Search Results (11,342)

The brewing process generates substantial by-products rich in potentially bioactive compounds (e.g., polyphenols and fermentation metabolites), providing a sustainable and appealing source of cosmetic ingredients. Oil-in-water (O/W) emulsions containing 20% (w/w) aqueous extracts from Bionda Triplo Malto beer, wort, and key brewing by-products (hops, yeast, and spent grain) were developed and evaluated using a combined in vitro–in vivo approach. Aqueous extracts were first screened on human immortalized dermal fibroblasts (BJ-5ta) at 0.25–1 mg/mL for cytocompatibility and antioxidant activity. Within this concentration range, no significant changes in cell viability or intracellular antioxidant capacity under UV stress were detected, suggesting cytocompatibility but limited inherent activity. When incorporated into O/W emulsions and tested at an active-equivalent concentration of 10 mg/mL, the formulations increased fibroblast metabolic activity and antioxidant response. In contrast, free extracts at 10 mg/mL showed concentration-dependent cytotoxicity for some matrices, with beer- and yeast-based emulsions demonstrating the strongest effects. The emulsions exhibited good physicochemical stability (pH ~5.7–6.2; viscosity 4750–5150 mPa·s), passed the ISO 11930:2012 challenge test, and were well tolerated in patch testing. In a double-blind, randomized split-forearm study on 50 healthy volunteers over 30 days, beer, yeast, and spent grain-based formulations improved skin parameters versus baseline. TEWL decreased (e.g., beer: 16.22 ± 5.12 to 10.77 ± 2.22 mg·m⁻²·h⁻¹; yeast: 16.29 ± 5.66 to 10.18 ± 1.08; spent grain: 14.45 ± 4.34 to 11.66 ± 2.28), hydration increased (beer: 35.15 ± 5.93 to 42.26 ± 3.78; yeast: 33.27 ± 4.87 to 42.92 ± 2.48; spent grain: 34.22 ± 5.19 to 41.16 ± 3.17, and elasticity improved for beer and yeast formulations (62.33 ± 3.27 to 70.24 ± 2.12 N/m) and yeast (61.21 ± 4.72 to 72.13 ± 5.55 N/m). Based on these findings, brewing-derived ingredients demonstrate potential as cosmetic actives, with formulation critically determining their clinical efficacy. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Emerging evidence shows that mechanotransduction, driven by matrix stiffness and mechanical signaling, promotes TNBC invasion and metastasis. As breast cancer progresses, expansion of fibroblasts and tumor-reactive stroma increases extracellular matrix deposition, generating matrix tension and enhancing mechanotransduction, which promotes cell proliferation, invasion, and metastatic potential through altered gene expression patterns. To investigate the molecular mechanisms underlying these changes, human TNBC cells were subjected to constant or oscillatory strain, followed by comprehensive transcriptomic analysis. Results revealed pronounced differential expression of genes involved in cell migration, adhesion, and transforming growth factor-β (TGFβ) signaling, with RT-PCR validation confirming SKI Like Proto Oncogene (SKIL) as the most strongly upregulated gene. Analysis of The Cancer Genome Atlas (TCGA) datasets indicated that SKIL is highly expressed in multiple breast cancer subtypes. Cross-sectional comparison of oscillatory strain-induced genes with TCGA data revealed coordinated upregulation of TGFβ, SKIL, and other genes associated with invasive phenotypes, immune suppression, and drug resistance, highlighting the vital role of TGFβ signaling. Transcription factor enrichment analysis further identified regulators linked to oncogenic pathways, including TGFβ effectors and Hippo signaling, supporting a mechanotransduction-driven transcriptional program in breast cancer. Full article

Naphthyridine derivatives have emerged as privileged scaffolds with diverse pharmacological activities, particularly in anticancer and antiviral drug discovery. In this study, a series of naphthyridine-based derivatives (1–10b) was designed, synthesized, and structurally characterized using IR, ¹H/¹³C NMR, and mass spectrometry, and evaluated as dual-function antiproliferative and anti-fowlpox virus agents supported by integrated computational analyses. The synthesized compounds were screened for in vitro antiproliferative activity against HeLa, HCT-116, and MCF-7 cancer cell lines, as well as normal WI-38 lung fibroblasts. Several derivatives exhibited potent cytotoxic activity with enhanced selectivity toward cancer cells. Compound 5b showed the highest activity against HeLa cells, compound 1 was most effective against HCT-116 cells, while compounds 7 and 8 displayed remarkable activity against MCF-7 cells, with compound 7 surpassing doxorubicin and compound 8 demonstrating excellent selectivity toward normal cells. Mechanistic investigations revealed that compounds 7 and 8 acted as dual topoisomerase I/IIβ inhibitors, inducing G2/M cell cycle arrest and intrinsic apoptosis associated with caspase-9 activation and downregulation of topoisomerase II protein expression. Selected derivatives were further evaluated for antiviral activity against fowlpox virus using in ovo and in vivo SPF embryonated chicken egg models, where compounds 2 and 9a exhibited the highest therapeutic indices, comparable to ribavirin, and compound 9a markedly suppressed viral replication and titers in vivo. ADMET profiling, molecular docking, molecular dynamics simulations, and DFT calculations supported the experimental findings and identified compound 10a as the most favorable theoretical candidate. Overall, this integrated experimental–computational approach establishes naphthyridine derivatives as a rationally designed multifunctional chemotype for simultaneous anticancer and antiviral drug development. Full article

Hypertension-induced renal injury is a major cause of chronic kidney disease and end-stage renal disease. Increasing evidence indicates that disease progression is not driven solely by hemodynamic stress but results from the interplay of multiple molecular mechanisms. In this review, we propose a stage-structured and network-based framework to systematically integrate current mechanistic insights into hypertension-induced renal injury. Early events, mainly including endothelial dysfunction and renal hypoxia, establish a permissive microenvironment for disease progression. These insults activate amplifying pathways such as the renin–angiotensin–aldosterone system (RAAS) overactivation, oxidative stress, immune and inflammatory responses, and sympathetic nervous system hyperactivity, which interact through cross-talk and positive feedback loops. Ultimately, these signals converge on fibrotic programs characterized by epithelial–mesenchymal transition (EMT), fibroblast activation, and extracellular matrix deposition, leading to irreversible structural remodeling and functional decline. Furthermore, epigenetics, the gut–kidney axis, autophagy dysfunction and renal aging also contribute to this process. We highlight two critical and underappreciated aspects: the existence of a permissive ‘early-window’ dominated by endothelial dysfunction and hypoxia, which sets the stage for later amplification; and the hierarchical interplay between amplifying mechanisms where cross talk creates self-reinforcing loops that may explain therapeutic resistance. In addition, this review highlights emerging biomarkers for early diagnosis and disease monitoring, and discusses therapeutic advances that extend beyond blood pressure control to disease-modifying interventions that confer renoprotective effects. By integrating molecular mechanisms with diagnostic and therapeutic perspectives, this review provides a comprehensive framework for early detection and precision intervention in hypertension-induced renal injury. Full article

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with aortic pathologies such as atherosclerosis and thoracic aortic aneurysm posing significant risks due to their asymptomatic nature and potential fatal complications. This study investigates molecular mechanisms underlying CVDs by examining key cellular components of the aortic wall—vascular smooth muscle cells (VSMCs), fibroblasts, and macrophages—and their responses to low-density lipoproteins (LDLs). Using in vitro models, we analyzed phenotypic characteristics, LDL internalization capacity, and secretion/expression of pro-inflammatory mediators (IL-6, IL-8, IL-1β, CCL2) in primary VSMCs (from tunica intima and media), fibroblasts (977hTERT), and THP-1 macrophages. Fluorescence staining with BDP 630/650 revealed that all cell types internalize LDLs, with macrophages showing the highest lipid accumulation. ELISA and RT-qPCR demonstrated cell-specific patterns of cytokine secretion and gene expression, both in control conditions and after LDL exposure. The results indicate that VSMCs and fibroblasts, normally involved in vascular tone maintenance and extracellular matrix (ECM) synthesis, acquire pro-inflammatory features under pathological conditions, including increased secretion of IL-6, IL-8, and CCL2. Macrophages exhibited enhanced expression of the scavenger receptor CD36 and pro-inflammatory cytokines (especially IL-1β) after LDL treatment. Full article

Background: Punica granatum L. (pomegranate) is a medicinal plant traditionally used for its antimicrobial and antioxidant effects. Recent evidence supports its expanding applications in dermatology and dermocosmetics. Purpose: This systematic review aimed to evaluate the skin-related biological activities of pomegranate extracts, identify the key bioactive compounds involved, and elucidate the underlying molecular mechanisms relevant to skin health and aging. Methods: A total of 732 studies were screened using AIReviewer clustering. Fifty-four original articles were selected on the basis of inclusion criteria prioritizing molecular evidence, in vitro and in vivo assays, and clinical relevance. Results: Pomegranate extracts exhibit a broad range of dermocosmetic properties, including antioxidant, anti-inflammatory, antibacterial, wound healing, moisturizing, photoprotective, and collagen-preserving effects. These effects are primarily attributed to ellagitannins (punicalagin and punicalin), ellagic and gallic acid, triterpenoids (oleanolic, maslinic, and asiatic acids), flavonoids (quercetin and catechins), anthocyanins, and fatty acids (punicic acid). Pomegranate extracts modulate oxidative stress by scavenging reactive oxygen species and upregulating Nrf2-mediated antioxidant pathways. They inhibit matrix metalloproteinases (MMP-1 and MMP-3), suppress proinflammatory cytokines (TNF-α and IL-6), and stimulate fibroblast proliferation, extracellular matrix remodeling, and hyaluronic acid synthesis. Their photoprotective activity provides enhanced UVB resistance and higher SPF values. Recent advances in fermentation and nanotechnology have been shown to increase the bioavailability and stability of compounds found in pomegranate, offering new formulation strategies. Conclusions: Pomegranates are a promising source of multifunctional phytochemicals with validated dermocosmetic applications. Their incorporation into advanced delivery systems may increase their therapeutic potential for skin protection, regeneration, and antiaging interventions. Full article

This study aimed to manufacture and characterize highly porous dressings based on gellan gum (GG) and sodium alginate (Alg) hydrogels modified with zinc oxide (ZnO) and bacitracin (BAC) intended for infected and exuding wounds. ZnO nanoparticles (ZnO(n)) were 26 ± 4 nm in size according to atomic force microscopy (AFM), while the size of the microparticles (ZnO(m)) was 1.02 ± 0.01 µm according to laser diffraction measurements. Their relative surface areas were 39.16 m²/g and 4.56 m²/g, respectively. Microbiological studies showed that ZnO(n) exhibited antibacterial activity in contact with the Gram+ Staphylococcus aureus; thus, they were selected for embedding in a hydrogel matrix. Four types of composite hydrogel samples were manufactured: GG/Alg, GG/Alg+ZnO, GG/Alg+BAC, and GG/Alg+ZnO+BAC, which were subjected to freeze drying. The water absorption of all materials exceeded 4000%, showing excellent liquid absorbability. Burst release of BAC was found at a level of 90% in the first 2 h. In vitro cytotoxicity studies on L929 fibroblasts did not show a toxic effect of extracts from the GG/Alg and GG/Alg+BAC samples, contrary to samples supplemented with ZnO(n). In microbiological studies, the enhanced antibacterial effect of ZnO(n) and BAC was observed in contact with Staphylococcus aureus and Staphylococcus epidermidis strains. Therefore, GG/Alg+BAC+ZnO is the most promising dressing system for the treatment of infected and exuding wounds. Full article

Artocarpin, a prenylated flavonoid isolated from Artocarpus altilis heartwood, has emerged as a promising multi-targeted bioactive compound for combating UV-induced skin aging. This review provides a comprehensive overview of the molecular mechanisms and photoprotective efficacy of artocarpin across in vitro, in vivo and clinical study, based on the peer-reviewed literature published between 2012 and 2025, retrieved from PubMed, Scopus, and Web of Science. Delivery strategies designed to overcome the inherent physicochemical limitations of artocarpin on skin penetration are also discussed. Artocarpin demonstrates antioxidant effects through both direct free radical scavenging and activation of the Nrf2-ARE pathway, providing sustained cellular defense. Its anti-inflammatory properties target multiple signaling cascades, including the NF-κB and MAPK pathways, effectively mitigating UV-induced inflammatory response. The compound maintains dermal matrix homeostasis by inhibiting matrix metalloproteinase-1 (MMP-1) expression while preserving collagen synthesis and fibroblast mechanical function. Additionally, artocarpin exhibits selective apoptosis modulation, being cytoprotective in normal keratinocytes while acting as pro-apoptotic in damaged or abnormal cells, thereby supporting tissue homeostasis. It also inhibits melanogenesis through anti-inflammatory mechanisms rather than direct tyrosinase inhibition. Furthermore, artocarpin has been shown to induce autophagic cell death in certain cell lines; however, its role in UV-induced skin damages remains to be clarified. Despite these promising biological activities, the poor water solubility (<0.1 mg/mL) and high lipophilicity (log P ≈ 5) of artocarpin significantly limit its skin penetration. Lipid-based delivery systems, including liposomes, transfersomes, ethosomes, and nanostructured lipid carriers (NLCs), are presented as effective strategies to enhance transepidermal delivery, with each system offering distinct mechanistic advantages. Further investigations should prioritize the safety of artocarpin within each delivery system, as well as the synergistic co-encapsulation with complementary natural antioxidants to simultaneously target multiple mechanisms involved in UV-induced skin damage, thereby broadening its application in the cosmeceutical industry. Full article

Transforming growth factor-β (TGF-β) signaling plays a central role in lung tissue homeostasis, coordinating epithelial repair, immune resolution, and stromal remodeling following injury. However, persistent or dysregulated TGF-β activation is a hallmark of both idiopathic pulmonary fibrosis (IPF) and lung cancer, two devastating pulmonary diseases that are traditionally studied as distinct entities. Emerging evidence suggests that this dichotomous view may obscure shared pathogenic mechanisms driven by aberrant TGF-β signaling dynamics. In this review, we synthesize experimental, translational, and clinical findings to propose a unifying framework in which IPF and lung cancer represent endpoints along a shared TGF-β–driven pathological continuum. We highlight how the duration and intensity of TGF-β signaling determine divergent cellular outcomes across epithelial cells, fibroblasts, and immune compartments—ranging from physiological wound repair to irreversible fibrotic remodeling and the establishment of a pro-tumorigenic niche. Particular emphasis is placed on the temporal transition from acute injury responses to chronic signaling states that promote epithelial plasticity, fibroblast fixation, immune suppression, and genomic instability. By integrating fibrosis and tumorigenesis into a single pathophysiological model, this review reframes TGF-β signaling as a time-dependent disease modifier rather than a disease-specific factor. This perspective provides a conceptual basis for therapeutic strategies targeting TGF-β signaling windows to intercept disease progression before irreversible fibrosis or malignant transformation occurs. Full article

This study presents an efficient, environmentally benign approach for synthesizing chitosan-entrapped titanium dioxide (TiO₂) nanocomposites utilizing aqueous orange peel extract playing its role in reduction and stabilization of the nanoparticles and exploring its anticancer activity in vitro. TiO₂ nanoparticles were initially synthesized via a modified sol-gel method incorporating the orange peel extract. Subsequently, these nanoparticles were entrapped within a chitosan matrix. The orange peel extract was thoroughly characterized using analysis of phytochemicals present, and Gas Chromatography–Mass Spectrometry (GC–MS) analysis of a reconstructed methanolic extract to identify potential biomolecules responsible for the reduction and capping processes. The synthesized chitosan-entrapped TiO₂ nanoparticles were subjected to comprehensive characterization using various analytical techniques, like UV–visible spectroscopy, Dynamic Light Scattering (DLS) and Zeta Potential analysis, X-ray Diffraction (XRD), FTIR, High-Resolution Scanning Electron Microscopy (HR-SEM) and Energy-Dispersive X-ray Spectroscopy (EDAX). An absorption peak was observed at 296 nm, a hydrodynamic diameter of 400 nm, a+ 35.88 mV zeta potential, and an SEM image showing a diameter in the range of 300–645 nm, indicating polymer entrapment with enhanced size. Brine shrimp assay, MTT assay using normal fibroblasts, 3T3-L1, and zebrafish embryo assay were done to observe the biocompatibility of the synthesized nanostructure. The concentration of 50 μg/mL was found to be inert in both in vitro and in vivo. Furthermore, cervical cancer cells, SiHa, were treated with the nanoparticles to exhibit their cancer-killing capability with an IC₅₀ value of 30.74 μg/mL. The results demonstrate the effectiveness of orange peel extract as a sustainable agent for TiO₂ nanoparticle synthesis and the successful formation of a stable chitosan-entrapped nanocomposite. This approach offers a promising pathway for producing functional metal oxide nanomaterials with reduced environmental impact and enhanced properties for diverse biomedical applications. Future studies using other types of cancer cells and animal models for cancerous tumors need to be explored. Full article

Polysaccharide-based nanocarriers offer a novel delivery system for improving the stability, controlled release, and biological functionality of plant-derived bioactive materials. Olive leaf extract (OLE), rich in polyphenolic compounds with antioxidant and other bioactive properties, is limited by low stability and bioavailability. In this study, OLE-loaded alginate–chitosan nanoparticles were prepared using ionotropic gelation–polyelectrolyte complexation (IG-PEC) method, and their physicochemical properties, cytotoxic behavior, and potential prebiotic effects were evaluated. The resulting nanoparticles (232–237 nm) exhibited uniform spherical morphology, negative zeta potentials, and improved colloidal stability. Free OLE demonstrated concentration-dependent and selective cytotoxicity toward A549 and MCF-7 cancer cells, while exhibiting lower toxicity toward normal fibroblasts. In contrast, unloaded and OLE-loaded nanoparticles (1X, 2X) showed low cytotoxicity, suggesting superior biocompatibility of the polysaccharide nanocarrier. Notably, cultures supplemented with OLE-loaded nanoparticles showed a trend toward higher probiotic growth compared to free OLE, indicating a potential prebiotic effect and improved microbial tolerance to polyphenols during extended exposure. These findings highlight the advantages of polysaccharide-based nanoencapsulation for both stabilizing bioactive materials and supporting favorable microbial responses. The developed OLE nanocarriers may serve as a promising platform for nutraceutical, biomedical, and functional food applications. Full article

A high-entropy strategy has emerged as a promising approach to enhance the functional properties of piezoelectric ceramics for biomedical applications. For this reason, we have designed two novel high-entropy ceramics, (Bi_1/2Na_1/2)(Zr_1/3Sn_1/3Ti_1/3)O₃(BNZST) and (Bi_1/2Na_1/2)(Zr_1/4Sn_1/4Hf_1/4Ti_1/4)O₃(BNZSHT), which were synthesized via a two-step solid-state reaction. The phase structure, surface morphology, biocompatibility, and in vitro bioactivity were assessed. The results showed both ceramics adopted perovskite structures. BNZST and BNZSHT ceramics had relatively even crystallite sizes and element distribution, as well as achieving piezoelectric (d₃₃ ≥ 78 pC/N) properties. In vitro tests confirmed a high relative cell growth rate (RSG, >80%) after co-culturing BNZST or BNZSHT ceramic with murine fibroblasts L929 for more than 3 days. In particular, the surface with electric charge enhanced L929 with more extensive, widespread, and dense proliferation for the BNZST ceramic compared to ceramics without BNZST or unpolarized BNZST. The above indicated that multi-element doping and entropy stabilization established a novel pathway for developing a high-entropy bio-piezoelectric ceramics with high biocompatibility and bioactivity, providing the possibility for their use in bone repair materials. Full article

This study evaluated the anti-inflammation and anti-photoaging effects of Camellia sinensis seed flavonoids (CSF) against UVB and UVA irradiation and elucidated the underlying mechanisms. Using UVB-irradiated human keratinocytes and UVA-irradiated human dermal fibroblasts, we found that CSF significantly reduced intracellular ROS and suppressed the secretion of inflammatory factors (PGE-2, TNF-α, IL-6, IL-8) by inhibiting the p38/JNK and NF-κB pathways, along with iNOS and COX-2 expression. In keratinocytes, CSF also downregulated Caspase-3 and upregulated barrier proteins filaggrin and Claudin-1. In fibroblasts, CSF counteracted UVA damage by upregulating collagen IV and XVII at the dermo-epidermal junction and enhancing the production of collagen I, III, and hyaluronic acid in the dermis, mediated via AP-1 inhibition and TGF-β/Smad pathway modulation. These results demonstrate that CSF coordinated anti-inflammatory, barrier-repair, and anti-photoaging actions, highlighting its potential as a promising skincare ingredient. Full article

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus that contributes substantially to chronic kidney failure and increased cardiovascular risk. Beyond progressive deterioration of renal function, DKD is associated with disturbances in endocrine and vascular regulation. Among these, alterations in vitamin D homeostasis and blood pressure (BP) control represent clinically relevant, yet incompletely integrated aspects of DKD pathophysiology. This narrative review synthesizes current evidence on the multidirectional relationships between DKD, vitamin D deficiency, and arterial hypertension (AH). Attention is given to renal mechanisms responsible for reduced vitamin D availability in DKD, including proteinuria-related loss of vitamin D-binding proteins, impaired proximal tubular reabsorption, decreased renal activation of vitamin D, and hormonal regulators such as fibroblast growth factor-23. It further discusses how insufficient vitamin D signaling may influence renal and vascular pathways involved in BP regulation. Mechanistic links between vitamin D deficiency and AH in DKD are discussed, with emphasis on maladaptive activation of the renin–angiotensin–aldosterone system (RAAS), persistent inflammation, oxidative stress, endothelial dysfunction, and insulin resistance. These interdependent processes promote both renal injury progression and sustained elevations in BP, forming a self-reinforcing pathogenic loop. Finally, available data on vitamin D-based therapeutic strategies in DKD are reviewed, including native vitamin D supplementation, active vitamin D metabolites, and vitamin D receptor agonists. Although experimental and observational studies suggest potential nephroprotective and vasculoprotective effects, evidence from randomized clinical trials remains heterogeneous. Further well-designed prospective studies are required to clarify the clinical utility of vitamin D interventions in patients with DKD and coexisting AH. Full article

Current wound healing strategies must confront numerous challenges. Helminth-induced immunomodulation offers a promising therapeutic avenue for inflammatory diseases and injury repair. However, research on the role of helminths in damage recovery remains limited. We utilized glycogen—a naturally occurring biomaterial—to encapsulate SJMHE1, a bioactive peptide derived from Schistosoma japonicum, and successfully developed a facilely prepared hydrogel formulation denoted as SJMHE1-gel. The properties of SJMHE1-gel, its effect on cell activity, and its performance in a murine full-thickness skin defect model were evaluated. The glycogen-based hydrogel exhibited a uniform pore size, excellent biocompatibility, and sustained release of SJMHE1. Topical application of SJMHE1-gel enhanced collagen deposition, promoted angiogenesis, facilitated the regeneration of hair follicles and sebaceous glands, and accelerated full-thickness wound healing. SJMHE1-gel also promoted M2 macrophage polarisation and suppressed inflammatory cytokine expression both in vivo and in vitro. Mechanistically, SJMHE1-treated macrophages upregulate TGF-β, which in turn promotes the migration of L929 fibroblasts and human umbilical vein endothelial cells (HUVECs) via the Smad3 pathway. Neutralization of TGF-β attenuates phosphorylated Smad3 (p-Smad3) levels and impairs the migratory capacity of both fibroblasts and HUVECs. Additionally, SJMHE1-treated macrophages upregulate VEGFA, thereby enhancing angiogenic tube formation in HUVECs. This easy-to-prepare hydrogel can regulate macrophage polarization, inhibit inflammation, promote angiogenesis, and accelerate collagen deposition, acting across wound healing stages to provide a novel therapeutic strategy. Full article