Search Results (1,515)

Flavonoids are a structurally diverse class of plant-derived polyphenolic compounds widely recognized for their pleiotropic biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In oncology, these compounds have demonstrated the ability to modulate key signaling pathways involved in cell proliferation, apoptosis, angiogenesis, and metastasis, highlighting their potential as multitarget therapeutic agents. However, their clinical translation remains significantly limited by unfavorable pharmacokinetic properties, such as poor aqueous solubility, extensive first-pass metabolism, rapid systemic clearance, and consequently low oral bioavailability. In this context, nanotechnology has emerged as a promising strategy to overcome these limitations. This review provides a comprehensive and critical analysis of current nanocarrier-based delivery systems for flavonoids, including polymeric nanoparticles, lipid-based nanocarriers (liposomes, solid lipid nanoparticles, and nanoemulsions), micelles, and cyclodextrin complexes, emphasizing their role in improving drug stability, enhancing cellular uptake, and enabling targeted delivery to tumor tissues through both passive mechanisms, such as the enhanced permeability and retention effect, and active targeting approaches. In addition, recent in vitro and in vivo studies demonstrating the superior antitumor efficacy of nanoencapsulated flavonoids compared to free compounds are discussed. Finally, the major translational challenges, safety considerations, and future perspectives for the clinical application of flavonoid-based nanomedicines in cancer therapy are highlighted. Full article

Fibroblast activation protein (FAP) has emerged as a promising target for the development of cancer radiotheranostics due to its selective overexpression in cancer-associated fibroblasts (CAFs) within the tumor stroma. Affinity and selectivity refer to the binding affinities of FAP inhibitors toward FAP and related family members, whereas the accumulation of radiolabeled-FAP inhibitors varies by tumor type. Although monomeric FAP inhibitors (FAPIs) have shown extraordinary utility in diagnostic imaging, their clinical application in radiotherapy has been limited by short tumor retention times and heterogeneous uptake. To address these challenges, homomultimeric FAPI ligands—featuring two or more identical FAP-targeting motifs—have been developed with the aim of enhancing binding avidity and prolonging tumor residence. This review comprehensively examines the evolution of homomultimeric FAPI ligands, from molecular design and preclinical validation to early clinical implementation. We highlight how dimeric and higher-order multimeric constructs improve tumor retention and therapeutic efficacy compared to monomers, while also discussing the impact of linker chemistry, valency, and scaffold architecture on pharmacokinetics and targeting efficiency. Preclinical studies demonstrate that optimized dimers and trimers achieve superior tumor-to-background ratios and sustained tumor uptake, whereas excessive multimerization can lead to steric hindrance and reduced efficacy. Clinical data from pioneering studies using agents such as [¹⁷⁷Lu]Lu-DOTAGA.(SA.FAPi)₂ and [¹⁷⁷Lu]Lu-DOTAGA.Glu.(FAPi)₂ confirm prolonged tumor retention, encouraging therapeutic responses and a favorable safety profile in advanced cancers. However, translational challenges remain, including the need for better preclinical models that reflect stromal FAP heterogeneity, optimized radiometal–chelator pairs, and standardized dosing protocols for comparative clinical trials. Overall, homomultimeric FAPI ligands represent a significant advance in FAP-targeted theranostics, offering a robust platform for personalized cancer management. Full article

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic relapsing inflammatory disorder characterized by epithelial barrier dysfunction, immune dysregulation, microbiota imbalance, and progressive tissue remodeling. Because the pathogenesis of IBD involves complex interactions among genetic, immunological, microbial, and environmental factors, experimental animal models have become indispensable tools for investigating disease mechanisms and evaluating therapeutic strategies. Various experimental colitis models have been developed to reproduce distinct pathological features of human IBD, including chemically induced models, genetically engineered systems, adoptive immune-transfer models, and infectious or microbiota-associated models. Rodent models remain the most widely used experimental platforms because of their accessibility, reproducibility, and well-established genetic manipulation technologies. These systems have significantly contributed to understanding inflammatory signaling pathways, epithelial barrier injury, immune cell dysregulation, and gut microbial crosstalk. However, important species-specific differences in intestinal anatomy, immune responses, microbiota composition, and pharmacokinetics limit direct translation of rodent findings into clinical applications. To overcome these limitations, increasing attention has been directed toward large-animal models, particularly pig and minipig systems, which more closely resemble human gastrointestinal anatomy, digestive physiology, immune regulation, and microbiome-related characteristics. Porcine models additionally support clinically relevant procedures, including repeated colonoscopy, serial biopsy sampling, pharmacokinetic evaluation, and longitudinal therapeutic monitoring. Recent advances in genome-editing technologies and multi-omics approaches have further enhanced the translational utility of porcine IBD models. This review summarizes major experimental colitis animal models, discusses their pathological and translational characteristics, and highlights the growing importance of pig and minipig systems as human-applicable platforms for preclinical therapeutic evaluation and translational IBD research. Full article

The immune response is essential in the protection of our body against pathogens; however, the inflammatory response caused by the immune system can become a disease itself. In fact, anti-inflammatory and immune-suppressive drugs are applied to limit the immune response to treat inflammatory diseases. Flavonoids are plant-derived polyphenols extensively investigated for their anti-inflammatory and antioxidant properties in inflammatory diseases. Studies applying isolated compounds as well as using supplements as nutraceuticals based on flavonoids have been conducted. Our review systematically analyzed the top five studied flavonoids between 2020 and 2025: quercetin (1742 articles), kaempferol (642), luteolin (589), apigenin (419), and epicatechin (354), highlighting their major therapeutic applications in diseases affecting the liver (12%), nervous system (11%), and lungs (10%). Mechanistically, these compounds act as multi-target agents mainly by inhibiting NF-κB and inducing Nrf2-dependent antioxidant programs. Application of advanced delivery systems, which increase oral bioavailability by up to 20-fold, overcomes pharmacokinetic bottlenecks. Clinical highlights demonstrated promising therapeutic effects, including reduced intrahepatic lipid accumulation in non-alcoholic fatty liver disease patients following quercetin supplementation (11.5% to 9.6%) and accelerated SARS-CoV-2 clearance after quercetin phytosome administration. The translation of flavonoids into standardized clinical therapies remains limited by the lack of large-scale, well-controlled clinical trials. Full article

Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice. Full article

Background/Objectives: Cyclotides are plant-derived macrocyclic peptides distinguished by their head-to-tail cyclized backbone and cystine knot motif, which confer remarkable stability against thermal, enzymatic, and chemical degradation. These features, combined with a compact and rigid structure, position cyclotides as promising scaffolds for future antibacterial agents in response to the escalating threat of multidrug-resistant (MDR) pathogens and the stagnation of conventional antibiotic discovery pipelines. This review summarizes the structural features, antibacterial mechanisms, bioengineering strategies, and translational potential of cyclotides against MDR infections. Methods: A narrative review of the literature was conducted using recent original research articles and reviews on cyclotide structure, antibacterial activity, bioengineering, computational modeling, and pharmaceutical applications. Results: Cyclotides exhibit potent antimicrobial activity, primarily through membrane disruption mediated by amphipathic surfaces and affinity for anionic bacterial membranes. Some variants also demonstrate anti-virulence and antibiofilm properties, broadening their therapeutic relevance for difficult-to-treat infections. Bioengineering approaches, including epitope grafting and rational design, have improved selectivity and potency while reducing cytotoxicity. Advances in computational modeling, molecular dynamics, and artificial intelligence have accelerated the prediction and optimization of antimicrobial activity, toxicity, and pharmacokinetic properties. Conclusions: Innovations in synthesis, including recombinant expression and enzymatic ligation, are helping overcome translational barriers related to cost and scalability. Although challenges remain in oral bioavailability and systemic delivery, strategies such as lipidation and scaffold modification support the development of cyclotide-based therapeutics as adaptable platforms for peptide drug discovery. Full article

Efficient delivery systems are essential for transporting chemotherapeutic agents to target sites, enhancing cellular uptake and reducing off-target side effects. Peptides, owing to their intrinsic biocompatibility and structural tunability, have emerged as promising carriers for delivering labile chemotherapeutics and improving pharmacokinetics and therapeutic outcomes. Along these lines, a wide variety of peptide-based delivery strategies have been developed to achieve desirable pharmaceutical properties for anticancer agents. Particularly, stimuli-responsive peptide-based nanocarriers have attracted high levels of attention due to their ability to exploit overexpressed or tumor-specific stimuli, enabling selective disassembly and controlled drug release within cancer cells. In this review, we highlight recent advances in the development of stimuli-responsive peptide nanocarriers and their applications in anticancer therapy, and discuss key challenges and future directions toward their clinical translation. Full article

Scorpion venom peptides, with their stable disulfide backbone, compact structural framework, and highly selective regulation of ion channels, have long been regarded as important molecular probes in neuropharmacology. However, recent studies have revealed their potential for regulating oxidative stress, inflammation, and neuroprotection, making them a new research frontier. In this article, we focus on scorpion venom peptides as drugs, constructing an integrated knowledge framework from structural classification to clinical translation. First, scorpion venom peptides are systematically classified based on cysteine arrangement patterns and three-dimensional folding topology, and their structure–activity relationships are summarized. Based on this, the molecular mechanisms by which scorpion venom peptides regulate ion channels are systematically analyzed. We review the emerging pharmacological activities of scorpion venom peptides. Of particular note, the representative molecule SVHRSP has shown multi-target synergistic antioxidant and neuroprotective activity in models of Parkinson’s disease. We also systematically evaluate the application of engineering strategies, including cyclisation modification, nanodelivery, recombinant expression, and AI-assisted optimization, to overcome the translational bottlenecks in the development of scorpion venom peptides. However, it should be noted that most SVHRSP-related findings have been reported by a single research group; independent replication, pharmacokinetic characterization, and human efficacy data are still lacking. Its IND approval permits clinical investigation but does not yet constitute proven therapeutic benefit in patients. By integrating molecular structure, redox regulation mechanisms, and translational medicine perspectives, this review aims at providing a theoretical basis and practical pathways for scorpion venom peptides as precision therapeutic molecules for oxidative stress-related diseases. Full article

Background/Objectives: Colistin is a complex polymyxin antibiotic with a narrow therapeutic window and significant interindividual pharmacokinetic variability, necessitating precise concentration monitoring. Current analytical methods often utilize colistin mixtures or require large sample volumes, potentially limiting the precision and resolution of individual component quantification. This study aimed to develop a sensitive and component-specific bioanalytical assay for the simultaneous quantification of colistin A and colistin B in human plasma. Methods: A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed using pure, component-specific reference standards to ensure rigorous independent quantification of each component. Analytes were efficiently extracted from a small volume of plasma (50 µL) using solid-phase extraction. Chromatographic separation was achieved on a C18 column with a total runtime of 4 min, and detection was performed using negative-ion multiple reaction monitoring (MRM). Results: Calibration curves showed excellent linearity over a range of 0.1–20 µg/mL for both colistin A and B (R² > 0.99). The precision (%CV ≤ 8.8%) and accuracy (86.4–105.7%) for both components met the predefined regulatory criteria. This method was clinically validated using 60 plasma samples from 15 patients, demonstrating its applicability for capturing individual concentration–time profiles within the clinically relevant range (0.323–19.579 µg/mL for colistin A and 0.065–6.132 µg/mL for colistin B). Conclusions: This validated bioanalytical assay enables precise clinical pharmacokinetic assessments in a high-throughput workflow using a small plasma volume. Therefore, it serves as a practical tool for therapeutic drug monitoring (TDM)-guided dose optimization and further clinical investigations of colistin therapy. Full article

Astragalus membranaceus, a medicinal plant used in traditional Chinese medicine for centuries, has attracted growing scientific attention for its potential anti-aging and anticancer properties, particularly for skin and bone health. Its key bioactive compounds like astragalosides, cycloastragenol, and its commercial derivative TA-65, have been associated with telomerase activation and telomere maintenance, suggesting a possible role in modulating cellular senescence and tissue repair processes. In addition to the claimed telomere maintenance, A. membranaceus exhibits antioxidant, anti-inflammatory, and DNA-protective activities, properties that contribute to its anti-aging effects. Emerging evidence also suggests that telomerase modulation by A. membranaceus influences cancer cell dynamics, either suppressing tumor progression through immune regulation and apoptosis induction or, in some contexts, potentially promoting tumor growth. This duality highlights the importance of dose, formulation, and targeted application. Clinically, TA-65 has been reported to improve vascular health, bone mineral density, and skin elasticity in aging individuals. Preclinical studies further support its protective effects against osteoporotic bone loss and photoaging-induced dermal degeneration. This review summarizes the phytochemical composition of A. membranaceus and critically evaluates the mechanistic and therapeutic evidence underlying its anti-aging and anticancer actions on skin and bone tissues. It also discusses the pharmacokinetic properties of A. membranaceus, including its absorption, bioavailability, and safety profile. The integration of A. membranaceus into evidence-based senile therapeutic strategies holds promise, but further mechanistic and clinical studies are required to optimize its safety and efficacy. Full article

Imaging of infections has the potential to improve clinical outcomes, but pathogen-specific imaging strategies are currently unavailable. Given their target specificity, antimicrobials may be useful as molecular imaging ligands to target infections. Despite substantial development efforts, no antimicrobial-based ligands are approved for clinical use. This scoping review comprehensively surveys radiolabeled antimicrobials across antibacterial, antimycobacterial, antiviral, and antifungal drug classes, examining their progression through the translational pipeline. The review utilized PubMed and Google Scholar databases (1970–2025), following PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. Two reviewers independently screened titles, abstracts, and full-text articles; data were extracted, and content duplicates were removed. In total, 143 preclinical and 25 clinical articles met the selection criteria. In clinical studies, most tracers showed suboptimal specificity for infections, while some proved useful for pharmacokinetic characterization. Among preclinical studies, radiolabeled plazomicin and echinocandins (caspofungin and anidulafungin) exhibited the greatest number of preferred characteristics. In conclusion, ideal antimicrobial pharmacologic properties can be counterproductive for imaging, where rapid background clearance and a high target-to-non-target ratio (T/NT) are essential. Many radioligands demonstrate good tissue penetration but suboptimal washout, limiting their diagnostic value. In vivo pharmacokinetic applications during active infections are promising, though significant challenges remain for infection imaging. Full article

Background: Malnutrition, encompassing both undernutrition and overnutrition, is a common complication in children with cancer and is associated with impaired treatment tolerance, increased infection risk, altered pharmacokinetics, reduced quality of life, and poorer survival outcomes. Despite its importance, nutritional management in pediatric oncology lacks a unified, systematically organized clinical framework applicable to the full trajectory of the disease. Objective: This study aimed to develop expert consensus recommendations for nutritional intervention in pediatric oncology patients aged 4 to 18 years. Methods: A modified electronic Delphi (e-Delphi) process was conducted with a multidisciplinary expert panel of 22 specialists, including pediatric oncologists, pediatric gastroenterologists, clinical nutrition specialists, radiotherapy specialists, and pediatric surgeons. Statements were rated on a 9-point Likert scale across two anonymous rounds, with consensus predefined as ≥80% agreement. Results: Forty-one consensus recommendations were formulated across nine domains: nutritional screening and assessment, energy and protein requirements, micronutrient supplementation, physical activity, nutritional support escalation, refeeding syndrome prevention, treatment-specific management, survivorship, and palliative care. All recommendations achieved the predefined consensus threshold. Conclusions: This Delphi consensus provides a structured, multidisciplinary, and clinically actionable framework for nutritional management across the full trajectory of childhood cancer and is intended to reduce institutional variability and improve patient outcomes. Full article

Sambucus ebulus L. (dwarf elder) is a polyphenol-rich medicinal plant with a long history of ethnopharmacological use whose biological potential remains substantially underexplored. This narrative review examines the anti-inflammatory, antimicrobial, and anti-proliferative properties of S. ebulus fruit preparations and their molecular mechanisms. Literature was retrieved from PubMed, Scopus, and Web of Science (no lower date limit; upper limit May 2026) using “Sambucus ebulus” and related terms combined with relevant biological and pathway keywords; studies restricted to non-fruit tissues or lacking phytochemical characterization were excluded or flagged. The fruits contain anthocyanins, flavonols, phenolic acids, proanthocyanidins, and stilbenes that collectively modulate NF-κB, MAPK, JAK/STAT, PI3K/Akt, and Nrf2 signaling. Available evidence is predominantly in vitro, with limited in vivo data, and two human intervention studies. Data support anti-inflammatory, antimicrobial, and anti-proliferative activities that appear to arise from the combined action of multiple phytochemicals. Critical limitations of available research include the absence of clinical trials, limited pharmacokinetic data, lack of standardized preparations, and insufficient formal safety characterization, all of which must be addressed before translational application can be considered. Full article

Background/Objectives: Natural macromolecule-based drug delivery carriers have gained extensive attention for biomedical applications. This study aimed to construct an efficient oral delivery system for the widely used antitumor drug docetaxel (DTX) by utilizing natural nanoparticles derived from Ganoderma (LZ-Nnps). Methods: LZ-Nnps loaded with DTX (LZ-Nnps-DTX) were fabricated via an optimized heat-induced self-assembly approach and characterized for morphology, particle size, zeta potential, stability, drug loading, encapsulation efficiency, and molecular interactions with DTX. Intestinal absorption, pharmacokinetics, and tissue distribution were respectively assessed, while antitumor efficacy, macrophage internalization mechanisms, and immunomodulatory activation were further investigated. Results: The optimized formulation showed a particle size of 361.3 ± 5.3 nm, zeta potential of −39.55 ± 1.31 mV, drug loading of 1.51 ± 0.08%, and near-complete encapsulation efficiency (99.97 ± 0.02%), with favorable stability in gastrointestinal fluids. Hydrogen bonding and hydrophobic interactions effectively kept DTX in a stable amorphous state. LZ-Nnps-DTX markedly improved DTX aqueous solubility, dissolution, and intestinal absorption. In vivo assays showed oral LZ-Nnps-DTX achieved 34-fold higher C_max and 7.8-fold larger plasma AUC_0-t than free DTX, and mainly accumulated in the liver and lung. The nanoparticles entered Caco-2 cells via macropinocytosis and mainly accumulated in the liver. LZ-Nnps-DTX exerted strong cytotoxicity against HepG2, A549, and HCT116 cells, was internalized by RAW264.7 macrophages through caveolae-mediated endocytosis and phagocytosis, and stimulated TNF-α and NO production to suppress tumor growth. Conclusions: These findings demonstrate that LZ-Nnps-DTX effectively enhances oral bioavailability, exerts potent antitumor effects, and activates macrophage-mediated immunity, supporting its promise as an oral DTX delivery system. Full article

Single-domain antibodies (sdAbs) are the smallest antigen-binding antibody (Ab) fragments (12–15 kDa) and have emerged as a versatile therapeutic platform. Their compact size, high solubility, stability, and ability to access cryptic epitopes distinguish them from conventional monoclonal Abs (mAbs) and larger Ab fragments. These properties are particularly attractive in ophthalmology, where molecular size, tissue penetration, and formulation constraints critically influence therapeutic performance. This narrative review summarizes the structural features, engineering strategies, immunogenicity considerations, and production platforms of sdAbs, with a focus on ocular applications. Preclinical studies demonstrate promising efficacy in retinal vascular diseases through targeting of VEGFA, ANG2, TNFα, and complement components, as well as in inflammatory and anterior segment disorders. SdAbs can be formatted as multimeric or Fc-fused constructs to extend intraocular half-life or delivered via gene therapy vectors as a sustained intraocular “biofactory” approach. Notably, recent work demonstrates the feasibility of vector-encoded sdAbs targeting complement C3 in vivo. While challenges remain regarding immunogenicity, pharmacokinetics, and regulatory pathways, the approval of several sdAb-based drugs in other fields underscores their clinical potential. SdAbs represent a promising next-generation modality for ocular therapeutics, enabling innovative strategies beyond conventional antibody formats. Full article