, Ringer’s solution, and saline—against Staphylococcus epidermidis, Staphylococcus aureus MRSA, Cutibacterium acnes, Corynebacterium amycolatum, Pseudomonas aeruginosa, and Candida albicans. Using microplate models (Minimum Inhibitory Concentration, Minimum Biofilm Eradication Concentration, and Biofilm-Oriented Antiseptic Test assays), flow-based models (Bioflux system), and surfaces relevant to orthopedic implants (e.g., stainless steel disks/screws, Co-Cr-Mo, Ti-Al-Nb orthopedic alloys, and ultra-high-molecular-weight polyethylene), as well as a bio-nano-cellulose scaffold representing tissue, we assessed the solutions’ activity. The cytotoxicity of the solutions was evaluated using osteoblast and keratinocyte cell lines, with additional in vivo insights gained through the Galleria mellonella larval model. The results show that polyhexanide-based solutions outperformed povidone–iodine in biofilm eradication in most tests applied, particularly on complex surfaces, whereas iodine demonstrated higher cytotoxicity in applied in vitro and in vivo tests. Low-concentration hypochlorite solutions exhibited minimal antibiofilm activity but also showed no cytotoxicity in cell line and G. mellonella larval models. These findings highlight the importance of careful antiseptic selection and rinsing protocols to balance infection control efficacy with tissue compatibility in orthopedic applications.
Exploring the Genetic Basis of Drought Tolerance in Alhagi camelorum: A Comprehensive Transcriptome Study of Osmotic Stress Adaptations
Authors: Tang Gangliang , Li Xiangyi , Zeng Fanjiang , Ma Junning , Guan Pingyin , Zhang Bo
Published: November 2024

Alhagi camelorum, a desert shrub known for its impressive drought tolerance, exhibits notable resilience under arid conditions. However, the underlying mechanisms driving its drought resistance remain largely unexplored. This study aims to investigate these mechanisms by exposing A. camelorum to osmotic stress using varying polyethylene glycol (PEG) concentrations (1%, 5%, 10%) in a controlled laboratory setting. Growth analysis revealed significant inhibition and phenotypic changes with increasing PEG levels. Transcriptomic analysis, including differentially expressed gene identification, GO enrichment analysis, and hierarchical cluster analysis of genes in roots and shoots, identified key pathways associated with drought adaptation, such as ABA-activated signaling, cell wall biogenesis, photosynthesis, and secondary metabolite biosynthesis. Notably, some genes involved in these pathways exhibited tissue-specific expression patterns and showed PEG concentration-dependent regulation. Key findings include the dose-dependent (R2 > 0.8) upregulation of a proline-rich protein (Asp01G030840) and a BURP domain-containing protein (Asp02G039780), as well as critical genes involved in cell wall biogenesis (encoding Pectinesterase inhibitor domain-containing and Fasciclin-like arabinogalactan protein), and secondary metabolite biosynthesis (encoding enzymes for terpenoid and flavonoid biosynthesis). The regulation of these genes is likely influenced by phytohormones such as ABA and other stress-related hormones, along with significant transcription factors like ABI4, TALE, MYB61, GRAS, and ERF. These insights lay the groundwork for further research into the functional roles of these genes, their regulatory networks, and their potential applications in enhancing drought resistance in desert plants and agricultural crops.
Comparison of Orthogonal Determination Methods of Acid/Base Constants with Meta-Analysis
Authors: Pálla Tamás , Mazák Károly , Alkhazragee Dania Mohammed , Balogh György Tibor , Noszál Béla , Mirzahosseini Arash
Published: November 2024

The accurate determination of acid/base constants (proton dissociation constants—pKa, or equivalently protonation constants—logK) is essential for the physicochemical characterization of new molecules, especially in drug design and development, as these parameters thoroughly influence the pharmacokinetics and pharmacodynamics of drug action. While pH/potentiometric titration remains the gold standard method for determining acid/base constants, spectroscopic techniques—particularly nuclear magnetic resonance spectroscopy (as NMR/pH titrations)—have emerged as powerful alternatives for specific challenges in analytical chemistry, providing also information on the structure and site of protonation. In this study, we performed a comprehensive meta-analysis of protonation constants reported in the literature, measured using both potentiometry and NMR titrations. Our analysis compiled the available literature data and assessed the agreement between the two methods, taking into consideration various experimental conditions, such as temperature and ionic strength. The results provide insights into the reliability and applicability of NMR titrations compared with potentiometry, offering guidance for selecting appropriate methodologies in drug design.
Are the Soluble Receptors sRAGE, sRANKL, and Osteoprotegerin Associated with Anemia in Rheumatoid Arthritis?
Authors: Stefanova Katya , Delcheva Ginka , Stankova Teodora
Published: November 2024

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with articular and systemic manifestations, and one of the most common is anemia. This study aims to investigate whether the levels of the soluble receptors sRAGE, sRANKL, and OPG are affected by the distribution of RA patients in subgroups according to soluble transferrin receptor/log ferritin (sTfR-F index) and hemoglobin (Hb) levels and to examine their correlation with indicators of iron metabolism, disease activity, and autoimmune and inflammatory changes. The levels of sRANKL and sRAGE were significantly higher in the subgroup of anemia of chronic disease combined with iron deficiency anemia (ACD/IDA) compared to the ACD group: p < 0.0001 and p < 0.0001. The level of OPG tended to decrease in ACD/IDA (p = 0.053). sRAGE was positively correlated with prohepcidin, RF and anti-CCP antibodies, sRANKL, CRP, and IL-6 only in the ACD group. A negative correlation was found between sRAGE, sRANKL, and serum iron only in the ACD/IDA group. sRANKL was positively correlated with OPG, prohepcidin, CRP, IL-6, RF, anti-CCP antibodies, and DAS28 only in the ACD group. Positive correlations were observed between OPG and ferritin, sTfR, CRP, IL-6, RF, and DAS28, and a negative correlation was observed with serum iron only in the ACD group. Therefore, the investigated soluble receptors may serve as reliable biomarkers involved in the pathogenesis of RA and may contribute to the identification of patients at risk of developing combined anemia.
Extracellular Vesicles from a Novel Chordoma Cell Line, ARF-8, Promote Tumorigenic Microenvironmental Changes When Incubated with the Parental Cells and with Human Osteoblasts
Authors: Nguyen Khoa N. , Graner Arin N. , Fringuello Anthony R. , Zizzo Zoe , Valenzuela Lorena , Anyanwu Kamara , Lillehei Kevin O. , Youssef A. Samy , Guzman Samuel , Coughlan Christina , Graner Michael W.
Published: November 2024

Chordomas are rare, generally slow-growing spinal tumors that nonetheless exhibit progressive characteristics over time, leading to malignant phenotypes and high recurrence rates, despite maximal therapeutic interventions. The tumors are notoriously resistant to therapies and are often located in regions that complicate achieving gross total resections. Cell lines from these tumors are rare as well. We cultured a new chordoma cell line (ARF-8) derived from an extensive clival chordoma that extended back to the cervical spine. We characterized the ARF-8 cellular and extracellular vesicle (EV) proteomes, as well as the impacts of ARF-8 EVs on the proteomes and secretomes of recipient cells (both ARF-8 and human osteoblasts) in autocrine and paracrine settings. Our proteomic analyses suggested roles for transforming growth factor beta (TGFB/TGFβ), cell–matrix interactions involving the epithelial-to-mesenchymal transition (EMT), and cell–extracellular matrix interactions in cell migration, consistent with a migratory/metastatic tumor phenotype. We demonstrated that ARF-8 tumor cell migration was dependent on general (arginine–glycine–aspartic acid [RGD]-based) integrin activity and that ARF-8 EVs could promote such migration. ARF-8 EVs also prompted proteomic/secretomic changes in human osteoblast cells, again with indications that cell–cell and cell–extracellular matrix interactions would be activated. All the characteristics typically associated with chordomas as cancers—migration and invasion, therapeutic resistance, metastatic potential—can be driven by tumor EVs. Overall, ARF-8 EVs promoted predicted tumorigenic phenotypes in recipient cells and suggested novel therapeutic targets for chordomas.
Dysbindin-1 Mutation Alters Prefrontal Cortex Extracellular Glutamate and Dopamine In Vivo
Authors: Szumlinski Karen K. , Datko Michael C. , Lominac Kevin D. , Jentsch J. David
Published: November 2024

Elevated risk for schizophrenia is associated with a variation in the DTNBP1 gene encoding dysbindin-1, which may underpin cognitive impairments in this prevalent neuropsychiatric disorder. The cognitive symptoms of schizophrenia involve anomalies in glutamate and dopamine signaling, particularly within the prefrontal cortex (PFC). Indeed, mice with Dtnbp1 mutations exhibit spatial and working memory deficits that are associated with deficits in glutamate release and NMDA receptor function as determined by slice electrophysiology. The present study extended the results from ex vivo approaches by examining how the Dtnbp1 mutation impacts high K+- and NMDA receptor-evoked glutamate release within the PFC using in vivo microdialysis procedures. Dntbp1 mutant mice are also reported to exhibit blunted K+-evoked dopamine release within the PFC. Thus, we examined also K+- and NMDA-evoked dopamine release within this region. Perfusion of high-concentration K+ or NMDA solutions increased the PFC levels of both dopamine and glutamate in wild-type (WT) but not in Dtnbp1 mutants (MUT), whereas mice heterozygous for the Dtnbp1 mutation (HET) exhibited blunted K+-evoked dopamine release. No net-flux microdialysis procedures confirmed elevated basal extracellular content of both glutamate and dopamine within the PFC of HET and MUT mice. These in vivo microdialysis results corroborate prior indications that Dtnbp1 mutations perturb evoked dopamine and glutamate release within the PFC, provide in vivo evidence for impaired NMDA receptor function within the PFC, and suggest that these neurochemical anomalies may be related to abnormally elevated basal neurotransmitter content.
Malvidin-3-O-Glucoside Mitigates α-Syn and MPTP Co-Induced Oxidative Stress and Apoptosis in Human Microglial HMC3 Cells
Authors: Sood Rachit , Sanjay  , Kang Sung-Ung , Yoon Na Young , Lee Hae-Jeung
Published: November 2024

Parkinson’s disease (PD) is a widespread age-related neurodegenerative disorder characterized by the presence of an aggregated protein, α-synuclein (α-syn), which is encoded by the SNCA gene and localized to presynaptic terminals in a normal human brain. The α-syn aggregation is induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mitochondrial neurotoxin and is therefore used to mimic PD-like pathology in various in vitro and in vivo models. However, in vitro PD-like pathology using α-syn and MPTP in human microglial cells has not yet been reported. Malvidin-3-O-glucoside (M3G) is a major anthocyanin primarily responsible for pigmentation in various fruits and beverages and has been reported to possess various bioactivities. However, the neuroprotective effects of M3G in humanized in vitro PD-like pathologies have not been reported. Therefore, individual and co-treatments of α-syn and MPTP in a human microglial (HMC3) cell line were used to establish a humanized PD-like pathology model in vitro. The individual treatments were significantly less cytotoxic when compared to the α-syn and MPTP co-treatment. This study examined the neuroprotective effects of M3G by treating HMC3 cells with α-syn (8 μg/mL) and MPTP (2 mM) individually or in a co-treatment in the presence or absence of M3G (50 μM). M3G demonstrated anti-apoptotic, anti-inflammatory, and antioxidative properties against the α-syn- and MPTP-generated humanized in vitro PD-like pathology. This study determined that the cytoprotective effects of M3G are mediated by nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling.
Rosmarinic Acid Ameliorates Dermatophagoides farinae Extract-Induced Atopic Dermatitis-like Skin Inflammation by Activating the Nrf2/HO-1 Signaling Pathway
Authors: Shim Ki-Shuk , Kim Hye Jin , Ji Kon-Young , Jung Dong Ho , Park Sun Haeng , Song Hyun-Kyung , Kim Taesoo , Kim Ki Mo
Published: November 2024

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. AD pathogenesis is associated with increased oxidative stress, impairment of the skin barrier, and activation of the immune response. Rosmarinic acid (RA), a caffeic acid ester, is known for its anti-inflammatory and antioxidant properties. However, the effects of RA on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation, as well as its ability to regulate oxidative stress through the Nrf2/HO-1 pathway in TNF-α/IFN-γ-treated keratinocytes, remain unclear. We investigated RA activity in a DfE-induced AD-like skin inflammation mouse model and IFN-γ/TNF-α-stimulated keratinocytes. We found that RA attenuates DfE-induced inflammation by decreasing dermatitis scores and serum inflammatory marker levels and mast cell infiltration. Additionally, RA significantly suppressed IFN-γ/TNF-α-induced chemokine production in keratinocytes and reduced Th cytokine levels in concanavalin A-stimulated splenocytes. Importantly, RA also increased Nrf2/HO-1 expression in TNF-α/IFN-γ-treated keratinocytes. In conclusion, this study demonstrated that RA effectively alleviates DfE-induced AD-like skin lesions by reducing the levels of inflammatory cytokines and chemokines. Furthermore, RA promotes Nrf2/HO-1 signaling in keratinocytes, which may help mitigate DfE-induced oxidative stress, thereby alleviating AD-like skin inflammation. These findings highlight the potential of RA as a therapeutic agent for treating AD and other skin inflammation.
Current and Potential Use of Biologically Active Compounds Derived from Cannabis sativa L. in the Treatment of Selected Diseases
Authors: Bukowska Bożena
Published: November 2024

Cannabis sativa L. contains numerous compounds with antioxidant and anti-inflammatory properties, including the flavonoids and the cannabinoids, particularly Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoids have an effect on the endocannabinoid system (ECS), a cellular communication network, and are, hence, widely studied for medical applications. Epidiolex®, a 99% pure oral CBD extract, has been approved by the FDA for the treatment of epilepsy. Nabiximols (Sativex) is an oromucosal spray containing equal volume of THC and CBD, and it is commonly used as an add-on treatment for unresponsive spasticity in multiple sclerosis (MS) patients. Several in vitro and in vivo studies have also shown that cannabinoids can be used to treat various types of cancer, such as melanoma and brain glioblastoma; the first positive clinical trials on the anticancer effect of a THC:CBD blend with temozolomide (TMZ) in the treatment of highly invasive brain cancer are very promising. The cannabinoids exert their anticancer properties in in vitro investigations by the induction of cell death, mainly by apoptosis and cytotoxic autophagy, and the inhibition of cell proliferation. In several studies, cannabinoids have been found to induce tumor regression and inhibit angiogenic mechanisms in vitro and in vivo, as well as in two low-numbered epidemiological studies. They also exhibit antiviral effects by inhibiting ACE2 transcription, blocking viral replication and fusion, and acting as anti-inflammatory agents; indeed, prior CBD consumption (a study of 93,565 persons in Chicago) has also been associated with a much lower incidence of SARS-CoV-2 infections. It is postulated that cannabis extracts can be used in the treatment of many other diseases such as systemic lupus erythematosus, type 1 diabetes, or various types of neurological disorders, e.g., Alzheimer’s disease. The aim of this review is to outline the current state of knowledge regarding currently used medicinal preparations derived from C. sativa L. in the treatment of selected cancer and viral diseases, and to present the latest research on the potential applications of its secondary metabolites.
Poly-D,L-Lactic Acid Fillers Increase Subcutaneous Adipose Tissue Volume by Promoting Adipogenesis in Aged Animal Skin
Authors: Byun Kyung-A , Seo Suk Bae , Oh Seyeon , Jang Jong-Won , Son Kuk Hui , Byun Kyunghee
Published: November 2024

During aging, subcutaneous white adipose tissue (sWAT) thickness and the adipogenic potential of adipose-derived stem cells (ASCs) decline. Poly-D,L-lactic acid (PDLLA) fillers are commonly used to restore diminished facial volume. Piezo1 increases polarizing macrophages towards the M2 phenotype, which promotes the secretion of fibroblast growth factor 2 (FGF2), thereby increasing ASC survival. This study evaluated whether PDLLA enhances adipogenesis in ASCs by modulating M2 polarization in an in vitro senescence model and in aged animals. Lipopolysaccharide (LPS)-induced senescent macrophages showed decreased Piezo1, which was upregulated by PDLLA. CD163 (an M2 marker) and FGF2 were downregulated in senescent macrophages but were upregulated by PDLLA. We evaluated whether reduced FGF2 secretion from senescent macrophages affects ASCs by applying conditioned media (CM) from macrophage cultures to ASCs. CM from senescent macrophages decreased ERK1/2 and proliferation in ASCs, both of which were restored by CM from PDLLA-stimulated senescent macrophages. Adipogenesis inducers (PPAR-γ and C/EBP-α) were downregulated by CM from senescent macrophages but upregulated by CM from PDLLA-stimulated senescent macrophages in ASCs. Similar patterns were observed in aged animal adipose tissue. PDLLA increased Piezo1 activity, M2 polarization, and FGF2 levels. PDLLA also enhanced ERK1/2, cell proliferation, PPAR-γ, and C/EBP-α expression, leading to increased adipose tissue thickness. In conclusion, our study showed that PDLLA increased adipose tissue thickness by modulating adipogenesis.
Roles of 4′-O-Methylalpinum Isoflavone on Activation of Microglia Induced by Oxysterols
Authors: Son Yonghae , Kim Miran , Lee Dongho , Kwon Ryuk Jun , Kim Koanhoi
Published: November 2024

Microglia play a crucial role as immune cells responsible for the brain’s defense mechanisms. Similar to the actions of macrophages in the body, microglial cells elicit an inflammatory immune response in the brain. Recent papers highlight activated microglial cells as pivotal contributors to inflammatory responses in the brain, leading to damage to nerve tissue and the onset of Alzheimer’s disease (AD). In the brains of AD patients, elevated levels of inflammatory cytokines such as interleukin-6 (IL-6) and oxidized cholesterol metabolites (oxysterols) are observed. These factors are closely associated with inflammatory diseases in the brain. 4′-O-Methylalpinum isoflavone (mAI), derived from Cudrania tricuspidata fruit, possesses antioxidant, neuroprotective, and anti-inflammatory properties. Consequently, this study examined the effect of mAI on the expression of IL-6, a major inflammatory cytokine. The HMC3 microglial cell line was treated with oxysterols to assess the effectiveness of mAI in mitigating this inflammatory response. The results indicated that mAI inhibited the gene expression and protein secretion of IL-6 induced by 25-hydroxycholesterol (25OHChol) and 27-hydroxycholesterol (27OHChol). Furthermore, the expression of MHC class II, a marker for microglial activation, was reduced to baseline levels. These findings suggest that mAI may serve as a viable option for suppressing and treating brain inflammatory diseases induced by cholesterol oxidation products. This is achieved by curtailing the expression of the inflammatory cytokine resulting from the activation of microglial cells by immuno-oxysterol.
Enhancing Antifungal Drug Discovery Through Co-Culture with Antarctic Streptomyces albidoflavus Strain CBMAI 1855
Authors: Giordano Ana Luisa Perini Leme , Rodrigues Marili Villa Nova , dos Santos Karen Gabriela Araujo , Legabão Barbara Cipulo , Pontes Lais , de Angelis Derlene Attili , Garboggini Fabiana Fantinatti , Schreiber Angelica Zaninelli
Published: November 2024

Fungal infections pose a growing public health threat, creating an urgent clinical need for new antifungals. Natural products (NPs) from organisms in extreme environments are a promising source for novel drugs. Streptomyces albidoflavus CBMAI 1855 exhibited significant potential in this regard. This study aimed to (1) assess the antifungal spectrum of the CBMAI 1855 extract against key human pathogens, (2) elicit NP production through co-cultivation with fungi, correlating the metabolites with the biosynthetic gene clusters (BGCs), and (3) perform in silico toxicity predictions of the identified compounds to analyze their suitability for drug development. The crude extract of CBMAI 1855 exhibited broad-spectrum antifungal activity. The metabolomic analysis identified antifungal NPs such as antimycin A, fungimycin, surugamides, 9-(4-aminophenyl)-3,7-dihydroxy-2,4,6-trimethyl-9-oxo-nonoic acid, and ikarugamycin, with the latter two predicted to be the most suitable for drug development. Genome mining revealed three cryptic BGCs potentially encoding novel antifungals. These BGCs warrant a detailed investigation to elucidate their metabolic products and harness their potential. CBMAI 1855 is a prolific producer of multiple antifungal agents, offering a valuable source for drug discovery. This study highlights the importance of exploring microbial interactions to uncover therapeutics against fungal infections, with a detailed exploration of cryptic BGCs offering a pathway to novel antifungal compounds.
Molecular Characteristics of Circ_002156 and Its Effects on Proliferation and Differentiation of Caprine Skeletal Muscle Satellite Cells
Authors: Gu Yuanhua , Shen Jiyuan , Hao Zhiyun , Zhen Huimin , Wu Xinmiao , Wang Jiqing , Li Mingna , Ren Chunyan , Liu Yuan , Zhao Yuan , Yang Pan , Wang Xuanyu
Published: November 2024

The proliferation and differentiation of skeletal muscle satellite cells (SMSCs) are responsible for the development of skeletal muscle. In our previous study, circ_002156 was found to be highly expressed in caprine Longissimus Dorsi muscle, but the regulatory role of the circular RNAs (circRNA) in goat SMSCs remains unclear. In this study, the authenticity of circ_002156 was validated, and its structurally characteristic and cellular localization as well as tissue expression of circ_002156 and its parent genes were investigated. Moreover, the effects of circ_002156 on the viability, proliferation, and differentiation of SMSCs were also studied. The circ_002156 is located on caprine chromosome 19 with a length of 36,478. The circRNA structurally originates from myosin heavy chain 2 (MYH2), MYH1, and MYH4 as well as intergenic sequences among the parent genes. RT-PCR and Sanger sequencing confirmed the authenticity of circ_002156. Most circ_002156 (55.5%) was expressed in the nuclei of SMSCs, while 44.5% of circ_002156 was located in the cytoplasm. The circ_002156 and its three parent genes had higher expression levels in the triceps brachii, quadriceps femoris, and longissimus dorsi muscle tissues than in the other five tissues. The expression of circ_002156 and its parent genes MYH1 and MYH4 reached the maximum on day 8 of differentiation, while MYH2 in expression reached the peak on day 4 after differentiation. The Pearson correlation coefficients revealed that circ_002156 had moderate or high positive correlations with the three parent genes in the expression of both quadriceps femoris muscle and SMSCs during different differentiation stages. The small interfering RNA circ_002156 (named si-circ_002156) remarkably increased the viability of the SMSCs. The si-circ_002156 also increased the number and parentage of Edu-labeled positive SMSCs as well as the expression levels of four cell proliferation marker genes. These suggest that circ_002156 inhibited the proliferation of SMSCs. Meanwhile, si-circ_002156 decreased the area of MyHC-labeled positive myotubes, the myotube fusion index, and myotube size as well as the expression of its three parent genes and four cell differentiation marker genes, suggesting a positive effect of circ_002156 on the differentiation of SMSCs. This study contributes to a better understanding of the roles of circ_002156 in the proliferation and differentiation of SMSCs.
Plastic-Degrading Microbial Consortia from a Wastewater Treatment Plant
Authors: Salini Andrea , Zuliani Luca , Gonnelli Paolo Matteo , Orlando Marco , Odoardo Andrea , Ragno Daniele , Aulitto Martina , Zaccone Claudio , Fusco Salvatore
Published: November 2024

Plastic waste pollution has become a global crisis, with millions of tons of plastic expected to accumulate in landfills and in natural environments, posing a serious threat to wildlife and human health. As current recycling methods remain inefficient, there is an urgent need for innovative enzymatic solutions to break down plastics and enable a circular economy approach. In this study, we explore the plastic-degrading potential of microorganisms enriched from activated sludge (AS) sourced from a municipal wastewater treatment plant (WWTP)—a known microplastic-contaminated industrial niche. Five microbial consortia (i.e., microbiomes) were enriched under selective pressure using low-carbon conditions and high concentrations of polyester polymers, including post-consumer PET, post-consumer PLA, and virgin PLA. Enrichment was performed for 100 days at 37 °C and 50 °C, followed by microbiomes isolation and metagenomic analysis to identify plastic-active bacteria and their enzymes. The results revealed that PLA polymers, but not post-consumer PET, were effectively degraded by the microbiomes, as confirmed by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC), showing significant molecular weight reduction compared to the abiotic controls. Microbial community analysis highlighted a distinct enrichment profile driven by the polymer composition and the temperature. At 50 °C, the Bacillales order became the predominant population, whereas at 37 °C, a more diverse community within the Proteobacteria and Actinobacteria phyla were selected. Nonetheless, the enriched microbial communities at both temperatures included phyla with members known for polyester degradation. Moreover, at 50 °C, enrichment of putative PET/PLA hydrolases was also observed. These findings suggest that AS microorganisms are a reservoir of polyester-active enzymes, particularly PLA-depolymerases, and hold promise for advancing biotechnological strategies to mitigate plastic pollution through re- and up-cycling.
Isolation, Characterization, and Unlocking the Potential of Mimir124 Phage for Personalized Treatment of Difficult, Multidrug-Resistant Uropathogenic E. coli Strain
Authors: Golomidova Alla , Kupriyanov Yuriy , Gabdrakhmanov Ruslan , Gurkova Marina , Kulikov Eugene , Belalov Ilya , Uskevich Viktoria , Bespiatykh Dmitry , Letarova Maria , Efimov Alexander , Kuznetsov Alexander , Shitikov Egor , Pushkar Dmitry , Letarov Andrey , Zurabov Fedor
Published: November 2024

Escherichia coli and its bacteriophages are among the most studied model microorganisms. Bacteriophages for various E. coli strains can typically be easily isolated from environmental sources, and many of these viruses can be harnessed to combat E. coli infections in humans and animals. However, some relatively rare E. coli strains pose significant challenges in finding suitable phages. The uropathogenic strain E. coli UPEC124, isolated from a patient suffering from neurogenic bladder dysfunction, was found to be resistant to all coliphages in our collections, and initial attempts to isolate new phages failed. Using an improved procedure for phage enrichment, we isolated the N4-related phage Mimir124, belonging to the Gamaleyavirus genus, which was able to lyse this “difficult” E. coli strain. Although Mimir124 is a narrow-spectrum phage, it was effective in the individualized treatment of the patient, leading to pathogen eradication. The primary receptor of Mimir124 was the O antigen of the O101 type; consequently, Mimir124-resistant clones were rough (having lost the O antigen). These clones, however, gained sensitivity to some phages that recognize outer membrane proteins as receptors. Despite the presence of nine potential antiviral systems in the genome of the UPEC124 strain, the difficulty in finding effective phages was largely due to the efficient, non-specific cell surface protection provided by the O antigen. These results highlight the importance of an individualized approach to phage therapy, where narrow host-range phages—typically avoided in pre-fabricated phage cocktails—may be instrumental. Furthermore, this study illustrates how integrating genomic, structural, and functional insights can guide the development of innovative therapeutic strategies, paving the way for broader applications of phage therapy in combating multidrug-resistant bacterial pathogens.