Search Results (4,163)

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

Background: Thallium is a metal that is ubiquitous in our natural environment. Despite its potential for high toxicity, thallium is understudied and not regulated in food. The California Department of Public Health was alerted to a household cluster of elevated urine thallium levels noted among a mother (peak 5.6 µg/g creatinine; adult reference: ≤0.4 µg/g creatinine) and her three young children (peak 10.5 µg/g creatinine; child reference: ≤0.8 µg/g creatinine). Objectives: This case report identifies questions raised after a public health investigation linked a household’s thallium exposure to a commercially available food product. We provide an overview of the public health investigation. We then explore concerns, such as gaps in toxicological data and limited surveillance of thallium in the food supply, which make management of individual and population exposure risks challenging. Methods: We highlight findings from a cross-agency investigation, including a household exposure survey, sampling of possible environmental and dietary exposures (ICP-MS analysis measured thallium in kale chips at 1.98 mg/kg and 2.15 mg/kg), and monitoring of symptoms and urine thallium levels after the source was removed. We use regulatory and research findings to describe the challenges and opportunities in characterizing the scale of thallium in our food supply and effects of dietary exposures on health. Discussion: Thallium can bioaccumulate in our food system, particularly in brassica vegetables like kale. Thallium concentration in foods can also be affected by manufacturing processes, such as dehydration. We have limited surveillance data nationally regarding this metal in our food supply. Dietary reviews internationally show increased thallium intake in toddlers. Limited information is available about low-dose or chronic exposures, particularly among children, although emerging evidence shows that there might be risks associated at lower levels than previously thought. Improved toxicological studies are needed to guide reference doses and food safety standards. Promising action towards enhanced monitoring of thallium is being pursued by food safety agencies internationally, and research is underway to deepen our understanding of thallium toxicity. Full article

Background/Objectives: Cancer represents a significant health challenge, with high mortality and morbidity rates. Its diagnosis often triggers chronic stress, adversely affecting patient outcomes. Exercise has emerged as complementary therapy, enhancing treatment adherence and mitigating the side effects of chemotherapy. This study examines the effects of mild exercise during chemotherapy on patient anxiety. Methods: This prospective paired cohort study was conducted in the General Oncology Hospital of Kifisia “Agioi Anargyroi” in Athens, Greece. Adult cancer patients undergoing chemotherapy participated, excluding those with cognitive, hearing, or motor impairments, those who experienced side effects, or those who declined consent. Anxiety was measured before and after a 20-minute exercise routine performed during chemotherapy, using the Greek-translated State–Trait Anxiety Inventory (STAI). The exercise regimen included warm-up, full-body stretching, and cool-down exercises. Pre- and post-exercise scores were analyzed using the Wilcoxon signed-rank test. Results: Forty-five patients (20 women, 25 men; mean age 69.02 ± 10.62 years) with various cancer backgrounds participated. Pre-intervention anxiety levels were in the borderline “moderate” range, dropping post-exercise to the “low” range. Mean STAI scores decreased from 37.73 ± 13.33 to 32.00 ± 14.22 (p < 0.0001), with a medium-large effect size (Cohen’s d for paired samples = −0.646). No significant correlation was found between age and anxiety scores. Discussion: This study found a significant short-term reduction in anxiety, suggesting that incorporating mild exercise during chemotherapy may help in alleviating patient stress. The medium-to-large effect size supports the potential for meaningful short-term benefits. Conclusions: Incorporating mild exercise during chemotherapy may help reduce anxiety and psychological burden. These findings underscore the need for more comprehensive research in larger, more diverse populations to better understand the benefits of incorporating mild exercise during chemotherapy. Full article

Background: Cerebral palsy (CP) is a lifelong neurodevelopmental disorder characterised by motor impairment and commonly associated with comorbidities such as cognitive, communicative, and behavioural difficulties. While the physical and functional aspects of CP have been extensively studied, the mental health needs of this population remain largely underexplored, particularly concerning suicidal ideation and self-injurious behaviours. The purpose of this review is to synthesise the existing literature on suicidality in individuals with CP, explore theoretical and clinical risk factors, and identify key gaps in the current evidence base. Methods: A narrative literature review was conducted focusing on studies addressing suicidal ideation, self-harm, or related psychiatric outcomes in individuals with CP. Additional literature on risks and protective factors was included to support theoretical inferences and clinical interpretations. Results: Only a limited number of studies addressed suicidality directly in CP populations. However, several reports document elevated rates of depression, anxiety, and emotional distress, particularly among adults and individuals with higher levels of functioning. Communication barriers, chronic pain, social exclusion, and lack of accessible mental health services emerged as critical risk factors. Protective elements included strong family support, inclusive environments, and access to augmentative communication. Conclusions: Suicidality in individuals with CP is a neglected yet potentially serious concern. Evidence suggests underdiagnosis due to factors such as communication barriers and diagnostic overshadowing. Future research should prioritise disability-informed methodologies and validated tools for suicidal ideation, while clinicians should incorporate routine, adapted mental health screening in CP care to ensure early detection and person-centred management. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics. Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology. In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity. Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders. Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use. Full article

The global rise in antimicrobial resistance poses a major threat to public health, with multidrug-resistant bacterial infections expected to surpass cancer in mortality by 2050. As traditional antibiotic pipelines stagnate, novel therapeutic alternatives are critically needed. Antimicrobial peptides (AMPs), particularly those derived from marine organisms, have emerged as promising antimicrobial candidates due to their broad-spectrum activity, structural diversity, and distinctive mechanisms of action. Unlike conventional antibiotics, AMPs can disrupt microbial membranes, inhibit biofilm formation, and even modulate immune responses, making them highly effective against resistant bacteria. This review highlights the potential of marine AMPs as next-generation therapeutics, emphasizing their efficacy against multidrug-resistant pathogens and biofilm-associated infections. Furthermore, marine AMPs show promise in combating persister cells and disrupting quorum sensing pathways, offering new strategies for tackling chronic infections. Despite their potential, challenges such as production scalability and limited clinical validation remain; nevertheless, the use of new technologies and bioinformatic tools is accelerating the discovery and optimization of these peptides, paving the way for bypassing these challenges. This review consolidates current findings on marine AMPs, advocating for their continued exploration as viable tools in the fight against antimicrobial resistance. Full article

Monoclonal B Lymphocytosis (MBL) is considered the pre-malignant state of chronic lymphocytic leukemia (CLL) and atypical chronic lymphocytic leukemia (aCLL). Both entities are rarely found in association with other hematological tumors; still, they naturally tend to progress to more aggressive lymphomas. This manuscript reports the case of an 81-year-old Caucasian male under follow up for MBL who presented to the Emergency Department with severe anemia and thrombocytopenia. A complete diagnostic workup revealed the simultaneous presence of atypical CLL and B-acute lymphoblastic leukemia, with minimal blast presence in peripheral blood. Full article

Hospital in the Home (HITH) programs are emerging as a key pillar of smart city healthcare infrastructure, leveraging technology to extend care beyond traditional hospital walls. The global healthcare sector has been conceptualizing the notion of a care without walls hospital, also called HITH, where virtual care takes precedence to address the multifaceted needs of an increasingly aging population grappling with a substantial burden of chronic disease. HITH programs have the potential to significantly reduce hospital bed occupancy, enabling hospitals to better manage the ever-increasing demand for inpatient care. Although many health providers and hospitals have established their own HITH programs, there is a lack of research that provides healthcare executives and HITH program managers with management models and frameworks for such initiatives. There is also a lack of research that provides strategies for improving HITH management in the health sector. To fill this gap, the current study ran a systematic literature review to explore state-of-the-art with regard to this topic. Out of 2631 articles in the pool of this systematic review, 20 articles were deemed to meet the eligibility criteria for the study. After analyzing these studies, nine management models were extracted, which were then categorized into three categories, namely, governance models, general models, and virtual models. Moreover, this study found 23 strategies and categorized them into five groups, namely, referral support, external support, care model support, technical support, and clinical team support. Finally, implications of findings for practitioners are carefully provided. These findings provide healthcare executives and HITH managers with practical frameworks for selecting appropriate management models and implementing evidence-based strategies to optimize program effectiveness, reduce costs, and improve patient outcomes while addressing the growing demand for home-based care. Full article

Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article

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

Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

Biofilms are structured communities of microorganisms encased in a self-produced extracellular matrix, and they represent one of the most widespread forms of microbial life on Earth. Their presence poses serious challenges in both environmental and clinical settings. In natural and industrial systems, biofilms contribute to water contamination, pipeline corrosion, and biofouling. Clinically, biofilm-associated infections are responsible for approximately 80% of all microbial infections, including endocarditis, osteomyelitis, cystic fibrosis, and chronic sinusitis. A particularly critical concern is their colonization of medical devices, where biofilms can lead to chronic infections, implant failure, and increased mortality. Implantable devices, such as orthopedic implants, cardiac pacemakers, cochlear implants, urinary catheters, and hernia meshes, are highly susceptible to microbial attachment and biofilm development. These infections are often recalcitrant to conventional antibiotics and frequently necessitate surgical revision. In the United States, over 500,000 biofilm-related implant infections occur annually, with prosthetic joint infections alone projected to incur revision surgery costs exceeding USD 500 million per year—a figure expected to rise to USD 1.62 billion by 2030. To address these challenges, surface modification of medical devices has emerged as a promising strategy to prevent bacterial adhesion and biofilm formation. This review focuses on recent advances in chemical surface functionalization using non-antibiotic agents, such as enzymes, chelating agents, quorum sensing quenching factors, biosurfactants, oxidizing compounds and nanoparticles, designed to enhance antifouling and mature biofilm eradication properties. These approaches aim not only to prevent device-associated infections but also to reduce dependence on antibiotics and mitigate the development of antimicrobial resistance. 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