Search Results (4,983)

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

The growth potential of Crinum bulbispermum was evaluated on gold mine tailings. The primary objectives were to model the species’ climatic niche in relation to gold mining regions, assess its germination success on tailings, and compare seedling survival and growth on tailings versus other soil types. Species distribution modelling identified the South African Grassland Biome on the Highveld (1000+ m above sea level), where the majority of gold mines are located, as highly suitable for the species. Pot trials demonstrated above 85% germination success across all soil treatments, including gold mine tailings, indicating its potential for restoration through direct seeding. An initial seedling establishment rate of 100% further demonstrated the species’ resilience to mine tailings, which are often seasonally dry, nutrient-poor, and may contain potentially toxic metals. However, while C. bulbispermum was able to germinate and establish in mine tailings, long-term growth potential (over 12 months) was constrained by low organic carbon content (0.11%) and high salinity (194.50 mS/m). These findings underscore the critical role of soil chemistry and organic matter in supporting long-term plant establishment and growth on gold tailings. Building on previous research, this study confirms the ability of this thick-rooted geophyte to tolerate chemically extreme soil conditions. Crinum bulbispermum shows promise for phytostabilization and as a potential medicinal plant crop on tailings. However, future research on microbial community interactions and soil amendment strategies is essential to ensure its long-term sustainability. Full article

The advancement of artificial intelligence (AI), deep learning, and radiomics has introduced novel methodologies for the detection, classification, prognosis, and treatment evaluation of pancreatic ductal adenocarcinoma (PDAC). As the integration of AI into medical imaging continues to evolve, its potential to enhance early detection, refine diagnostic precision, and optimize treatment strategies becomes increasingly evident. However, despite significant progress, various challenges remain, particularly in terms of clinical applicability, generalizability, interpretability, and integration into routine practice. Understanding the current state of research is crucial for identifying gaps in the literature and exploring opportunities for future advancements. This literature review aims to provide a comprehensive overview of the existing studies on AI applications in PDAC, with a focus on disease detection, classification, survival prediction, treatment response assessment, and radiogenomics. By analyzing the methodologies, findings, and limitations of these studies, we aim to highlight the strengths of AI-driven approaches while addressing critical gaps that hinder their clinical translation. Furthermore, this review aims to discuss future directions in the field, emphasizing the need for multi-institutional collaborations, explainable AI models, and the integration of multi-modal data to advance the role of AI in personalized medicine for PDAC. Full article

Despite advances in medicine, cancer remains one of the foremost global health concerns. Conventional treatments like surgery, radiotherapy, and chemotherapy have advanced with the emergence of targeted and immunotherapy approaches. However, therapeutic resistance and relapse remain major barriers to long-term success in cancer treatment, often driven by cancer stem cells (CSCs). These rare, resilient cells can survive therapy and drive tumour regrowth, urging deeper investigation into the mechanisms underlying their persistence. CSCs express ion channels typical of excitable tissues, which, beyond electrophysiology, critically regulate CSC fate. However, the underlying regulatory mechanisms of these channels in CSCs remain largely unexplored and poorly understood. Nevertheless, the therapeutic potential of targeting CSC ion channels is immense, as it offers a powerful strategy to disrupt vital signalling pathways involved in numerous pathological conditions. In this review, we explore the diverse repertoire of ion channels expressed in CSCs and highlight recent mechanistic insights into how these channels modulate CSC behaviours, dynamics, and functions. We present a concise overview of ion channel-mediated CSC regulation, emphasizing their potential as novel diagnostic markers and therapeutic targets, and identifying key areas for future research. Full article

The Amazon region is home to a remarkable diversity of plant species that are used in traditional medicine and cuisine. This study aimed to evaluate the functional, antioxidant, and antimicrobial properties of the leaves of Allium schoenoprasum, Brugmansia candida (white and pink), and Cyclanthemum bipartitum. Bioactive compounds (L-ascorbic acid, organic acids, carotenoids, phenolic compounds, and chlorophylls) were quantified using liquid chromatography. The ABTS and DPPH methods were used to assess the antioxidant capacity. Additionally, the antimicrobial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus mutans, Candida albicans, and Candida tropicalis was evaluated. The results revealed a high content of L-ascorbic acid (7.6 mg/100 g dry weight) and total carotenoids (509.0 mg/100 g dry weight), as well as high antioxidant capacity (4.5 mmol TE/100 g dry weight) and broad antimicrobial activity in Brugmansia candida ‘pink’. The White variety had the highest concentration of total chlorophylls (1742.8 mg/100 g DW), Cyclanthemum bipartitum had the highest total organic acid content (2814.5 mg/100 g DW), and Allium schoenoprasum had the highest concentration of total phenolic compounds (11,351.6 mg/100 g DW). These results constitute a starting point for future research, emphasizing the potential health risks that certain species may pose. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article

Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency and therapeutic outcomes. Methods: This review synthesizes the current literature and recent advancements in non-viral transfection technologies. It focuses on the mechanisms, advantages, and limitations of various delivery systems, including lipid nanoparticles, biodegradable polymers, electroporation, peptide-based carriers, and microfluidic platforms. Comparative analysis was conducted to evaluate their performance in terms of transfection efficiency, cellular uptake, biocompatibility, and potential for clinical translation. Several academic search engines and online resources were utilized for data collection, including Science Direct, PubMed, Google Scholar Scopus, the National Cancer Institute’s online portal, and other reputable online databases. Results: Non-viral systems demonstrated superior performance in delivering mRNA, siRNA, and antisense oligonucleotides, particularly in clinical applications. Biodegradable polymers and peptide-based systems showed promise in enhancing biocompatibility and targeted delivery. Electroporation and microfluidic systems offered precise control over transfection parameters, improving reproducibility and scalability. Collectively, these innovations address key challenges in gene delivery, such as stability, immune response, and cell-type specificity. Conclusions: The continuous evolution of transfection technologies is pivotal for advancing gene and cell-based therapies. Non-viral delivery systems, particularly LNPs and emerging platforms like microfluidics and biodegradable polymers, offer safer and more adaptable alternatives to viral vectors. These innovations are critical for optimizing therapeutic efficacy and enabling personalized medicine, immunotherapy, and regenerative treatments. Future research should focus on integrating these technologies to develop next-generation transfection platforms with enhanced precision and clinical applicability. Full article

Background: Point-of-care ultrasound (POCUS) is gaining recognition as a valuable diagnostic tool in various fields of medicine, including pediatrics. Its application at the point of care enables real-time clinical decision-making, which is particularly advantageous in pediatric settings. Although global interest in POCUS is growing, many European countries—including Poland—still lack formal training programs for POCUS at both the undergraduate and postgraduate levels. Nevertheless, the number of pediatricians incorporating POCUS into their daily clinical practice in Poland is increasing. However, the extent of its use and perceived value among pediatricians remains largely unknown. This study aimed to evaluate the current level of POCUS utilization in pediatric care in Poland, focusing on pediatricians’ self-assessed competencies, perceptions of its clinical utility, and key barriers to its implementation in daily practice. Methods: This cross-sectional study was conducted between July and August 2024 using an anonymous online survey distributed to pediatricians throughout Poland via national professional networks, with a response rate of 7.3%. Categorical variables were analyzed using the chi-square test of independence to assess the associations between key variables. Quantitative data were analyzed using descriptive statistics, and qualitative data from open-ended responses were subjected to a thematic analysis. Results: A total of 210 pediatricians responded. Among them, 149 (71%) reported access to ultrasound equipment at their workplace, and 89 (42.4%) reported having participated in some form of POCUS training. Only 46 respondents (21.9%) reported frequently using POCUS in their clinical routine. The self-assessed POCUS competence was rated as low or very low by 136 respondents (64.8%). While POCUS was generally perceived as a helpful tool in facilitating and accelerating clinical decisions, the main barriers to implementation were a lack of formal training and limited institutional support. Conclusions: Although POCUS is perceived as clinically valuable by the surveyed pediatricians in Poland, its routine use remains limited due to training and systemic barriers. Future efforts should prioritize the development of a validated, competency-based training framework and the implementation of a larger, representative national study to guide the structured integration of POCUS into pediatric care. Full article

Background: Mesenchymal stem cells (MSCs) are a promising tool in regenerative medicine due to their ability to secrete paracrine factors that modulate tissue repair. Extracellular vesicles (EVs) released by MSCs contain bioactive molecules (e.g., mRNAs, miRNAs, proteins) and play a key role in intercellular communication. Methods: This study compared the transcriptomic profiles (mRNA and miRNA) of equine MSCs derived from adipose tissue (AT-MSCs), bone marrow (BM-MSCs), and ovarian fibroblasts (as a differentiated control). Additionally, miRNAs present in EVs secreted by these cells were characterized using next-generation sequencing. Results: All cell types met ISCT criteria for MSCs, including CD90 expression, lack of MHC II, trilineage differentiation, and adherence. EVs were isolated using ultracentrifugation and validated with nanoparticle tracking analysis and flow cytometry (CD63, CD81). Differential expression analysis revealed distinct mRNA and miRNA profiles across cell types and their secreted EVs, correlating with tissue origin. BM-MSCs showed unique regulation of genes linked to early development and osteogenesis. EVs contained diverse RNA species, including miRNA, mRNA, lncRNA, rRNA, and others. In total, 227 and 256 mature miRNAs were detected in BM-MSCs and AT-MSCs, respectively, including two novel miRNAs per MSC type. Fibroblasts expressed 209 mature miRNAs, including one novel miRNA also found in MSCs. Compared to fibroblasts, 60 and 92 differentially expressed miRNAs were identified in AT-MSCs and BM-MSCs, respectively. Conclusions: The results indicate that MSC tissue origin influences both transcriptomic profiles and EV miRNA content, which may help to interpret their therapeutic potential. Identifying key mRNAs and miRNAs could aid in future optimizing of MSC-based therapies in horses. Full article

Background/Objectives: Male infertility is a major health concern with a complex etiopathology, yet a substantial proportion of cases remain idiopathic. Mitochondrial dysfunction and non-coding RNA (ncRNA) deregulation have both been implicated in impaired spermatogenesis, but their interplay remains poorly understood. This study aimed to identify infertility-specific variants in ncRNAs that affect mitochondrial dynamics and homeostasis and to explore their roles. Methods: Whole-genome sequencing (WGS) was performed on genomic DNA samples from teratozoospermic, asthenozoospermic, oligozoospermic, and normozoospermic men. Variants uniquely present in infertile individuals and mapped to ncRNAs that affect mitochondrial dynamics were selected and prioritized using bioinformatics tools. An independent transcriptomic validation was conducted using RNA-sequencing data from testicular biopsies of men with non-obstructive azoospermia (NOA) to determine whether the ncRNAs harboring WGS-derived variants were transcriptionally altered. Results: We identified several infertility-specific variants located in lncRNAs known to interact with mitochondrial regulators, including GAS5, HOTAIR, PVT1, MEG3, and CDKN2B-AS1. Transcriptomic analysis confirmed significant deregulation of these lncRNAs in azoospermic testicular samples. Bioinformatic analysis also implicated the disruption of lncRNA–miRNA–mitochondria networks, potentially contributing to mitochondrial membrane potential loss, elevated reactive oxygen species (ROS) production, impaired mitophagy, and germ cell apoptosis. Conclusions: Our integrative genomic and transcriptomic analysis highlights lncRNA–mitochondrial gene interactions as a novel regulatory layer in male infertility, while the identified lncRNAs hold promise as biomarkers and therapeutic targets. However, future functional studies are warranted to elucidate their mechanistic roles and potential for clinical translation in reproductive medicine. Full article

Background and Clinical Significance: Brugada syndrome (BrS) is a rare inherited cardiac channelopathy, often associated with SCN5A loss-of-function mutations. Clinical presentations range from asymptomatic to malignant arrhythmias and sudden cardiac death. Physiological and pharmacological stressors affecting sodium channel function—such as pyrexia, certain medications, and possibly pregnancy—may unmask or exacerbate arrhythmic risk. However, there is limited information regarding pregnancy and obstetric outcomes. Obstetric management remains largely informed by isolated case reports and small case series. A literature review was conducted using OVID Medline and Embase, identifying case reports, case series, and one retrospective cohort study reporting clinical presentation, obstetric management, and outcomes in maternal BrS. A case is presented detailing coordinated multidisciplinary input, antenatal surveillance, and intrapartum and postpartum care to contribute to the growing evidence base guiding obstetric care in this complex setting. Case Presentation: A 30-year-old G2P0 woman with asymptomatic BrS (SCN5A-positive) was referred at 31 + 5 weeks’ gestation for multidisciplinary antenatal care. Regular review and collaborative planning involving cardiology, anaesthetics, maternal–fetal medicine, and obstetrics guided a plan for vaginal delivery with continuous cardiac and fetal monitoring. At 38 + 0 weeks, the woman presented with spontaneous rupture of membranes and underwent induction of labour. A normal vaginal delivery was achieved without arrhythmic events. Epidural block with ropivacaine and local anaesthesia with lignocaine were well tolerated, and 24 h postpartum monitoring revealed no abnormalities. Conclusions: This case adds to the limited but growing literature suggesting that with individualised planning and multidisciplinary care, pregnancies in women with BrS can proceed safely and without complication. Ongoing case reporting is essential to inform future guidelines and optimise maternal and fetal outcomes. Full article

The interaction between bacteria and fungi is one of the key interactions of microbial ecology, including mutualism, antagonism, and competition, which profoundly affects the balance and functions of animal microbial ecosystems. This article reviews the interactive dynamics of bacteria and fungi in more concerned microenvironments in animals, such as gut, rumen, and skin. Moreover, we summarize the molecular mechanisms and ecological functions of the interaction between bacteria and fungi. Three major bacterial–fungal interactions (mutualism, antagonism, and competition) are deeply discussed. Understanding of the interactions between bacteria and fungi allows us to understand, modulate, and maintain the community structure and functions. Furthermore, this summarization will provide a comprehensive perspective on animal production and veterinary medicine, as well as guide future research directions. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Valued for their nutritional content, eggs have recently gained attention as a versatile biomaterial owing to their biocompatibility, biodegradability, and unique structural and biochemical composition. This review highlights the biomedical potential of various egg components—eggshell, eggshell membrane, egg white, and egg yolk—and their applications in bone grafting, tissue engineering, wound healing, drug delivery, and biosensors. Eggshells serve as a natural, calcium-rich source for bone tissue engineering and regenerative medicine. The eggshell membrane, with its antimicrobial and structural properties, offers promise as a wound healing scaffold. Egg white, known for its gelation and film-forming capabilities, is utilized in hydrogel-based systems for drug delivery and biosensing. Egg yolk, rich in lipids and immunoglobulin Y (IgY) antibodies, is being explored for diagnostic and therapeutic applications. This review critically examines the advantages and limitations of each egg-derived component and outlines current research gaps, offering insights into future directions for the development of egg-based biomaterials in biomedical engineering. Full article

Endotoxemia is commonly observed in donkeys, secondary to colic, pleuropneumonia, or diarrhea among other disorders. Hematologic ratios are new biomarkers widely used in the diagnosis and prognosis of multiple conditions in human medicine, including sepsis. While the utility of these ratios has been proved in septic foals, no data are available on donkeys. Moreover, reference intervals (RIs) have not been studied in this species. In this study, RIs of the most commonly reported hematologic ratios were determined in 73 healthy adult donkeys. In addition, variations in these ratios in response to LPS infusion were also evaluated in six healthy adult donkeys. Most of the ratios evaluated showed significant variations after induced endotoxemia, with most of them showing values outside of the established RIs. Similarly to septic foals, the neutrophil to lymphocyte ratio was significantly reduced after LPS infusion. No significant changes were observed in the red cell distribution width to platelet ratio, contrary to reports on septic foals. Previously reported cut-off values for both of these ratios should not be extrapolated to donkeys. Future studies evaluating these ratios in natural endotoxemia or other diseases in donkeys, as well as establishing species-specific cut-off values, are necessary. Full article