Pharmaceuticals最新文献

Background/Objectives: Microbe-derived extracellular vesicles (MEVs) provide a biocompatible, naturally derived platform for drug delivery. Methods: We encapsulated doxorubicin in Lactobacillus plantarum-derived EVs and evaluated their ability at delivering doxorubicin to colorectal cancer cells in vitro. Endocytosis inhibitors were used to investigate the mechanisms by which the MEVs entered the cells. Results: The MEVs maintained structural stability under physiological conditions. Cellular internalization of doxorubicin-loaded MEVs involve clathrin/caveolae-dependent endocytosis, and dynamin- and clathrin-mediated pathways. Conclusions: These findings highlight the role of the microbe-cancer cell biointerface in mediating drug uptake and enabling intracellular delivery. The study supports the potential of MEVs as nanocarriers for anticancer drugs and provides mechanistic insights into the intracellular trafficking pathways that influence drug activity.

Background: Amidst escalating global challenges such as antimicrobial resistance and post-COVID therapeutic gaps, dihydropyrimidines (DHPs) and their thione derivatives have emerged as a highly promising scaffold for drug development. This systematic review aims to consolidate recent advancements (2020-2025) and evaluate the synthetic innovation, structure-activity relationships (SAR), and preclinical potential of these compounds. Methods: A systematic review was conducted according to PRISMA guidelines, searching multiple electronic databases (Scopus, PubMed, Web of Science). Sixty original studies from 2020 to 2025 meeting predefined inclusion criteria were selected for data extraction and qualitative synthesis. Results: The analysis reveals a surge in publications (over 300% since 2020). Key structural modifications, such as N-methylation to improve bioavailability and specific substitutions at C4/C5 positions, significantly enhance biological potency, yielding strong inhibitory effects against viral proteases and cancer cell lines. Notable compounds include the apoptosis inducer LaSOM 65 and multitarget Ru(II)-Biginelli hybrids. Conclusions: This review affirms the timeliness and translational potential of the DHP scaffold. The field shows bright prospects for advancing to phase I trials by 2030, urging intensified exploration to unlock novel pharmaceuticals from this versatile chemotype.

Background/Objectives: Anatolia hosts a rich diversity of Hypericum taxa; however, the chemical and biological properties of most species remain insufficiently characterized. Methods: This study combined liquid chromatography-high-resolution mass spectrometry (LC-HRMS) with high-performance liquid chromatography coupled to diode-array detection (HPLC-DAD) to profile 14 extracts obtained from 12 Anatolian species together with H. perforatum, and to examine whether metabolic variation aligns with bioactivity trends. Results: Chemometric analyses (Principal Component Analysis-PCA-and Hierarchical Cluster Analysis-HCA) revealed distinct chemotypes primarily driven by phenolic acids and flavonol glycosides, with hyperoside emerging as a consistently abundant marker. Phenolic-rich extracts displayed enhanced functional properties in multiple assays. Among them, H. triquetrifolium showed the strongest acetylcholinesterase inhibition and notable antioxidant capacity, whereas the selected taxa exhibited comparatively high tyrosinase or α-glucosidase inhibition. Antimicrobial testing indicated narrow-spectrum activity limited to Gram-positive bacteria and Candida spp. Conclusions: The integration of metabolite profiling with chemometric and functional data highlights clear chemotype-bioactivity associations across Anatolian Hypericum taxa and underscores the analytical value of LC-HRMS-guided chemotyping for pharmacognostic assessments. These results broaden the phytochemical and bioactivity landscape of this genus and provide a comparative framework for prioritizing species for future targeted investigations.

Inhalation has been employed for millennia as a means to deliver therapeutic agents directly to the respiratory tract, particularly for the local management of airway diseases such as asthma, bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis [...].

Background: Analgesics are widely used in competitive sports, but their patterns of use and detection in anti-doping controls vary significantly across drug classes. This study examined a decade of Italian anti-doping reports with three aims: to describe trends involving non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and narcotics; to characterize the distribution of specific active ingredients; and to analyze the relative contribution of these classes to anti-doping violations, placing the findings within the regulatory framework. Methods: Data from national anti-doping reporting systems were analyzed from 2013 to the first half of 2023. Yearly data included tested athletes, athlete declarations of NSAID use, and laboratory analytical findings for prohibited substances (glucocorticoids and narcotics). NSAID prevalence was calculated relative to tested athletes, while glucocorticoid and narcotic findings were assessed as absolute counts and proportions of total violations. Temporal trends were assessed using the Cochran-Armitage test. Results: NSAIDs consistently ranked as the most frequently reported medication, with nearly half of the tested athletes reporting their use and no significant linear trend in overall prevalence. However, a significant shift was observed within the NSAID class, with a marked decrease in declarations of COX-2 selective agents over time. Glucocorticoids accounted for a significant portion of prohibited substances, with fluctuating proportions (showing no significant linear trend), betamethasone being the most common active ingredient. Narcotics appeared only sporadically, although the use of non-prohibited opioids such as tramadol and codeine-absent from official reports-remains relevant for understanding analgesic practices. Conclusions: Analgesic use in Italian elite sports shows distinct patterns driven by therapeutic needs and anti-doping regulations. NSAIDs remain the primary choice for routine pain management, though the type of NSAID reported has shifted significantly. Glucocorticoids represent a notable share of prohibited findings with a fluctuating, rather than steadily increasing, pattern. Narcotics appear only sporadically in violation data. Ongoing monitoring will be crucial to understanding how evolving clinical practices and recent regulatory changes influence future detection trends and athlete health.

Background: It is well known that host factors are capable of regulating microbial behaviours such as growth, metabolic pathways, virulence properties, and antimicrobial susceptibilities. In this respect, the present study aimed to investigate the relationship between insulin and various virulence properties of Pseudomonas aeruginosa ATCC 27853. Methods: Growth alterations, biofilm formation, motility, haemolytic activity, and pigment production (pyocyanin and pyoverdine) were determined in the presence/absence of three different insulin concentrations (10 µU/mL -20 µU/mL -200 µU/mL) under in vitro conditions. In addition, changes in bacterial virulence were evaluated in an in vivo animal (Caenorhabditis elegans) model. Alterations in growth, haemolytic activity, and pigment production were investigated spectrophotometrically. Biofilm formation was examined using the crystal violet well-plate assay. A soft agar plate method was used to detect swimming motility. Results: According to the results, all three insulin concentrations enhanced the bacterial growth. On the other hand, biofilm production, swimming motility, and haemolytic activity decreased in the presence of all insulin concentrations. Pyocyanin production was shown to be increased in the presence of only 10 µU/mL of insulin, but pyoverdine production did not change. In vivo animal survival rates showed that 200 µU/mL of insulin decreased bacterial virulence. Conclusions: This research demonstrates that P. aeruginosa can sense and respond to mammalian hormones (insulin), which can modulate microbial virulence through diverse mechanisms, providing new insights that may be relevant to infection dynamics.

West Nile Virus (WNV) is becoming a significant and enduring public health menace in Europe, propelled by climate changes and accelerated population aging. Most infections are asymptomatic but older adults are more prone to develop neuroinvasive disease, which is characterized by high morbidity and mortality, as well as long-term neurological disturbances and disability. To date, there is still no licensed human vaccine or specific antiviral treatment, and management is mostly supportive. This review brings together the most recent information about WNV epidemiology, pathogenesis, and clinical manifestations, with a special focus on older people in Europe. We critically analyze current and novel pharmaceutical strategies, encompassing drug repurposing, nucleoside analogues, interferon-based therapies, peptides, monoclonal antibodies, and host-directed agents, emphasizing their therapeutic potential alongside the challenges presented by age-related pharmacokinetic and immunological alterations. We also discuss some important gaps in the current evidence base, such as the frequent exclusion of older adults from clinical studies and the lack of a coordinated clinical trial infrastructure that can be quickly activated during seasonal outbreaks. Lastly, we suggest a framework that combines systematic antiviral screening with the creation of a Europe-wide network of clinical trial readiness that is built into current One Health surveillance systems.

Natural products (NPs) have long been a cornerstone of pharmaceutical innovation, contributing to approximately 50% of FDA-approved drugs over the past four decades. However, traditional NP drug discovery faces significant hurdles, including laborious isolation processes, biodiversity constraints, and low hit rates in high-throughput screening. These hurdles often extend the development timelines to 10-15 years with costs exceeding $2 billion per drug. Artificial intelligence (AI) emerges as a transformative force, leveraging machine learning (ML), deep learning (DL), and generative models (Gen. AI) to expedite these processes. AI facilitates virtual screening of vast chemical libraries, predicts molecular interactions with unprecedented accuracy, and designs novel NP-inspired scaffolds, potentially reducing discovery time by up to 70%. This interdisciplinary approach not only addresses unmet medical needs but also aligns with global sustainability goals, potentially increasing success rates from <1% in traditional pipelines to over 10%. Ultimately, AI hints at revitalizing NP drug discovery, fostering innovative, eco-friendly therapeutics. This study reviews recent advancements in AI applications for NP drug discovery, including the challenges such as NPs representing only ~5% of screened compounds in many datasets, interpretability issues in "black-box" models, and ethical concerns over bioprospecting in biodiverse regions.

Bone metastasis is among the most common complications of advanced malignant tumors and severely affects prognosis in patients. Nuclear medicine, particularly bone-targeted radiopharmaceuticals, plays a unique and pivotal role in the diagnosis and treatment of bone metastases. This review systematically outlines the evolutionary trajectory of bone-targeted radiopharmaceuticals. It revisits functional bone imaging agents based on Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET), as well as recently developed therapeutic radiopharmaceuticals for bone metastases. Building on this foundation, this article focuses on the advanced paradigm of "theranostics" in nuclear medicine, encompassing strategies for theranostic radionuclide pairing and the development of single-radionuclide theranostic agents, aiming to achieve individualized and precise dosimetry. Moreover, this review emphasizes bone-targeting molecular scaffolds, such as bisphosphonates, and highlights their potential and direction for optimization through rational drug design, with the goal of developing a new generation of highly effective and low-toxicity theranostic platforms. This work aims to provide systematic insights for enhancing the precise management of bone metastases.

Introduction: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated unprecedented efficacy in the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, its rapid clinical widespread use has ignited a debate regarding long-term safety, particularly concerning the risk of specific neoplasms and its ability to modulate cardiovascular health, not only as primary prevention but also as a potential agent to mitigate cardiotoxicity. Objectives: This narrative review aims to analyze the most recent evidence from clinical trials and post-marketing surveillance to evaluate the correlation between semaglutide use and the incidence of cancer, as well as the drug's efficacy in reducing cardiotoxicity induced by anticancer therapies. Results and Discussion: While preclinical rodent models suggested a link to medullary thyroid carcinoma, human epidemiological data remain reassuring, though caution is advised in patients with genetic predisposition. Regarding pancreatic cancer, current meta-analyses do not confirm a significant increase in risk, suggesting that metabolic benefits outweigh potential concerns. Conclusions: Semaglutide is confirmed as a therapeutic tool with a highly favorable benefit-risk profile. While oncological monitoring must continue, the drug's cardioprotective and anti-inflammatory properties open new frontiers not only in metabolic management but also in safeguarding cardiovascular integrity in complex clinical scenarios.