Search Results (6,098)

Aortic aneurysms (AAs), both abdominal and thoracic, remain one of the most lethal cardiovascular diseases, with increasing prevalence and incidence, especially in sporadic forms, in our populations, primarily represented by elderly individuals. The high mortality risk is primarily due to delayed management, although their management has shown progress, particularly regarding imaging techniques that facilitate diagnosis and otherwise complex surgical procedures. This is due to the clinical decision-making approach, which, unfortunately, is still based, according to guidelines, on the maximum aortic diameter. The maximum aortic diameter, as repeatedly emphasized, fails to capture the biological and biomechanical complexity of these pathological conditions, which are influenced, among other things, by highly individual factors (genetics, gender, lifestyle, etc.). Thanks to the advent of network medicine and omics sciences, diverse and complex clinical, imaging, and biomarker datasets are available. Artificial intelligence (AI) could process this data to facilitate the complex management of aneurysms and accurately predict risk. AI could prove an excellent tool for aneurysm management, improving risk prediction and radically transforming the way we understand, monitor, and manage aneurysm patients, despite some limitations, as well as improving its therapeutic applications towards personalized strategies. This narrative review provides an overview of these aspects based on current evidence. Full article

Background: Toxoplasma gondii (T. gondii) is one of the most prevalent parasitic zoonoses worldwide, and the host’s immunological state significantly influences its clinical manifestations, which can be potentially fatal in immunocompromised hosts. The unavailability of a vaccine, combined with the considerable toxicity of existing medications, necessitates the urgent search for new therapies or adjunctive techniques, including regenerative and immunomodulatory approaches. Hence, the present study investigated, for the first time, the therapeutic potential of syngeneic platelet rich plasma (PRP) against T. gondii ME49 strain-induced chronic toxoplasmosis in both immunocompetent and immunosuppressed mouse models. Methods: 72 albino mice were divided into two sections, immunocompetent and immunosuppressed. Each section contained six groups: healthy, model, cotrimoxazole (CTZ)-treated, PRP-treated, half-dose of both CTZ and PRP-treated, and full-dose of both CTZ and PRP-treated. Treatment efficacy was assessed via parasitological, histological, immunohistochemical, and immunological analyses. Results: PRP, especially when coadministered with the CTZ, mitigated the consequences of toxoplasmosis by significantly reducing brain cyst counts (p < 0.0001), restoring brain tissue architecture, modulating apoptotic pathways by restoring caspase-3 expression in the brain, and normalizing systemic IFN-γ, TNF-α, and IL-10 cytokine profiles. Conclusions: The findings highlight PRP as an adjunct to the reference treatment, CTZ, for controlling toxoplasmosis in both immunocompetent and immunosuppressed conditions via anti-infective, neuroprotective, and immunomodulatory activities. Full article

Monoclonal antibodies (mAbs) have been the subject of extensive study in recent years due to their recognition as highly promising therapeutic molecules offering high specificity and a low risk of side effects. Monitoring the structure of these molecules is crucial for developing new therapeutics, characterizing interactions with antigens or receptors, and explaining potential changes in activity between antibody production batches. However, commonly used biophysical approaches provide only low-spatial-resolution information, and conventional structural biology techniques such as crystallography and cryo-electron microscopy (cryo-EM) are difficult to apply to these highly dynamic proteins. Solution nuclear magnetic resonance (NMR) spectroscopy is the method of choice for structural studies of flexible proteins at atomic resolution; however, it has traditionally been limited to low-molecular-weight biological systems. In this review, we present recent advances in NMR spectroscopy and advanced isotopic labeling methods that have enabled the atomic-resolution study of both the crystallizable (Fc) and antigen-binding (Fab) fragments of antibodies. We show how NMR is becoming a powerful tool for investigating full-length mAbs at an atomic level, opening up new possibilities for the characterization and in-depth quality control of therapeutic antibodies in solution. Full article

Background/Objectives: Gliclazide’s limited water solubility restricts its absorption across the gastrointestinal tract and compromises its therapeutic performance. This study developed a thermoresponsive solid dispersion based on the inverted thermoresponsive behavior of poloxamer 188 in propylene glycol. Methods: A solubility study was conducted to select components for the thermoresponsive solid dispersion. An I-optimal mixture design was used to optimize the concentrations of the thermoresponsive solid dispersion components (poloxamer 188, propylene glycol, and labrasol). FTIR and XRD were used to investigate the mechanism underlying the inverted thermoresponsive behavior. Finally, the influence of the thermoresponsive solid dispersion on gliclazide dissolution was evaluated through in vitro dissolution testing. Results: Surfactant screening identified labrasol as the optimal surfactant owing to a superior increase in gliclazide solubility compared to propylene glycol alone (2.29-fold). The optimized thermoresponsive solid dispersion (poloxamer 188, propylene glycol, and labrasol at 13.89, 21.43, and 64.68% w/w, respectively) achieved a drug solubility of 10.68 mg/g and a phase transition temperature of 36 °C. XRD and FTIR confirmed that hydrogen bonding is responsible for the system’s conversion between the solid and liquid states. Compared with raw gliclazide, the optimized formulation demonstrated an 8.4-fold increase in the initial dissolution rate and significantly improved dissolution efficiency from 21.77 ± 4.74% to 74.85 ± 2.33%. Conclusions: The present thermoresponsive solid dispersion provides a green alternative to conventional solid dispersion techniques. It avoids reliance on organic solvents, processing that demands high energy input, and additional post-processing operations. Full article

Background: Sapropelic mud from Techirghiol Lake has been used therapeutically under medical supervision for more than 170 years; however, its comprehensive physicochemical characterization under application-relevant conditions remains insufficiently documented. This study aimed to evaluate the physicochemical properties, mineral and organic composition, ion-exchange capacity, and potential therapeutic mechanisms of Techirghiol sapropelic mud. Methods: Mud samples were analyzed using standardized physicochemical and analytical techniques to determine pH, water content, granulometry, mineral composition, organic fraction, and trace elements. Results: The results indicate that Techirghiol mud is a highly hydrated alkaline peloid characterized by a complex mineral–organic system. Major elements included sodium, calcium, and magnesium, while trace elements such as manganese, iron, and zinc were present in relevant concentrations. The organic fraction, composed of humic substances, lipids, and proteins, reflected advanced but incomplete humification processes. Conclusions: The findings demonstrate the complex physicochemical composition of Techirghiol sapropelic mud and provide a scientific basis for further studies regarding its properties and applications. Full article

Intramyocardial hemorrhage (IMH) is a severe form of post-ischemic microvascular injury that may occur after myocardial infarction, particularly in the setting of extensive ischemia and reperfusion. IMH is closely related to microvascular obstruction (MVO), larger infarct size, impaired left-ventricular (LV) function, and adverse clinical outcomes. Cardiovascular magnetic resonance (CMR), especially susceptibility-sensitive techniques such as T2* or R2* mapping, enables in vivo detection of hemorrhagic microvascular injury and may refine post-MI risk stratification. Mechanistic and translational studies suggest that erythrocyte degradation and infarct-core iron deposition may contribute to persistent inflammation, maladaptive healing, adverse remodeling, and possibly arrhythmogenic substrate formation. However, most clinical evidence remains observational, and IMH-guided management has not yet been prospectively validated. This narrative review summarizes current evidence on the pathophysiology, imaging diagnosis, prognostic significance, and emerging therapeutic implications of IMH, while highlighting unresolved questions regarding standardized imaging, clinical implementation, and future phenotype-directed therapies. Full article

Aim: This review summarizes the current evidence on cognitive impairment in patients with glioma, with particular emphasis on the underlying mechanisms, methods for objective assessment of cognitive deficits, and currently available therapeutic strategies. Methods: Relevant literature was identified through searches of the PubMed, Cochrane Library, and Google Scholar databases. Studies addressing the mechanisms, assessment, and management of cognitive impairment in patients with glioma published between January 2000 and February 2026 were reviewed to summarize current evidence and emerging therapeutic strategies. A structured literature search and study selection process was performed. Results: Cognitive deficits represent a heterogeneous clinical problem affecting the majority of patients diagnosed with gliomas. These impairments are multifactorial in origin, resulting both from direct infiltration of white matter by the tumor process and from the cumulative toxicity of treatment modalities, including radiotherapy, chemotherapy, corticosteroid therapy, and long-term use of antiseizure medications. Analysis of the current literature confirms that modern radiotherapy techniques (e.g., hippocampal-sparing approaches) and isocitrate dehydrogenase (IDH)-targeted therapies, such as vorasidenib, may significantly delay cognitive decline. Standardized neuropsychological batteries for the objective assessment of these disturbances remain the preferred tools recommended by the International Cognition and Cancer Task Force (ICCTF). Regarding therapeutic interventions, potential benefits have been demonstrated for supportive pharmacotherapy (including memantine), while individualized neuropsychological rehabilitation has also been shown to improve patients’ quality of life. Full article

In this review, we explore the evolving role of endoscopic ultrasound (EUS) in diagnosing and managing pancretobiliary malignancies. For solid pancreatic lesions, techniques like fine-needle biopsy (FNB), contrast-enhanced EUS (CE-EUS), and macroscopic on-site evaluation (MOSE) improve sample quality and diagnostic accuracy. In cystic pancreatic lesions, fine-needle aspiration (FNA), molecular testing, and confocal laser endomicroscopy (nCLE) aid in distinguishing benign from malignant cysts. For cholangiocarcinoma, EUS guided sampling is more accurate than CT in assessing distal lesions and lymph node metastases, while combining EUS with magnetic resonance cholangiography (MRC) enhances diagnostic sensitivity. In gallbladder cancer, EUS surpasses CT and MRI in detecting lymphadenopathy and staging tumors. EUS-FNB (Fine needle biopsy) improves biopsy accuracy, especially for unresectable cases. These advancements highlight EUS as a critical tool for early cancer detection, staging, and tissue acquisition. Beyond diagnosis, EUS plays a pivotal therapeutic role in managing complications such as malignant biliary obstruction and gastric outlet obstruction, offering minimally invasive alternatives like EUS-guided biliary drainage and gastroenterostomy with high clinical success and improved patient outcomes. Full article

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an emerging intervention that provides a minimally invasive approach to drainage of the gallbladder, showing promising results in treating acute cholecystitis (AC) and malignant biliary obstruction (MBO). This review summarizes the current applications of EUS-GBD and compares its clinical effectiveness with traditional methods such as percutaneous transhepatic gallbladder drainage (PT-GBD) and endoscopic transpapillary gallbladder drainage (ET-GBD). Available evidence suggests that EUS-GBD may offer potential advantages in terms of success rates and complication profiles, particularly in patients who are not candidates for surgery or those at high surgical risk. The method is effective in reducing inflammation, alleviating symptoms from obstruction, and improving patient quality of life. This article also discusses the technical evolution of EUS-GBD, its indications, complications, and its comparative advantages over other drainage techniques. These observations suggest that EUS-GBD may represent a valuable addition to the therapeutic armamentarium for selected high-risk patients. Full article

Coronary artery calcification (CAC) represents a clear sign of advanced atherosclerosis and a strong indicator of coronary artery disease burden and cardiovascular risk. Beyond its established prognostic value, CAC significantly influences plaque biology, lesion morphology, and the technical complexity of percutaneous coronary intervention (PCI). This review summarizes current knowledge on the mechanisms of vascular calcification, its clinical determinants, diagnostic assessment, and therapeutic implications. Vascular calcification is now understood as an active, regulated process involving osteogenic transdifferentiation of vascular smooth muscle cells, inflammatory signaling pathways, extracellular vesicle release, and disturbances in mineral metabolism. Distinct calcification phenotypes exert different effects on plaque stability: micro- and spotty calcifications are frequently linked to plaque vulnerability, whereas dense, sheet-like calcification is more typical of stable fibrocalcific lesions. The prevalence of CAC increases with age and differs between sexes, while cardiometabolic risk factors, chronic kidney disease, systemic inflammation, and genetic predisposition further contribute to its development. Noninvasive computed tomography remains the cornerstone for CAC detection and quantification, enabling reliable cardiovascular risk stratification. Intravascular imaging techniques, particularly intravascular ultrasound and optical coherence tomography, provide detailed characterization of calcified plaque morphology and support optimal procedural planning. In patients with heavily calcified lesions, intravascular imaging-guided lesion preparation and stent optimization represent the most effective strategy for improving PCI outcomes. Full article

Background: Allergic rhinitis (AR) is a common inflammatory disorder with an unclear role of lytic cell death (LCD). This study aimed to identify LCD-associated genes associated with AR and investigate their underlying regulatory pathways. Methods: Transcriptomic data from AR patients (GSE19187, GSE206149) were retrieved from public repositories, and LCD-associated genes were collected from the literature. A combination of differential expression analysis, machine learning techniques, validation of expression levels, and ROC curve analysis was employed to screen for biomarkers. These biomarkers were then subjected to comprehensive functional characterization via GSEA, subcellular localization prediction, immune infiltration profiling, construction of molecular regulatory networks, and drug prediction. Finally, clinical relevance was confirmed through expression levels in patient specimens. Results: Two key indicators, ALOX15 and TIMP1, were successfully pinpointed. GSEA revealed significant enrichment of ALOX15 and TIMP1 in several biological processes, specifically chromatin organization, immune system response, and extracellular substance transport. Subcellular distribution studies showed that ALOX15 predominantly localized in the cytosol and plasma membrane, while TIMP1 was mainly detected extracellularly. Immune infiltration studies demonstrated notable modifications in seven immune cell populations, with significant associations with megakaryocyte–erythroid progenitors and conventional dendritic cells. Based on these findings, a regulatory network composed of transcription factors and microRNAs was established, and several potential therapeutic candidates (e.g., quercetin) were identified through prediction. Consistent with predictions, mRNA expression levels of both genes were significantly upregulated in the AR group compared to controls (p < 0.01), confirming reliability. Conclusions: In summary, ALOX15 and TIMP1 were identified as exploratory biomarkers associated with AR, providing preliminary insights into its molecular mechanisms and potential therapeutic implications. Full article

Fever of unknown origin (FUO) remains a persistent diagnostic challenge in clinical medicine despite significant advances in laboratory testing and imaging techniques. The definition of FUO has evolved since the original criteria proposed in 1961 and currently refers to persistent fever exceeding approximately 38.2–38.3 °C without a definitive diagnosis after an adequate diagnostic evaluation. Gastrointestinal diseases represent an important but often underrecognized group of conditions associated with FUO. The aim of this review is to synthesize current evidence on the gastroenterological causes of FUO, with particular emphasis on pathophysiological mechanisms, diagnostic strategies, and therapeutic management. The analysis highlights the role of inflammatory, infectious, and neoplastic gastrointestinal disorders in the etiology of prolonged fever. Key mechanisms involve systemic inflammatory responses mediated by cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor, as well as immune processes associated with the gut-associated lymphoid tissue (GALT) and interactions between intestinal microbiota and host immunity. Among the most frequently reported gastroenterological causes of FUO are inflammatory bowel diseases, intra-abdominal infections and abscesses, hepatobiliary disorders, pancreatitis, and gastrointestinal malignancies. Diagnostic evaluation requires a stepwise approach integrating laboratory testing, microbiological studies, imaging modalities, and endoscopic procedures, with advanced techniques such as computed tomography and fluorodeoxyglucose positron emission tomography improving detection of occult inflammatory or neoplastic processes. Therapeutic management is primarily guided by the identification of the underlying cause, while empirical treatment should be carefully considered to avoid masking diagnostic clues. A better understanding of the gastrointestinal mechanisms underlying FUO and the development of more efficient diagnostic algorithms may improve clinical outcomes and reduce the number of undiagnosed cases. Full article

Background and Objectives: Head and neck cancers are heterogeneous malignancies with variable biological behavior and treatment response, contributing to high morbidity and mortality. Conventional imaging techniques are limited in their ability to capture tumor biology, highlighting the need for advanced functional imaging. This review aims to evaluate the role of multiparametric magnetic resonance imaging (MRI) in characterizing the tumor microenvironment. Materials and Methods: A narrative review was conducted based on a targeted literature search of databases, including PubMed and Google Scholar. Studies addressing advanced MRI techniques for assessing tumor cellularity, vascularity, molecular features, and oxygenation were selected and analyzed. Results: Perfusion techniques, such as dynamic contrast-enhanced MRI (DCE-MRI) and arterial spin labeling (ASL), provide a quantitative assessment of tumor vascularity and show value in predicting treatment response. Diffusion-based methods, including diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI), enable evaluation of tissue cellularity and heterogeneity. Molecular approaches, such as chemical exchange saturation transfer (CEST) and amide proton transfer (APT), offer insights into protein content and proliferation. Oxygenation-sensitive techniques, such as blood oxygenation level dependent MRI (BOLD MRI) and oxygen-enhanced MRI (OE-MRI), allow non-invasive assessment of tumor hypoxia. Conclusions: Multiparametric MRI provides a comprehensive and biologically relevant evaluation of the tumor microenvironment in head and neck cancer, with potential to improve treatment prediction and support personalized therapeutic strategies. Full article

Cancer research has undergone a fundamental transformation in recent decades due to the integration of artificial intelligence (AI) models into the study of tumor biology. However, tumor evolution, driven by genetic and phenotypic alterations leading to heterogeneity, resistance and metastasis, remains a major challenge in oncology. To understand these processes is crucial for developing effective therapeutic strategies and improving patient outcomes. Conventional methods often fail to capture the complexity and dynamics of these processes. In contrast, AI tools have the ability to integrate and analyze large-scale multi-omics, imaging and clinical data, offering the capability to decode tumor complexity. AI-driven methods facilitate multi-modal data integration, enabling the recognition of patterns that connect molecular alterations with phenotypic outcomes. In functional genomics, AI tools predict the effects of genetic variants, identify regulatory elements and map dysregulated pathways, thus clarifying mechanisms underlying tumor development and resistance. In the imaging field, deep learning techniques improve tumor segmentation, characterization and longitudinal monitoring, providing more accurate insights into tumor progression and treatment response. Predictive modeling could allow the anticipation of tumor evolution and drug response, supporting adaptive therapeutic plans and real-time treatment adjustments. Moreover, AI supports biomarker discovery, patient stratification and decision support systems that can improve clinical trial design and accelerate the development of personalized therapies. However, these advances raise important ethical challenges, including data privacy, algorithmic bias and the preservation of patient autonomy. Addressing these concerns is essential to ensure the responsible deployment of AI in oncology. Full article

Traditional drug discovery is a high-risk, time-consuming, and costly endeavor. Drug repurposing has emerged as a pivotal strategy to overcome these challenges by identifying new therapeutic indications for approved drugs, thereby significantly reducing development timelines, costs, and safety risks. This review aims to provide a comprehensive methodological survey of computational strategies for drug repurposing. It seeks to clarify the core principles, applicability, and limitations of various approaches, offering a clear technological landscape and valuable insights for future research directions. We categorize and elaborate on the prevailing methodologies, following a logical progression. The review begins with biological mechanism-driven methods, including structure-based, omics-based, fuzzy logic-based, and adverse event-based methods. It then details network-based methods that integrate multi-source data, encompassing graph mining and matrix factorization/completion techniques. Finally, we explore data-driven paradigms, tracing the evolution from traditional text mining-based methods to cutting-edge large language model (LLM)-based methods. Each methodological category presents unique advantages and challenges. While structure-based, omics-based, fuzzy logic-based, and adverse event-based methods provide deep mechanistic insights, network-based methods enable systematic prediction. Text mining unlocks information from vast literature, a potential greatly amplified by LLMs. This review highlights that the future of drug repurposing lies in the intelligent integration of diverse methodologies. In the future, we believe that network-based methods and data-driven methods will mark the beginning of large-scale drug repurposing, but ultimately, biological mechanism-driven methods will still be necessary for rigorous validation and explanation. Full article