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Diagnosis and endoradiotherapy using copper radioisotopes-defined as Theranostics or, more specifically, CopperNostics-have the potential to play a prominent role in modern precision medicine, as demonstrated by the FDA approval of [⁶⁴Cu]Cu-DOTA-TATE (Detectnet). In this review we highlight current developments in the production, radiochemical purification, quality control, availability, logistics, and regulatory hurdles of the most relevant copper radioisotopes, ⁶⁰Cu, ⁶¹Cu, ⁶²Cu, ⁶⁴Cu, and ⁶⁷Cu, for nuclear medicine. Radiopharmaceuticals based on their application in registered clinical trials, either as molecular imaging agents, companion diagnostics or therapeutic agents, are also presented addressing unmet medical needs.

Asthma is a prevalent chronic disease posing substantial health and economic challenges globally. Its progression involves key hallmarks such as inflammation and airway remodeling, mediated by multiple inflammatory biomarkers and pathways. Despite the availability of potent therapeutic options, many patients continue to suffer from uncontrolled asthma. The plasminogen activator inhibitor-1 (PAI-1) signaling pathway is critical in asthma exacerbation and remodeling, with elevated PAI-1 levels linked to disease progression. Anthocyanins (ACNs), potent antioxidants and anti-inflammatory compounds, have shown promise in asthma management. Epidemiological studies associate higher ACN intake with a lower risk of asthma and improved lung function. Preclinical models further demonstrate ACNs' effectiveness in reducing asthma-related inflammatory cytokines, chemokines, and signaling pathways. Additionally, a human trial suggests ACNs can improve symptom control and lung function. While no direct evidence links ACNs to PAI-1 reduction in asthma, studies in other chronic conditions show ACNs reduce PAI-1 levels, supporting their potential role in asthma. This suggests a promising avenue for exploring their effects on airway remodeling. The lack of robust human studies remains a gap. Future research should focus on establishing direct evidence of ACNs' impact on PAI-1 levels and remodeling in asthma, providing novel insights into managing asthma as an adjunct.

Antibody-drug conjugates (ADCs) represent a transformative class of targeted therapies designed to deliver potent cytotoxic agents specifically to tumor cells, minimizing systemic toxicity. This review provides a comprehensive overview of ADCs, detailing their mechanisms of action, design strategies, and clinical advancements. ADCs utilize monoclonal antibodies to selectively bind tumor-associated antigens, enabling the precise delivery of toxic payloads to cancer cells. The review explores the critical components of ADCs, including the antibody, linker, and payload, and highlights how these elements can be optimized to improve efficacy and minimize off-target effects. We examine the evolution of ADC design from early constructs to the latest innovations and the development of novel payloads that extend therapeutic possibilities beyond traditional cytotoxic agents. Additionally, we discuss the clinical success of ADCs, with examples from approved therapies such as gemtuzumab ozogamicin, brentuximab vedotin, and trastuzumab emtansine, which have redefined the treatment landscape for various cancers. Despite their success, ADCs face challenges such as tumor heterogeneity, resistance mechanisms, and toxicity, which are actively being addressed through ongoing research. The review concludes with an outlook on the future of ADCs, highlighting emerging strategies in conjugation technology, payload design, and combination therapies that are poised to enhance their therapeutic potential across oncology and other disease areas.

Background: Plasma fibrinogen (FIB) levels exhibit a significant elevation during the acute phase of ischemic stroke (IS), and their dynamic fluctuations serve as important biomarkers for stroke onset, disease progression, and long-term prognosis. Tong-Qiao-Huo-Xue Decoction (TQHXD) is highly effective in treating blood stasis syndromes affecting the head and face. Nevertheless, the association between TQHXD and FIB in the underlying mechanism of treating IS warrants further investigation. Methods: Proteomics analysis predicted the potential therapeutic targets of TQHXD for IS. An in vivo model of middle cerebral artery occlusion followed by reperfusion (MCAO/R) was created in mice. To explore the interaction between FIB and NLRP3, as well as to verify the particular healing outcomes of TQHXD. Results: An increased blood-brain barrier (BBB) permeability was observed after MCAO/R, accompanied by substantial accumulation of FIB in the brain. In vivo experiments demonstrated that FIB triggered the activation of the NLRP3 inflammasome in microglia. Proteomic analysis revealed a significant increase in FIB levels following model induction, which were markedly reduced after treatment with TQHXD; KEGG pathway enrichment analysis indicated that these changes were primarily associated with the NOD-like receptor signaling pathway. Laser speckle contrast imaging showed that TQHXD treatment significantly improved cerebral blood flow and attenuated brain injury in mice. Fluorescence imaging, ELISA, and Western blotting results collectively demonstrated that TQHXD effectively reduced FIB accumulation and suppressed NLRP3 inflammasome activation. MD and pull-down experiments further demonstrated a strong interaction strength between FIB and NLRP3. Conclusions: FIB accumulates in the ischemic penumbra following CIRI, while TQHXD can effectively down-regulate FIB expression and inhibit NLRP3 inflammasome activation to mitigate CIRI. These findings provide a novel theoretical foundation and treatment direction for stroke management in clinical settings.

Background: Advanced lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths, with existing treatments hampered by drug resistance. This underscores the urgent need to identify novel therapeutic targets. The role of neuropeptide Y (NPY) receptors in LUAD remains unclear, and this study aimed to investigate their expression profiles, prognostic significance, and the antitumor potential of Euphorbia Factor L2 (EFL2). Methods: Bioinformatics analyses were performed to evaluate NPY receptors in LUAD. Lentivirus-mediated stable neuropeptide Y receptor 5 (NPY5R) knockdown, functional assays including CCK-8, flow cytometry, and scratch assay, PRESTO-Tango, RNA sequencing (RNA-seq), and qPCR were employed to validate the antitumor effects of EFL2 and the functional role of NPY5R. Results: High expression of NPY5R correlated with poor prognosis and immune cell infiltration in LUAD. EFL2 targeted NPY5R, inhibiting A549 cell proliferation and migration while inducing apoptosis. NPY5R knockdown further enhanced these antitumor effects, and the combination of NPY5R knockdown and EFL2 treatment synergistically enriched extracellular matrix (ECM), phosphatidylinositol 3-kinase (PI3K)-Akt, and mitogen-activated protein kinase (MAPK) pathways. Four potential molecular targets were identified. Conclusions: NPY5R is a promising therapeutic target for LUAD. While no clinical drugs targeting NPY5R are currently available, preclinical evidence supports its potential for anticancer drug development. EFL2 exerts antitumor effects via targeting NPY5R, offering useful guidance for developing novel LUAD therapies.

Objective: To compare metastatic lesion detection on [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT in metastatic breast and lung cancers and to assess the relationship between PET-derived imaging parameters and progression-free survival (PFS). Methods: In this prospective dual-cohort study, 45 patients (23 breast cancer, 22 lung adenocarcinoma) underwent paired [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT within four weeks. Semiquantitative (SUVmax, SUVmean) and volumetric (MTV, TLG, STV, TLF) PET parameters were measured. Metastatic detection was compared, and correlations with PFS were assessed. Results: In breast cancer, [18F]FDG demonstrated higher primary tumor uptake, whereas [68Ga]Ga-DOTA.SA.FAPi showed lower background activity, resulting in higher tumor-to-background ratios for brain and bone metastases. Whole-body volumetric indices (wbTLG, wbTLF) showed strong inverse correlations with PFS. In lung adenocarcinoma, volumetric FAPi-derived parameters (wbTLF, wbSTV) demonstrated modest but significant correlations with PFS. [68Ga]Ga-DOTA.SA.FAPi PET/CT detected more brain metastases than [18F]FDG PET/CT in both cohorts (breast: 15/15 vs. 8/15; lung: 14/14 vs. 4/14). Conclusions: [68Ga]Ga-DOTA.SA.FAPi and [18F]FDG PET/CT provide complementary diagnostic and prognostic information. In metastatic breast cancer, FAPi-derived volumetric parameters strongly correlate with PFS and improve detection of brain metastases. In lung adenocarcinoma, [68Ga]Ga-DOTA.SA.FAPi PET/CT offers low background uptake and prognostically relevant stromal metrics. These findings support a potential role for integrating [68Ga]Ga-DOTA.SA.FAPi PET/CT into disease staging, prognostication, and treatment monitoring. This study did not involve prospective assignment to health-related interventions and therefore did not require clinical trial registration.

Background/Objectives: The objective of this study was to evaluate real-world evidence (Food & Drug Administration database, FAERS) on ibuprofen adverse events (AE) through descriptive and disproportionality analyses. Methods: Signal assessment involved analyzing the top 30 entries with the most reports. The disproportionality analysis of signals based on Evans' criteria (number of reports > 2, chi-square > 4, and PRR > 2) was performed. A total of 70,792 reports submitted to FAERS by the end of 2024 (collected from 97 countries worldwide) indicate ibuprofen as the main suspect. Results: Of these, the highest percentage was attributed to females (n = 33,262, 47.0%) and adult patients (18-65 years) (n = 22,005, 31.1%). In the elderly group (12.4%) and in children and adolescents (11.2%), similar frequencies were reported. Oral administration was the most frequently mentioned route (n = 25,035, 35.4%). A total of 21,077 reports had an unfavorable outcome, of which 3018 (4.3%) reported death. Conclusions: The results highlight potential risks associated with ibuprofen and emphasize the importance of responsible, clinically well-founded administration. The disproportionality analysis can provide valuable information for effectively selecting drug-adverse-effect pairs that warrant further attention.

Glaucoma is increasingly recognized as an ischemic neurodegenerative disorder that extends beyond elevated intraocular pressure (IOP) to involve complex vascular, metabolic, and inflammatory mechanisms. Retinal ganglion cells are particularly vulnerable to ischemia-reperfusion injury, oxidative stress, and chronic neuroinflammation, leading to progressive disconnection from central visual pathways. Current therapies primarily target IOP reduction but fail to address ischemia-driven neurodegeneration or to restore lost neuronal connectivity. Ischemia triggers excitotoxicity, oxidative stress, and a maladaptive inflammatory response involving activated microglia and astrocytes, perpetuating neuronal injury and suppressing intrinsic regenerative capacity. Thus, restoring neural plasticity and mitigating neuroinflammation represent key unmet therapeutic needs. Psychoplastogens are a class of compounds capable of rapidly enhancing structural and functional neuroplasticity and have recently emerged as promising multitarget agents. Compounds such as ketamine, psilocybin, N,N-dimethyltryptamine (DMT), and some newly synthesized non-hallucinogenic analogs act through convergent signaling pathways involving BDNF-TrkB-mTOR, promoting dendritic growth, synaptogenesis, and glial modulation. Beyond their neurotrophic effects, psychoplastogens seem to exert potent immunomodulatory actions. In this review we will explore the interplay between ischemia, neurodegeneration, neuroinflammation, and impaired plasticity in glaucoma, integrating mechanistic insights from cerebral ischemia. We discuss emerging preclinical evidence supporting psychoplastogens as neurorestorative and anti-inflammatory agents, propose their potential application in ocular ischemic neurodegeneration, and outline translational challenges for future studies.

Multiple myeloma (MM) is an oncohematological neoplasm characterized by the abnormal proliferation of neoplastic plasma cells in the bone marrow and the excessive secretion of monoclonal antibodies into the bloodstream. Approximately 3 to 5% of patients present with a variant form of the disease where there is no secretion of monoclonal proteins, characterizing the non-secretory MM picture. It exhibits a highly complex and heterogeneous genetic signature, allowing the disease to be classified into premalignant entities and symptomatic forms. In this context, an integrative narrative review was conducted, encompassing genomic, epigenomic, proteomic, metabolomic, and radiomic biomarkers described in the literature between 2018 and 2025. Emphasis was placed on their translational potential, current limitations in clinical practice, and gaps within recent recommendations. Several categories of biomarkers, particularly ctDNA methylome, single-cell multiomics, proteomics of surface antigens, functional ex vivo assays, and PET/CT radiomics, demonstrate strong potential for enhancing risk stratification, detecting early progression, guiding therapy selection, and identifying novel therapeutic targets. These applications extend beyond existing guideline frameworks. Thus, integrating advanced biomarker platforms can overcome limitations of current diagnostic and therapeutic models and enhance precision strategies across plasma cell disorders.

Inflammatory bowel diseases, comprising Crohn's disease and ulcerative colitis, represent chronic inflammatory disorders with rising global incidence, underscoring the pivotal role of modifiable environmental factors in disease pathogenesis. Diet and intestinal microbiota have emerged as critical bidirectional therapeutic targets through complex interactions with host immune responses. Epidemiological evidence demonstrates that healthy and high fiber diets reduce disease risk, while ultra-processed foods and inflammatory dietary patterns increase susceptibility. Therapeutic nutritional interventions, including exclusive enteral nutrition, the Crohn's Disease Exclusion Diet combined with partial enteral nutrition, and the Mediterranean diet can induce and maintain clinical remission while promoting favorable microbiome modifications characterized by the enrichment of butyrate-producing taxa such as Faecalibacterium prausnitzii and Roseburia species, alongside a reduction in pathogenic Proteobacteria. Micronutrient deficiencies affect up to 78% of patients through malabsorption, chronic blood losses, dietary restrictions, and drug-nutrient interactions. Nutritional status significantly impacts surgical outcomes, with preoperative malnutrition and sarcopenia associated with increased postoperative complications, and it reciprocally influences biologic therapy response. Integration of personalized, microbiome-informed dietary strategies as complementary components of comprehensive treatment plans represents a promising therapeutic frontier, requiring multidisciplinary collaboration, rigorous clinical trials with standardized microbiome analyses, and precision nutrition algorithms accounting for disease phenotype, baseline microbial composition, and individual patient characteristics to optimize outcomes and improve quality of life.