bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotype-by-Environment Interactions in Nonalcoholic Fatty Liver Disease and Chronic Illness among Mexican Americans: The Role of Acculturation Stress
Authors: Manusov Eron G. , Diego Vincent P. , Almeida Marcio , Ortiz David , Curran Joanne E. , Galan Jacob , Leandro Ana C. , Laston Sandra , Blangero John , Williams-Blangero Sarah
Published: August 2024

This study examines the complex interplay of genetic and environmental interactions that shape chronic illness risk. Evidence is mounting for the role of genetic expression and the immune response in the pathogenesis of chronic disease. In the Rio Grande Valley of south Texas, where 90% of the population is Mexican American, chronic illnesses (including obesity, diabetes, nonalcoholic liver disease, and depression) are reaching epidemic proportions. This study leverages an ongoing family study of the genetic determinants of risk for obesity, diabetes, hypertension, hyperlipidemia, and depression in a Mexican American population. Data collected included blood pressure, BMI, hepatic transaminases, HbA1c, depression (BDI-II), acculturation/marginalization (ARSMA-II), and liver health as assessed by elastography. Heritability and genotype-by-environment (G×E) interactions were analyzed, focusing on the marginalization/separation measure of the ARSMA-II. Significant heritabilities were found for traits such as HbA1c (h2 = 0.52), marginalization (h2 = 0.30), AST (h2 = 0.25), ALT (h2 = 0.41), and BMI (h2 = 0.55). Genotype-by-environment interactions were significant for HbA1c, AST/ALT ratio, BDI-II, and CAP, indicating that genetic factors interact with marginalization to influence these traits. This study found that acculturation stress exacerbates the genetic response to chronic illness. These findings underscore the importance of considering G×E interactions in understanding disease susceptibility and may inform targeted interventions for at-risk populations. Further research is warranted to elucidate the underlying molecular pathways and replicate these findings in diverse populations.
MSCAC: A Multi-Scale Swin–CNN Framework for Progressive Remote Sensing Scene Classification
Authors: Solomon A. Arun , Agnes S. Akila
Published: August 2024

Recent advancements in deep learning have significantly improved the performance of remote sensing scene classification, a critical task in remote sensing applications. This study presents a new aerial scene classification model, the Multi-Scale Swin–CNN Aerial Classifier (MSCAC), which employs the Swin Transformer, an advanced architecture that has demonstrated exceptional performance in a range of computer vision applications. The Swin Transformer leverages shifted window mechanisms to efficiently model long-range dependencies and local features in images, making it particularly suitable for the complex and varied textures in aerial imagery. The model is designed to capture intricate spatial hierarchies and diverse scene characteristics at multiple scales. A framework is developed that integrates the Swin Transformer with a multi-scale strategy, enabling the extraction of robust features from aerial images of different resolutions and contexts. This approach allows the model to effectively learn from both global structures and fine-grained details, which is crucial for accurate scene classification. The model’s performance is evaluated on several benchmark datasets, including UC-Merced, WHU-RS19, RSSCN7, and AID, where it demonstrates a superior or comparable accuracy to state-of-the-art models. The MSCAC model’s adaptability to varying amounts of training data and its ability to improve with increased data make it a promising tool for real-world remote sensing applications. This study highlights the potential of integrating advanced deep-learning architectures like the Swin Transformer into aerial scene classification, paving the way for more sophisticated and accurate remote sensing systems. The findings suggest that the proposed model has significant potential for various remote sensing applications, including land cover mapping, urban planning, and environmental monitoring.
Transformation of a Classified Image from Pixel Clutter to Land Cover Map Using Geometric Generalization and Thematic Self-Enrichment
Authors: Strand Geir-Harald , Heggem Eva Solbjørg Flo , Aune-Lundberg Linda , Hościło Agata , Waśniewski Adam
Published: August 2024

Land cover maps are frequently produced via the classification of satellite imagery. There is a need for a practicable and automated approach for the generalization of these land cover classification results into scalable, digital maps while minimizing information loss. We demonstrate a method where a land cover raster map produced using the classification of Sentinel 2 imagery was generalized to obtain a simpler, more readable land cover map. A replicable procedure following a formal generalization framework was applied. The result of the initial land cover classification was separated into binary layers representing each land cover class. Each binary layer was simplified via structural generalization. The resulting images were merged to create a new, simplified land cover map. This map was enriched by adding statistical information from the original land cover classification result, describing the internal land cover distribution inside each polygon. This enrichment preserved the original statistical information from the classified image and provided an environment for more complex cartography and analysis. The overall accuracy of the generalized map was compared to the accuracy of the original, classified land cover. The accuracy of the land cover classification in the two products was not significantly different, showing that the accuracy did not deteriorate because of the generalization.
Metabolic Compartmentalization in Colorectal Cancer Hepatic Metastases and Correlation with Tumor Aggressiveness
Authors: Castro Nuno , Fernandes Mariana , Pereira Ana , Costa Mariana , Machado Nuno , Branco Cláudio , Veiga Carlos , Longatto-Filho Adhemar , Martins Sandra F.
Published: August 2024

At the time of colorectal cancer (CRC) diagnosis, approximately 25% of patients present with liver metastases, and 70% develop them during follow-up. This is the primary cause of therapeutic failure and most associated deaths, making it imperative to understand the molecular mechanisms involved in this process and the biological components involved. In the process of anaerobic glycolysis occurring in these cells, to maintain cellular homeostasis, excess lactate is removed via monocarboxylate transporters (MCTs). This study aimed to characterize monocarboxylate transporter 4 (MCT4), human glucose transporter protein isoform 1(GLUT1), cluster of differentiation 147 (CD147), and the acidic cell surface adhesion protein (CD44) in various cellular and histological compartments of liver metastases from CRC in 45 patients diagnosed with metastatic CRC. The characterization revealed significant correlations between the compartmentalization of these markers and the patients’ clinicopathological data. The findings for MCT4, GLUT1, CD147, and CD44 obtained in this study are very promising in relation to considering these markers as therapeutic targets in further investigations.
Sex-Specific Variations in Glycated Hemoglobin Responses to Structured Exercise in Type 2 Diabetes: Healthcare Implications of Walking and Strength Training on Glycemic Control
Authors: King Alexis C. , Villalobos Cynthia , Vosti Paul , Jensen Courtney D.
Published: August 2024

Type 2 diabetes mellitus (T2DM) affects one in ten individuals in the United States, with rates expected to rise significantly. This novel study aimed to evaluate the impact of a structured exercise program on glycated hemoglobin (HbA1c) levels among males and females with T2DM, and to compare the effects of different volumes of combined aerobic and resistance exercise. A total of 67 adult participants with T2DM were randomly assigned to two groups: Group 1 (exercise classes and walking sessions) and Group 2 (exercise classes only). After 10 weeks, 39 participants completed the intervention and 34 had complete HbA1c records. Results indicated a significant improvement in HbA1c levels overall, with males exhibiting a greater decrease compared to females. Minimal baseline differences were observed between the walking and non-walking groups and improvements in HbA1c were noted in both groups with no significant differences. These findings suggested potential sex-specific differences in response to structured exercise programs. The study highlighted the importance of tailored exercise interventions in healthcare while managing T2DM. Further research is necessary to optimize exercise prescriptions and evaluate long-term benefits, but the current evidence supports structured exercise as a valuable component of comprehensive diabetes care. This research underscores the need for personalized approaches in exercise regimens, contributing to the growing body of knowledge on sex-specific responses to T2DM interventions.
Intensity of Symptoms and Perception of Quality of Life on Admission to Palliative Care: Reality of a Portuguese Team
Authors: Gonçalves Florbela , Gaudêncio Margarida , Paiva Ivo Cristiano Soares , Rego Francisca , Nunes Rui
Published: August 2024

Background: Palliative care (PC) corresponds to an approach that enhances the quality of life for patients facing life-threatening diseases, such as cancer, as well as for their families. There are various models for providing palliative care. Early referral to PC of patients with advanced cancer has a significant positive impact on their quality of life. However, the criteria for early referral still remain controversial. Objectives: To evaluate patients’ symptomatic intensity and perception of quality of life on admission to a PC unit and to analyze these two variables according to different models of approach (outpatient and inpatient care). Methods: A cross-sectional, descriptive, and correlational study was conducted with a sample of 60 patients sequentially admitted to a PC unit from palliative outpatient consultations or other inpatient services in a tertiary hospital dedicated to oncology care. The evaluation protocol included a sociodemographic and medical questionnaire, the Edmonton Symptom Assessment Scale (ESAS), and the Palliative Care Outcome Scale (POS) completed by patients within the first 24 h after admission. Results: The participants were mostly male (61.7%), with a median age of 72 years. The majority of patients (n = 32; 53.3%) were undergoing outpatient treatment, while the remaining individuals (n = 28; 46.7%) were transferred from other hospital services (inpatient care). In the outpatient care group, higher scores for fatigue and dyspnea were observed. Conversely, in the inpatient care group, higher scores were observed for pain, depression, and anxiety. There were significant differences between the two groups regarding the POS dimensions of meaning of life, self-feelings, and lost time. In the inpatient group, there was a longer time between diagnosis and referral to PC; however, it was also in the inpatient group that there was less time between PC referral and first PC evaluation, between PC referral and PC unit admission, and between PC referral and death. There were no significant correlations between referral times and ESAS/POS scores in the inpatient and outpatient groups. Conclusions: The patients admitted to the Palliative Care Unit presented a high symptom burden and changes in the perception of quality of life. However, there are no statistically significant differences between one model of approach in relation to the other. It was found that poorer symptom control and quality of life were associated with a shorter referral time for PC, because this was only initiated after curative care was suspended, particularly in our institutional context. Early referrals to the PC team are essential not only to relieve symptom-related distress but also to improve treatment outcomes and quality of life for people with cancer.
Strategies for the Management of Cardiorenal Syndrome in the Acute Hospital Setting
Authors: Chandramohan Deepak , Simhadri Prathap Kumar , Jena Nihar , Palleti Sujith Kumar
Published: August 2024

Cardiorenal syndrome (CRS) is a life-threatening disorder that involves a complex interplay between the two organs. Managing this multifaceted syndrome is challenging in the hospital and requires a multidisciplinary approach to tackle the many manifestations and complications. There is no universally accepted algorithm to treat patients, and therapeutic options vary from one patient to another. The mainstays of therapy involve the stabilization of hemodynamics, decongestion using diuretics or renal replacement therapy, improvement of cardiac output with inotropes, and goal-directed medical treatment with renin–angiotensin–aldosterone system inhibitors, beta-blockers, and other medications. Mechanical circulatory support is another viable option in the armamentarium of agents that improve symptoms in select patients.
Response to Abiotic Stresses in Horticultural Crops
Authors: Benavides-Mendoza Adalberto , González-García Yolanda , Pérez-Labrada Fabián , González-Morales Susana
Published: August 2024

Horticultural production systems provide multiple benefits: economic, social, and health [...]
Effectiveness of Multidisciplinary Pre-Discharge Conferences on Concordance Rate in Place of End-of-Life Care and Death: A Single-Center Retrospective Study
Authors: Miura Hisayuki , Goto Yuko
Published: August 2024

Backgrounds: The pre-discharge conference (PDC) is crucial for ensuring care continuity based on patients’ preferences and goals. However, there is no quantitative on its effectiveness. We investigated the effectiveness of multidisciplinary PDC on the concordance rate between the preferred (PPEoLC) and actual place of end-of-life care and death. Methods: Overall, 551 older homebound patients (median age, 83.0 years; female, 49.4%; male, 50.6%) receiving continuous home medical care through clinics were enrolled in hospital ward admission from March 2011 to September 2018. Patient demographics, presence or absence of PDCs, statements from patients and their families regarding PPEoLC, and place of death of deceased patients were confirmed from the patients’ medical records, followed by concordance rate analyses between PPEoLC and place of death and a multivariate analysis of home mortality. We used the Mann–Whiney U test to assess attribute data, hypothesis testing to assess the difference in the population proportions, and binominal logistic regression analyses to evaluate the relationship between valuables. Results: In the conference group, the home mortality rate, patients’ and their families’ expression rates, and preferences for their home of PPEoLC were higher (p < 0.001) than those in the non-conference group. The place of death was significantly influenced by family preferences. Conclusions: PDC can affect the place of death of homebound patients, but family preferences rather than patient preferences influence the decision of the patient’s place of death. To better reflect the patient preferences, patient-centered decision support should be provided earlier in the disease process.
The Antimicrobial Resistance Pandemic Is Here: Implementation Challenges and the Need for the One Health Approach
Authors: Ponzo Elena , De Gaetano Silvia , Midiri Angelina , Mancuso Giuseppe , Giovanna Presti , Giuliana Danna , Zummo Sebastiana , Biondo Carmelo
Published: August 2024

The issue of antibiotic resistance represents a significant threat that extends beyond human health, encompassing animal welfare and the sustainability of the natural environment. The inappropriate use of antibiotics, poor sanitation and inadequate control measures have contributed to the emergence of drug-resistant bacteria, which can spread at the human–animal–environment interface. The documented presence of antimicrobials in agriculture, veterinary medicine and human medicine has convinced all stakeholders of the need to contribute to the development of a “One Health” approach, which recognises the interrelationships between animals, humans and their environment and the need to adopt a common strategy encompassing these sectors to limit the spread of bacterial antimicrobial resistance (AMR). Although a number of countries have implemented integrated surveillance systems to monitor antibiotic use and antimicrobial resistance, available data suggest that the use of antibiotics in humans, animals and the environment is increasing worldwide. Consequently, the emergence of antibiotic-resistant pathogens is becoming a recurring concern. This review provides a comprehensive overview of the measures that are necessary to be taken and implemented in order to guarantee global health security.
Adolescent Health and Dark Personalities: The Role of Socioeconomic Status, Sports, and Cyber Experiences
Authors: Lee Ilrang , Chang Yonghwan , Lei Ye , Yoo Taewoong
Published: August 2024

By investigating the impact of dark personality traits on adolescent health, this study explores the interplay among economic disadvantage, spectator sports involvement, and cyber victimization. We analyzed data from 1844 students aged 13–17 in a school district in the USA, and our findings reveal positive associations between economic disadvantage and both Machiavellianism and psychopathy, influencing negative emotions-driven eating. Spectator sports engagement exhibits links with Machiavellianism and narcissism, suggesting potential drawbacks to competitive behaviors. Cyber victimization shows associations with psychopathy and negative emotions-driven eating. The results illuminate the dynamic associations between emotional eating and health outcomes, including BMI and perceived quality of life. These findings deepen our understanding of how dark personality is shaped and subsequently influences adolescents’ well-being, offering insights for targeted interventions.
The Perception and Roles of School Mental Health Professionals Regarding School Bullying (Suluk Audwani) in Oman: A Qualitative Study in an Urban Setting
Authors: Al Saadoon Muna , Eltayib Rawaa Abubakr Abuelgassim , Alhaj Amjad Hassan , Chan Moon Fai , Aldhafri Said , Al-Adawi Samir
Published: August 2024

With increasing mental health risks among school populations and prevalent bullying, school mental health professionals (SMHP) are crucial globally. This study explores the perspectives of SMHP on bullying in Omani schools, focussing on definitions, types, current practices, and future strategies. Involving 50 Omani SMHP from Muscat Governorate with at least three years of experience, data was collected through structured interviews and analyzed using Braun and Clarke’s six-step thematic analysis. Six key themes emerged: The definition of bullying, its components, common types, current anti-bullying practices, challenges, and future suggestions. Bullying, termed “سلوكعدواني” (Suluk Audwani), meaning aggressive behavior, includes five components: perpetrators, victims, harmful behavior, spectators, and psychosocial factors. Verbal bullying, physical bullying, and cyberbullying are common and vary by age. SMHP frequently employ awareness-raising and psychological first aid. Challenges include resistance from students and parents and institutional barriers. In the future, SMHP will emphasize greater awareness to effectively address Suluk Audwani. Oman has adopted international best practices to recruit SMHP. SMHP’s perspectives on Suluk Audwani reflect both their training and Omani cultural influences. Future research should explore various social strata to improve evidence-based understanding and prevention of Suluk Audwani.
A Comparison of Oral Function in Older In- and Outpatients: An Observational Study
Authors: Eggimann Anna K. , Badura Leo , Zehnder Rahel , Koemeda Miriam , Buser Ramona , Schimmel Martin
Published: August 2024

(1) Background: Insufficient data exist regarding oral function among older adults in Europe. Therefore, we aimed to assess and compare oral function between older in- and outpatients and identify predictors of low masticatory performance. (2) Methods: Patients were consecutively recruited from the outpatient center (n = 31) and the inpatient geriatric department (n = 31) at a tertiary University Hospital in Switzerland in 2023. Assessments on oral function included the total number of intraoral eruptive teeth, number of supporting zones with dentures, maximal bite force (Dental Prescale II, Fuji Film Corp., Tokyo, Japan), and masticatory performance (Hue-Check Gum©, University of Bern, Bern, Switzerland) using a visual (SA1–SA5) and a digital (SD_Hue) scale. The visual and digital assessment of masticatory performance showed a strong correlation (Kendall tau = 0.83). Low masticatory performance was defined as SA-Grade 1–2 (vs. SA3–SA5 as reference). In a multivariate model adjusting for age, sex, and clinical setting, we investigated associations of maximal bite force, few eruptive teeth, and few supporting zones with low masticatory performance. (3) Results: Mean age was 81.9 (standard deviation (sd) 5.2) years, and 62.9% were female. Overall, maximal bite force was 247 N (sd 261). A total of 39 patients (63.9%) had a low masticatory performance, 62.9% a low maximal bite force, and 50% a low number of eruptive teeth (<10). Masticatory performance, number of eruptive teeth, and maximal bite force did not significantly differ between in- and outpatients. The number of supporting zones was significantly higher in outpatients compared to inpatients (median 4, interquartile range (IQR) 4–4; vs. 4, IQR 2–4; p = 0.03). In the multivariate model, maximal bite force and a low number of eruptive teeth were independently associated with low masticatory performance (adjusted odds ratio 7.4 (95% CI, 1.8–30.4; p < 0.01), and OR 7.8 (95% CI, 1.7–36.4; p < 0.01), respectively). (4) Conclusions: Impaired oral function is highly prevalent in both European older in- and outpatients to a similar degree. The association of low masticatory performance with maximal bite force and with a low number of eruptive teeth may indicate that a basic screening should include either of these parameters to identify impaired oral function.
Gambling Harm-Minimisation Tools and Their Impact on Gambling Behaviour: A Review of the Empirical Evidence
Authors: Riley Ben J. , Oakes Jane , Lawn Sharon
Published: August 2024

The harms accompanying disordered gambling are well documented. Additionally, there is growing attention to the harms that arise from people who gamble heavily but do not meet the criteria for a gambling disorder. Accordingly, there has been an increasing interest in the effectiveness of consumer protection tools for consumers of gambling products. Subsequently, there is a need to properly evaluate the evidence for their effectiveness. This review aimed to conduct a narrative synthesis of empirical studies to identify gaps, weaknesses, and strengths in the existing evidence for the effectiveness of harm minimisation tools available to people who gamble. This review includes studies published between January 2015 to July 2022 and comprises 55 peer-reviewed studies for final synthesis. Findings reveal that while more research is needed to examine the effectiveness of active and passive consumer protection tools, uptake of tools is low in part because users view them as tools for individuals already experiencing gambling harm as opposed to protective tools for all users. Research is needed to determine effective ways of communicating the value of consumer protection tools for gambling.
Empowering Personal Trainers to Work with Individuals with Disabilities to Improve Their Fitness
Authors: Beattie Cassandra , Streetman Aspen E. , Heinrich Katie M.
Published: August 2024

The benefits of regular physical activity for individuals with disabilities (IWDs) are well recognized. Nonetheless, IWDs report several barriers to physical activity participation, including limited access to qualified and experienced personal trainers. Limited research exists from personal trainers’ perspective. This qualitative study aimed to examine the experiences of personal trainers who successfully improve the fitness of IWDs. Individual interviews were conducted with ten personal trainers, focusing on educational and occupational background, experiences training IWDs, and experiences training IWDs within gyms. Thematic analysis produced five themes: (1) personal trainers working with IWDs need specialized education and extensive, often multidisciplinary, experience; (2) personal trainers are most successful when they have the opportunity to work with IWDs who have a diverse range of disabilities and differing expressions of each; (3) a robust network between personal trainers and allied healthcare providers is necessary to support IWDs; (4) access to physical activity is enhanced when trainers manage resources appropriately; and (5) personal trainers can empower IWDs to be advocates for their physical activity needs. Future research could examine the effects of an adaptive hands-on educational intervention among personal trainers to enhance IWDs’ health and fitness.
Mutational Profile in Romanian Patients with Hemophilia A
Authors: Grigore Andra , Dragomir Mihaela , Călugăru Onda-Tabita , Jardan Dumitru , Jardan Cerasela , Brînză Melen , Bălănescu Paul , Coriu Daniel
Published: August 2024

Hemophilia A (HA) is an X-linked recessive bleeding disorder caused by mutations in the F8 gene, resulting in deficient or dysfunctional factor VIII (FVIII). This study aimed to characterize the mutational profile of HA in Romanian patients using next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA). A total of 107 patients were analyzed, revealing pathogenic or likely pathogenic variants in 96.3% of cases. The identified mutations included missense (30.5%), nonsense (9.1%), small deletions (6.4%), small insertions (2.1%), splice-site variants (4.3%), large deletions (1.6%), and large duplications (1.1%). Large intron inversion was previously found in 37.5% of the patients. Novel variants accounted for 21.5% of identified mutations, expanding the spectrum of F8 variants in this population. This study underscores the genetic heterogeneity of HA and provides insights into genotype–phenotype correlations, aiding in clinical management and prenatal diagnosis.
Insulin–Heart Axis: Bridging Physiology to Insulin Resistance
Authors: Caturano Alfredo , Galiero Raffaele , Vetrano Erica , Sardu Celestino , Rinaldi Luca , Russo Vincenzo , Monda Marcellino , Marfella Raffaele , Sasso Ferdinando Carlo
Published: August 2024

Insulin signaling is vital for regulating cellular metabolism, growth, and survival pathways, particularly in tissues such as adipose, skeletal muscle, liver, and brain. Its role in the heart, however, is less well-explored. The heart, requiring significant ATP to fuel its contractile machinery, relies on insulin signaling to manage myocardial substrate supply and directly affect cardiac muscle metabolism. This review investigates the insulin–heart axis, focusing on insulin’s multifaceted influence on cardiac function, from metabolic regulation to the development of physiological cardiac hypertrophy. A central theme of this review is the pathophysiology of insulin resistance and its profound implications for cardiac health. We discuss the intricate molecular mechanisms by which insulin signaling modulates glucose and fatty acid metabolism in cardiomyocytes, emphasizing its pivotal role in maintaining cardiac energy homeostasis. Insulin resistance disrupts these processes, leading to significant cardiac metabolic disturbances, autonomic dysfunction, subcellular signaling abnormalities, and activation of the renin–angiotensin–aldosterone system. These factors collectively contribute to the progression of diabetic cardiomyopathy and other cardiovascular diseases. Insulin resistance is linked to hypertrophy, fibrosis, diastolic dysfunction, and systolic heart failure, exacerbating the risk of coronary artery disease and heart failure. Understanding the insulin–heart axis is crucial for developing therapeutic strategies to mitigate the cardiovascular complications associated with insulin resistance and diabetes.
The Complex FtBBX22 and FtHY5 Positively Regulates Light-Induced Anthocyanin Accumulation by Activating FtMYB42 in Tartary Buckwheat Sprouts
Authors: Deng Jiao , Zhang Lan , Wang Lijuan , Zhao Jiali , Yang Chaojie , Li Hongyou , Huang Juan , Shi Taoxiong , Zhu Liwei , Damaris Rebecca Njeri , Chen Qingfu
Published: August 2024

Anthocyanin is one important nutrition composition in Tartary buckwheat (Fagopyrum tataricum) sprouts, a component missing in its seeds. Although anthocyanin biosynthesis requires light, the mechanism of light-induced anthocyanin accumulation in Tartary buckwheat is unclear. Here, comparative transcriptome analysis of Tartary buckwheat sprouts under light and dark treatments and biochemical approaches were performed to identify the roles of one B-box protein BBX22 and ELONGATED HYPOCOTYL 5 (HY5). The overexpression assay showed that FtHY5 and FtBBX22 could both promote anthocyanin synthesis in red-flower tobacco. Additionally, FtBBX22 associated with FtHY5 to form a complex that activates the transcription of MYB transcription factor genes FtMYB42 and FtDFR, leading to anthocyanin accumulation. These findings revealed the regulation mechanism of light-induced anthocyanin synthesis and provide excellent gene resources for breeding high-quality Tartary buckwheat.
Tick-Derived Peptide Blocks Potassium Channel TREK-1
Authors: Du Canwei , Chen Linyan , Liu Guohao , Yuan Fuchu , Zhang Zheyang , Rong Mingqiang , Mo Guoxiang , Liu Changjun
Published: August 2024

Ticks transmit a variety of pathogens, including rickettsia and viruses, when they feed on blood, afflicting humans and other animals. Bioactive components acting on inflammation, coagulation, and the immune system were reported to facilitate ticks’ ability to suck blood and transmit tick-borne diseases. In this study, a novel peptide, IstTx, from an Ixodes scapularis cDNA library was analyzed. The peptide IstTx, obtained by recombinant expression and purification, selectively inhibited a potassium channel, TREK-1, in a dose-dependent manner, with an IC50 of 23.46 ± 0.22 μM. The peptide IstTx exhibited different characteristics from fluoxetine, and the possible interaction of the peptide IstTx binding to the channel was explored by molecular docking. Notably, extracellular acidification raised its inhibitory efficacy on the TREK-1 channel. Our results found that the tick-derived peptide IstTx blocked the TREK-1 channel and provided a novel tool acting on the potassium channel.
In Vitro Superparamagnetic Hyperthermia Employing Magnetite Gamma-Cyclodextrin Nanobioconjugates for Human Squamous Skin Carcinoma Therapy
Authors: Caizer-Gaitan Isabela-Simona , Watz Claudia-Geanina , Caizer Costica , Dehelean Cristina-Adriana , Bratu Tiberiu , Crainiceanu Zorin , Coroaba Adina , Pinteala Mariana , Soica Codruta-Marinela
Published: August 2024

In vitro alternative therapy of human epidermoid squamous carcinoma (A431) by superparamagnetic hyperthermia (SPMHT) using Fe3O4 (magnetite) superparamagnetic nanoparticles (SPIONs) with an average diameter of 15.8 nm, bioconjugated with hydroxypropyl gamma-cyclodextrins (HP-γ-CDs) by means of polyacrylic acid (PAA) biopolymer, is presented in this paper. The therapy was carried out at a temperature of 43 °C for 30 min using the concentrations of Fe3O4 ferrimagnetic nanoparticles from nanobioconjugates of 1, 5, and 10 mg/mL nanoparticles in cell suspension, which were previously found by us to be non-toxic for healthy cells (cell viabilities close to 100%), according to ISO standards (cell viability must be greater than 70%). The temperature for the in vitro therapy was obtained by the safe application (without exceeding the biological limit and cellular damage) of an alternating magnetic field with a frequency of 312.4 kHz and amplitudes of 168, 208, and 370 G, depending on the concentration of the magnetic nanoparticles. The optimal concentration of magnetic nanoparticles in suspension was found experimentally. The results obtained after the treatment show its high effectiveness in destroying the A431 tumor cells, up to 83%, with the possibility of increasing even more, which demonstrates the viability of the SPMHT method with Fe3O4-PAA–(HP-γ-CDs) nanobioconjugates for human squamous cancer therapy.
Synthetic Amphipathic Helical Peptide L-37pA Ameliorates the Development of Acute Respiratory Distress Syndrome (ARDS) and ARDS-Induced Pulmonary Fibrosis in Mice
Authors: Chernov Aleksandr S. , Telegin Georgii B. , Minakov Alexey N. , Kazakov Vitaly A. , Rodionov Maksim V. , Palikov Viktor A. , Kudriaeva Anna A. , Belogurov Alexey A.
Published: August 2024

In this study, we evaluated the ability of the synthetic amphipathic helical peptide (SAHP), L-37pA, which mediates pathogen recognition and innate immune responses, to treat acute respiratory distress syndrome (ARDS) accompanied by diffuse alveolar damage (DAD) and chronic pulmonary fibrosis (PF). For the modeling of ARDS/DAD, male ICR mice were used. Intrabronchial instillation (IB) of 200 µL of inflammatory agents was performed by an intravenous catheter 20 G into the left lung lobe only, leaving the right lobe unaffected. Intravenous injections (IVs) of L-37pA, dexamethasone (DEX) and physiological saline (saline) were used as therapies for ARDS/DAD. L37pA inhibited the circulating levels of inflammatory cytokines, such as IL-8, TNFα, IL1α, IL4, IL5, IL6, IL9 and IL10, by 75–95%. In all cases, the computed tomography (CT) data indicate that L-37pA reduced lung density faster to −335 ± 23 Hounsfield units (HU) on day 7 than with DEX and saline, to −105 ± 29 HU and −23 ± 11 HU, respectively. The results of functional tests showed that L-37pA treatment 6 h after ARDS/DAD initiation resulted in a more rapid improvement in the physiological respiratory lung by 30–45% functions compared with the comparison drugs. Our data suggest that synthetic amphipathic helical peptide L-37pA blocked a cytokine storm, inhibited acute and chronic pulmonary inflammation, prevented fibrosis development and improved physiological respiratory lung function in the ARDS/DAD mouse model. We concluded that a therapeutic strategy using SAHPs targeting SR-B receptors is a potential novel effective treatment for inflammation-induced ARDS, DAD and lung fibrosis of various etiologies.
Proteomic Profiling of Tears in Blau Syndrome Patients in Identification of Potential Disease Biomarkers
Authors: Galozzi Paola , Bindoli Sara , Baggio Chiara , Battisti Ilaria , Leonardi Andrea , Basso Daniela , Arrigoni Giorgio , Sfriso Paolo
Published: August 2024

Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils’ azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies.
Which Constituents Determine the Antioxidant Activity and Cytotoxicity of Garlic? Role of Organosulfur Compounds and Phenolics
Authors: Furdak Paulina , Bartosz Grzegorz , Sadowska-Bartosz Izabela
Published: August 2024

Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTS● decolorization, DPPH● decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S-allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p-coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.
The Combined Use of Cinnamaldehyde and Vitamin C Is Beneficial for Better Carcass Character and Intestinal Health of Broilers
Authors: Huang Yihong , Lang Aling , Yang Shan , Shahid Muhammad Suhaib , Yuan Jianmin
Published: August 2024

The use of cinnamaldehyde and Vitamin C can improve immunity and intestinal health. A two-way factorial design was employed to investigate the main and interactive effects of cinnamaldehyde and vitamin C on the growth, carcass, and intestinal health of broiler chickens. A total of 288 one-day-old female Arbor Acres broiler chicks were randomly distributed among four treatment groups, consisting of six replicate cages with 12 birds each. Four treatments were basal diet or control (CON), supplemental cinnamaldehyde (CA) 300 g/ton (g/t), vitamin C (VC) 300 g/t, and cinnamaldehyde 300 g/t, and vitamin C 300 g/t (CA + VC), respectively. The results showed that supplemental CA did not affect the growth performance or slaughter performance of broilers at 21 days (d), 42 days (d), and 1–42 days (d); however, it could improve intestinal barrier function at 42 d of age and reduce the mRNA expression of inflammatory factors in the intestine at 21 d and 42 d of age. Supplemental VC showed a trend towards increasing body weight gain (BWG) at 21 d (p = 0.094), increased breast muscle rate (at 21-d 5.33%, p < 0.05 and at 42-d 7.09%, p = 0.097), and decreased the abdominal fat (23.43%, p < 0.05) and drip loss (20.68%, p < 0.05) at 42-d. Moreover, VC improves intestinal morphology and intestinal barrier function and maintains a balanced immune response. The blend of CA and VC significantly upregulated the mRNA expression of myeloid differentiation factor 88 (MyD-88) in the intestine at 21 d of age, the mRNA expression of catalase (CAT), Occludin, Claudin-1, Mucin-2, nuclear factor-kappa B (NF-κB) and toll-like receptor 4 (TLR-4) in the intestine at 42 d of age (p < 0.01), and downregulated the mRNA expression of interleukin 10 (IL-10), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) in the intestine at 21-d and 42-d of age, and interleukin-1 beta (IL-1β) mRNA in intestine at 42 d of age (p < 0.01). This study suggested that the combination of CA and VC had the potential to regulate intestinal health and result in better carcass character of broilers.
Effect of Ferulic Acid Loaded in Nanoparticle on Tissue Transglutaminase Expression Levels in Human Glioblastoma Cell Line
Authors: Dell’Albani Paola , Carbone Claudia , Sposito Giovanni , Spatuzza Michela , Chiacchio Maria Assunta , Grasso Rosaria , Legnani Laura , Santonocito Debora , Puglia Carmelo , Parenti Rosalba , Puglisi Giovanni , Campisi Agatina
Published: August 2024

Glioblastoma (GBM) is one of the most aggressive cancers, characterized by a decrease in antioxidant levels. Evidence has demonstrated that ferulic acid (FA), a natural antioxidant particularly abundant in vegetables and fruits, could be a promising candidate for GBM treatment. Since FA shows a high instability that compromises its therapeutic application, it has been encapsulated into Nanostructured Lipid Carriers (NLCs) to improve its bioavailability in the brain. It has been demonstrated that tissue transglutaminase (TG2) is a multi-functional protein implicated in many physiological and pathological processes, including cancer. TG2 is also involved in GBM correlated with metastasis formation and drug resistance. Therefore, the evaluation of TG2 expression levels and its cellular localization are important to assess the anti-cancer effect of FA against GBM cancer. Our results have demonstrated that treatment with free FA and FA-NLCs in the U87-MG cancer cell line differently modified TG2 localization and expression levels. In the cells treated with free FA, TG2 appeared expressed both in the cytosol and in the nucleus, while the treatment with FA-NLCs showed that the protein is exclusively localized in the cytosol, exerting its pro-apoptotic effect. Therefore, our data suggest that FA loaded in NLCs could represent a promising natural agent for supplementing the current anti-cancer drugs used for the treatment of GBM.
Obesity Arrhythmias: Role of IL-6 Trans-Signaling
Authors: Aromolaran Kelly A. , Corbin Andrea , Aromolaran Ademuyiwa S.
Published: August 2024

Obesity is a chronic disease that is rapidly increasing in prevalence and affects more than 600 million adults worldwide, and this figure is estimated to increase by at least double by 2030. In the United States, more than one-third of the adult population is either overweight or obese. The global obesity epidemic is a major risk factor for the development of life-threatening arrhythmias occurring in patients with long QT, particularly in conditions where multiple heart-rate-corrected QT-interval-prolonging mechanisms are simultaneously present. In obesity, excess dietary fat in adipose tissue stimulates the release of immunomodulatory cytokines such as interleukin (IL)-6, leading to a state of chronic inflammation in patients. Over the last decade, increasing evidence has been found to support IL-6 signaling as a powerful predictor of the severity of heart diseases and increased risk for ventricular arrhythmias. IL-6′s pro-inflammatory effects are mediated via trans-signaling and may represent a novel arrhythmogenic risk factor in obese hearts. The first selective inhibitor of IL-6 trans-signaling, olamkicept, has shown encouraging results in phase II clinical studies for inflammatory bowel disease. Nevertheless, the connection between IL-6 trans-signaling and obesity-linked ventricular arrhythmias remains unexplored. Therefore, understanding how IL-6 trans-signaling elicits a cellular pro-arrhythmic phenotype and its use as an anti-arrhythmic target in a model of obesity remain unmet clinical needs.
Correction: Neubert et al. Effects of Normobaric Hypoxia and Adrenergic Blockade over 72 h on Cardiac Function in Rats. Int. J. Mol. Sci. 2023, 24, 11417
Authors: Neubert Elias , Rassler Beate , Hoschke Annekathrin , Raffort Coralie , Salameh Aida
Published: August 2024

In the original publication [...]
Human RNA Polymerase II Segregates from Genes and Nascent RNA and Transcribes in the Presence of DNA-Bound dCas9
Authors: Pessoa João , Carvalho Célia
Published: August 2024

RNA polymerase II (Pol II) dysfunction is frequently implied in human disease. Understanding its functional mechanism is essential for designing innovative therapeutic strategies. To visualize its supra-molecular interactions with genes and nascent RNA, we generated a human cell line carrying ~335 consecutive copies of a recombinant β-globin gene. Confocal microscopy showed that Pol II was not homogeneously concentrated around these identical gene copies. Moreover, Pol II signals partially overlapped with the genes and their nascent RNA, revealing extensive compartmentalization. Using a cell line carrying a single copy of the β-globin gene, we also tested if the binding of catalytically dead CRISPR-associated system 9 (dCas9) to different gene regions affected Pol II transcriptional activity. We assessed Pol II localization and nascent RNA levels using chromatin immunoprecipitation and droplet digital reverse transcription PCR, respectively. Some enrichment of transcriptionally paused Pol II accumulated in the promoter region was detected in a strand-specific way of gRNA binding, and there was no decrease in nascent RNA levels. Pol II preserved its transcriptional activity in the presence of DNA-bound dCas9. Our findings contribute further insight into the complex mechanism of mRNA transcription in human cells.
Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV
Authors: Barroso Sergio , Guitart-Mampel Mariona , García-García Francesc Josep , Cantó-Santos Judith , Valls-Roca Laura , Andújar-Sánchez Félix , Vilaseca-Capel Adrià , Tobías Ester , Arias-Dimas Angela , Quesada-López Tania , Artuch Rafael , Villarroya Francesc , Giralt Marta , Martínez Esteban , Lozano Ester , Garrabou Glòria
Published: August 2024

This study aimed to comprehensively assess the metabolic, mitochondrial, and inflammatory effects of first-line efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) single-tablet regimen (STR) relative to untreated asymptomatic HIV infection. To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-naïve PWH. Excellent therapeutic activity was accompanied by significant alterations in metabolic parameters. The treatment group showed increased plasmatic levels of glucose, total cholesterol and its fractions (LDL and HDL), triglycerides, and hepatic enzymes (GGT, ALP); conversely, bilirubin levels (total and indirect fraction) decreased in the treated cohort. Mitochondrial performance was preserved overall and treatment administration even promoted the recovery of mitochondrial DNA (mtDNA) content depleted by the virus, although this was not accompanied by the recovery in some of their encoded proteins (since cytochrome c oxidase II was significantly decreased). Inflammatory profile (TNFα, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNFα levels correlated to mtDNA cell restoration. Thus, although this regimen causes subclinical metabolic alterations, its antiviral and anti-inflammatory properties may be associated with partial improvement in mitochondrial function.