Search Results (2,796)

Cardiovascular diseases remain a leading cause of mortality in the United States, driving the need for advanced cardiovascular devices and pharmaceuticals. Mock Circulatory Loops (MCLs) have emerged as essential tools for in vitro testing, replicating pulsatile pressure and flow to simulate various physiological and pathological conditions. While many studies focus on custom MCL designs tailored to specific applications, few have systematically reviewed their use in device testing, and none have assessed their broader utility across diverse biomedical domains. This comprehensive review categorizes MCL designs into three types: mechanical, computational, and hybrid. Applications are classified into four major areas: Cardiovascular Devices Testing, Clinical Training and Education, Hemodynamics and Blood Flow Studies, and Disease Modeling. Most existing MCLs are complex, highly specialized, and difficult to reproduce, highlighting the need for simplified, standardized, and programmable hybrid systems. Improved validation and waveform fidelity—particularly through incorporation of the dicrotic notch and other waveform parameters—are critical for advancing MCL reliability. Furthermore, integration of machine learning and artificial intelligence holds significant promise for enhancing waveform analysis, diagnostics, predictive modeling, and personalized care. In conclusion, the development of MCLs should prioritize standardization, simplification, and broader accessibility to expand their impact across biomedical research and clinical translation. Full article

This protocol paper outlines a robust and reproducible framework for a ¹H nuclear magnetic resonance (NMR) metabolomics analysis of rodent plasma, designed to facilitate preclinical biomarker discovery. The protocol details optimised steps for plasma collection in a preclinical rodent model, sample preparation, and NMR data acquisition using presaturation Carr–Purcell–Meiboom–Gill (PRESAT-CPMG) pulse sequences, ensuring high-quality spectral data and effective suppression of macromolecule signals. Comprehensive spectral processing and metabolite assignment are described, with guidance on multivariate and univariate statistical analyses to identify metabolic changes and potential biomarkers. The framework emphasises methodological rigour and reproducibility, enabling accurate quantification and interpretation of metabolites relevant to disease mechanisms or therapeutic interventions. By providing a standardised approach, this protocol supports longitudinal and translational studies, bridging findings from rodent models to clinical applications and advancing the reliability of metabolomics-based biomarker discovery in preclinical research. Full article

Intravascular biosensors have become a crucial and novel class of devices in healthcare, enabling the constant real-time monitoring of essential physiological parameters directly within the circulatory system. Recent developments in micro- and nanotechnology have relevantly improved the sensitivity, miniaturization, and biocompatibility of these devices, thereby enabling their application in precision medicine. This review summarizes the latest advances in intravascular biosensor technologies, with a special focus on glucose and oxygen level monitoring, blood pressure and heart rate assessment, and early disease diagnostics, as well as modern approaches to drug therapy monitoring and delivery systems. Key challenges such as long-term biostability, signal accuracy, and regulatory approval processes are critical considerations. Innovative strategies, including biodegradable implants, nanomaterial-functionalized surfaces, and integration with artificial intelligence, are regarded as promising avenues to overcome current limitations. This review provides a comprehensive roadmap for upcoming research and the clinical translation of advanced intravascular biosensors with a strong emphasis on their transformative impact on personalized healthcare. Full article

Pseudomonas aeruginosa poses significant health threats due to its multidrug-resistant profile, particularly affecting immunocompromised individuals. The pathogen’s ability to produce virulence factors and antibiotic-resistant biofilms, orchestrated through quorum-sensing (QS) mechanisms, complicates conventional therapeutic interventions. This review aims to critically assess the potential of anti-QS strategies as alternatives to antibiotics against P. aeruginosa infections. Comprehensive literature searches were conducted using databases such as PubMed, Scopus, and Web of Science, focusing on studies addressing QS inhibition strategies published recently. Anti-QS strategies significantly attenuate bacterial virulence by disrupting QS-regulated genes involved in biofilm formation, motility, toxin secretion, and immune evasion. These interventions reduce the selective pressure for resistance and enhance antibiotic efficacy when used in combination therapies. Despite promising outcomes, practical application faces challenges, including specificity of inhibitors, pharmacokinetic limitations, potential cytotoxicity, and bacterial adaptability leading to resistance. Future perspectives should focus on multi-target QS inhibitors, advanced delivery systems, rigorous preclinical validations, and clinical translation frameworks. Addressing current limitations through multidisciplinary research can lead to clinically viable QS-targeted therapies, offering sustainable alternatives to traditional antibiotics and effectively managing antibiotic resistance. 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

The 3rd Annual Meeting of the International Network on Ectopic Calcification (INTEC) was held in Faro, Portugal on 12–13 September 2024. This hybrid meeting brought together researchers and clinicians focused on the molecular, (patho)physiological, and clinical aspects of ectopic calcification in hereditary and acquired conditions, as well as in aging. The findings presented in this year’s meeting emphasised the complexity of the field, offering new insights into both mechanistic pathways and translational hurdles. The abstracts of this year’s meeting are collected in this conference paper, with permission from the corresponding authors. Full article

Polyethylenimine (PEI) is a cationic polymer with a high density of amine groups suitable for strong electrostatic interactions with biological molecules to preserve their bioactivities during encapsulation and after delivery for biomedical applications. This review provides a comprehensive overview of PEI as a drug and gene carrier, describing its polymerization methods in both linear and branched forms while highlighting the processing methods to manufacture PEIs into drug carriers, such as nanoparticles, coatings, nanofibers, hydrogels, and films. These various PEI carriers enable applications in non-viral gene and small molecule drug deliveries. The structure–property relationships of PEI carriers are discussed with emphasis on how molecular weights, branching degrees, and surface modifications of PEI carriers impact biocompatibility, transfection efficiency, and cellular interactions. While PEI offers remarkable potential for drug and gene delivery, its clinical translation remains limited by challenges, including cytotoxicity, non-degradability, and serum instability. Our aim is to provide an understanding of PEI and the structure–property relationships of its carrier forms to inform future research directions that may enable safe and effective clinical use of PEI carriers for drug and gene delivery. Full article

Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, and clinically significant drug–drug interactions, partly mediated by modulation of P-glycoprotein and cytochrome P450 3A4 metabolism. This review explores advanced delivery strategies designed to overcome these limitations. We critically evaluate lipid-based systems, such as solid lipid nanoparticles, liposomes, transferosomes, ethosomes, and cubosomes; polymer-based nanoparticles; microneedles; and implants, including drug-eluting stents. These systems ensure targeted delivery, improve pharmacokinetics, and reduce toxicity. Additionally, we discuss chemical derivatization approaches, such as prodrugs, codrugs, and strategic ring modifications (A-, B-, and C-rings), aimed at optimizing both the efficacy and safety profile of colchicine. Combinatorial nanoformulations that enable the co-delivery of colchicine with synergistic agents, such as glucocorticoids and statins, as well as theranostic platforms that integrate therapeutic and diagnostic functions, are also considered. These innovative delivery systems and derivatives have the potential to transform colchicine therapy by broadening its clinical applications while minimizing adverse effects. Future challenges include scalable manufacturing, long-term safety validation, and the translation of research into clinical practice. Full article

Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. 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: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy arising from the nasopharyngeal mucosa. Despite treatment advances such as the use of intensity-modulated radiotherapy and immune checkpoint inhibitors, resistance remains a significant clinical challenge. Many tumours are also diagnosed at an advanced stage associated with poor prognosis. Objective: This review aims to explore the biological roles of autophagy in NPC, primarily highlighting its involvement in disease pathogenesis and treatment resistance. Methods: We performed a review of the recent literature examining the role of autophagy-related pathways in NPC pathogenesis, biomarker discovery, and therapeutic targeting. Results: Autophagy plays a dual role in NPC as it contributes to both tumour suppression and progression. It is involved in tumour initiation, metastasis, immune modulation, and treatment resistance. Autophagy-related genes such as SQSTM1, Beclin-1, and AURKA may serve as prognostic and therapeutic biomarkers. Various strategies are being investigated for their role to modulate autophagy using pharmacologic inhibitors, RNA interventions, and natural compounds. Conclusions: Further research into autophagy’s context-dependent roles in NPC may inform the development of personalised therapies and allow progress in translational and precision oncology. 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

Tumor treatments have substantially advanced through various approaches, including chemotherapy, radiotherapy, immunotherapy, and gene therapy. However, efficient treatment necessitates overcoming physiological barriers that impede the delivery of therapeutic agents to target sites. Drug delivery systems (DDSs) are a prominent research area, particularly in tumor therapy. This review provides a comprehensive overview of hydrogel-based DDSs for tumor treatment, focusing on the strategies and designs of DDSs based on the unique pathophysiological characteristics of tumors. The design and preparation of hydrogel systems for DDSs are summarized and highlighted. The challenges and opportunities for translating hydrogel-based DDSs into clinical applications are discussed. Full article

Conventional immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, has revolutionized cancer therapy over the past decade. Yet, the efficacy of these therapies is limited by tumor resistance, antigen escape mechanisms, poor persistence, and T-cell exhaustion, particularly in the treatment of solid tumors. The emergence of unconventional immunotherapies offers novel opportunities by leveraging diverse immune cell subsets and synthetic biologics. This review explores various immunotherapy platforms, including gamma delta T cells, invariant natural killer T cells, mucosal-associated invariant T cells, engineered regulatory T cells, and universal CAR platforms. Additionally, it expands on biologics, including bispecific and multispecific antibodies, cytokine fusions, agonists, and oncolytic viruses, showcasing their potential for modular engineering and off-the-shelf applicability. Distinct features of unconventional platforms include independence from the major histocompatibility complex (MHC), tissue-homing capabilities, stress ligand sensing, and the ability to bridge adaptive and innate immunity. Their compatibility with engineering approaches highlights their potential as scalable, efficient, and cost-effective therapies. To overcome translational challenges such as functional heterogeneity, immune exhaustion, tumor microenvironment-mediated suppression, and limited persistence, novel strategies will be discussed, including metabolic and epigenetic reprogramming, immune cloaking, gene editing, and the utilization of artificial intelligence for patient stratification. Ultimately, unconventional immunotherapies extend the therapeutic horizon of cancer immunotherapy by breaking barriers in solid tumor treatment and increasing accessibility. Continued investments in research for mechanistic insights and scalable manufacturing are key to unlocking their full clinical potential. Full article

A wide range of strategies have been developed to modulate dysfunctional brain activities. This narrative review provides a comparative analysis of biophysical, genetic, and biological neuromodulation approaches with an emphasis on their known or unknown molecular targets and translational potential. The review incorporates data from both preclinical and clinical studies covering deep brain stimulation, transcranial electrical and magnetic stimulation, focused ultrasound, chemogenetics, optogenetics, magnetogenetics, and toxin-based neuromodulation. Each method was assessed based on specificity, safety, reversibility, and mechanistic clarity. Biophysical methods are widely used in clinical practice but often rely on empirical outcomes due to undefined molecular targets. Genetic tools offer cell-type precision in experimental systems but face translational barriers related to delivery and safety. Biological agents, such as botulinum neurotoxins, provide long-lasting yet reversible inhibition via well-characterized molecular pathways. However, they require stereotaxic injections and remain invasive. To overcome individual limitations and improve targeting, delivery, and efficacy, there is a growing interest in the synthesis of multiple approaches. This review highlights a critical gap in the mechanistic understanding of commonly used methods. Addressing this gap by identifying molecular targets may help to improve therapeutic precision. This concise review could be valuable for researchers looking to enter the evolving field of the neuromodulation of brain function. Full article