Search Results (6,564)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Background: In high-risk and frail patients with multivessel coronary artery disease (MV CAD), guidelines indicated complete revascularization with or without the use of cardiopulmonary bypass (CPB) bears a high morbidity and mortality risk. In cases where catheter interventions were deemed unsuitable and conventional coronary artery bypass grafting (CABG) posed an unacceptable perioperative risk, patients were scheduled for minimally invasive direct coronary artery bypass (MIDCAB) grafting or minimally invasive multivessel coronary artery bypass grafting (MICS-CABG). We called this approach “palliative revascularization.” This study assesses the safety and impact of palliative revascularization on clinical outcomes and overall survival. Methods: A consecutive series of 57 patients undergoing MIDCAB or MICS-CABG as a palliative surgery between 2008 and 2018 was included. The decision for palliative surgery was met in heart team after carefully assessing each case. The patients underwent single or double-vessel revascularization using the left internal thoracic artery and rarely radial artery/saphenous vein segments, both endoscopically harvested. Inpatient data could be completed for all 57 patients. The mean follow-up interval was 4.2 ± 3.7 years, with a follow-up rate of 91.2%. Results: Mean patient age was 79.7 ± 7.4 years. Overall, 46 patients (80.7%) were male, 26 (45.6%) had a history of atrial fibrillation and 25 (43.9%) of chronic kidney disease. In total, 13 patients exhibited a moderate EuroSCORE II, while 27 were classified as high risk, with a EuroSCORE II exceeding 5%. Additionally, 40 patients (70.2%) presented with three-vessel disease, 17 (29.8%) suffered an acute myocardial infarction within three weeks prior to surgery and 50.9% presented an impaired ejection fraction. There were 48 MIDCAB and nine MICS CABG with no conversions either to sternotomy or to CPB. Eight cases were planned as hybrid procedures and only 15 patients (26.3%) were completely revascularized. During the first 30 days, four patients (7%) died. A myocardial infarction occurred in only one case, no patient necessitated immediate reoperation. The one-, three- and five-year survival rates were 83%, 67% and 61%, respectively. Conclusions: MIDCAB and MICS CABG can be successfully conducted as less invasive palliative surgery in high-risk multimorbid patients with MV CAD. The early and mid-term results were better than predicted. A higher rate of hybrid procedures could improve long-term outcome in selected cases. Full article

Recent studies have demonstrated that the development and progression of hypertensive kidney injury comprise not only elevated systemic blood pressure but also a complex interplay of cellular, molecular, and genetic mechanisms. In this report, we outline the key emerging pathways—ranging from dysregulated renin–angiotensin system signaling, oxidative stress, immune-mediated inflammation, and metabolic abnormalities to epigenetic alterations and genetic susceptibilities—that contribute to kidney damage in hypertensive conditions. In addition, we also discuss precision medicine approaches like biomarker-directed therapies, pharmacologically targeted therapies, and device-based innovations for modulating these pathways. This integrative review emphasizes the application of omics technologies and genetically guided interventions to better stratify patients and offer personalized care for hypertensive kidney disease. Full article

This study investigated the evolving trends, current research hotspots, and future directions of radiotherapy combined with nanobiomaterials through a bibliometric analysis. Publications related to nanobiomaterials used in radiotherapy between 2004 and 2024 were retrieved from the Web of Science Core Collection database and analyzed using VOSviewer, R, and CiteSpace. China emerged as the leading contributor, accounting for 1051 publications (50.41%), followed by the USA. Liu Zhuang is the most productive author in this field. American Chemical Society (ACS) Nano published the most influential articles and accumulated the highest number of citations. Advanced Targeted Therapies in Cancer: Drug Nanocarriers, the Future of Chemotherapy was the most cited, with 1255 citations. Citation bursts have revealed emerging research trends in targeted delivery, cellular studies, co-delivery strategies, immunogenic cell death, polymeric nanoparticles, tumor research, and drug delivery systems, indicating potential avenues for future research. Over the past two decades, nanomaterials for radiotherapy have gained substantial attention. Key areas of focus include enhancing the efficacy of radiotherapy, achieving targeted drug delivery, minimizing adverse effects, and integrating nanomaterials with other therapeutic modalities. Future investigations are expected to improve the precision of radiotherapy, augment radiation effects, and optimize the tumor microenvironment. Full article

Multidrug-resistant (MDR) strains of Klebsiella pneumoniae present an acute threat as they continue to disseminate globally. Phage therapy has shown promise as a powerful approach to combat MDR infections, but narrow phage host ranges make development of broad acting therapeutics more challenging. The goal of this effort was to use in vitro directed evolution (the “Appelmans protocol”) to isolate K. pneumoniae phages with broader host ranges for improved therapeutic cocktails. Five myophages in the genus Jiaodavirus (family Straboviridae) with complementary activity were mixed and passaged against a panel of 11 bacterial strains including a permissive host and phage-resistant clinical isolates. Following multiple rounds of training, we collected phage variants displaying altered specificity or expanded host ranges compared with parental phages when tested against a 100 strain diversity panel of K. pneumoniae. Some phage variants gained the ability to lyse previously phage-resistant strains but lost activity towards previously phage-susceptible strains, while several variants had expanded activity. Whole-genome sequencing identified mutations and recombination events impacting genes associated with host tropism including tail fiber genes that most likely underlie the observed changes in host ranges. Evolved phages with broader activity are promising candidates for improved K. pneumoniae therapeutic phage cocktails. Full article

Curcumin, a polyphenolic compound derived from Curcuma longa, has drawn significant attention for its pleiotropic pharmacological activities, including anti-inflammatory and anticancer effects. Pyroptosis, an inflammatory form of programmed cell death mediated by inflammasome activation and gasdermin cleavage, has emerged as a critical target in both chronic inflammatory diseases and cancer therapy. This review comprehensively explores the dual roles of curcumin in the regulation of NLRP3 inflammasome-mediated pyroptosis. Curcumin exerts inhibitory effects by suppressing NF-κB signaling, attenuating mitochondrial reactive oxygen species (ROS) and ER stress, preventing potassium efflux, and disrupting inflammasome complex assembly. Conversely, in certain cancer contexts, curcumin promotes pyroptosis by stabilizing NLRP3 through the inhibition of Smurf2-mediated ubiquitination. Molecular docking studies support curcumin’s direct binding to several pyroptosis-associated proteins, including NLRP3, AMPK, caspase-1, and Smurf2. These context-dependent regulatory effects underscore the therapeutic potential of curcumin as both an inflammasome suppressor in inflammatory diseases and a pyroptosis inducer in cancer. 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

Amblyopia, commonly affecting children aged 0–6 years, results from disrupted visual processing during early development and often leads to reduced visual acuity in one eye. This study presents the development and preliminary usability assessment of a non-invasive ocular monitoring device designed to support oculomotor engagement and therapy adherence in amblyopia management. The system incorporates an interactive maze-navigation task controlled via gaze direction, implemented during monocular and binocular sessions. The device tracks lateral and anteroposterior eye movements and generates visual reports, including displacement metrics and elliptical movement graphs. Usability testing was conducted with a non-probabilistic adult sample (n = 15), including individuals with and without amblyopia. The System Usability Scale (SUS) yielded an average score of 75, indicating good usability. Preliminary tests with two adults diagnosed with amblyopia suggested increased eye displacement during monocular sessions, potentially reflecting enhanced engagement rather than direct therapeutic improvement. This feasibility study demonstrates the device’s potential as a supportive, gaze-controlled platform for visual engagement monitoring in amblyopia rehabilitation. Future clinical studies involving pediatric populations and integration of visual stimuli modulation are recommended to evaluate therapeutic efficacy and adaptability for early intervention. Full article

Heart failure (HF) is a major global health challenge, characterized by high morbidity, mortality, and frequent hospital readmissions. Despite the advent of guideline-directed medical therapies (GDMTs), the burden of HF continues to grow, necessitating a shift toward comprehensive, multidisciplinary care models. Heart Failure Disease Management Programs (HF-DMPs) have emerged as structured frameworks that integrate evidence-based medical therapy, patient education, telemonitoring, and support for social determinants of health to optimize outcomes and reduce healthcare costs. This review outlines the key components of HF-DMPs, including patient identification and risk stratification, pharmacologic optimization, team-based care, transitional follow-up, remote monitoring, performance metrics, and social support systems. Incorporating tools such as artificial intelligence, pharmacist-led titration, and community health worker support, HF-DMPs represent a scalable approach to improving care delivery. The success of these programs depends on tailored interventions, interdisciplinary collaboration, and health equity-driven strategies. 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: Parkinson’s disease (PD) often involves autonomic dysfunction, most notably impaired baroreflex sensitivity (BRS), which disrupts cardiovascular homeostasis and contributes to orthostatic hypotension (OH). Pharmacological and invasive treatments, including deep brain stimulation, have yielded inconsistent benefits and carry procedural risks, highlighting the need for safer, more accessible alternatives. In this systematic review, we evaluated non-invasive interventions—spanning somatosensory stimulation, exercise modalities, thermal therapies, and positional strategies—aimed at improving cardiovascular autonomic function in PD. Methods: We searched PubMed, Embase, MEDLINE (Ovid), Google Scholar, ScienceDirect, and Web of Science for studies published between January 2014 and December 2024. Eight original studies (n = 8) including 205 participants met the inclusion criteria for analyzing cardiac sympathovagal balance. Results: Five studies demonstrated significant post-intervention increases in BRS. Most reported favorable shifts in heart rate variability (HRV) and favorable changes in the low-frequency/high-frequency (LF/HF) ratio. Across modalities, systolic blood pressure (SBP) decreased by an average of 5%, and some interventions produced benefits that persisted up to 24 h. Conclusion: Although sample sizes were small and protocols heterogeneous, the collective findings support the potential of non-invasive neuromodulation to enhance BRS and overall cardiovascular regulation in PD. Future research should focus on standardized, higher-intensity or combined protocols with longer follow-up periods to establish durable, clinically meaningful improvements in autonomic function and quality of life for people living with PD. Full article

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional and neuroplastic effects of CE rehabilitation post-ACLR. Following PRISMA-ScR and JBI guidelines, PubMed, Scopus, Web of Science, and PEDro were searched up to February 2025. A bibliometric analysis was also conducted to report keyword co-occurrence and identify trends in this line of research. Of 333 screened references, 14 studies (price index: 43% and low-to-moderate risk of bias) involving 721 participants (aged 17–45 years) met inclusion criteria. CE protocols (6–12 weeks; 2–5 sessions/week) incorporating isometric, concentric, and eccentric exercises demonstrated strength gains (10–31%) and strength preservation, alongside improved limb symmetry (5–14%) and dynamic balance (7–18%). There is growing interest in neuroplasticity and corticospinal excitability, although neuroplastic changes were assessed heterogeneously across studies. Findings support CE as a feasible and low-cost strategy to complement early-stage ACLR rehabilitation, especially when direct loading of the affected limb is limited. Standardized protocols for clinical intervention and neurophysiological assessment are needed. 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