Search Results (2,563)

Melanoma incidence is steadily on the rise but widespread prevention awareness and novel treatment approaches have substantially ameliorated the prognosis of the disease. Microphthalmia-associated transcription factor (MITF) is an essential transcription factor that plays a central role in the transcriptional circuitry of both normal melanocytes and malignant melanoma. Since over 30 years have elapsed since its discovery in mice, a large number of its target genes have been identified in pigment cells. Many upstream regulators of MITF have also been identified. Despite these substantial discoveries, MITF function, especially in melanomas, still remains elusive in several aspects. MITF is absolutely required for melanin formation because it transcribes virtually all genes required for the synthesis, storage, and transport of the pigment. Importantly, MITF is necessary for prevention of apoptosis in melanomas, at least at the early stages. However, in some metastases, MITF may be absent in most cells and its antiapoptotic function is evidently replaced by other proteins that not yet been fully identified. Furthermore, MITF is a specific nevus and melanoma marker, which is routinely used in immunohistochemistry, along with other markers, to distinguish pigmented and other skin lesions. In melanomas, high-MITF melanoma cell subpopulations are considered differentiated, i.e., pigmented and rapidly proliferating. In contrast, low-MITF cells proliferate slowly but are invasive with cancer stem cell-like properties. Although MITF activates mostly antiapoptotic and pro-proliferative genes, it also activates typical cell cycle inhibitors such as the p16 and p21 proteins. Here we discuss the issues of MITF multifunctionality in melanoma and associated research prospects. Full article

Glioblastoma multiforme (GBM), isocitrate dehydrogenase (IDH)-wildtype, is the most aggressive primary malignant tumor of the central nervous system, characterized by poor prognosis and high recurrence rates despite standard multimodal treatment. This study investigates the molecular response of glioblastoma cells to 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT), focusing on gene expression changes associated with apoptosis, ferroptosis, and oxidative stress. Human glioblastoma T98G cells were treated with 5-ALA followed by light irradiation, and gene expression was analyzed using RT-qPCR. PDT induced moderate upregulation of pro-apoptotic genes (BAX, CASP3, FAS) alongside increased expression of the anti-apoptotic gene BCL2, indicating simultaneous activation of cell death and survival pathways. Ferroptosis-related genes showed mixed responses, with slight upregulation of ACSL4 and downregulation of GPX4, suggesting increased susceptibility to lipid peroxidation. The most significant change was observed in GCH1 expression, reflecting activation of oxidative stress response mechanisms. However, none of the observed changes reached statistical significance, likely due to the limited sample size. These findings demonstrate that PDT induces a complex and dual biological response in glioblastoma cells, involving both cytotoxic and adaptive mechanisms. This may limit therapeutic efficacy and contribute to treatment resistance. The results support the rationale for combining PDT with targeted molecular therapies aimed at inhibiting antioxidant defenses and anti-apoptotic pathways. Additionally, personalized therapeutic strategies based on tumor molecular profiles may enhance treatment outcomes. Further studies with larger sample sizes and functional validation are required to confirm these preliminary observations. Full article

Epilepsy is a common chronic neurological disorder characterized by recurrent seizures. Gastrodia elata, the dried tuber of G. elata Bl. (Orchidaceae), is a valuable medicinal and edible botanical resource. This study optimized the preparation of Yellow Rice Wine-Processed G. elata (YPGE) and investigated its antiepileptic effects and underlying mechanisms in a pentylenetetrazol (PTZ)-kindled rat model. Processing parameters were optimized using single-factor experiments combined with an analytic hierarchy process (AHP)-entropy weight method (EWM) weighting strategy and Box–Behnken design–response surface methodology. The optimal parameters were determined as 18% alcohol by volume, 72 °C drying temperature, and 32 h drying time. Compared with unprocessed G. elata (GE), YPGE exhibited 0.54-, 0.13-, 1.87-, and 3.58-fold increases in the contents of gastrodin (GAS), G. elata polysaccharides (GEPs), p-hydroxybenzyl alcohol (p-HBA), and total parishins (TP), respectively, and demonstrated significantly enhanced in vitro antioxidant activity (IC50 values of 2.604, 2.719, and 4.046 mg/mL for DPPH, ABTS, and hydroxyl radicals). In vivo, both GE and YPGE significantly reduced seizure severity, decreased inflammatory cytokines (TNF-α, IL-1β), alleviated oxidative stress (increased SOD and GSH-Px, decreased MDA), and modulated neurotransmitter balance (reduced Glu, increased GABA) in brain tissues. YPGE also upregulated P-glycoprotein expression and reduced neuronal apoptosis in the hippocampal CA1 region by upregulating Bcl-2 and downregulating Bax. These findings suggest that YPGE exerts multi-target antiepileptic effects through synergistic anti-inflammatory, antioxidant, and anti-apoptotic actions, providing experimental evidence for the development of novel antiepileptic therapies based on processed G. elata. Full article

Diabetes mellitus (DM) markedly increases the risk of cardiovascular complications through mechanisms involving hyperglycemia-induced oxidative stress, inflammation, and apoptosis. Humanin (HN), a mitochondria-derived peptide with established cytoprotective properties, has been reported to exert antioxidant and anti-apoptotic effects in several experimental models. However, its role in diabetic cardiac injury remains insufficiently understood. The present study investigated the protective effects of repeated HN treatment against diabetes-induced cardiac injury in a streptozotocin (STZ)-induced mouse model. Mice were divided into four groups: control, HN-treated, STZ-induced diabetic, and STZ + HN-treated groups (n = 10/group). HN (4 mg/kg) was administered daily for 15 consecutive days. Biochemical analyses were performed to evaluate oxidative stress, inflammatory cytokines, and apoptotic markers. STZ-induced diabetes significantly increased oxidative stress markers, pro-inflammatory cytokines, and apoptotic activity while reducing antioxidant defenses and anti-inflammatory cytokines compared with controls. Repeated HN treatment markedly attenuated these alterations and restored redox and inflammatory balance in diabetic cardiac tissue. These findings demonstrate that repeated HN treatment attenuates oxidative stress, inflammation, and apoptosis in the hearts of diabetic mice. The results further suggest that HN may represent a promising therapeutic candidate for limiting diabetes-associated cardiac complications. Full article

Ovarian cancer (OVC) is a leading cause of gynecological cancer mortality due to late-stage diagnosis and chemoresistance. Among the multiple molecular mediators, oncogenic epidermal growth factor receptor (EGFR) signaling has emerged as a key regulator of tumor progression and drug resistance, ultimately governing cancer survival. Therefore, this review focused on the molecular mechanisms of aberrant EGFR signaling to promote chemoresistance in ovarian cancer through multiple interlinking pathways, including the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascades. These pathways act in concert to confer resistance, including proliferation, antiapoptotic effects, cancer stem cell maintenance, and facilitating epithelial-mesenchymal transition (EMT), which function together to decrease sensitivity towards platinum-based and taxane chemotherapies. Furthermore, we incorporate novel evidence regarding EGFR cross-talk with extracellular matrix (ECM) and metabolic reprogramming, especially their relevance to immune evasion mechanisms, hypoxia, and extracellular vesicles (EVs)-mediated signaling. In addition, we elaborated on the limitation of the current EGFR targeting therapy, which will be beneficial for further designing new combinatorial treatment approaches by using EGFR inhibitors with immunotherapy, nanocarriers, and microbiota modulators. Overall, this review highlights the updated role of EGFR signaling as a key regulator of chemoresistance in ovarian cancer, providing insights for developing targeted therapies to overcome drug resistance and improve patient survival. Full article

The treatment of type 2 diabetes (T2DM) faces numerous challenges. Oral insulin (Ins) and other short-acting compounds still encounter significant obstacles in the hostile gastrointestinal environment, including low bioavailability and rapid metabolic clearance. Platycodin D (PD) is a natural compound with demonstrated hypoglycemic and lipid-lowering effects. In this study, PD was encapsulated using alginate to prepare orally administrable, pH-responsive, gut-targeted gel microspheres (PD@MPs), and their efficacy in improving T2DM prognosis was investigated. In vitro release studies demonstrated that PD@MPs avoided degradation by gastric acid and were released in the intestine. Cell experiments indicated that PD possessed significant antioxidant and anti-apoptotic properties. Masson, immunohistochemistry, and immunofluorescence staining revealed that PD@MPs alleviated inflammation in key metabolic organs and maintained normal pancreatic tissue function and morphology. Western blot analysis assessed the expression of proteins related to hepatic glycogen synthesis, including IRS-1, GLUT2, GSK-3β, and AKT. The research results indicate that the assembly strategy using sodium alginate (SA) as the coating layer has enabled the oral administration of PD and has demonstrated its potential in the treatment of diabetes. Full article

Carnosine is a naturally occurring endogenous dipeptide with great potential to improve reproductive function and fertility. In this study, supplementation of 1 μg/mL carnosine during in vitro maturation (IVM) significantly enhanced the developmental competence and quality of the resulting bovine embryos. Carnosine treatment effectively elevated mitochondrial membrane potential, mitochondrial activity, and ATP content in oocytes. Moreover, it strengthened the antioxidant and anti-apoptotic capacities of oocytes, as evidenced by reduced intracellular reactive oxygen species (ROS) levels, lowered DNA damage and an early apoptosis rate, alongside increased glutathione (GSH) content, an elevated BCL2/BAX mRNA ratio, and upregulation of antioxidant genes SOD1, CAT, GPx1, and GPx4. Notably, combined application of 1 μg/mL carnosine during IVM and 10⁻⁷ M melatonin during in vitro culture (IVC) synergistically improved both blastocyst development and quality. Collectively, these findings provide novel evidence supporting the therapeutic potential of carnosine in optimizing in vitro embryo production in bovine, and highlight the value of stage-specific supplementation strategies to further improve embryonic development efficiency. Full article

Canine distemper virus (CDV) is a highly contagious morbillivirus associated with severe neurological disease in dogs. Although apoptosis is recognized as an important mechanism in CDV-associated neurodegeneration, the relationship between regional viral RNA load and apoptosis-related transcriptional responses remains poorly defined. This study aimed to quantify CDV RNA load and the expression of apoptosis-related genes, including the pro-apoptotic markers Bax, caspase-3 and caspase-8 and the anti-apoptotic marker Bcl-2, in the frontal cortex, hippocampus, and cerebellum of 21 dogs naturally infected with CDV, compared with four neurologically normal controls. Viral RNA load and gene expression were assessed by quantitative reverse transcription PCR (qRT-PCR). CDV RNA was detected in all brain regions of infected dogs, with no significant differences in viral RNA load among the frontal cortex, hippocampus and cerebellum (p > 0.05). In contrast, apoptosis-related gene expression showed a region-specific pattern. In the hippocampus, Bax (2.56-fold, p < 0.05), caspase-8 (4.33-fold, p < 0.05) and caspase-3 (2.01-fold, p < 0.05) were significantly upregulated in CDV-infected dogs compared with controls. In the cerebellum, Bax (2.07-fold, p < 0.05) and caspase-3 (1.97-fold, p < 0.05) were also increased, whereas no significant differences were observed in any apoptotic marker in the frontal cortex. Pearson correlation analysis revealed no significant association between regional viral RNA load and expression of Bcl-2, Bax, caspase-3 or caspase-8 in any of the brain regions examined. These findings suggest that CDV-associated apoptosis-related transcriptional responses in the central nervous system are region-dependent and are not linearly associated with local viral RNA load. This study provides new insights into the heterogeneous neuropathogenesis of CDV and supports the importance of regional brain susceptibility in viral encephalitis. Full article

Background/Objectives: Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant malignancies, driven in part by heterogeneous, therapy-resistant glioma stem cells (GSCs). Improving clinical outcomes will require innovative therapeutic approaches that target unique molecular vulnerabilities. The mitogen-activated protein kinase (MAPK) pathway drives tumor progression across multiple cancers, including GBM. MAPK-interacting kinases (MNK1/2) represent MAPK downstream effectors that phosphorylate eukaryotic translation initiation factor 4E (eIF4E), a regulator of oncogenic and anti-apoptotic mRNA translation. We previously identified pharmacological MNK inhibition as a promising therapeutic strategy for GBM, but most available MNK inhibitors lack specificity. Methods: Novel MNK inhibitor compounds were developed using medicinal chemistry optimization and evaluated through molecular docking and kinome profiling analyses. Antineoplastic activity was assessed in established GBM cell lines and patient-derived glioma stem cell models cultured as 3-D neurospheres under stem cell-permissive conditions. Effects on MNK signaling, cell viability, neurosphere growth, migration, invasion, and apoptosis were analyzed using immunoblotting, flow cytometry, viability assays, wound healing assays, and 3-D invasion assays. In addition, a compound screen was performed to identify therapeutic agents that enhance MNK-targeted therapy, followed by validation using pharmacological inhibition and siRNA-mediated knockdown approaches. Results: Our next-generation MNK inhibitor NUCC-201893 exhibited high target specificity and greater potency than the lead compound NU808, effectively suppressing eIF4E phosphorylation, GBM cell viability, neurosphere growth, migration, and invasion. Compound screening identified DNA methyltransferase (DNMT) inhibition as a potent enhancer of MNK blockade. Pharmacological DNMT inhibition enhanced the cytotoxic effects of siRNA-mediated MNK1 knockdown, while concurrent pharmacological inhibition of MNKs and DNMT resulted in greater suppression of neurosphere growth and robust induction of apoptotic responses in GSCs. Conclusions: These findings identify dual MNK and DNMT inhibition as a promising combinatorial strategy that effectively triggers antineoplastic effects in GBM cells and GSCs. Full article

Endoplasmic reticulum (ER) stress is a common state of cellular adversity experienced by tumor cells under unfavorable conditions such as hypoxia, nutrient deprivation, and oncogene activation. As the most conserved signaling branch of the unfolded protein response (UPR), the inositol-requiring enzyme 1α (IRE1α)- X-box-binding protein 1 (XBP1) pathway plays a central role in sustaining tumor cell survival, driving malignant progression, and remodeling the tumor microenvironment (TME). XBP1, the terminal transcription factor of this pathway, finely orchestrates tumor cell fate through both its canonical and non-canonical functions. This review systematically summarizes the dual mechanisms of XBP1 in cancer: within cancer cells, XBP1 promotes proliferation, metastasis, and chemoresistance via metabolic reprogramming, anti-apoptotic proteins, and DNA repair; within immune cells (macrophages, dendritic cells, T cells), XBP1 fosters an immunosuppressive microenvironment, while also modulating cancer-associated fibroblasts, endothelial cells, and osteoclasts. Despite its therapeutic promise, several major unresolved questions remain, including the precise molecular switch governing XBP1’s pro-tumorigenic versus anti-tumorigenic functions, the functional divergence between XBP1u and XBP1s isoforms in different cellular contexts, and the lack of reliable predictive biomarkers for patient stratification. Key translational challenges involve the on-target toxicity of systemic XBP1/IRE1α inhibition due to its essential roles in normal tissues, the cell-type-specific and context-dependent effects that complicate therapeutic outcomes, and the limited selectivity and off-target effects of current inhibitors, as well as compensatory activation of other UPR branches that may drive adaptive resistance. Finally, this review discusses XBP1-targeted therapeutic strategies, including small-molecule inhibitors, nucleic acid-based drugs, immunotherapeutic combination approaches, and XBP1-based tumor vaccines, and provides perspectives on future research directions, aiming to establish a theoretical foundation for the development of more effective and precise XBP1-targeted therapies for tumorigenesis and cancer progression. Full article

Background: Apoptosis is a fundamental process for maintaining tissue homeostasis, and its dysregulation is closely linked to the development of numerous diseases, including colorectal cancer. In recent years, dietary polyphenols have gained interest due to their antioxidant, pro-apoptotic, and chemopreventive properties. Artichoke (Cynara scolymus L.) by-products are rich source of hydroxycinnamic acids and flavonoids, making them promising source of bioactive compounds. Methods: In this study we evaluated the cytotoxic and pro-apoptotic activity of four aqueous extracts obtained from artichoke bract by-products, including one commercial hybrid (CAPB) and three local Apulian varieties (BriB, VaMB, LMTB), in human colorectal adenocarcinoma cell lines (Caco-2 and HT29). The extracts were characterized according to their total polyphenol content and phenolic profile. Results: The selected artichoke by-product extracts exhibited significant cytotoxic effects both in a concentration- and time-dependent manner, with concentrations ≥ 2 mg/mL significantly reducing cell viability and nearly abolishing it at 4 mg/mL after 48 h. Moreover, treatment with the extracts modulated the expression of apoptosis-related proteins, characterized by an increase in pro-apoptotic markers (Bax, caspase-9, caspase-3) and a decrease in the anti-apoptotic protein Bcl-2, suggesting activation of the mitochondrial apoptotic pathway. In particular, the BriB extract was able to induce an apoptosis rate higher than 80% in Caco-2 cells and achieved comparable rates in HT29 cells at concentrations of 2–3 mg/mL. Conclusions: Overall, these findings demonstrate that artichoke by-product extracts exert significant pro-apoptotic effects in colorectal cancer cells and highlight their potential as sustainable sources of bioactive compounds for nutraceutical or adjuvant anticancer applications. Full article

Photobiomodulation (PBM) is a non-invasive therapeutic strategy that uses red and near-infrared (NIR) light in the 590–950 nm range to modulate the cellular and molecular pathways involved in retinal homeostasis. At the molecular level, PBM acts primarily through photon absorption by cytochrome c oxidase (CcO, complex IV of the mitochondrial electron transport chain), whose four metal centres—two copper (CuA and CuB) and two heme groups (heme a and heme a₃)—absorb light across approximately 600–1000 nm. Photon capture promotes photodissociation of inhibitory nitric oxide (NO) from the binuclear CuB–heme a₃ centre, accelerates electron transfer, restores the proton-motive force and increases ATP synthesis. These primary events trigger a coordinated molecular programme that includes (i) transient mitochondrial reactive oxygen species (ROS) bursts that activate the Nrf2/Keap1/ARE axis and upregulate phase II antioxidant enzymes (HO-1, NQO1, GCLC, SOD2, catalase, GPx); (ii) calcium- and cAMP-dependent secondary signalling that converges on PI3K/Akt, MAPK/ERK, AMPK and mTOR pathways; (iii) suppression of NF-κB-driven cytokine production (TNF-α, IL-1β, IL-6) and of NLRP3 inflammasome activation; (iv) downregulation of the HIF-1α/VEGF axis, particularly at 590 nm; (v) anti-apoptotic remodelling of the Bcl-2/Bax ratio with reduced cytochrome c release and caspase-3/9 activation; and (vi) PGC-1α/TFAM/NRF1-driven mitochondrial biogenesis, alongside restoration of fission/fusion homeostasis (Drp1, Mfn1/2, Opa1) and PINK1/Parkin-mediated mitophagy. Wavelength specificity has a defined molecular basis: 590 nm modulates VEGF signalling and RPE pump activity, 660 nm interacts with the CuB centre and enhances O₂ binding at CcO, and 850 nm is absorbed by CuA and supports electron entry into complex IV. A second molecular axis is the bidirectional crosstalk between PBM and the circadian system: mitochondrial respiration, ATP turnover and CcO activity oscillate over the 24 h cycle under the control of the BMAL1/CLOCK and PER/CRY core machinery, the NAD⁺/SIRT1–SIRT3 axis and REV-ERBα. Preliminary preclinical and human observations suggest that NIR-induced bioenergetic and functional gains may be coupled to this rhythm, with greater benefit reported when light is delivered in the morning window (≈08:00–11:00); this time dependence should be regarded as an emerging hypothesis rather than an established clinical principle. The clinical evidence is unevenly developed across indications. It is most robust for non-exudative age-related macular degeneration, where multiwavelength PBM (590/660/850 nm; Valeda Light Delivery System) has shown disease-modifying potential in randomized controlled trials (LIGHTSITE I–III and the LIGHTSITE IIIB extension), with sustained BCVA gains and reduced incidence of geographic atrophy over 24 months and beyond. Evidence for retinitis pigmentosa, central serous chorioretinopathy and, with red-light monotherapy, childhood myopia is at present limited to small or short-term studies and remains preliminary. This narrative review synthesizes the molecular machinery engaged by PBM, integrates clinical findings across retinal diseases and discusses how chronotherapeutic delivery of light, aligned with the molecular clock, may further optimize therapeutic efficacy. Full article

This study aimed to investigate the selective anticancer activity of the curcumin analog PAC (3,5-Bis-4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone). Normal gingival epithelial cells (GECs), cancerous gingival cells (Ca9-22) and tongue squamous carcinoma cells (CAL27) were exposed to increasing concentrations of PAC (0–10 µM) for 24 h. Cell viability and cytotoxicity were evaluated using MTT and LDH assays, while apoptosis and caspase activation were analyzed by Annexin V/PI staining and flow cytometry. Gene-expression profiling was performed using RT² Profiler PCR arrays. PAC significantly inhibited Ca9-22 and CAL27 cell proliferation in a concentration-dependent manner, with an IC₅₀ value of 5 µM, while exerting no noticeable cytotoxic effects on normal GEC. PAC treatment induced significant early and late apoptosis associated with increased caspase activity in both oral cancer cell lines. Transcriptomic analyses revealed extensive modulation of apoptosis-related genes. In Ca9-22 cells, PAC predominantly suppressed anti-apoptotic and survival-associated genes, including BCL2, BIRC3, BIRC5, XIAP, CFLAR, and NFKB1. In contrast, CAL27 cells exhibited a more pronounced pro-apoptotic transcriptional profile characterized by upregulation of TP53, APAF1, CASP1, BID, and TNF. Gene interaction network analyses further demonstrated that PAC targets highly interconnected apoptotic signaling pathways. Collectively, these findings demonstrate that PAC exerts potent selective anticancer activity against OSCC cells through modulation of intrinsic and extrinsic apoptotic pathways. These results further support the therapeutic potential of PAC as a promising multitarget candidate for oral cancer treatment. Full article

Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm² in the ulcer control group to 143.70 ± 0.76 mm² and 115.50 ± 0.76 mm², corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers. Full article

UVA radiation affects communication between the cells that create the human skin. To prevent UVA-induced damage, there is a constant search for compounds protecting all skin cells and homeostasis in their communication. Therefore, the aim of this study was to evaluate the effect of 24 h incubation with 3-O-ethyl ascorbic acid (EAA; 150 µM) on the intracellular proteome of co-cultured keratinocytes and fibroblasts after UVA irradiation (total dose 15 J/cm²), and on the protein profiles released into the medium by both cell types. A proteomic approach (nanoHPLC/QOrbiTrap) allowed the identification of proteins significantly modified by UVA and EAA. In keratinocytes, UVA radiation enhanced expression of pro-inflammatory and pro-proliferative/keratinizing proteins and decreased expression of antiapoptotic and antioxidant proteins, while in fibroblasts, UVA radiation induced expression mainly of pro-inflammatory proteins, simultaneously decreasing levels of proteins involved in the antioxidant response and growth factors. Increased pro-inflammatory protein and decreased growth factor levels were also observed in the medium. EAA restored the levels of these proteins compared to control cultures. The results of this study show that EAA may protect epidermal and dermal cells by reducing levels of pro-inflammatory proteins, increasing antioxidant system activity in skin keratinocytes and fibroblasts, and normalizing intercellular signaling. Full article