Search Results (1,594)

The demand for eco-friendly photoprotection has increased due to the observed adverse effects of conventional UV filters on marine ecosystems. In this study, we developed a broad-spectrum, reef-friendly sunscreen emulsion containing Perilla frutescens seed extract. The extraction process was optimized using 95% ethanol maceration for one week, yielding the highest SPF of 22.61. Gas chromatography–mass spectrometry (GC-MS/MS) was used to identify linolenic acid (43.54%) as the predominant fatty acid. Cytotoxicity test results for HaCaT keratinocytes were used to confirm the extract’s safety, with an IC₅₀ of 12.9 mg/mL. The formulated sunscreen met environmental safety standards based on persistence, bioaccumulation, and toxicity (PBT) criteria. A clinical safety evaluation using a 24 h closed patch test (n = 17) demonstrated that the formulation induced no significant alterations in TEWL or erythema levels (p > 0.05), confirming its dermatological safety. In a clinical efficacy evaluation involving 30 volunteers, the formulation containing 1% perilla extract reduced both erythema values and the melanin index, with no statistically significant difference observed (p > 0.05). These findings demonstrate that P. frutescens seed extract is a potent bioactive ingredient for sustainable cosmeceuticals, offering effective sun protection while ensuring safety for both human skin and marine environments. Full article

Conventional organic and inorganic ultraviolet (UV) filters often face limitations related to photostability, skin penetration, and potential toxicity arising from their photocatalytic activity. In this study, graphitic carbon nitride (g-C₃N₄) was investigated as a candidate biocompatible UV-shielding pigment. g-C₃N₄ powders were synthesized via thermal polymerization using urea and melamine as precursors. The melamine-derived samples exhibited a dense, block-like morphology with a strong yellow coloration and poor spreadability. In contrast, the urea-derived samples formed a distinctive porous and rounded structure. This morphology, originating from multistage gas evolution during polymerization, significantly reduced the static friction coefficient, resulting in a smoother texture and improved skin adaptability. Preliminary biological evaluation indicated high cell viability in cytotoxicity tests. Combined with the observed low photocatalytic activity, these findings suggest a favorable biocompatibility profile for topical applications. Overall, the results demonstrate that precursor engineering using urea enables the synthesis of high-performance g-C₃N₄ pigments with improved texture, desirable optical properties, and reduced biological reactivity. Full article

Background/Objectives: Chronic inflammatory skin diseases are frequently associated with pruritus, in which the neurokinin-1 receptor (NK₁R) and its ligand substance P (SP) play a central role. The development of compounds combining anti-inflammatory and antipruritic effects represents a promising therapeutic strategy. This study aims to identify fiscalin B derivatives as anti-inflammatory agents with high affinity to NK₁R using an integrated in silico and in vitro approach. Methods: A library of fiscalin B derivatives was screened through molecular docking against NK₁R to identify high-affinity ligands. Selected compounds were further evaluated using in silico ADMET and toxicity predictions. In vitro assays were conducted in HaCaT keratinocytes, RAW264.7 macrophages, and NIH/3T3 fibroblasts to assess cytotoxicity, nitric oxide production, inflammatory proteins expression, and cell migration. Results: Docking studies identified several derivatives with predicted binding affinities comparable to or exceeding those of aprepitant, a well-established NK₁R antagonist. Several compounds, particularly 2, 3, 4, 6, and 7, reduced lipopolysaccharide-induced nitric oxide production to 41–51% without relevant cytotoxicity. This effect was associated with reduced iNOS protein levels, suggesting modulation of inflammatory pathways rather than direct nitric oxide scavenging. Most compounds showed positive safety profiles, although in silico analysis indicated limited biodegradability and potential aquatic toxicity. Conclusions: The fiscalin B derivatives, 2, 3, and 4, demonstrate potential as anti-inflammatory agents, in vitro, and as NK₁R high affinity ligands, in silico. These findings support their potential as lead compounds for topical therapies for inflammatory skin disorders associated with pruritus, although further optimization and validation are required. Full article

Itraconazole is an antifungal drug used to treat chytridiomycosis, one of the leading causes of global amphibian decline in species such as the critically endangered Panamanian golden frog (Atelopus zeteki). Despite its widespread use for prophylaxis and treatment in both assurance colonies and free-ranging amphibians, there is minimal pharmacologic information to guide dosing. In experiment A, frogs were exposed to 0.01% itraconazole for 10 min and tissue samples were analyzed at various time points from 1 to 84 h. In experiment B, frogs were divided into six groups and exposed to itraconazole in different combinations of concentration (0.01% or 0.001%) and time (5, 10, or 15 min) over 10 days of treatment. Tissue concentrations were quantified via high-performance liquid chromatography. In experiment A, following a one-time dose, itraconazole concentrations remained high until the end of the experiment at 84 h. In experiment B, at 0.01% itraconazole daily for 10 days, skin and liver concentrations were high and increased substantially over the 10-day treatment course. Frogs exposed at the lower concentration (0.001%) had tissue concentrations that appeared to remain steady. At the reported doses over 10 days, there was no histologic evidence of hepatic toxicity, although one frog was found dead in the low-dose bath at 84 h and could not be further analyzed. This experiment is an excellent example of assurance colonies providing evidence-based information for the improved care and welfare of amphibians in order to prepare for future free-ranging populations. Full article

Introduction: In the treatment of hormone receptor-positive (HR+), HER2-negative (HER2−) metastatic breast cancer (MBC), the current guidelines recommend endocrine therapy combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors as the preferred first-line treatment to preserve quality of life. Ribociclib is a CDK4/6 inhibitor that has been used in combination with aromatase inhibitors or fulvestrant in patients with HR+, HER2− metastatic breast cancer. Various adverse drug reactions associated with ribociclib have been reported, including cutaneous reactions, hepatotoxicity, and hematologic toxicity. In this study, we aimed to evaluate the clinical manifestations and risk factors of dermatologic toxicities in patients with metastatic breast cancer treated with ribociclib. Methods: This retrospective study included patients with metastatic/recurrent breast cancer who were prescribed ribociclib from April 2021 to December 2024 at a single institution. We retrospectively reviewed the medical records of these patients to identify the frequency of cutaneous adverse events, the time of onset, and the clinical characteristics of skin reactions. Logistic regression analysis was performed on several clinical factors, including body surface area (BSA) and concomitant medications, to identify risk factors associated with the occurrence of cutaneous adverse events. Results: A total of 110 patients with MBC were enrolled during the study period. The median age was 53 years (range, 28–82); all 110 patients (100.0%) were female; the median BSA was 1.56 m² (range, 1.29–2.07); and 32 patients (29.1%) were premenopausal. Ribociclib plus letrozole was administered in 48 patients (43.6%) and ribociclib plus fulvestrant in 29 patients (26.4%). An additional 33 patients (30.0%) received ribociclib plus letrozole with a gonadotropin-releasing hormone (GnRH) agonist. Cutaneous adverse events occurred in 29 patients (26.4%), and the median time to onset was 84 days (range, 3–498). The cutaneous adverse event patterns included pruritus, erythematous macular rash, eczematous rash/contact dermatitis, vitiligo, urticarial reactions, polymorphous light eruption, toxic epidermal necrolysis (TEN), and desquamation. Grade 1 or 2 cutaneous adverse events occurred in 93.1% of patients; Grade 3 toxicity occurred in one patient; and Grade 4 toxicity, namely toxic epidermal necrolysis (TEN), was reported in one patient. Dose reduction was required in three patients (10.3%), and permanent discontinuation of ribociclib occurred in one patient. Clinical improvement was achieved in the majority of patients (86.2%) with cutaneous adverse events following supportive care. Logistic regression analysis revealed that age, Eastern Cooperative Oncology Group (ECOG) performance status, body surface area (BSA), treatment regimen, and use of cholesterol-lowering medications were not independently associated with the development of cutaneous adverse events. Conclusion: CDK4/6 inhibitors represent one of the most important treatment options for HR+/HER2− metastatic breast cancer. Regardless of their clinical efficacy, cutaneous adverse events remain a common source of patient discomfort. Therefore, careful clinical attention and appropriate supportive care are essential to improve patients' quality of life. Full article

Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy, characterized by the involvement of multiple organs, including the skin, bone marrow and blood, lymph nodes and the central nervous system. According to tumor location, the disease is classified as skin-only, systemic-only, and skin and systemic. The cutaneous manifestations of disease are typical and are represented by violaceous single tumors or multiple plaques present in sun-exposed cutaneous areas. BPDCN is issued from the malignant transformation of dendritic cell progenitors and is diagnosed using the classical immunophenotypes CD123, CD4 and CD56 in addition to specific membrane markers of plasmocytoid dendritic cells. BPDCN is an aggressive disease and is associated with a short survival. Upfront therapies involve either chemotherapy regimens in fit patients and CD123-targeted therapies, including interleukin-3 conjugated with diphtheria toxin (Tagraxofusp, SL-401), or Pivekimab sunirine, an anti-IL-3R-drug conjugate, for both fit and unfit patients. Targeted treatments limit the toxicities of chemotherapy and allow the bridging of a consistent proportion of patients to hematopoietic stem cell transplantation, the only treatment associated with potential long-term survival. Full article

The human microbiota, comprising bacteria, fungi, and viruses, primarily resides in the gut, skin, and oral and nasal cavities. The gut microbiota represents the largest and most functionally relevant microbial community, playing a crucial role in digestion, metabolism and immunity. Microbiota composition and diversity have been associated with several diseases such as cancer, affecting drug efficacy, toxicity and clinical outcome. Interactions between the gut microbiota and the host immune system may contribute to the aetiology and progression of childhood acute lymphoblastic leukaemia (ALL). In this review, we summarized the general features of the gut microbiota in cancer patients and its specific role in aetiology, treatment and prognosis of paediatric ALL. Profiling the gut microbiota may help to shed the light on the mechanism of onset and to support the development of personalized treatment strategies and follow-up in children with ALL, contributing to precision medicine. Full article

The potent toxicity of tetrodotoxin (TTX) has long constrained sustainable growth in pufferfish aquaculture. Takifugu bimaculatus, an economically important species farmed along the coast of Fujian, China, remains poorly understood regarding how it transports and accumulates this potent neurotoxin. To address this gap, we combined transcriptomic and proteomic analyses to characterize the molecular responses of T. bimaculatus to TTX exposure. After oral administration, TTX primarily accumulated in the liver, ovaries, and skin. Multi-omics profiling revealed 163 differentially expressed genes (DEGs) and 88 differentially expressed proteins (DEPs) in liver tissue, together with 239 DEGs and 179 DEPs in ovarian tissue. KEGG pathway analysis suggests that the liver maintains homeostasis by regulating ion concentrations and restructuring lipid raft architectures, alongside coordinated carrier protein activity. This likely supports active TTX uptake and directed transport toward the ovaries and skin, followed by metabolic clearance. By contrast, ovarian tissues appear to establish a stable, long-term reservoir through cytoskeletal remodeling, enhanced interactions with the extracellular matrix, and activated endocytic pathways. Together, these findings offer insights into how T. bimaculatus accumulates and transports TTX, laying groundwork for identifying key transporter genes, clarifying TTX metabolic pathways, and developing practical food safety controls. Full article

Sulforaphane, a bioactive isothiocyanate found abundantly in cruciferous vegetables, has attracted significant attention for its chemopreventive and therapeutic potential, particularly in cancer. There is now an abundance of peer-reviewed research documenting true synergies between sulforaphane and (a) cancer treatment drugs, (b) pharmaceuticals in development but not yet on the market or in the regulatory pipeline, (c) other phytochemicals, and (d) proprietary mixtures such as leaf extracts and other botanicals, as well as evidence that some cell lines resistant to various cancer drugs become more susceptible when treated with sulforaphane. Most of the published studies demonstrate evidence for synergy in cancer, including cancers of the bladder, blood, brain, breast, colon, esophagus, liver, lung, ovaries, prostate, and skin, where reducing drug dosages could yield substantial patient benefits. Importantly, non-cancer indications have also been reported, such as mitigation of cardiac toxicity, inflammation, obesity, and pain (including antihyperalgesic and antinociceptive effects). Synergistic effects are most often demonstrated in cell line models, with many studies providing robust mechanistic evidence, and some employing the gold-standard Chou–Talalay method for quantifying synergy. Current evidence on the synergistic interactions of sulforaphane with both phytochemicals and pharmaceuticals highlights underlying mechanisms such as modulation of oxidative stress, inflammation, apoptosis, and epigenetic regulation, suggesting significant clinical and therapeutic implications. By providing a comprehensive overview of sulforaphane synergies in both cancer and non-cancer contexts, we aim to inform future research and support the development of integrated therapeutic strategies. Full article

Evaluating the safety of botanical extracts for cosmetics has become mandatory, but it is often challenging because of their phytochemical complexity and limited toxicological data. In this study, the safety of aqueous Sophora flavescens root extract (SFRE), widely used in cosmetics, was assessed using an integrated approach combining in vitro, in silico, margin of safety (MoS), threshold of toxicological concern (TTC), and history of safe use (HSU). Chemical characterization was performed by literature review and LC–MS/MS analysis. SFRE was classified as non-irritant in in vitro skin and eye irritation tests conducted according to OECD TG439 and 492. Whole-extract and constituent-level in silico analysis and literature evaluation were conducted to assess genotoxicity and skin sensitization potential. For systemic toxicity, a 13-week oral repeat dose no-observed-adverse-effect level (NOAEL) of 10 mg/kg bw/day for a decocted Sophorae radix extract was employed without compositional adjustment to calculate the acceptable systemic exposure dose of 0.10 mg/kg bw/day, which was slightly lower than the current usage of SFRE in cosmetics (up to 0.13 mg/kg/day). The TTC approach revealed that many bioactive constituents fell outside the applicability domain due to steroid moieties. HSU data from dietary supplements (32–64.67 mg/kg/day) could support the safety of the current use of SFRE in cosmetics. The findings highlight that a combined, case-by-case application of MoS, TTC, and HSU is essential for the robust safety assessment of complex botanical ingredients. Full article

Background: Pembrolizumab combined with pemetrexed–platinum chemotherapy is the standard first-line treatment for patients with metastatic non-squamous non-small-cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of 1–49%. Real-world data on treatment outcomes and the prognostic relevance of immune-related adverse events (irAEs) in this population remain limited, particularly in Eastern Europe. Methods: We conducted a retrospective, single-center real-world study including patients with metastatic non-squamous NSCLC and PD-L1 TPS of 1–49% treated with first-line pembrolizumab plus pemetrexed–platinum chemotherapy between June 2024 and May 2025. Progression-free survival (PFS) was estimated using the Kaplan–Meier method. Cox proportional hazards models were used to evaluate factors associated with PFS, including baseline clinical characteristics and organ-specific irAEs graded according to CTCAE v5.0. Results: A total of 107 patients were included. Median PFS for the entire cohort was 7.03 months (95% CI, 4.81–9.26). Immune-related adverse events occurred in 52 patients (48.6%), with thyroid (21.5%) and skin (13.1%) irAEs being the most frequent. The majority of irAEs were grade 1–2, while grade 3–4 events were rare (4.7%) and limited to hepatic toxicity and pneumonitis, all leading to treatment discontinuation. In multivariate analysis, ECOG performance status 2 was independently associated with inferior PFS (HR 3.09, 95% CI 1.74–5.48; p < 0.001). Conversely, the occurrence of thyroid irAEs (HR 0.36, 95% CI 0.17–0.78; p = 0.009) and skin irAEs (HR 0.28, 95% CI 0.10–0.79; p = 0.016) was independently associated with prolonged PFS, whereas pulmonary, hepatic, and gastrointestinal irAEs were not. Conclusions: In this real-world cohort of patients with metastatic non-squamous NSCLC treated with first-line pembrolizumab–chemotherapy, clinical outcomes were consistent with prior real-world experience. These findings suggest that low-grade, manageable immune toxicities may serve as pragmatic on-treatment markers of benefit. However, given the retrospective design, limited sample size, and the absence of time-dependent analyses, these associations should be interpreted with caution and considered hypothesis-generating rather than causal. Full article

Environmental contaminants such as per- and polyfluoroalkyl substances (PFAS) and toxic metals have been implicated in biological aging, yet their combined effects remain poorly understood. This study evaluated the associations of PFAS, lead, and cadmium mixtures with multiple DNA methylation-based measures of epigenetic aging in a nationally representative sample of U.S. adults aged ≥ 50 years. Data were obtained from the 1999–2000 and 2001–2002 National Health and Nutrition Examination Survey (NHANES). The analytic sample included 1119 participants with available data on seven PFAS, blood lead, cadmium, and DNA methylation measures. Epigenetic aging outcomes included HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge, and DunedinPoAm. Multivariable linear regression and Bayesian Kernel Machine Regression (BKMR) were used to assess individual and joint exposure–response relationships. Cadmium showed the most consistent positive associations with epigenetic aging measures, particularly for the second-generation clocks PhenoAge and GrimAge. Lead was positively associated with GrimAge, while PFAS showed more variable and generally weaker associations, with PFNA demonstrating the most consistent signal. Mixture analyses indicated that higher combined exposure levels were associated with higher DNA methylation age estimates, with stronger patterns observed for second-generation clocks. These findings suggest that combined exposure to PFAS, lead, and cadmium is associated with higher epigenetic aging in older U.S. adults, with cadmium emerging as a key contributor to the observed mixture effects. Evaluating environmental exposures as mixtures may provide important insight into how co-occurring contaminants jointly influence biological aging. Full article

Melanoma is an aggressive skin cancer with rapid progression and high metastatic potential, and resistance to current therapies remains a major clinical challenge. In this study, Listeria monocytogenes-derived membrane vesicles (LM MVs) were isolated, characterized, and evaluated for their immunomodulatory and antitumor activities. LM MVs showed an average diameter of approximately 160 nm and contained multiple bacterial proteins, including listeriolysin O. In vitro, LM MVs promoted pro-inflammatory activation of RAW264.7 macrophages, as indicated by increased CD80/CD86 expression and enhanced transcription of inflammatory mediators. LM MV treatment was accompanied by IκB-α degradation and NF-κB p65 nuclear translocation, whereas pharmacological inhibition of NF-κB attenuated macrophage activation. In a macrophage–melanoma co-culture system, LM MVs-activated macrophages reduced the viability, migration, and invasion of B16 melanoma cells and increased tumor cell apoptosis. Additional inhibition and immunofluorescence analyses suggested that iNOS and TNF-α-associated mechanisms contributed to these tumor-suppressive effects. In a murine melanoma model, LM MVs significantly inhibited tumor growth without overt systemic toxicity, whereas macrophage depletion markedly weakened this effect. These findings indicate that LM MVs exert antitumor activity against melanoma, at least in part through macrophage activation involving NF-κB signaling. Full article

Background: Given the severe toxicity of organophosphates and the efficient catalytic hydrolysis of organophosphates by organophosphorus hydrolase (OPH) against them, a rapidly dissolving microneedle patch loaded with OPH offers a promising therapeutic strategy to provide timely detoxification conveniently. Methods: The microneedles were prepared with sulfobutylether-β-cyclodextrin (SCD) matrix to load OPHDS5, one of the mutants of OPH, and were characterized in vitro and in vivo to determine tip loading capacity, skin insertion efficiency, and protective efficacy against ethyl paraoxon poisoning. Results: Microneedles prepared with 60% w/v SCD displayed well-defined square-pyramidal tips and a mechanical strength of 4 N/needle at 1200 μm. When containing 1.2 mg OPHDS5, the microneedles enabled SD rats to completely survive a lethal challenge of ethyl paraoxon, achieving a 100% survival rate, significantly alleviating the symptoms resulting from transdermal exposure and markedly attenuating the symptoms resulting from transdermal exposure. Conclusions: A rapidly dissolving microneedle patch encapsulating OPH was successfully developed. The patch effectively penetrated the skin and exhibited robust prophylactic and therapeutic activity against ethyl paraoxon poisoning. Full article

In recent years, nanotechnology has made remarkable progress in the fight against infectious diseases. However, the development of safe and effective antiviral drugs remains a challenge, as viruses rely on host cells for replication. Plant-derived, environmentally friendly nanoparticles have gained significant attention due to their low toxicity, which enables them to target viruses without damaging host cells. In this study, we describe the synthesis of silver nanoparticles (AgNPs) using Arctostaphylos uva-ursi leaf extract and explore their potential antiviral activity. The uva-ursi AgNPs were initially characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). We then optimized two different gellan gum/alginate film formulations (1.6:0.4 and 1.2:0.8) as delivery matrices for the AgNPs and assessed Ag⁺ skin permeation using a Franz diffusion cell system. The antiviral potential of the uva-ursi AgNPs—both alone and incorporated into the films—was tested against herpes simplex virus type 1 (HSV-1). Our findings indicate that uva-ursi AgNPs may directly interact with the viral envelope, disrupting the lipid membrane and/or interfering with viral surface proteins. Overall, green-synthesized uva-ursi AgNPs may represent a natural, cost-effective, and safe alternative strategy for managing herpetic infections. Full article