Search Results (118)

Many approved oral paediatric medicines continue to have poor taste acceptance, suggesting that the ingredient blends employed in these medicines are not adequately effective in taste-masking drugs with strongly aversive tastes. To address this inadequacy, this narrative review provides a comparative evaluation of taste-masking ingredients used by the pharmaceutical industry with those employed in the food industry, as well as food items used by caregivers to mask the unpalatable taste of medicines for young children. Information was sourced from academic databases, industry publications, and caregiver forums on informal social platforms. Ingredients were classified into sweeteners, salts, acids, fats, peptides/amino acids, flavourants, cyclodextrins and polymers, with their taste-masking mechanisms delineated into receptor-level interactions and the creation of physical barriers and alternative dominant taste. Their applications are compared across the regulated medicinal and consumer food products, and in home remedies. Sweeteners show the highest cross-domain convergence as they are used in medicinal and food products and are recommended by caregivers. Peptides, amino acids, salt and texture modifiers applied in food and home remedies may have translational potential in medicines. Challenges, including drug–food interactions, regulatory constraints, and the need for combination approaches, are addressed. A decision framework is also designed to guide the development of simple, acceptable, and effective ingredient-based taste-masking systems for drugs with aversive tastes. Full article

Background/Objectives: The F3 peptide, a tumor-homing peptide known to bind cell-surface nucleolin, is frequently employed as a targeting vector in cancer research. However, the impact of the modification site on its cellular binding properties has not been investigated yet. In this work, we aimed to design an improved F3-based radioconjugate by identifying the optimal conjugation site and establishing a protocol for its biological evaluation in vitro. To achieve this, we compared F3 peptide derivatives modified at their N- or C-termini with DOTA for complexation of indium-111 (¹¹¹In) for SPECT or Auger electron therapy or a fluorophore (FITC) for optical imaging. Methods: N-and C-terminal DOTA-modified F3 peptides were radiolabeled with indium-111 and compared for their in vitro stability in different physiologically relevant media. Suitable nucleolin-positive cell lines for further in vitro studies were identified by confocal microscopy of a FITC-labeled F3 peptide derivative. The radioconjugates were then investigated on MDA-MB-231 (breast cancer) and PC-3 (prostate cancer) cells for nucleolin-specific cell binding and uptake, and several parameters of the in vitro assays were varied to establish a suitable protocol. Results: In general, in vitro assays with F3 peptide conjugates are challenging, as the outcome depends on a number of experimental parameters, leading, in some cases, to varying results. In particular, the presence of Ca²⁺ and Mg²⁺ had a decisive impact on the results, likely because the metal ions compete with the binding of F3 conjugates to nucleolin. The C-terminal modified, ¹¹¹In-labeled F3 radioconjugate performed better than the N-terminal modified analog. While several parameters of the in vitro experiments were optimized, the overall cell uptake in vitro of radioactivity was still low (<2% of applied radioactivity). Conclusions: A standardized in vitro protocol for evaluating F3 peptide conjugates on cancer cells was established, revealing that the C-terminus is the preferred site for modification. Because the cellular uptake of the radiotracer was shown to likely not be sufficient for radiotracer development, further studies on the optimization of the F3 peptide conjugates, including structural modifications, are required. Full article

Drug repurposing in oncology is often framed as a drug–target matching exercise, yet many candidates with plausible biological rationales fail in the clinic. In solid tumors, therapeutic outcomes are constrained not only by pharmacological target relevance but also by limited tumor accessibility, heterogeneous intratumoral exposure, loss of context-dependent activity, and dose-limiting systemic toxicity. This perspective argues that repurposing strategies should treat exposure engineering as a design principle alongside molecular selectivity. Peptides that bind cell- or matrix-associated molecules at the tumor site have the potential to implement spatial, temporal, and subcellular control over where and when a drug engages its pharmacological target, thereby enabling confinement of polypharmacology to tumor contexts. Mechanistic modes of peptide-enabled exposure selectivity (homing, anchoring/retention, conditional activation, penetration enhancement, and subcellular biasing), key failure modes, and translational constraints are discussed, together with an exposure-centric screening workflow to prioritize repurposed agents most amenable to peptide-guided rescue. Emphasizing the combination of exposure control and the addressing-element layer clarifies when and how pharmacologically promiscuous drugs may be repurposed safely and effectively. Full article

Epigenetics involves heritable changes in gene expression—such as DNA methylation (5-methylcytosine; 5mC), histone modifications, and regulation by non-coding RNAs at the mRNA translation level—without altering the underlying DNA sequence. As targeting these mechanisms enables intervention at the root cause of disease rather than the symptoms alone, epigenetics has become a rapidly advancing field in pharmaceutical sciences. Various epigenetic modulators, including histone deacetylase (HDAC) inhibitors, histone acetyltransferase (HAT) inhibitors, DNA methyltransferase (DNMT) inhibitors, and microRNAs (miRNAs), have been developed, and some have already been approved for cancer therapy. However, these agents often face significant challenges such as poor membrane permeability, enzymatic instability, and suboptimal biodistribution. Incorporating functionalized accessory units—serving as vectors (e.g., transporter recognition units, cell-penetrating peptides, tumor-homing peptides, monoclonal antibodies) or as carriers (e.g., monoclonal antibodies, nanoparticles)—into epigenetic modulators may help overcome these delivery barriers. In this narrative review, I discuss the potential and advantages of effective non-invasive delivery of epigenetic drugs using such functionalized accessory unit conjugates. Full article

Background/Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to pose a significant global health challenge due to its high transmissibility and potential for severe clinical outcomes. Early identification of patients at risk of hospitalization is essential for effective triage in emergency departments and for the optimal allocation of healthcare resources. Methods: This prospective study included 84 patients aged over 18 years who presented to the emergency department on 23 December 2020, with suspected SARS-CoV-2 infection. Initially, 100 patients were evaluated, and 16 were excluded based on predefined exclusion criteria. The mean age of the participants was 53.65 ± 13.62 years, and 39 (46.4%) were women. Results: At admission, the mean signal peptide, CUB domain, EGF (SCUBE-1) level among SARS-CoV-2 patients was 0.16 ± 0.08 ng/mL. There was no significant difference in SCUBE-1 levels between patient and control groups (n = 59 vs. 25), but levels differed significantly between hospitalized and home-treated patients (n = 37 vs. 22; p = 0.001). Neutrophil count (p = 0.001) and NLR (p = 0.010) were higher in patients than controls and also higher in hospitalized than home-treated patients (p = 0.003 and p = 0.015). ROC analysis revealed that SCUBE-1 predicted hospitalization with 84.6% sensitivity and 88.9% specificity. A positive correlation was observed between SCUBE-1 levels and length of hospital stay (p = 0.007, r = 0.554), with a median stay of 9.0 (5.0–11.0) days. Conclusions: SCUBE-1 levels were significantly associated with disease severity in SARS-CoV-2 patients and may serve as a promising biomarker to support clinical decision-making for hospitalization versus home-based management. Full article

Magnetic nanoparticles (MNPs) provide a platform for target detection because of their magnetic responsiveness to alternating magnetic fields (AMFs). We developed a detection method using MNPs modified with tumor-homing peptides (THPs), PL1 and PL3, which selectively bind to protein components enriched in malignant tissues. THP-MNPs were synthesized using maleimide-PEG-NHS linkers and characterized using transmission electron microscopy. Human glioblastoma cancer U87MG and normal tissue-derived HEK293 cells were incubated with THP-MNPs, and the magnetic signals were measured using a high-temperature superconducting quantum interference device (SQUID) magnetometer under an AMF (1.06 kHz). Dark-field microscopy confirmed the preferential binding of THP-MNPs to U87MG cells. In the absence of cells, THP-MNPs exhibited AMF-dependent signal enhancement, which correlated with particle size reduction due to THP release. This increase was completely suppressed in the presence of U87MG cells, indicating a strong THP-mediated interaction. PL3-MNPs exhibited superior discrimination between malignant and non-malignant cells. These results demonstrate that SQUID-based magnetic measurements using THP-MNPs enable rapid and label-free cancer cell detection. Full article

Antimicrobial peptides have been increasingly recognized as potential anticancer agents, with the KLA peptide (KLAKLAK₂) being one of the most well-known and successful examples. The research interest in the KLA peptide is attributed to its ability to induce apoptosis in cancer cells by disrupting the mitochondrial membrane. However, the KLA peptide exhibits poor cellular uptake and it lacks targeting specificity, limiting its clinical potential in cancer therapy. In this review, recent advances in nano-engineered delivery platforms for overcoming the limitations of KLA peptides and enhancing their anticancer efficacy are discussed. Specifically, various nanocarrier systems that enable targeted delivery, controlled release and/or improved bioavailability, including pH-responsive nanosystems, photo-chemo combination liposomes, self-assembled peptide-based nanostructures, nanogel-based delivery systems, homing domain-conjugated KLA structures, inorganic-based nanoparticles, and biomimetic nanocarriers, are highlighted. Additionally, synergistic strategies for combining KLA with chemotherapeutic agents or immunotherapeutic agents to overcome resistance mechanisms in cancer cells are examined. Finally, key challenges for the clinical application of these nanotechnologies are summarized and future directions are proposed. Full article

Background/Objectives: Cell-mediated and peptide-assisted delivery systems have emerged as powerful platforms at the intersection of chemistry, nanotechnology, and molecular medicine. By leveraging the intrinsic targeting, transport, and signaling capacities of living cells and bioinspired peptides, these systems facilitate the delivery of therapeutic agents across otherwise restrictive biological barriers such as the blood–brain barrier (BBB) and the tumor microenvironment. This review aims to summarize recent advances in engineered cell carriers, peptide vectors, and hybrid nanostructures designed for enhanced intracellular and tissue-specific delivery. Methods: We surveyed recent literature covering molecular design principles, mechanistic studies, and in vitro/in vivo evaluations of cell-mediated and peptide-enabled delivery platforms. Emphasis was placed on neuro-oncology, immunotherapy, and regenerative medicine, with particular focus on uptake pathways, endosomal escape mechanisms, and structure–function relationships. Results: Analysis of current strategies reveals significant progress in optimizing cell-based transport systems, peptide conjugates, and multifunctional nanostructures for the targeted delivery of drugs, nucleic acids, and immunomodulatory agents. Key innovations include improved BBB penetration, enhanced tumor homing, and more efficient cytosolic delivery enabled by advanced peptide designs and engineered cellular carriers. Several platforms have progressed toward clinical translation, underscoring their therapeutic potential. Conclusions: Cell-mediated and peptide-assisted delivery technologies represent a rapidly evolving frontier with broad relevance to next-generation therapeutics. Despite notable advances, challenges remain in scalability, manufacturing, safety, and regulatory approval. Continued integration of chemical design, molecular engineering, and translational research will be essential to fully realize the clinical impact of these delivery systems. Full article

Background: Colorectal cancer (CRC), particularly the microsatellite-stable (MSS) subtype, remains largely unresponsive to immune checkpoint inhibitors (ICIs) due to immune escape, tumor-associated macrophage (TAM) enrichment, and cytokine-driven suppression that sustain a TAM-dominant tumor microenvironment (TME). To overcome these barriers, a pH-responsive solid lipid nanoparticle (SLN) system was engineered to co-deliver CB-5083 (a VCP/p97 inhibitor), miR-142 (a PD-L1-targeting microRNA), and imiquimod (R, a TLR7 agonist) for spatially confined induction of endoplasmic reticulum stress (ERS) and immune reprogramming in MSS CRC. Methods: The SLNs were coated with PEG–PGA for pH-triggered de-shielding and functionalized with PD-L1- and EGFR-binding peptides plus an ER-homing peptide, enabling tumor-selective and subcellular targeting. Results: The nanoplatform displayed acid-triggered PEG–PGA detachment, selective CRC/TAM uptake, and ER localization. CB-mediated VCP inhibition activated IRE1α/XBP1s/LC3II, PERK/eIF2α/ATF4/CHOP, and JNK/Beclin signaling, driving apoptosis and autophagy, while miR-142 suppressed PD-L1 expression and epithelial–mesenchymal transition markers. R facilitated dendritic cell maturation and M1 polarization. Combined CB + miR + R/SLN-CSW suppressed IL-17, G-CSF, and CXCL1, increased infiltration of CD4⁺ and CD8⁺ T cells, reduced Tregs and M2-TAMs, and inhibited tumor growth in CT-26 bearing mice. The treatment induced immunogenic cell death, reprogramming the TME into a T cell-permissive state and conferring resistance to tumor rechallenge. Biodistribution analysis confirmed tumor-preferential accumulation with minimal off-target exposure, and biosafety profiling demonstrated low systemic toxicity. Conclusions: This TME-responsive nanoplatform therefore integrates ERS induction, checkpoint modulation, and cytokine suppression to overcome immune exclusion in MSS CRC, representing a clinically translatable strategy for chemo-immunotherapy in immune-refractory tumors. Full article

Background and Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying, raising concerns about periprocedural safety in elective endoscopy. We aimed to evaluate the association between pre-procedural GLP-1 RA use and post-procedural complications such as aspiration pneumonia. Methods: In this retrospective cohort study, adults (18–89 years) undergoing outpatient esophagogastroduodenoscopy or colonoscopy within the HCA Healthcare network from 1 July 2021 to 31 March 2024 were identified. Patients were classified as GLP-1 RA users (n = 953) or non-users (n = 3289) based on home medication records. Primary outcomes included aspiration, post-procedural oxygen requirement, hypotension, hospitalization, ICU admission, length of stay, and all-cause inpatient mortality. Multivariable logistic and negative-binomial regression models, incorporating an interaction term for anesthesia type, were adjusted for age, sex, body mass index, ASA class, and key comorbidities. Results: No aspiration events were reported in either group. GLP-1 RA use was associated with lower odds of post-procedural oxygen requirement (OR 0.43, 95% CI 0.25–0.76), hospitalization (OR 0.73, 95% CI 0.39–1.36), and mortality (0.1 vs. 0.9%, p = 0.014), and a shorter hospital stay (IRR 0.54, 95% CI 0.40–0.71). Rates of hypotension and ICU admission were similar between both groups. In anesthesia-stratified analysis among GLP-1 RA users, those receiving MAC/MS had higher odds of hospitalization compared with GA (OR 1.87, 95% CI 1.23–2.85, p = 0.003), whereas other outcomes were not significant. Conclusions: Pre-procedural GLP-1 RA therapy was not associated with increased peri-procedural complications. Although hospitalization was more frequent with MAC/MS, this difference did not extend to other clinically significant outcomes. Further prospective studies are needed to clarify the clinical implications of anesthesia choice. Full article

Background: The skin microbiome plays a key role in maintaining skin health, and its composition can be influenced by cosmetic treatments. This study aimed to investigate the effects of SMART DNA Therapy treatment on facial skin microbiome composition, with specific focus on changes in commensal and pathogenic bacterial populations following multi-component anti-aging intervention. Methods: This clinical study included 10 Caucasian female participants aged 28–50 years (Clinical trial registration number: 0406/2023). Each participant received three Retix.C SMART DNA THERAPY treatments at 14-day intervals over 6 weeks. The protocol included three phases: chemical peeling with ferulic acid, peptide microinjections for DNA repair, and home-care products with antioxidants. Bacterial samples were collected from forehead and cheek skin before treatment and 2 weeks after the final treatment. Samples were analyzed using bacterial culture and PCR methods. Results: After treatment, the skin microbiome showed beneficial changes with increased numbers of helpful bacteria and elimination of harmful bacteria: complete removal of Cutibacterium acnes and Staphylococcus aureus was observed, Staphylococcus epidermidis and other beneficial bacteria increased on both forehead and cheek areas. Overall bacterial diversity decreased, and participants exhibited more similar microbiome patterns after treatment. Conclusions: SMART DNA Therapy treatment successfully modified the skin microbiome by increasing protective bacteria and eliminating pathogenic species. The treatment may support skin health through microbiome modulation and the potential antioxidant effects of its active ingredients, although these were not directly assessed in this study. Full article

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article

Peptide–drug conjugates (PDCs) have emerged as a next-generation therapeutic platform, combining the target specificity of peptides with the pharmacological potency of small-molecule drugs. As an evolution beyond antibody–drug conjugates (ADCs), PDCs offer distinct advantages, including enhanced cellular permeability, improved drug selectivity, and versatile design flexibility. This review provides a comprehensive analysis of the fundamental components of PDCs, including homing peptide selection, linker engineering, and payload optimization, alongside strategies to address their inherent challenges, such as stability, bioactivity, and clinical translation barriers. Therapeutic applications of PDCs span oncology, infectious diseases, metabolic disorders, and emerging areas like COVID-19, with several conjugates advancing in clinical trials and achieving regulatory milestones. Innovations, including bicyclic peptides, supramolecular architectures, and novel linker technologies, are explored as promising avenues to enhance PDC design. Additionally, this review examines the clinical trajectory of PDCs, emphasizing their therapeutic potential and highlighting ongoing trials that exemplify their efficacy. By addressing limitations and leveraging emerging advancements, PDCs hold immense promise as targeted therapeutics capable of addressing complex disease states and driving progress in precision medicine. Full article

Background/Objectives: Low-grade systemic inflammation, characteristic of heart failure (HF), is a nonspecific inflammatory syndrome that affects the entire body. Macrophage migration inhibitory factor 1 (MIF-1) is a pro-inflammatory cytokine, a key mediator of the innate immune response, and may serve as a potential biomarker of monocyte homing and activation in HF with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Methods: We evaluated 70 hemodynamically stable patients with left ventricular EF (LVEF) < 50% by means of echocardiography and blood sampling. Results: We report significant correlations between MIF-1, LVEF (r = −0.33, p = 0.005), LV global longitudinal strain (LVGLS, r = 0.41, p = 0.0004), and tricuspid annular plane systolic excursion (TAPSE, r = −0.37, p = 0.001). MIF-1 levels in HFrEF patients were relatively higher, but not significantly different from those observed in HFmrEF. MIF-1 showed significant associations with TAPSE to systolic pulmonary artery pressure ratio (TAPSE/sPAP, p < 0.0001). Also, patients with TAPSE/sPAP < 0.40 mm/mmHg had significantly higher levels of MIF-1 (p = 0.009). Moreover, ischemic cardiomyopathy (ICM) was more frequent in patients with MIF-1 concentrations above 520 pg/mL (57.1% MIF-1^hi vs. 28.6% MIF-1^lo, p = 0.029). In terms of congestion, MIF-1 showed significant associations with the presence of peripheral edema (p = 0.007), but none was found with self-reported dyspnea (p = 0.307) and New York Heart Association (NYHA) class (p = 0.486). Also, no relationship was reported with N-terminal pro-B-type natriuretic peptide concentrations (NT-proBNP, r = 0.14, p = 0.263). However, the six-minute walk distance was greater in individuals in the MIF-1^lo group when compared to those in the MIF-1^hi group (404.0 ± 127.4 vs. 324.8 ± 124.1 m, p = 0.010). Conclusions: Beyond identifying inflammatory biomarkers related to disease severity, linking MIF-1 to various pathophysiological mechanisms may highlight the active involvement of the monocyte-macrophage system in HF. This system holds notable significance in congestion-related conditions, acting as a major source of reactive oxygen species that perpetuate inflammation. Full article

Engineered exosomes have emerged as transformative drug carriers, uniquely equipped to overcome biological barriers in central nervous system (CNS) disorders and cancer therapy. These natural extracellular vesicles, derived from cell membranes, offer inherent biocompatibility, low immunogenicity, and the ability to traverse physiological obstacles such as the blood–brain barrier (BBB) and dense tumor stroma. Recent advances in exosome engineering—including surface modification (e.g., ligand conjugation for receptor-mediated targeting) and cargo loading (siRNA, CRISPR-Cas systems, and chemotherapeutics)—have enhanced their precision and therapeutic utility. For CNS delivery, exosomes functionalized with brain-homing peptides (e.g., RVG or TfR ligands) have enabled the efficient transport of neuroprotective agents or gene-editing tools to treat Alzheimer’s disease or glioblastoma. In oncology, engineered exosomes loaded with tumor-suppressive miRNAs or immune checkpoint inhibitors exploit tumor microenvironment (TME) features, such as acidity or enzyme overexpression, for spatially controlled drug release. Furthermore, hybrid exosome–liposome systems and exosome–biomaterial composites are being explored to improve payload capacity and stability. Despite progress, challenges persist in scalable production, batch consistency, and regulatory standardization. This review critically evaluates engineering strategies, preclinical success, and translational hurdles while proposing innovations such as AI-driven exosome design and patient-derived exosome platforms for personalized therapy. By bridging nanotechnology and biomedicine, engineered exosomes can represent a paradigm shift in targeted drug delivery, offering safer and more effective solutions for historically intractable diseases. Full article