Search Results (4,953)

Drug resistance remains a critical barrier to effective treatment in several cancers, particularly triple-negative breast cancer (TNBC). Estrogen receptor α36 (ERα36), a variant of the estrogen receptor in ER-negative breast cancer cells, plays important roles in cancer cell proliferation. We investigated the role of ERα36 in regulating multidrug resistance protein 1 (MDR1) in MDA-MB-231 human breast cancer cells. The activation of ERα36 by BSA-conjugated estradiol (BSA-E2) increased cell viability under Adriamycin exposure, suggesting its involvement in promoting drug resistance. BSA-E2 treatment significantly reduced the intracellular rhodamine-123 levels by activating the MDR1 efflux function, which was linked to increased MDR1 transcription and protein expression. The mechanical ERα36-mediated BSA-E2-induced activation of EGFR and downstream signaling via c-Src led to an activation of the Akt/ERK pathways and transcription factors, NF-κB and CREB. Additionally, ERα36 is involved in activating Wnt/β-catenin pathways to induce MDR1 expression. The silencing of ERα36 inhibited the BSA-E2-induced phosphorylation of Akt and ERK, thereby reducing MDR1 expression via downregulation of NF-κB and CREB as well as Wnt/β-catenin signaling. These findings demonstrated that ERα36 promotes MDR1 expression through multiple non-genomic signaling cascades, including Akt/ERK-NF-κB/CREB and Wnt/β-catenin pathways, and highlight the role of ERα36 as a promising target to enhance chemotherapeutic efficacy in TNBC. Full article

Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article

Photobiomodulation (PBM) utilizes different wavelengths of light to modulate cellular functions and has emerged as a promising approach in regenerative medicine. In this study, we examined the effects of blue (455 nm), red (660 nm), and near-infrared (810 nm) light, both individually and in combination, on human adipose-derived mesenchymal stem/stromal cells (adMSCs). A single, short-term exposure of adMSCs in suspension to these wavelengths using an integrating sphere revealed distinct wavelength- and dose-dependent cellular responses. Blue light exposure led to a dose-dependent increase in intracellular reactive oxygen species, accompanied by reduced cell proliferation, metabolic activity, interleukin-6/interleukin-8 secretion, and adipogenic differentiation. In contrast, red and near-infrared light preserved cell viability and metabolic function while enhancing cell migration, consistent with their documented ability to stimulate proliferation and mitochondrial activity in mesenchymal stem cells. These findings highlight the necessity of precise wavelength and dosage selection in PBM applications and support the potential of PBM as a customizable tool for optimizing patient-specific regenerative therapies. Full article

Osteolforte, a compound with potential bone-regenerative properties, was investigated for its effects on human bone marrow stromal cells (hBMSCs). This study aimed to evaluate its impact on cell viability, osteogenic differentiation, and both gene and protein expression using a combination of assays, including CCK-8, Alizarin Red S staining, Quantitative Real-Time PCR (qRT-PCR), and Western blot analysis. The results demonstrated that Osteolforte significantly enhanced osteogenic differentiation in hBMSCs. Alizarin Red S staining revealed increased mineralization, indicating elevated calcium deposition. Gene expression analysis showed an upregulation of key osteogenic markers, including runt-related transcription factor-2 (RUNX-2), collagen type I (COL-1), and bone morphogenetic protein-2 (BMP-2), supporting the role of Osteolforte in promoting osteoblastic activity. In particular, the elevated expression of RUNX-2—a master transcription factor in osteoblast differentiation along with COL-1, a major bone matrix component, and BMP-2, a key bone morphogenetic protein—highlights the compound’s osteogenic potential. In conclusion, Osteolforte enhances early-stage osteogenesis and mineralization in hBMSCs and represents a promising candidate for bone regeneration. Full article

Three-dimensional cell culture systems are relevant in vitro models for studying cellular behavior. In this regard, this present study investigates the interaction between human osteoblast-like cells and 3D-printed scaffolds mimicking physiological and osteoporotic bone structures under simulated microgravity conditions. The objective is to assess the effects of scaffold architecture and dynamic culture conditions on cell adhesion, proliferation, and metabolic activity, with implications for osteoporosis research. Polylactic acid scaffolds with physiological (P) and osteoporotic-like (O) trabecular architectures were 3D-printed by means of fused deposition modeling technology. Morphometric characterization was performed using micro-computed tomography. Human osteoblast-like SAOS-2 and U2OS cells were cultured on the scaffolds under static and dynamic simulated microgravity conditions using a rotary cell culture system (RCCS). Scaffold biocompatibility, cell viability, adhesion, and metabolic activity were evaluated through Bromodeoxyuridine incorporation assays, a water-soluble tetrazolium salt assay, and an enzyme-linked immunosorbent assay of tumor necrosis factor-α secretion. Both scaffold models supported osteoblast-like cell adhesion and growth, with an approximately threefold increase in colonization observed on the high-porosity O scaffolds under dynamic conditions. The dynamic environment facilitated increased surface interaction, amplifying the effects of scaffold architecture on cell behavior. Overall, sustained cell growth and metabolic activity, together with the absence of detectable inflammatory responses, confirmed the biocompatibility of the system. Scaffold microstructure and dynamic culture conditions significantly influence osteoblast-like cell behavior. The combination of 3D-printed scaffolds and a RCCS bioreactor provides a promising platform for studying bone remodeling in osteoporosis and microgravity-induced bone loss. These findings may contribute to the development of advanced in vitro models for biomedical research and potential countermeasures for bone degeneration. Full article

Tendinopathies are a significant challenge in musculoskeletal medicine, with current treatments showing variable efficacy. Electromagnetic transduction therapy (EMTT) has emerged as a promising therapeutic approach, but its biological effects on tendon cells remain largely unexplored. Here, we investigated the effects of EMTT on primary cultured human tenocytes’ behavior and functions in vitro, focusing on cellular responses, senescence-related pathways, and molecular mechanisms. Primary cultures of human tenocytes were established from semitendinosus tendon biopsies of patients undergoing anterior cruciate ligament (ACL) reconstruction (n = 6, males aged 17–37 years). Cells were exposed to EMTT at different intensities (40 and 80 mT) and impulse numbers (1000–10,500). Cell viability (MTT assay), proliferation (Ki67), senescence markers (CDKN2a/INK4a), migration (scratch test), cytoskeleton organization (immunofluorescence), and gene expression (RT-PCR) were analyzed. A 40 mT exposure elicited minimal effects, whereas 80 mT treatments induced significant cellular responses. Repeated 80 mT exposure demonstrated a dual effect: despite a moderate decrease in overall cell vitality, increased Ki67 expression (+7%, p ≤ 0.05) and significant downregulation of senescence marker CDKN2a/INK4a were observed, suggesting potential senolytic-like activity. EMTT significantly enhanced cell migration (p < 0.001) and triggered cytoskeletal remodeling, with amplified stress fiber formation and paxillin redistribution. Molecular analysis revealed upregulation of tenogenic markers (Scleraxis, Tenomodulin) and enhanced Collagen I and III expressions, particularly with treatments at 80 mT, indicating improved matrix remodeling capacity. EMTT significantly promotes tenocyte proliferation, migration, and matrix production, while simultaneously exhibiting senolytic-like effects through downregulation of senescence-associated markers. These results support EMTT as a promising therapeutic approach for the management of tendinopathies through multiple regenerative mechanisms, though further studies are needed to validate these effects in vivo. Full article

Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-κB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue^® assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-κB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80–100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases. Full article

Plant flowers are recognized as a rich source of bioactive phenolic compounds. In this study, for the first time, the recovery of antioxidant phenolic compounds from Cytisus striatus flowers (CF) was optimized using microwave-assisted extraction (MAE). The variables (% of ethanol, temperature, and time) were studied using a response surface methodology (RSM). Extraction efficiency was assessed by total phenol content, total flavonoid content, and the antioxidant capacity through DPPH, ABTS, FRAP, and CUPRAC assays. Additionally, cytotoxicity and anti-inflammatory properties were evaluated in different cell lines. The optimal extraction conditions (87.6% ethanol, 160.8 °C and 8.76 min) yielded extracts rich in phenolics (85.9 mg GAE/g CF) and flavonoids (120.3 mg RE/g CF), with strong antioxidant capacity. LC-MS/MS analysis identified 27 phenolic compounds, including chrysin, apigenin, and quercetin derivatives. Cytotoxicity tests showed that CF extract maintained high viability (>80%) in human embryonic kidney (HEK293T) and human lung adenocarcinoma (A549) cells up to 2000 µg/mL, indicating low cytotoxicity. The anti-inflammatory potential was evidenced by a decrease in IL-1β levels and an increase in IL-10 cytokine production in LPS-stimulated macrophages. These results highlight the great potential of CF as a promising bioresource to obtain value-added compounds for the development of functional foods, nutraceuticals, and cosmetic products. 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

Environmental exposure to per- and polyfluoroalkyl substances (PFASs) has been increasingly associated with skin disorders, including atopic dermatitis (AD); however, the underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of perfluorononanoic acid (PFNA) and perfluorooctanoic acid (PFOA)—two widely detected PFASs—on epidermal function and gene expression in Human Epithelial Keratinocyte, neonatal (HEKn). We assessed cell viability, morphology, and transcriptomic changes using in vitro assays and RNA-seq analysis from a neonatal cohort. PFASs induced dose-dependent cytotoxicity and downregulation of barrier-related genes. Ingenuity pathway analysis identified calcitriol as a suppressed upstream regulator. Functional validation revealed that calcitriol partially reversed the PFAS-induced suppression of antimicrobial peptide genes. These findings support the hypothesis that PFASs may contribute to AD-like skin pathology by impairing vitamin D receptor signaling and antimicrobial defense, and calcitriol demonstrates potential as a protective modulator. This study provides mechanistic insights into the impact of environmental toxicants on skin homeostasis and suggests a potential protective role for calcitriol in PFAS-induced skin barrier damage. Full article

Nanoceria is a multifaceted enzyme-like catalyst of ROS-mediated (reactive oxygen species) reactions, which results in its multiple biomedical applications. Biodegradable polysaccharide coatings improve biocompatibility, while the effects of these coatings on the ROS-related activity of nanoceria in cells need thorough studies. Here, we used human embryonic lung fibroblasts to study the effects of maltodextrin and chitosan coatings on cellular oxidative metabolism of nanoceria by examining cell viability, mitochondrial potential, accumulation of nanoparticles in cells, intracellular ROS, expression of NOX4 (NADPH oxidase 4), NRF2 (nuclear factor erythroid 2-related factor 2), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and STAT3 (signal transducer and activator of transcription 3) proteins as well as the expression of biomarkers of DNA damage/repair, cell proliferation, and autophagy. Both types of polysaccharide-coated nanoceria were non-toxic up to millimolar concentrations. For maltodextrin-coated nano-CeO₂, in contrast to bare nanoparticles, there was no oxidative DNA damage/repair with moderate activation of NOX4 expression. Like bare nanoceria, maltodextrin-coated nanoparticles demonstrate the proliferative impact and do not activate autophagy. However, maltodextrin-coated nanoparticles have an activating impact on mitochondrial potential and the NF-κB pathway. Chitosan-coated nanoceria causes short-term intracellular oxidative stress, activation of the expression of NOX4, STAT3, and NRF2, oxidative DNA damage, and double-strand breaks accompanied by activation of DNA repair systems. In contrast to maltodextrin-coated nanoparticles, chitosan-coated nanoceria inhibits the NF-κB pathway and activates autophagy. These findings would be useful in the development of advanced nanoceria-based pharmaceuticals and contribute to the understanding of the biochemical properties of nanoceria as a modulator of ROS-dependent signaling pathways. Full article

The scientific community’s interest in natural compounds with antiviral properties has considerably increased after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), especially for their potential use in the treatment of the COVID-19 infection. From this perspective, bovine coronavirus (BCoV), member of the genus β-CoV, represents a valuable virus model to study human β-CoVs, bypassing the risks of handling highly pathogenic and contagious viruses. Pimarane diterpenes are a significant group of secondary metabolites produced by phytopathogenic fungi, including several Diplodia species. Among the members of this class of natural products, sphaeropsidin A (SphA) and its analog sphaeropsidin B (SphB) are well known for their bioactivities, such as antimicrobial, insecticidal, herbicidal, and anticancer. In this study, the antiviral effects of SphA and SphB were evaluated for the first time on bovine (MDBK) cells infected with BCoV. Our findings showed that both sphaeropsidins significantly increased cell viability in infected cells. These substances also caused substantial declines in the virus yield and in the levels of the viral spike S protein. Interestingly, during the treatment, a cellular defense mechanism was detected in the downregulation of the aryl hydrocarbon receptor (AhR) signaling, which is affected by BCoV infection. We also observed that the presence of SphA and SphB determined the deacidification of the lysosomal environment in infected cells, which may be related to their antiviral activities. In addition, in silico investigations have been performed to elucidate the molecular mechanism governing the recognition of bovine AhR (bAhR) by Sphs. Molecular docking studies revealed significant insights into the structural determinants driving the bAhR binding by the examined compounds. Hence, in vitro and in silico results demonstrated that SphA and SphB are promising drug candidates for the development of efficient therapies able to fight a β-CoV-like BCoV during infection. Full article

Zebrafish are model organisms for drug screening owing to their transparent bodies, rapid embryonic development, and genetic similarities with humans. However, using standard polystyrene culture plates can limit the oxygen supply, potentially affecting embryo survival and the reliability of assays conducted in zebrafish. In this study, we evaluated the application of a novel, highly oxygen-permeable culture plate (InnoCell^TM) in zebrafish development and drug screening assays. Under both normal and oxygen-restricted conditions, zebrafish embryos cultured on InnoCell^TM plates exhibited significantly improved developmental parameters, including heart rate and body length, compared with those cultured on conventional polystyrene plates. The InnoCell^TM plate enabled a significant reduction in medium volume without compromising zebrafish embryo viability, thereby demonstrating its advantages, particularly in high-throughput 384-well formats. Drug screening tests using antiangiogenic receptor tyrosine kinase inhibitors (TKIs) revealed enhanced sensitivity and more pronounced biological effects in InnoCell^TM plates, as evidenced by the quantification of intersegmental blood vessels and gene expression analysis of the vascular endothelial growth factor receptor (vegfr, also known as kdrl). These results indicate that the InnoCell^TM highly oxygen-permeable plate markedly improves zebrafish-based drug screening efficiency and assay reliability, highlighting its potential for widespread application in biomedical research. Full article

Nanoplastics (NPs), an emerging class of environmental pollutants, are increasingly recognized for their potential to interfere with critical cellular processes. Autophagy, a conserved degradative pathway essential for maintaining cellular homeostasis and adaptation to stress, has recently become a focal point of nanotoxicology research. This review synthesizes current evidence on the interactions between NPs and autophagic pathways across diverse biological systems. Findings indicate that NPs can trigger autophagy as an early cellular response; however, prolonged exposure may lead to autophagic dysfunction, contributing to impaired cell viability and disrupted signaling. Particular attention is given to the physiochemical properties of NPs such as size, surface charge, and polymer type, which influence cellular uptake and intracellular trafficking. We also highlight key mechanistic pathways, including oxidative stress and mTOR modulation. Notably, most available studies focus almost exclusively on polystyrene (PS)-based NPs, with limited data on other types of polymers, and several reports lack comprehensive assessment of autophagic flux or downstream effects. In conclusion, a better understanding of NP–autophagy crosstalk—particularly beyond PS—is crucial to evaluate the real toxic potential of NPs and guide future research in human health and nanotechnology. Full article

The cosmetic industry faces a critical need to balance commercial innovation with scientific validation, especially regarding the safety and efficacy of raw materials. Plant-derived materials (PDMs) offer a promising alternative to animal-derived ingredients in cosmetics, particularly due to their safety and compliance with vegan and ethical standards. Unlike compounds such as polydeoxyribonucleotide (PDRN), which is derived from the testis or seminal fluid of Salmonidae species and raises concerns regarding its origin, sustainability, and consumer acceptability, PDMs provide a cleaner, ethically preferable profile. In this study, we evaluated 50 PDM candidates using in vitro cell viability, wound healing, and immunocytochemistry assays, along with primary skin irritation tests in human participants. None of the samples showed harmful effects. Notably, sample Nos. 38 and 42 demonstrated significant wound-healing capacity and upregulated filaggrin expression without causing notable irritation in clinical testing. These findings support the biological activity and safety of specific PDMs as functional cosmetic ingredients. This study presents scientifically validated evidence for plant-based alternatives to animal-derived materials and offers a new milestone in the shift toward sustainable and ethical cosmetic development. By bridging the gap between consumer demand and scientific rigor, this study provides a robust platform for future innovations in vegan cosmetics. Full article