Search Results (79)

As primary producers in aquatic ecosystems, microalgae function not only as a natural source of nourishment for several economically important aquatic species but also as reservoirs of bioactive molecules. Microalgae can secrete exosome-like nanoparticles that transport functional biomolecules, such as proteins and nucleic acids, into the extracellular milieu, thereby mediating intercellular signaling and eliciting ecological or biomedical responses. Although plant-derived exosome-like nanoparticles have attracted attention for their utility in drug delivery and dermatology, the functional properties of microalgae-derived nanoparticles—particularly from species extensively applied in aquaculture—remain inadequately characterized. In this study, exosome-like nanovesicles were isolated from Nannochloropsis oculata (N-ELNs), a microalgal species widely used in aquaculture, and their skin-whitening potential was evaluated using the B16-F10 mouse melanoma cell model. The highest N-ELN yield was observed during the adaptation, exponential, and stationary growth phases. Uptake analyses confirmed the efficient internalization of N-ELNs by B16-F10 cells. Cell counting kit-8 assays indicated that N-ELNs exhibited no cytotoxic effects on melanoma cells or normal human dermal fibroblasts (HFF-1). Scratch wound healing assays revealed that N-ELNs exerted no significant effect on cellular migration. In B16-F10 cells, N-ELNs suppressed tyrosinase activity by downregulating Mitf and its downstream genes Tyr and Tyrp1, resulting in a substantial reduction in melanin synthesis (p < 0.05). The inhibitory effects of N-ELNs on melanin production, tyrosinase activity, and gene expression of Tyr, Tyrp1, and Mitf were comparable to those of the positive control, arbutin. Collectively, these findings suggest that N. oculata exhibits promising skin-whitening properties, providing a novel perspective for clinical applications and supporting the high-value utilization of the microalgae aquaculture industry. Full article

Background: Carcinogenic, Mutagenic, and Reprotoxic (CMR) substances are among the most significant occupational health hazards in healthcare and research laboratories. Despite preventive measures and regulations, exposure assessment and risk management remain complex due to varied working practices, mixed exposures, and the lack of harmonized monitoring protocols. This systematic review investigates occupational exposure to CMR substances in laboratory and healthcare environments. Methods: Searches were conducted in PubMed, Scopus, and Web of Science up to February 2025 using tailored keyword strategies. Studies published between 2020 and 2025 reporting exposure assessment, monitoring, and/or risk management of CMR chemicals were included; non-English papers and irrelevant studies were excluded. Titles/abstracts and full texts were screened independently by two reviewers with arbitration by a third. Risk of bias was assessed by three authors who independently evaluated each study. A narrative synthesis with frequency tables was performed; no meta-analysis was conducted. Results: Of 446 screened records, 50 studies were included. Formaldehyde (25 studies) and antineoplastic drugs (18 studies) were most frequently examined. Healthcare settings—e.g., hospital pharmacies, oncology wards, and pathology laboratories—were predominant, while research laboratories were underrepresented. Inhalation was the main exposure route for formaldehyde, whereas dermal uptake and surface contamination predominated for antineoplastic drugs. Monitoring methods included air sampling, surface wipe testing, and biological assays; preventive strategies varied and were inconsistently applied. Most included studies involved environmental monitoring and did not report participant numbers, so a total number of participants cannot be aggregated; for the main outcomes, participant counts were often not available. Limitations of the evidence include marked heterogeneity across settings, matrices, analytical methods, and reporting units, which precluded meta-analysis, as well as imprecision and incomplete reporting in several studies. Conclusions: Findings reveal persistent gaps in harmonized exposure limits, monitoring standards, and long-term health surveillance, underscoring the need for comprehensive prevention strategies. This review was not registered and did not receive any external funding. Full article

Urban green spaces (UGSs) provide essential ecological services but also accumulate heavy metals (HMs) in their soils, posing a paradoxical health risk through dermal exposure. Traditional risk assessments, based solely on total HM concentrations, often overestimate threats by ignoring bioavailability (the fraction actually absorbed by organisms) and dynamic skin microenvironment factors. This review synthesizes recent advances to propose a precision assessment framework that integrates bioavailability. The framework advocates for the incorporation of bioaccessibility (the fraction of pollutants dissolved in body fluids)-driven exposure metrics (e.g., physiologically based extraction tests), mechanistic dermal permeation models (e.g., Franz diffusion cells, 3D skin constructs), and population-specific susceptibility factors (e.g., children, individuals with compromised skin). We elucidate how soil properties (pH, organic matter) and metal speciation (e.g., Cr(III)/Cr(VI)) modulate cutaneous uptake, and detail toxicological mechanisms including oxidative stress, ferroptosis/cuproptosis, immunotoxicity, and pigmentation disorders. Case studies reveal heterogeneous HM hotspots in high-traffic and densely populated areas, while in vitro–in vivo extrapolation highlights the potential for misestimation in traditional models. Consequently, we discuss the limitations and future directions of this framework, aiming to shift UGS risk management from over-conservative assessment to bioavailability-based precision governance, thereby supporting the health security of sustainable urban habitats. Full article

Firefighters are exposed to complex combustion products and to contaminants carried on personal protective equipment (PPE). Occupational exposure as a firefighter is classified as carcinogenic. This review summarizes the current evidence on exposure environments, routes of uptake, contamination and secondary exposure from PPE, and the effectiveness and limits of decontamination approaches. Across incident types, smoke composition varies with the fuels and combustion conditions, but fine and ultrafine particles and semi-volatile organic chemicals are common. Biomonitoring confirms uptake after incidents. Self-contained breathing apparatus reduces inhalation exposure during active suppression, yet exposures persist through dermal absorption at ensemble interfaces and post-incident tasks. Protective ensembles can retain soot-bound polycyclic aromatic hydrocarbons, additive chemicals, and metals; volatiles and particles resuspension in vehicles and stations can extend exposure. Studies show that on-scene preliminary exposure reduction and laundering can lower contaminant burdens on PPE; however, removal remains incomplete and decreases when cleaning is delayed or when gear is aged. Emerging evidence raises additional concern for per- and polyfluoroalkyl substances from foams and coating materials, with limited data on exposure metrics and removability. The field lacks standardized, realistic contamination platforms and a dose-based definition of clean PPE. Integrated intervention studies linking exposure, secondary exposure pathways, biomarkers, and decontamination methods are needed to set performance-based targets and evaluate emerging hazards. Full article

Insulin injection remains the best therapy for diabetes mellitus, but subcutaneous injection continues to pose challenges, including patient discomfort, poor compliance and fluctuating plasma glucose profiles. Recently, transdermal insulin delivery has emerged as a non-invasive strategy that bypasses gastrointestinal degradation and first-pass hepatic metabolism, thereby increasing insulin bioavailability and enhancing patient acceptance. Recent developments in nanomedicine have facilitated the development of transdermal patches with enhanced drug encapsulation, uptake and controlled release. Nanostructured lipid carriers, polymeric nanocomposites, liposomes and SLNs have demonstrated a five-fold enhancement of transdermal flux and an extended insulin effect in preclinical models. The addition of ionic liquids and polymeric nanogels leads to an additional increase in insulin aqueous solubility and permeation, resulting from the temporary regulation of stratum corneum lipid organization. Bright and stimuli-responsive patches with glucose oxidase or phenylboronic acid functional groups enable regulated insulin delivery in response to changes in blood glucose, demonstrating near-normoglycemia for up to 48 h in animal testing. Nanocomposite systems assisted by microneedles have also been advanced to the early clinical phase, offering enhanced reproducibility of their pharmacokinetics and a low risk of dermal irritation. Despite these encouraging results, several translational challenges remain, such as biocompatibility, repeatability in the production of nanocarriers, long-term stability of formulations and regulatory standardization. This review examines the physicochemical design principles, materials innovations and permeation mechanism of nanomedicine-engineered insulin patches, the current state of preclinical and clinical advancements, challenges in production and future perspectives in viable patient-focused transdermal insulin delivery. Full article

Background: Microplastics and nanoplastics (MNPs) are ubiquitous environmental contaminants from plastic degradation, leading to human exposure through ingestion, inhalation, and dermal contact. While emerging evidence suggests potential health effects, comprehensive human-specific data remain limited. Objective: To systematically review evidence on MNP exposure and health impacts across human organ systems. Methods: Following PRISMA guidelines, we searched Embase, Environment Complete, MEDLINE, and Scopus for peer-reviewed English-language studies published between 2020 and 2025 that reported MNP exposure in adult human populations and addressed at least one organ system. Thirty studies met inclusion criteria, and all clinical studies were assessed for risk of bias using the Newcastle–Ottawa Scale (NOS) Results: Clinical studies consistently detected MNPs in human blood, thrombi, feces, and respiratory and reproductive tissues. Higher MNP burdens correlated with increased disease severity across cardiovascular, gastrointestinal, respiratory, musculoskeletal, and reproductive systems. In vitro studies using human-derived cell lines demonstrated that MNPs penetrate cells and disrupt cellular processes, inducing oxidative stress, cytotoxicity, mitochondrial dysfunction, inflammation, DNA damage, and apoptosis. Toxic effects were size-, polymer-, and concentration-dependent, with smaller particles exhibiting greater cellular uptake and toxicity. Conclusions: Human MNP exposure is widespread and associated with adverse biological effects across multiple organ systems. Further interdisciplinary research is needed to establish causal relationships and inform risk assessment and regulatory frameworks for plastic-associated contaminants. Other: This research received no external funding. The research protocol was registered with PROSPERO (Registration ID number CRD420261284559). Full article

The increasing use of Technology-Critical Elements (TCEs) in modern technology has led to widespread environmental release, raising questions about their biological effects, as emerging evidence suggests significant toxicity. We investigated the effects of three technology-critical elements, Indium oxide (In₂O₃), Lanthanum nitrate hexahydrate (La(NO₃)₃·6H₂O) and Cerium(III) nitrate hexahydrate (Ce(NO₃)₃·6H₂O), on human dermal fibroblasts (BJ) and hepatocarcinoma cells (HepG2), assessing their uptake, impact on viability, and induced cellular stress responses, quantified by markers of inflammation, oxidative stress, and membrane damage. Our results show a strong differential susceptibility: normal BJ fibroblasts proved vulnerable, whereas HepG2 cells were highly resistant. This divergence occurred despite substantial and comparable accumulation of all three TCEs in both cell lines, indicating that toxicity is uncoupled from the magnitude of the uptake. Mechanistically, the differential toxicity correlated strongly with opposing antioxidant responses. Additionally, low concentrations of cerium (III) nitrate (12.5–50 µg/mL) uniquely stimulated the proliferation of HepG2 cells (up to 129% of control). While these findings identify multiple mechanistic hazards regarding the potential of low-level technology-critical element exposure, they must be interpreted cautiously and warrant further investigation in more complex biological models. Full article

Aging results in decreased collagen synthesis and the disruption of extracellular matrix integrity, primarily due to increased oxidative stress. This study evaluated whether atelocollagen can restore collagen synthesis in aged skin by modulating glycine transporter 1 (GlyT1)-mediated glycine uptake, regulating oxidative stress, and influencing extracellular matrix remodeling factors in senescent human cells and the skin of older mice. Human dermal fibroblasts (HDFs) and aged mouse skin were treated with atelocollagen, with analyses of GlyT1 expression, glutathione and intracellular glycine concentrations, oxidative stress markers, nuclear factor-kappa-B (NF-κB) activity, matrix metalloproteinases (MMPs), SMAD proteins (SMADs) signaling, and collagen I/III. Treatment with GlyT1 inhibitors and glycine was tested. Atelocollagen significantly increased GlyT1 expression and intracellular glycine concentration, promoted glutathione synthesis, and reduced oxidative stress. These effects led to decreased NF-κB activity and MMP1/3/9 expression, increased SMAD2/3 phosphorylation, and upregulated type I/III collagen synthesis in senescent HDFs and aged mouse skin. All beneficial effects were blocked by GlyT1 inhibition and were generally superior to glycine alone. Histology showed increased collagen density and improved skin elasticity in atelocollagen-treated mice. In summary, atelocollagen enhances collagen synthesis and reduces oxidative stress in aged skin through GlyT1-dependent glycine transport, providing a potential strategy for skin rejuvenation. Full article

Background: Lipedema is a progressive adipofascial disorder marked by painful nodular fat deposition that is often mistaken for obesity. While tumescent liposuction reduces limb volume with relative lymphatic safety, persistent large, painful lobules frequently remain, and excisional strategies risk iatrogenic lymphatic injury. We evaluated the application of intraoperative indocyanine green (ICG) lymphography to identify and preserve lymphatic channels during debulking surgery for symptomatic lipedema. Methods: We conducted a single-center case series (University of Pittsburgh Medical Center, July 2023–December 2024) of adults with lipedema refractory to conservative therapy who underwent a selective dermato-lipectomy (lobule/skin excision) with or without tumescent liposuction. Patients with clinical lymphedema or dermal backflow in ICG were excluded. Near-infrared ICG (SPY-PHI) was used for pre-incision mapping and real-time intraoperative guidance; lymphatic trajectories were marked and spared during lobule excision. Primary measures included dermal backflow patterns and lymph node transit time; secondary outcomes were complications and symptom burden (Lymphedema Life Impact Scale, LLIS) through ≥24 months. Results: Eight patients (five female/three male; mean age 49.5 ± 14.4 years; median BMI 52.65 kg/m²) underwent ICG-guided surgery. Preoperatively, linear lymphatic patterns were visualized up to the knee in all patients, but dermal backflow patterns could not be visualized in 83% from the level of the knee to the groin. Still, 67% demonstrated inguinal nodal uptake (mean transit 24 min), suggesting preserved lymphatic transport. All cases achieved intraoperative confirmation of intact lymphatic flow after debulking. The mean liposuction aspirate was 925 ± 250 mL per lower extremity; the mean excision mass was 2209 ± 757 g per lower extremity. Complications included two superficial cellulitis events (25%) and one wound dehiscence (12.5%); no hematomas or skin necrosis occurred. No patient developed clinical or imaging evidence of iatrogenic lymphedema during follow-up. Conclusions: Intraoperative ICG lymphography is a practical adjunct for lymphatic-sparing debulking of symptomatic lipedema, enabling real-time identification and preservation of superficial collectors while addressing focal lobules. This hybrid approach—targeted tumescent liposuction followed by ICG-guided superficial dermato-lipectomy—was associated with meaningful symptom improvement and a low morbidity in this early series. Full article

This review provides a comprehensive overview of the fundamental aspects of nanoparticles (NPs), emphasizing their physicochemical properties and biological interactions, with particular focus on porous silica nanoparticles (PSNs). The review provides information on the Safe-by-design (SbD) S.A.F.E. (Standardised characterization, Assessment of biocompatibility, Facilitation of toxicity and exposure routes and Evaluation of clinical translation) framework. It discusses critical factors influencing NP toxicity and cellular uptake, including particle size, shape, pore size, surface charge, surface functionalisation, and crystallinity. The review also examines exposure routes of NPs—inhalation, dermal, oral, systemic and mucosal—and their subsequent biological effects. A key section is dedicated to the formation of the protein corona, a critical determinant of NP fate in biological systems, and its influence on circulation time, immune clearance and cellular responses. Particular attention is given to assessing the biological interactions of the PSNs and the mechanisms underlying PSN-induced cytotoxicity and genotoxicity, with a focus on the assays commonly employed to evaluate these effects. The review explores the use of gene expression profiling as a powerful tool to elucidate the molecular mechanisms underlying nanoparticle-induced cellular changes. This review aims to provide an integrated perspective on the SbD considerations and safety implications of nanomaterials. It highlights the need for a deeper understanding of complex biological interactions to establish SbD principles and enable the translation of PSNs into clinical applications. Finally, current regulatory frameworks and guidelines for testing nanomaterials, including PSNs, that support their safe and sustainable development are discussed. Full article

Wound healing is a complex process in which TGFβ plays a key role. Previous studies have shown that syringin, a phenylpropanoid glycoside present in lilac bark (Syringa vulgaris L.), stimulates TGFβ expression in human monocyte-derived macrophages in addition to inhibiting the secretion of pro-inflammatory cytokines. Here, we investigated the effect of syringin on migration, invasion, and TGFβ production, as well as the effect on the release of pro-inflammatory cytokines in human dermal fibroblasts (NHDF) and keratinocytes (HaCaT) and its mechanism of action. NHDF and HaCaT cells were treated with the tested compound (12.5–100 µM), and a scratch assay was performed. The effect of migration using modified Boyden chambers was analyzed. TGFβ and IL-6 release were also assessed using ELISA kits. Cell proliferation was assessed using MTT and BrdU incorporation tests, while cytotoxicity was assessed using a neutral red uptake test. Smad2 and Smad3 phosphorylation were assessed using Western Blotting. ACTA2, COL1A1, and TIMP3 expression was analyzed using qPCR. Cells treated with syringin showed an increase in invasion potential in the scratch assay. A significant increase in skin fibroblast migration through the porous membrane was also observed. Syringin increased TGFβ release and inhibited IL-6 release by NHDF and HaCaT cells. No effect of syringin on cell proliferation or cytotoxic effects was observed. Western blot analysis showed significant activation of Smad2 and Smad3 in the presence of syringin in NHDF cells, but not in HaCaT. Quantitative PCR analysis revealed a strong increase in ACTA2 and COL1A1 gene expression in fibroblast cells treated with syringin. The present study demonstrated that syringin present in S. vulgaris stem bark increased dermal fibroblasts and keratinocytes’ wound healing function through activation of cell migration. Full article

Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article

Hyaluronic acid (HA) dermal fillers represent a cornerstone of modern esthetic medicine, providing a minimally invasive solution for facial volume restoration and skin rejuvenation. However, the diversity of available products, each utilizing distinct crosslinking technologies, presents a challenge for objective comparison and clinical decision making. This study introduces a scientific framework to evaluate and categorize the physicochemical properties of HA fillers based on two key parameter groups: dynamic parameters (e.g., rheology and gel content) and consistency parameters (e.g., extrusion force, water uptake, and gel particle size). Using standardized methodologies, 23 commercially available fillers from five major manufacturers were analyzed, enabling cross-technology comparisons. The findings reveal how specific crosslinking approaches influence the rheological behavior, handling characteristics, and potential clinical applications. By offering an integrated and reproducible assessment, this work helps practitioners select the most suitable filler for individualized treatment plans and encourages manufacturers to enhance product transparency through harmonized testing protocols. Full article

This review reports some aspects of soil contaminant chemistry and its fundamental role in shaping the soil–human health relationship. Exposure to soil contaminants can occur through direct pathways, such as ingestion, inhalation, and dermal contact, as well as indirect pathways, including food chain contamination via plant uptake or groundwater leaching. The mobility and persistence of organic and inorganic pollutants in soil are primarily controlled by sorption–desorption processes, which involve a complex interplay of physical and chemical mechanisms. Soil properties, such as pH, organic matter content, clay minerals, and oxide hydroxides, play a crucial role in regulating these processes and determining contaminant behavior. A high sorption capacity enhances the soil’s ability to mitigate pollutant mobility, thereby reducing their infiltration into groundwater and accumulation in the food chain. Soils rich in organic matter and fine-textured minerals, such as clay, can effectively immobilize contaminants, limiting their bioavailability and potential harm to human health. A deeper understanding of how soil characteristics influence contaminant mobility and bioavailability is critical to addressing the hazards of soil pollution for human health. Beyond merely assessing contaminant concentrations, it is essential to consider the dynamic processes governing pollutant fate in soil, as they ultimately shape exposure pathways and health risks. This knowledge is the key to developing more effective strategies for mitigating soil contamination and protecting public health. Full article

Background and Clinical Significance: Breast cancer-related lymphedema (BCRL) is a chronic condition affecting up to 20% of breast cancer survivors. Manual lymphatic drainage (MLD) has traditionally included techniques to redirect lymph flow toward alternative pathways when axillary drainage is impaired. However, emerging imaging techniques suggest that most lymph continues to drain toward the ipsilateral axilla, and this has led to the widespread uptake of treatment protocols that exclude traditional redirecting movements, even in cases where personalized imaging is unavailable. Case Presentation: This case report describes a woman with BCRL affecting the right arm and hand who underwent 3 years of conservative lymphedema therapy, including MLD and self-massage techniques that incorporated traditional redirection strategies. Pre-operative indocyanine green (ICG) lymphography, performed after prolonged conservative treatment, confirmed the presence of an open alternative drainage pathway bypassing the axilla and demonstrated dermal flow along the redirected pathways towards a previously described “radial” pathway. These findings suggest that targeted manual therapy may have reinforced or optimized this compensatory route. Conclusions: This case highlights the potential risk of relying on a single form of assessment and generalized cohort imaging studies to guide individualized MLD protocols. In the absence of personal imaging, prematurely abandoning traditional redirection techniques may limit opportunities to establish functional alternative pathways, particularly in early edema in patients who have this anatomical variation. ICG lymphography provides valuable insight into compensatory lymphatic drainage. However, until imaging protocols are standardized and individual imaging is widely accessible, retaining traditional MLD techniques for newly diagnosed BCRL may be crucial for optimizing treatment outcomes. Future research should explore the long-term impact of manual therapy on alternative pathway development and function. Full article