Search Results (1,572)

The integration of exosomes into professional cosmetics marks a significant paradigm shift from traditional passive formulations to advanced regenerative esthetics. Rather than being defined solely by their nanometric dimensions or classical association with endosomal biogenesis, these vesicles function as highly targeted intercellular messengers capable of delivering complex bioactive payloads to modulate tissue repair and collagen synthesis. While robust preclinical and clinical trials validate their remarkable potential in skin rejuvenation, hair restoration, and hyperpigmentation management, significant translational barriers remain. A critical analysis of the current literature reveals that successful clinical outcomes frequently rely on physical penetration enhancers, such as microneedling or fractional lasers, making it challenging to isolate the autonomous efficacy of topical vesicles from the trauma-induced regenerative response. Furthermore, commercial viability is dictated by stringent regulatory frameworks. In the European Union, Regulation (EC) No 1223/2009 strictly prohibits human-derived biologicals, while the US Food and Drug Administration (FDA) aggressively monitors the unsubstantiated marketing of cellular therapies. To navigate these biosafety and legal constraints, the aesthetic industry is increasingly pivoting toward non-human and legally compliant alternatives. Consequently, Plant-Derived Extracellular Vesicles (PDEVs), microbiome-derived exosomes (such as those obtained from bacterial fermentation), and bioengineered synthetic analogues have become the focal point of market innovation. A practical evaluation of the MCCM Medical Cosmetics portfolio illustrates this strategic shift, demonstrating the clinical versatility of botanical sources. To secure the long-term credibility of exosome technology, the industry must overcome current manufacturing heterogeneity by aligning with international standardization frameworks, such as the MISEV2023 guidelines, thereby ensuring reliable delivery systems, batch-to-batch consistency, and uncompromised consumer safety. This review provides a comprehensive overview of the biological mechanisms, clinical efficacy, and translational challenges associated with exosome-based cosmetics. Full article

Background/Objectives: Fluoroquinolones (FQNs) are widely prescribed broad-spectrum antibiotics but are associated with central and peripheral nervous system adverse reactions (ARs). Regulatory agencies have issued multiple safety warnings regarding their neuropsychiatric effects; however, large-scale, comparative evaluations across individual FQNs remain limited. This study aimed to comprehensively characterise and compare neuropsychiatric profiles associated with Ciprofloxacin, Levofloxacin, and Moxifloxacin using pharmacovigilance data. Methods: A retrospective pharmacovigilance study was conducted using reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) between 2010 and 2025. Neuropsychiatric ARs were identified using MedDRA terms, including neurological and psychiatric manifestations. Reporting trends, demographic characteristics, and event frequencies were descriptively analysed. Signal detection was performed using the Information Component (IC), Proportional Reporting Ratio (PRR), and Reporting Odds Ratio (ROR). Results: A total of 95,968 individual case safety reports involving neuropsychiatric ARs were included. Levofloxacin accounted for the highest number of reported events, followed by Ciprofloxacin and Moxifloxacin. Disproportionality analyses identified peripheral neuropathy as the strongest neurological signal for Levofloxacin and Moxifloxacin, while Ciprofloxacin showed stronger central nervous system associations. Psychiatric ARs were drug-specific, with anxiety predominating for Ciprofloxacin and Moxifloxacin, and insomnia for Levofloxacin. All major signals were statistically robust (IC025 > 0), confirming distinct compound-specific neuropsychiatric risk profiles. Conclusions: The large-scale 16-year analysis demonstrates distinct, drug-specific neuropsychiatric risk profiles. The available evidence supports a non-interchangeable safety profile among FQNs and emphasises the importance of drug-specific risk–benefit assessment in clinical practice. Full article

Although mango is not classified among the nine major allergenic foods reported by the Food and Drug Administration (FDA), the increasing global and domestic consumption of mango has been accompanied by a growing number of reported cases of mango allergy. Currently, reports on cross-reactive allergens and cross-reactive linear epitopes in mango are limited. This study employed BLASTp (version 2.11.0+) to predict potential allergens that may cross-react with mango protein allergens and other food protein allergens. Subsequently, cross-reactive allergens were identified using sera from mango-allergic patients. Furthermore, similar sequences of the identified cross-reactive allergens were predicted by BLAST. These similar sequences were then synthesized by the solid-phase peptide synthesis method. Finally, the cross-reactive linear epitopes were determined by assessing their IgE-binding capacity using serum IgE from the same patient cohort. The results demonstrated that the sera from mango-allergic patients exhibited IgE-binding cross-reactivity with those from peanut, wheat, cashew, pistachio, and hazelnut, particularly with IgE-binding cross-reactivity to wheat and hazelnut, which has not been previously reported. The following novel cross-reactive linear epitopes were identified: the AA80–88 sequence of mango chitinase with the AA37–45 sequence of wheat Tri a 27 and the AA15–22 sequence of mango profilin with the AA65–72 sequence of pistachio Pis v 1. Furthermore, multiple cross-reactive epitopes were mapped between mango profilin and peanut Ara h 5, corresponding to the sequences AA31–51/AA31–50, AA50–65/AA52–65, AA76–96/AA76–96, and AA103–117/AA104–117, respectively. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited effective therapies. Two-dimensional (2D) in vitro models poorly recapitulate tumor microenvironment (TME) interactions, impeding the translational relevance of TNBC immunotherapy research. Three-dimensional patient-derived tumor organoids (3D PDTOs) have emerged as advanced preclinical models that better mimic tumor–immune interactions. The objective of this systematic review was to assess the landscape of 3D PDTO adoption in TNBC research and evaluate their application in addressing key bottlenecks in TNBC immunotherapy. We retrieved 394 studies published between 2015 and 2025 from the PubMed and ClinicalTrials.gov databases. Of those, 153 studies were included in the review. Fifty-eight (58) TNBC-specific studies met the inclusion criteria, including explicit mention of 3D PDTOs in the title or abstract, with confirmation in the Methods and Results sections. Studies were excluded if they used non-patient-derived tumor organoids or referred to other 3D models as 3D PDTOs. Data were collected from January 2025 through December 2025. Eligible studies were screened in three (3) tiers, grouped by relevant themes and graphed in Excel. We present an overview of the adoption of 3D PDTOs in TNBC research, highlighting the most common application trends within this scope. We also discuss the potential impact of artificial intelligence (AI) and regulatory guidance from the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) pertinent to the adoption of organoids as human-relevant models to improve translational outcomes. Overall, this review provides actionable insights for leveraging 3D PDTOs to advance translational TNBC research and precision oncology. Full article

Compound repurposing is an efficient method to save both time and costs by redirecting previously synthesized small molecules towards new biological targets. In this research, we employ computational methodologies to investigate and assess target engagement of small molecules as tyrosine kinase inhibitors (TKIs). Therefore, compounds TKI.2a, TKI.2b, TKI.6, TKI.16, TKI.19, and TKI.21b identified from our earlier research, undergo assessments of molecular similarity, docking studies, and pharmacophore modeling along with those discovered through database searches. Compounds TKI.2a, TKI.2b, TKI.6, and TKI.19 appear to exhibit multi-target tyrosine kinase inhibitory activities against VEGFR-2 (Vascular Endothelial Growth Factor Receptor), RET (proto-oncogene tyrosine–protein kinase receptor), PDGFRα (Platelet-Derived Growth Factor Receptor alpha), EGFR (Epidermal Growth Factor Receptor), and HER2 (Human Epidermal Receptor) receptors. Pharmacophore models were applied for ligand-based virtual screening using defined parameters to discover candidate compounds that exhibit drug-likeness with FDA (Food and Drug Administration)-approved tyrosine kinase inhibitors. Molecular docking studies identified lead compounds for each biological target based on their overall affinity values and established interactions. Compound ChEMBL2170947 was found to be the most promising candidate for the VEGFR-2 receptor, ChEMBL5019511 for PDGFRα, ChEMBL2216869 for EGFR, and ChEMBL3355044 for HER2. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, providing substantial survival benefits across a wide range of malignancies. However, ICI-associated renal toxicity encompasses a broad spectrum of clinical entities, ranging from nonspecific acute kidney injury to well-defined immune-mediated nephropathies with distinct pathophysiological mechanisms. Methods: We performed a large-scale pharmacovigilance study using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate immune-mediated nephropathy associated with ICIs from January 2014 to March 2025. To improve specificity and minimize misclassification, the analysis was restricted to well-defined immune-mediated renal adverse events identified using MedDRA Preferred Terms, excluding nonspecific acute kidney injury. Disproportionality analysis was conducted using reporting odds ratios (RORs) with 95% confidence intervals (CIs) to assess associations between individual ICIs, treatment regimens, and nephropathy reporting. Results: Among 203,652 ICI-related adverse event reports (irAEs), 2361 (1.12%) involved immune-mediated nephropathy. Compared with other irAEs (non-nephropathy), immune-mediated nephropathy was more frequently reported in patients aged ≥ 65 years and in those with lung and genitourinary malignancies. Tubulointerstitial nephritis was the predominant subtype. Higher reporting signals were observed with cemiplimab and pembrolizumab, whereas durvalumab and atezolizumab demonstrated lower reporting signals. Combination regimens involving PD-1 and CTLA-4 inhibitors were associated with higher reporting frequencies compared with monotherapy. Conclusions: This real-world pharmacovigilance analysis identifies clinically relevant differences in immune-mediated nephropathy reporting across ICI classes and treatment strategies. PD-1 inhibitors and PD-1/CTLA-4 combination regimens were associated with higher reporting signals, suggesting potential variation in renal safety profiles. These findings should be interpreted cautiously, given the inherent limitations of spontaneous reporting systems, but they provide hypothesis-generating evidence to support future prospective studies with detailed clinical and histopathological correlation. Full article

Background and objectives: Previous dynamic collimator system (DCS) developments included: (1) hardware construction and commissioning, (2) an accurate dose calculation algorithm, (3) a quality assurance approach, and (4) development of optimization tools for treatment planning. Clinical DCS implementation necessitates efficient treatment plan delivery and fully integrated tools. In this work, a novel algorithm for minimizing treatment time was developed with the goal of reducing the DCS time increase, relative to conventional pencil beam scanning, to one minute or less per beam. In this extensive end-to-end evaluation, treatment plans generated with a modified U.S. Food and Drug Administration (FDA)-cleared treatment planning system were delivered on an Ion Beam Applications (IBA) Proteus Plus proton therapy system, with and without a DCS, to evaluate delivery times and dosimetric accuracy for a relatively large patient dataset, providing evidence of the clinical potential of the approach. Methods: Ten previously treated brain patients were replanned, consisting of both deep-seated central and superficial targets, the latter of which required an external 4 cm polyethylene range shifter. DCS treatments were optimized using a maximum conformity planning technique exploiting per-spot collimator capabilities. An optimization algorithm was incorporated to minimize treatment delivery time by determining the optimal sequencing of spot positions and collimator settings. Plan quality was quantified using conformity and dose-volume histogram (DVH)-based metrics while delivery accuracy was validated through measurements using both patient-specific quality assurance (PSQA) and log file analysis at the Miami Cancer Institute (MCI). Results: The DCS reduced the dose gradient index on average by 26.4% (17.7–37.1%) and the mean dose to the adjacent healthy tissue (within 10 mm of the target) by 19.3% (16.3–26.2%). The average reduction to the mean and maximum dose to the involved optic nerves was 50% (25.7–80.7%) and 18.7%, respectively, and the mean and D_2cc dose to the involved brainstem was reduced by 63.9% (31.5–96.4%) and 60.4% (10.8–99.8%), respectively. PSQA pass rates among DCS-collimated and baseline uncollimated treatments were 99.7% and 99.2%, respectively. DCS treatment fields were delivered within an average of 49 s (32–61 s) from their uncollimated intensity modulated proton therapy (IMPT) counterparts. Average spot position errors were −0.05 ± 0.2 mm and 0.04 ± 0.2 mm for the x- and y-position, respectively. The maximum error in magnitude for collimator positioning was 0.2 mm or less. Conclusions: DCS collimated IMPT treatments can provide significant dosimetric improvements over uncollimated treatments. These highly collimated treatments can be delivered with sufficient accuracy for clinical use while incurring an additional time penalty of around one minute or less per field compared to uncollimated treatments. Full article

Despite transformative therapeutic advances, multiple myeloma (MM) remains an incurable malignancy characterized by sequential relapses and progressive treatment resistance. Patients with heavily pretreated relapsed or refractory MM continue to face limited therapeutic options and poor outcomes. Melflufen (melphalan flufenamide) is a peptide–drug conjugate that enhances intracellular delivery of alkylating agents via aminopeptidase-mediated activation. Early clinical studies demonstrated encouraging activity in advanced MM, leading to accelerated approval by the U.S. Food and Drug Administration in 2021. However, results from the phase III OCEAN trial raised concerns regarding overall survival, ultimately resulting in withdrawal of the drug from the U.S. market. In this review, we examine the biological rationale, clinical development, and regulatory trajectory of melflufen, and critically reassess its role within the evolving therapeutic landscape of MM. While the negative survival findings observed in the phase III OCEAN trial substantially limited the clinical development of melflufen, the biological principles underlying enzyme-targeted intracellular drug delivery may still provide relevant insights for biomarker-driven therapeutic strategies and future peptide–drug conjugate development in MM. Full article

Background: In recent years, case reports and case series have suggested an association between the use of second- (SGAs), but not first-generation antipsychotics (FGAs), also known as atypical and typical APDs, respectively, and hyperglycemic complications, notably diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). Although this evidence is informative, there is a need for more observational studies to strengthen this body of knowledge. Objective: To conduct a systematic review of evidence established in observational studies on adverse drug events, specifically DKA and HHS, associated with the use of FGAs and SGAs. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using appropriate index phrases and keywords through October 17, 2025. Exposure included at least one United States Food and Drugs Administration (US FDA)-approved antipsychotic drug (APD); outcomes were limited to DKA and HHS. Results: A total of 15 observational studies were included in this review, including seven analytical and eight descriptive studies. These studies varied in scope and used different case definitions, study populations, exposures, and outcomes. The observational studies support existing evidence of an association between atypical APDs and DKA, mainly. As a class, typical APDs were associated with an increased risk of DKA, when compared to non-antipsychotic drug use. Although some studies evaluated this association in relation to HHS, there is insufficient information to draw conclusions for this outcome at this time. Conclusions: This analysis provides additional evidence of an association between use of atypical APDs and DKA. Additional analytical studies using administrative health databases are needed to clarify this association. Full article

Transcatheter aortic valve replacement (TAVR) has transformed the management of severe aortic stenosis and is now widely used across a broad spectrum of surgical risk. With expanding indications and increasing use in younger patients, contemporary practice increasingly emphasizes lifetime management of aortic valve disease, a shift further supported by recent developments including findings from the EARLY TAVR trial and the May 2025 U.S. Food and Drug Administration approval of TAVR for asymptomatic severe aortic stenosis. This narrative review summarizes recent developments in TAVR, including advances in device technology, procedural techniques, and patient selection. Focus is placed on the importance of optimal first valve selection, prevention of prosthesis–patient mismatch (PPM), and planning for future reintervention such as valve-in-valve (ViV) TAVR. Emerging procedural strategies including bioprosthetic valve fracture and leaflet modification techniques have expanded treatment options for patients at risk of elevated gradients or coronary obstruction. The review also highlights evolving approaches to TAVR in complex clinical scenarios and discusses future directions in device design and imaging-based procedural planning. As TAVR continues to evolve, careful procedural planning and multidisciplinary heart team collaboration remain essential to optimizing long-term outcomes. Full article

Thymol has been granted “Generally Recognized as Safe” status by the US Food and Drug Administration. However, its application as a natural preservative is constrained by limitations such as poor water solubility and high volatility. In this study, a dual-protein complex was prepared using mung bean protein and whey protein isolate to stabilize thymol-loaded oil-in-water (O/W) Pickering emulsions. The results demonstrated that the dual-protein system was driven by hydrogen bonding, electrostatic attraction, and hydrophobic interactions. Compared to single-protein systems, the dual-protein Pickering emulsions possessed smaller droplet sizes, lower polydispersity indices, and higher surface charges and surface hydrophobicity. Additionally, the dual protein enhanced emulsifying activity, thermal stability, and 30-day storage stability. Notably, the complex formed a continuous three-dimensional porous network structure at the mung bean protein (MBP) to whey protein isolate (WPI) ratio of 50%:50%. Benefiting from this structure and high surface hydrophobicity, the 50%:50% formulation achieved the highest thymol encapsulation efficiency. In terms of functional properties, this optimized emulsion demonstrated notable antibacterial activity and antioxidant activity; it demonstrated antibacterial activity against Shewanella putrefaciens and Staphylococcus aureus. Furthermore, the IC₅₀ value for the 50%:50% formulation was 192.25 ± 1.93 μg/mL (DPPH) and 161.74 ± 0.71 μg/mL (ABTS). In summary, the 50%:50% formulation enhanced the emulsifying activity, encapsulation efficiency, and bioactivity of the emulsion. This system provides an effective strategy for the stabilization and encapsulation of hydrophobic active compounds in emulsions. Full article

Background/Objectives: Currently available treatments approved by the Food and Drug Administration for Alzheimer’s disease (AD) either only target the symptoms of AD or, if disease-modifying, have severe side effects. This study aims to explore the potential of the FDA-approved Rho-associated kinase (ROCK) inhibitor netarsudil to reduce tau, a pathological protein in AD. Methods: We explored the pharmacokinetic and pharmacodynamic properties of netarsudil following a single intraperitoneal (i.p.) injection in wild-type mice. The efficacy of netarsudil was assessed using ELISA targeting tau/phosphorylated tau (ptau), as well as mass spectrometry-based proteomics. Results: We found that netarsudil is brain permeable, reaches peak concentrations rapidly and has moderate but sustained exposure in the central nervous system (CNS). Additionally, there was a statistically significant negative association between brain netarsudil exposure and tau and phosphorylated tau at residue 181 (ptau181). The exploratory proteomic analysis of mouse brains exposed to netarsudil revealed changes in mitochondrial function, enrichment of metallothioneins Mt1 and Mt2, and suppression of the AD-related genes Pzp and Serpina3m. Conclusions: The apparent reduction in AD pathological protein tau/ptau and a neuroprotective proteomic profile in vivo suggest the potential for netarsudil to be developed as a new AD therapeutic agent. Full article

Apical prolapse, a common form of Pelvic Organ Prolapse (POP), is often linked to weakened support structures such as the uterosacral (USL) and cardinal ligaments (CL), influenced by factors like vaginal childbirth, aging, and obesity. Although surgical mesh use is expected to increase, the Food and Drug Administration (FDA) banned polypropylene mesh for transvaginal anterior compartment prolapse in 2019 due to safety concerns, highlighting the need for alternatives such as biodegradable implants. This study developed four biodegradable mesh implants (square and sinusoidal geometries) mimicking the USL and CL. These were applied within a computational pelvic model to assess biomechanical behavior during the Valsalva maneuver and to explore different fixation methods (continuous, interrupted and simple stitch sutures). Baseline analysis of the healthy model established vaginal displacement under normal conditions. Without implant support, complete CL rupture increased displacement by 34%, and complete USL rupture raised displacement by 69%. Polycaprolactone implants consistently reduced anterior vaginal wall displacement in all impairment scenarios. Square implants mimicking the USL reduced displacement by up to 10% in cases of complete USL rupture with intact CL. Similarly, square implants mimicking the CL reduced displacement by up to 15% with complete CL rupture and healthy USL. Simulations with both ligaments impaired showed that USL contribute to support, while CL play a key role in stabilization. These findings demonstrate the potential of biodegradable implants to enhance POP repair. However, further studies are needed to evaluate long-term degradation and clinical applicability. Full article

Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutation subtype in non-small cell lung cancer (NSCLC), accounting for approximately 4–12% of all EGFR-mutated cases. Unlike classical EGFR mutations, ex20ins mutations confer inherent resistance to first-, second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) due to unique structural alterations that lock the αC-helix in an active orientation, creating steric hindrance within the drug-binding pocket. Until recently, platinum-based chemotherapy remained the standard first-line treatment, with objective response rates (ORR) of 19–47% and a median progression-free survival (PFS) of 6–7 months. Over the past five years, the therapeutic landscape has shifted, driven by the development of selective inhibitors and bispecific antibodies. Amivantamab, a bispecific EGFR–mesenchymal–epithelial transition factor (MET) antibody combined with chemotherapy, demonstrated superior efficacy in the PAPILLON trial, with an ORR of 73% and a median PFS of 11.4 months in the first-line setting. Sunvozertinib, an oral, selective EGFR inhibitor, received U.S. Food and Drug Administration (FDA) accelerated approval in 2025, with an ORR of 46% and a median duration of response (DOR) of 11.1 months in platinum-pretreated patients. Emerging therapies, including zipalertinib and furmonertinib, have shown promising results in early-phase trials, with zipalertinib demonstrating activity in patients pretreated with amivantamab (ORR 31.5%) and furmonertinib achieving remarkable responses in treatment-naive patients (ORR 78.6% at 240 mg). This comprehensive review analyzes the molecular biology, structural mechanisms, current therapeutic options, and novel investigational agents for EGFR ex20ins-mutated NSCLC. Full article

Diffuse midline gliomas (DMGs) are rare but highly aggressive central nervous system (CNS) tumors that can present in both pediatric and adult populations. These tumors were redefined in the 2016 WHO classification of CNS tumors based on integrated histopathological and molecular features, and were initially designated as “DMG, H3 K27M-mutant”. In the 2021 WHO update, DMGs were incorporated into the newly defined category of primarily pediatric-type diffuse high-grade gliomas, and nomenclature was changed to “DMG, H3 K27-altered” to encompass additional molecular drivers beyond the canonical H3 K27M mutation. Clinically, DMGs arise as expansile, infiltrating tumors within midline structures and may present as non-enhancing or enhancing lesions on imaging. Diagnosis is based on neuroimaging and molecular confirmation by immunohistochemistry or sequencing when tissue is available. DMGs are categorized as WHO grade 4 malignant tumors due to their aggressive biology leading to rapid and infiltrative growth. Owing to their deep and midline location, surgical resection is typically not feasible. Radiation therapy is the backbone of treatment, but there is no standard regimen of chemotherapy that has demonstrated durable efficacy. Recent progress in therapeutic approaches has led to a major breakthrough on 6 August 2025 when the U.S. Food and Drug Administration granted the accelerated approval of dordaviprone (ONC201), marking it as the first systemic therapy for progressive DMG harboring H3 K27M mutation. Other novel approaches, including chimeric antigen receptor (CAR) T-cell directed therapies and convection-enhanced delivery, are actively under investigation. We aim to comprehensively review DMGs, including the recent insights into their biology, the evolving therapeutic landscape, and the opportunities to fuel this new momentum against one of the most formidable gliomas. Full article