Search Results (4,009)

Breast cancer remains one of the most frequently diagnosed malignancies and a leading cause of cancer-related mortality among women worldwide. The growing interest in natural bioactive compounds has highlighted plant-derived phytochemicals as promising agents for cancer prevention and adjunctive therapy due to their pleiotropic biological activities and relatively low toxicity. In parallel, increasing attention has been directed toward agro-industrial by-products generated during food processing, which represent abundant and sustainable sources of valuable phytochemicals. This review provides a comprehensive overview of recent advances in the identification, extraction, and biological evaluation of phytochemicals derived from plants and agro-industrial residues, using pomegranate (Punica granatum) peels, onion (Allium cepa) skins, and citrus by-products as representative examples of phytochemical-rich agro-industrial residues. These by-products are rich in polyphenols, flavonoids, and other secondary metabolites—including punicalagins, ellagic acid, quercetin, hesperidin, and naringin—that have demonstrated significant antioxidant, anti-inflammatory, and anticancer properties. Recent in vitro and in vivo studies indicate that these compounds can modulate key molecular pathways involved in breast cancer initiation and progression, such as oxidative stress regulation, apoptosis induction, inhibition of cell proliferation, and suppression of signaling cascades including PI3K/Akt, NF-κB, and MAPK pathways. Furthermore, the valorization of agro-industrial waste offers a sustainable strategy to recover high-value bioactive compounds while reducing environmental impact. Overall, phytochemicals obtained from plant materials and food processing by-products represent promising functional agents for breast cancer prevention and therapy, although further studies are required to improve bioavailability, elucidate mechanisms of action, and validate their clinical potential. Full article

Background/Objectives: Behçet’s disease is a chronic relapsing multisystem inflammatory disorder characterized by recurrent mucocutaneous ulceration, vasculitis, and exaggerated inflammatory responses to minor trauma. These features may adversely affect wound healing after major head and neck oncologic reconstruction. This case report describes repeated wound breakdown after oral cavity reconstruction in a patient with Behçet’s disease and advanced floor-of-mouth squamous cell carcinoma. Methods: A 51-year-old woman with Behçet’s disease and T4N2bM0 squamous cell carcinoma involving the floor of the mouth and tongue underwent tumor resection followed by reconstruction of the oral cavity defect using a right anterolateral thigh perforator free flap. Subsequent surgical procedures included debridement of necrotic tissue, negative-pressure wound therapy, split-thickness skin grafting of the thigh donor site, and salvage tumor resection with pectoralis major myocutaneous flap reconstruction after tumor recurrence. Results: After the initial anterolateral thigh free flap reconstruction, flap perfusion was satisfactory in the immediate postoperative period; however, delayed marginal necrosis developed from the distal tongue-side flap margin, whereas the floor-of-mouth portion remained relatively stable. The right thigh donor site also developed progressive suture-line necrosis and wound dehiscence, requiring operative debridement, negative-pressure wound therapy, and split-thickness skin grafting. Although skin grafting achieved eventual donor-site coverage, partial graft necrosis and delayed secondary healing occurred. Persistent fistula and wound instability delayed postoperative radiotherapy, and recurrent floor-of-mouth squamous cell carcinoma subsequently developed approximately 6 months after the initial surgery. After salvage resection and pectoralis major myocutaneous flap reconstruction, the flap appeared viable at inset, but marginal ecchymosis, partial necrosis, and wound dehiscence again developed, requiring additional debridement, quilting sutures, and negative-pressure wound therapy. The wound gradually stabilized with staged wound management. Conclusions: This case illustrates a multifactorial pattern of repeated marginal wound breakdown after technically successful flap reconstruction in a patient with Behçet’s disease. Behçet-related pathergy-like inflammation, vasculitis, and microcirculatory dysfunction may represent possible contributing mechanisms, but they were not directly proven in this patient. In oral cavity reconstruction, such wound instability may delay adjuvant therapy and adversely affect oncologic outcomes. Careful perioperative planning, close multidisciplinary coordination, meticulous tension-free closure, early recognition of wound compromise, and readiness for staged wound management are essential in patients with Behçet’s disease undergoing major head and neck oncologic reconstruction. Full article

Surface roughness of woven fabrics plays a key role in tactile comfort and skin–textile interaction, particularly in medical applications involving prolonged contact with human skin. This study focuses on the surface roughness of woven fabrics in plain and twill (1/3 S) weaves intended for hospital bed sheets and bedding applications. Plain weave represents a structurally symmetric system, while twill weave exhibits a pronounced diagonal structure. Roughness was evaluated using the Fabric Touch Tester (FTT) and further analyzed through amplitude (Rq), height distribution (Rku), and frequency-related parameters (linear peak density) obtained by signal processing and peak analysis in OriginPro 2026. The results showed that weave structure is the dominant factor influencing surface topography. Plain weave fabrics exhibited higher amplitude roughness and more uniform height distribution, while twill fabrics showed lower global roughness but stronger directional dependence, particularly in diagonal directions. Linear peak density was not significantly affected by laundering cycles, fiber composition, or finishing, but was strongly dependent on weave type. The findings demonstrate that due to the orthotropic nature of woven fabrics, surface roughness, derived from surface topography, cannot be adequately described by a single parameter, and that a combined analysis of amplitude and spatial descriptors is required, with the surface being evaluated not only along the principal symmetry directions (warp and weft) but also in off-axis directions. These results provide valuable insight for the design of hospital textiles with improved tactile comfort and reduced risk of skin irritation. Full article

Melasma is a chronic hyperpigmentation disorder that significantly impacts quality of life. Given the persistent challenges in melasma management, there is a need to evaluate therapies that may offer long-term treatment. This descriptive review analyzes interventional clinical studies involving melasma patients and placebo or hydroquinone (HQ) comparators published between 2014 and 2024. Two human authors screened studies and extracted data, with artificial intelligence used as a human-supervised support tool for screening assistance, data extraction, and discussion synthesis. Study limitations were evaluated descriptively. Treatments were grouped into five categories: HQ-based Standard Treatments, Isolated Molecules as Depigmenting Therapies, Botanical and Antioxidant-Based Therapies, Regenerative and Microenvironment-Modulating Therapies, and Procedure-Assisted and Combination Treatments. HQ remained a key benchmark, although recurrence and tolerability limitations were frequently observed. Several non-HQ or adjunctive approaches demonstrated benefit when administered orally, topically, intradermally, or via iontophoresis. Botanical antioxidants, synbiotics, epidermal growth factor, and platelet-rich plasma also showed promising efficacy. Nevertheless, the evidence base was constrained by small sample sizes, heterogeneous comparators, inconsistent endpoints, mixed objective and subjective assessments, and variable follow-up durations, which prevented meta-analysis. Research on melasma treatment is growing worldwide, with several promising non-HQ and adjunctive strategies emerging. However, standardization of outcomes, comparator selection, and longer follow-up periods is needed to clarify efficacy, tolerability, and relapse prevention throughout diverse skin tones. Full article

Carbonyl stress, chronic inflammation, and progressive tissue injury accompany type 2 diabetes mellitus (T2DM) and obesity. Yet, the molecular systems that connect these processes with cardiac, vascular and neuronal complications are incompletely defined. This review examines the AGE–RAGE–DIAPH1 axis as a mechanistic link between metabolic dysfunction and diabetic myocardial and neuronal injury, with emphasis on vascular and myocardial remodeling and emerging implications for autonomic neuronal vulnerability. We summarize current evidence on the formation and accumulation of advanced glycation end-products and other RAGE ligands in metabolic disease, DIAPH1’s structural and signaling role as an intracellular effector of RAGE, and the cellular consequences of pathway activation in vascular, neural, and cardiac tissues. Across experimental models, this signaling axis promotes oxidative stress and inflammatory activation, leading to endothelial dysfunction and barrier failure. Subsequent fibrotic remodeling provides a biologically plausible route through which metabolic stress may be translated into persistent organ injury. In the heart, these mechanisms are linked to coronary microvascular dysfunction, altered cardiomyocyte phenotype, calcium handling abnormalities, and myocardial fibrosis. In the autonomic nervous system, limited but emerging data connect RAGE activation to oxidative injury and mitochondrial dysfunction, abnormal neuronal excitability, and structural vulnerability. Direct evidence linking DIAPH1 to autonomic neurons is lacking. We also review biomarker candidates related to this pathway, including circulating AGEs and soluble RAGE isoforms, skin AGE measurements, imaging markers of myocardial remodeling, and autonomic functional measures. Finally, we discuss pharmacological and natural compounds that target AGE formation, ligand accumulation, RAGE signaling, or intracellular protein interactions linked to this axis. Overall, the available evidence supports the AGE–RAGE–DIAPH1 axis as a credible mechanistic concept and a potentially informative translational hypothesis in T2DM. However, the AGE–RAGE component is supported more strongly than DIAPH1-specific involvement in human diabetic myocardial disorder or cardiovascular autonomic neuropathy. The value of DIAPH1 as a biomarker or therapeutic target in these neurocardiac complications remains to be established. Full article

The valorization of agri-food by-products generated during juice extraction represents a key strategy within circular economy frameworks, as it reduces the environmental impact of waste disposal while creating added value and improving the food supply chain. In this work, five betaine-based natural deep eutectic solvents (NaDES) differing in their hydrogen-bond donors, namely citric acid, lactic acid, acetic acid, glycerol, and ethylene glycol, were used for the green extraction of blueberry pomace, a largely underutilized by-product that is nevertheless rich in bioactive compounds. The extracts were characterized by liquid chromatography coupled with diode-array and tandem mass spectrometric detection, allowing targeted profiling of anthocyanins and non-anthocyanin phenolics, including phenolic acids, flavonoids, and phenolic aldehydes. The extraction performance of NaDES was benchmarked against conventional solvents (water and ethanol) to evaluate differences in selectivity and efficiency toward distinct phenolic classes. Antioxidant capacity was determined using DPPH and ABTS radical scavenging assays. Among the NaDES systems, the betaine–citric acid NaDES extract exhibited notable phenolic recovery together with marked radical scavenging activity. After evaluating its inhibitory activity against elastase and tyrosinase, enzymes involved in the skin aging process, the selected NaDES extract was incorporated into a natural-based antiaging cosmetic formulation, and its main physicochemical properties were assessed to verify suitability for topical application. This study demonstrated that the use of NaDES represents an environmentally friendly and sustainable approach to transform blueberry by-products into high-value, safe, and ready-to-use cosmetic functional ingredients without the need for solvent removal. Full article

Background/Objectives: Pressotherapy is a method of controlled compression using special cuffs designed to improve lymphatic and blood circulation and support aesthetic treatments and therapies. The available literature lacks evidence of the effects of these treatments on skin parameters in healthy, untrained women. It was hypothesized that a series of pressotherapy treatments would positively impact skin firmness, hydration, friction resistance, and transepidermal water loss (TEWL). Methods: The study involved 15 healthy women aged 20–26 years who underwent a series of 10 pressotherapy treatments on the lower limbs (preliminary study, without a separate control group). The effects of the therapy were assessed by measuring skin hydration, transepidermal water loss (TEWL), elasticity, and resistance to friction, with measurements taken in standardized conditions before, during, and after the treatment cycle. Results: The study did not observe significant changes in skin hydration (Chi-square = 0.48; p = 0.923; Kendall’s W = 0.016) (CI 95% 6.07–16.22), transepidermal water loss (TEWL) (Chi-square = 6.24; p = 0.100; Kendall’s W = 0.208) (CI 95% 2.29–14.37) and skin friction coefficient (Chi-square = 6.27; p = 0.099; Kendall’s W = 0.209) (CI 95% 0.06–1.52), while analysis of elasticity and firmness parameters showed a significant improvement in selected biomechanical indicators (R0 (Chi-square = 13.32; p = 0.004; Kendall’s W = 0.440), R3 (Chi-square = 12.39; p = 0.006; Kendall’s W = 0.413), R8 (Chi-square = 9.00; p = 0.029; Kendall’s W = 0.300), Q1 (Chi-square = 11.64; p = 0.008; Kendall’s W = 0.388), Q2 (Chi-square = 7.54; p = 0.050; Kendall’s W = 0.251) (CI 95% 0.01–0.17)). Conclusions: A series of pressotherapy treatments on the lower limbs of young women may affect skin elasticity (selected parameters) but may not have a significant impact on skin hydration, transepidermal water loss (TEWL), or skin resistance to friction. Full article

This study aimed to formulate and evaluate a facial serum containing Cannabis extract, a prebiotic blend of glycerin, lactitol, and xylitol, as well as heat-treated Lactobacillus plantarum HEAL19, a non-viable probiotic-derived ingredient (postbiotic) that preserves beneficial structural components and biological activity. Additionally, alternative preservatives were tested to replace conventional ones, aligning with environmentally and consumer-friendly cosmetic trends. The formulation underwent stability testing, physicochemical analysis, and microbiological control, including a challenge test to assess preservative efficacy. The efficacy of the formulation was investigated through a randomized, placebo-controlled pilot study involving sixteen healthy female volunteers aged 24–53 years. Participants were instructed to apply the active serum to one side of the face and the placebo preparation to the opposite side twice daily for a period of 30 days. Study endpoints were evaluated through clinical measurements of transepidermal water loss (TEWL), skin hydration, elasticity, and skin surface topography, together with participant-reported outcome questionnaires. Results demonstrated that the formulation possessed suitable physicochemical properties and microbiological stability. The serum was well tolerated and improved skin hydration. Participants reported enhanced esthetic appearance and perceived efficacy. These findings support the potential of combining innovative active ingredients with alternative preservatives in skin-friendly cosmetic formulations. Full article

Sebaceous glands consist of epithelial cells, known as sebocytes, that undergo differentiation to deliver the components of sebum into the sebaceous duct and eventually to the hair and skin surface. The final step of the terminal differentiation program is called holocrine secretion because the entire cell content is converted into sebum. Holocrine secretion is a mode of programmed cell death, which involves the degradation of the nucleus and other organelles and the rupture of the cell membrane. Here, we review the current knowledge of differentiation-associated death of sebocytes and discuss open questions regarding its mechanism and functions. In vivo studies have provided evidence for degradation of nuclear and mitochondrial DNA by lysosomal deoxribonuclease 2 (DNase 2), indicating a key role of lysosomes in holocrine secretion. We discuss the influence of tight junctions on the spatial localization of holocrine secretion within glands, the regulation of holocrine cell death by autophagy and potential mediators of membrane lysis. Further studies of holocrine secretion are needed to fully uncover its molecular control and to determine potential clinical implications. Full article

Background: Atopic dermatitis is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, whereas major depressive disorder is a common psychiatric condition with a substantial impact on quality of life; increasing attention has been given to oxidative and nitrosative stress as a potential biological link between these disorders. Methods: This narrative review synthesizes current evidence on molecular biomarkers of oxidative and nitrosative stress in AD and MDD and examines shared mechanisms within the skin–brain axis. Results: Across both conditions, studies consistently report increased markers of lipid peroxidation (e.g., malondialdehyde, 4-hydroxynonenal), oxidative DNA damage (8-hydroxy-2′-deoxyguanosine), and nitrosative stress, alongside impaired antioxidant defenses, particularly involving glutathione; these alterations are closely associated with chronic inflammation, cytokine signaling, mitochondrial dysfunction, and dysregulation of neuroimmune and hypothalamic–pituitary–adrenal axis pathways. Conclusions: Although the available evidence is heterogeneous and largely based on cross-sectional studies, limiting causal inference, the findings support a biologically plausible link between AD and depression mediated by shared redox pathways and highlight the need for further longitudinal and mechanistic research. Full article

Background: Increasing antifungal resistance, poor mucosal retention, and systemic side effects limit the effectiveness of currently available drugs. This study explores a novel topical nanotherapeutic approach for the targeted treatment of vulvovaginal candidiasis (VVC), employing green-synthesized silver nanoparticles (AgNPs) derived from Ascophyllum nodosum (AN) and incorporating ibrexafungerp citrate (IBC) into a liposomal formulation. Methods: AgNPs were biosynthesized using AN extract and characterized. Liposomes were prepared by thin-film hydration, and optimised using Central Composite design and characterized and optimized. Optimised liposomes, co-loaded with IBC and AN-AgNPs, were incorporated into a Carbopol-CMC-based topical gel. Results: FTIR shifts in the –OH (3332.31 cm⁻¹) and carbonyl (1636.87 cm⁻¹) bands with reduced intensity confirmed their involvement in Ag⁺ reduction and nanoparticle surface coordination, while the persistence of the 1015 cm⁻¹ band indicated the role of polysaccharides in capping and stabilizing the AN-AgNP. Characterization of the optimized liposomes (IBCL-11) revealed a particle size of 127.2 nm, a zeta potential of −43.8 mV, and a polydispersity index (PDI) of 0.35. Transmission Electron Microscopy (TEM) confirmed the presence of intact, spherical vesicles, while Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD) validated the molecular dispersion and amorphous characteristics of the films. In vitro evaluations of the IBC liposomal gel demonstrated a sustained drug release of 72.6% over 24 h, alongside enhanced drug penetration across all skin layers. Antifungal assays highlighted the formulation’s potent efficacy, yielding Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) values below 1 µg/mL. Furthermore, the treatments exhibited strong anti-biofilm properties; at MIC and MBC levels, AN-AgNPs achieved biofilm reductions of 45.27 ± 3.16% and 27.62 ± 2.13%, respectively, whereas IBCL-11 produced reductions of 34.25 ± 2.43% and 16.28 ± 1.72%. Conclusion: Ultimately, this study successfully developed an eco-friendly liposomal formulation co-loaded with AN-AgNPs and IBC, offering a promising and targeted therapeutic approach for the treatment of vulvovaginal candidiasis. Full article

Background: Idiopathic inflammatory myopathies (IIMs) are a heterogenous group of disorders frequently complicated by interstitial lung disease (ILD). We sought to discern phenotypic and serological differences according to the presence of ILD and initial evaluating medical specialty, i.e., rheumatology vs. pulmonology, with the goal of advancing personalized medicine. Methods: A computer-assisted search was conducted to identify patients with a diagnosis of IIM seen at Attikon University Hospital, from January 2010 to December 2025. Medical records were reviewed for clinical, laboratory and serological features. Results: We identified 140 patients with IIM; 96 (68.6%) were female with a mean age at diagnosis of 55.8 years (SD 15.7). ILD was present in 75 patients (53.6%), being more common among males (30/44, 68.2% vs. 45/96 females, 46.9%, p = 0.019). Patients in the ILD subgroup were older at diagnosis (mean age 60.2 years vs. 50.7 years, p < 0.001) and presented more often with dyspnea (41 vs. 1, p < 0.001), higher CRP (median 5.95 mg/L vs. 2.9 mg/L, p = 0.024), and lower CPK (median 103 vs. 580, p < 0.001). Patients first seen by a pulmonologist were more likely to be older (mean age 60.5 years vs. 53 years, p = 0.002) and to present with dyspnea (33 vs. 9, p < 0.001) and ILD (48 vs. 27, p < 0.001). By contrast, skin involvement (61% vs. 27%, p = 0.04), muscle weakness (53 vs. 15, p < 0.001) and elevated CPK (median 301.5 vs. 103.5, p = 0.013) were less frequent in these patients as compared to patients first evaluated by a rheumatologist. Anti-tRNA synthetase, anti-Ro52 and anti-Pm/Scl antibodies were more frequent in the ILD subgroup. Anti-tRNA antibodies were also more frequent in patients first seen by a pulmonologist. Conclusions: Patients with IIM-ILD are more likely to present without overt clinical or biochemical characteristics of muscle involvement, thereby increasing the likelihood of initial evaluation by pulmonologists. Full article

Background: Acanthamoeba is a free-living protozoan widely distributed in the environment and causes Acanthamoeba keratitis, skin, and brain disease. Acanthamoeba can exchange genes, potentially increasing antimicrobial resistance and virulence. Therefore, this systematic review aimed to summarize published studies on horizontal gene transfer (HGT) between Acanthamoeba and its intracellular microorganisms and to evaluate the impact of HGTs on the pathogenicity of Acanthamoeba. Methods: This systematic review was conducted following the recommended reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guideline. The electronic databases PubMed, Embase, and Web of Science were used to search for relevant published research articles. Results: Nineteen studies that fulfilled the inclusion criteria were included in this systematic review. A total of 14 (73.6%) studies reported evidence of HGT involving Acanthamoeba, and five studies of the nineteen (26.3%) analysed the presence of intracellular microorganisms on the pathological effects of the host Acanthamoeba. Horizontally transferred genes were predominantly reported from Pseudomonas species, Legionella pneumophila, and Chlamydia species. Conclusions: HGT can occur among intracellular microorganisms and their host Acanthamoeba. Acanthamoeba harbouring intracellular microbes showed enhanced pathogenic effects on human corneal epithelial cells and in a mouse model. However, heterogeneity among the included studies precluded meta-analysis. Studies using clinical and environmental samples are needed to characterize the horizontal transfer of virulence and antimicrobial resistance genes. Full article

Olfactory (or odorant) receptors (ORs) were initially characterized in 1991 by Drs. Richard Axel and Linda Buck, and subsequent additional efforts have contributed to our understanding of their canonical function in odorant identification in the nasal cavity, including ligands for many of the ORs and the signaling pathways involved. More recently, OR transcripts and proteins have been identified in cells and organs outside of the nasal cavity, ranging from skin to sperm to tumors, suggesting that they have biological roles in ectopic locations other than their canonical function of odorant molecule detection in the nose. This mini narrative review discusses ectopic human ORs and their potential ligand-activated functions in the skin, lung, and sperm, as well as in diseases such as nonalcoholic steatohepatitis (NASH), melanoma and prostate cancer. Full article

The exact mechanisms of skin involvement in type 1 diabetes (DM1) remain poorly understood. This study aimed to evaluate the relationship between antioxidants, oxidative stress, protein glycation, and glycoxidation, as well as matrix metalloproteinase (MMP) activity, in the skin of rats with DM1, while investigating whether insulin administration improves skin homeostasis. Male Wistar rats were assigned to three groups: control, diabetes, and diabetes treated with insulin. Significantly higher expression of GSH (gluthatione) and GSH-Px (glutathione peroxidase), elevated levels of AGE (Advanced Glycation End products), DT (dityrosine), KN (kynurenine), NFKN (N-formylkynurenine) and ONOO- (peroxynitrite), as well as increased activity of GLU (β-D-glucuronidase), NADPH oxidase (NOX) and MMP-1, -2, -3, -7, -9, -11 and -13 were observed in the skin of rats with DM1. Insulin treatment normalizes the skin’s antioxidant barrier and eliminates oxidative stress. It also reduces the intensity of protein glycation and glycoxidation, though not to the levels observed in the control group. Summarizing, in diabetic skin there is a complex interaction between the thiol antioxidant barrier, oxidative damage, protein glycation and glycoxidation as well as MMP expression. Insulin restores physiological balance in skin cells; however, glycation and ECM remodeling are still more pronounced than in healthy skin. Full article