Search Results (19,506)

Estrogen (E2, 17β estradiol) is recognized for its regulatory role in numerous genes associated with energy metabolism and for its ability to disrupt mitochondrial function in various cancer types. However, the influence of E2 on the metabolism of colorectal cancer (CRC) cells remains largely unexplored. In this study, we examined how E2 affects mitochondrial function and energy production in CRC cells, utilizing two distinct CRC cell lines, HCT-116 and SW480. Cell viability, mitochondrial function, and the expression of several genes involved in oxidative phosphorylation (OXPHOS) were assessed in estrogen receptor α (ERα)-expressing and ERα-silenced cells treated with increasing concentrations of E2 for 48 h. Our results indicated that the cytotoxicity of E2 against CRC cells is mediated by the E2/ERα complex, which induces disturbances in mitochondrial function and the OXPHOS pathway. Furthermore, we identified two novel targets, RPS2 and TMEM177, which displayed overexpression, hypomethylation, and a negative association with ERα expression in CRC tissue. E2 treatment in CRC cells reduced the expression of both targets through promoter hypermethylation. Treatment with 5-Aza-2-deoxycytidine increased the expression of RPS2 and TMEM177. This epigenetic effect disrupts the mitochondrial membrane potential (MMP), resulting in decreased activity of the OXPHOS pathway and inhibition of CRC cell growth. Knockdown of RPS2 or TMEM177 in CRC cells resulted in anti-cancer effects and disruption of MMP and OXPHOS. These findings suggest that E2 exerts ERα-dependent epigenetic reprogramming that leads to significant mitochondria-related anti-growth effects in CRC. Full article

Alcohol enters the brain through the blood–brain barrier and causes neuronal damage in various ways, additionally long-term and heavy drinking also leads to both structural and functional changes in the central nervous system. Currently, there is a lack of specific therapeutic approaches for alcohol-induced nerve injury. Opuntia milpa alta polysaccharides (MAPs) have various physiological activities such as antioxidant, anti-inflammatory, and neuroprotective effects, but it is not clear how they protect against alcohol-induced nerve injury. In this study, firstly, we structurally characterized homemade MAPs and analyzed the relevance of MAPs in protecting against alcoholic neuronal cell injury and ferroptosis. The results showed that MAPs consisted of nine different monosaccharides and uronic acids. High performance gel permeation chromatography analysis showed that MAPs were homogeneous heteropolysaccharides with an average molecular weight of 8.79 × 106 Da. Fourier infrared spectroscopy showed that they had sulfated pyranopolysaccharides with uronic acids and both α-glycosidic and β-glycosidic bonds were present. Specific signals of these sugars were observed in 1H and 13C NMR spectra. Favorable thermal stability was manifested up to 256 °C. The MAPs had a three-stranded helical structure and a low overall crystallinity. Iron staining showed that alcohol caused significant brown deposition in cells. MAPs significantly ameliorated alcohol-induced cellular damage, reduced iron deposition, and orchestrated the expression of proteins associated with ferroptosis. These results suggest that MAPs protect against alcohol-induced neurological damage, possibly by impeding the onset of cellular ferroptosis. Full article

Background: This study systematically investigates the therapeutic effects of naringenin (NAR) and oleuropein (OLE) on prostate cancer through miR-155-5p regulation. Methods: Experimental studies conducted on MAT-LyLu prostate cancer cell lines revealed that the application of NAR (50 μM) and OLE (75 μM) significantly increased miR-155-5p expression by 2.89-fold and 1.74-fold, respectively (p < 0.05). Bioinformatics analyses have indicated that miR-155-5p interacts with critical oncogenic pathways such as KRAS, CDK2, NF-κB, and TGF-β/Smad2. Computational analyses have revealed that miR-155-5p interacts with 16 critical oncogenic targets, including KRAS and CDK2. Molecular docking studies showed that NAR binds to the Switch I/II region of KRAS with a binding energy of −8.2 kcal/mol, while OLE binds to the ATP-binding pocket of CDK2 with an affinity of −9.1 kcal/mol. Pharmacokinetic evaluations revealed that NAR indicated high oral bioavailability (93.763% HIA) and full compliance with Lipinski’s rules, while OLE required advanced formulation strategies due to its high polarity. Network pharmacology analyses have shown that NAR affects lysosomal functions and enzyme regulation, while OLE affects G protein-coupled receptors and oxidoreductase activity. Results: Results indicate that NAR and OLE exhibit antitumor effects through multiple mechanisms by increasing miR-155-5p expression and inhibiting critical oncogenic targets in prostate cancer. Conclusion: Findings suggest that the dietary intake of these natural compounds (citrus and olive products) should be considered in prostate cancer prevention strategies, shedding light on the epigenetic mechanisms of polyphenols in cancer treatment and contributing to the development of new therapeutic strategies. Full article

Cheese whey, the major by-product of the dairy industry, poses an environmental challenge due to its high organic load but simultaneously represents a nutrient-dense matrix suitable for biotechnological valorization. This review synthesizes recent advances positioning whey as (i) a fermentation substrate for lactic acid bacteria, yeasts/fungi, and microalgae, enabling the production of functional biomass, organic acids, bioethanol, exopolysaccharides, enzymes, and wastewater bioremediation; (ii) a platform for postbiotic generation, supporting cell-free preparations with functional activities; and (iii) a food-grade encapsulating material, particularly through whey proteins (β-lactoglobulin, α-lactalbumin), which can form emulsions, gels, and films that protect biotics and bioactive compounds during processing, storage, and gastrointestinal transit. We analyze key operational variables (whey type and pretreatment, supplementation strategies, batch and continuous cultivation modes), encapsulation routes (spray drying, freeze-drying, and hybrid protein–polysaccharide systems), and performance trade-offs relevant to industrial scale-up. Finally, we outline future directions, including precision fermentation, mixed-culture processes with in situ lactase activity, microfluidics-enabled encapsulation, and life-cycle assessment, to integrate product yields with environmental performance. Collectively, these strategies reframe whey from a high-impact waste into a circular bioeconomy resource for the food, nutraceutical, and environmental sectors. Full article

Carvacrol, a phenolic monoterpene predominantly found in Origanum species, has been reported to exhibit antimicrobial, anti-inflammatory, antioxidant, and cytotoxic effects. Formulations such as Vacrol and S-Mix, enriched with carvacrol and complementary essential oil compounds, may enhance therapeutic efficacy while reducing toxicity. Essential oil components were analyzed via GC-MS. Cell viability was assessed using the sulforhodamine B (SRB) assay at different concentrations and incubation periods. An in ovo chorioallantoic membrane (CAM) assay was performed to investigate tumor volume changes and histopathological alterations. Vacrol and S-Mix demonstrated concentration- and time-dependent cell viability-attenuating effects in MDA-MB-231 cells, with significant reductions in viability at higher concentrations (1–10 mM). In ovo, S-Mix induced ~40% reduction in tumor volume and promoted apoptotic morphology compared to controls. Combined effects of carvacrol with α-pinene, eugenol, and β-terpineol likely contributed to enhanced bioactivity. These findings support further preclinical and mechanistic investigations to validate their therapeutic potential. Full article

Background/Objectives: The objective was to analyze the effects of Dipeptidyl Peptidase-4 (DPP-4) inhibitors on glycemic control, insulin dose, and preservation of β-pancreatic function (C-peptide) in patients with type 1 diabetes mellitus (T1DM). Methods: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with a search in the PubMed database. Five randomized clinical trials evaluating the use of different DPP-4 inhibitors in patients with T1DM were selected, measuring parameters including glycated hemoglobin (HbA1c), C-peptide, time in glycemic target/range (TIR), and daily insulin dose. Results: HbA1c showed significant reduction in some studies and no significant alterations in others. TIR increased in one study (~77.87% → ~84.40%). C-peptide showed variable effects across studies. The insulin dose did not show a substantial reduction. Conclusions: DPP-4 inhibitors demonstrated modest benefits for glycemic control and preservation of β-cell function in T1DM, but these effects were inconsistent due to methodological heterogeneity. Standardized studies are needed to define beneficial subgroups and long-term efficacy. Full article

Magnetic nanoparticles (MNPs) are widely applied in biomedicine, including bioimaging, drug delivery, and cell tracking. As central mediators of immune surveillance, macrophages phagocytize foreign substances, rendering their interactions with MNPs particularly consequential. During MNP uptake, macrophages undergo cytoplasmic remodeling that can lead to morphological alterations. Although prior studies have predominantly focused on MNP uptake efficiency and cytotoxicity, systematic quantitative assessments of macrophage morphological alterations following MNP treatment remain scarce. In this study, phase-contrast microscopy images of macrophages before and after MNP treatment were analyzed using unsupervised variational autoencoder (VAE)-based frameworks. Specifically, the β-VAE, β-total correlation VAE, and multi-encoder VAE frameworks were employed to extract latent representations of cellular morphology. The analysis revealed that MNP-treated macrophages exhibited pronounced structural alterations, including membrane expansion, central density shifts, and shape distortions. These findings were further substantiated through quantitative evaluations, including effect size analysis, kernel density estimation, latent traversal, and difference mapping. Collectively, these results demonstrate that VAE-based unsupervised learning provides a robust framework for detecting subtle morphological responses of macrophages to nanoparticle exposure and highlights its broader applicability across varied cell types, treatment conditions, and imaging platforms. Full article

Black spot disease substantially impairs both the aesthetic quality and commercial viability of affected Pingguoli pears. Previous studies have shown that Alternaria alternata and A. tenuissima are the pathogens that cause black spot disease. Essential oils represent novel alternatives to synthetic fungicides to control these pathogens. This study extracted Artemisia sieversiana essential oil (AsEO) by hydro-distillation using a crystal tower pure dew essential oil machine. The chemical compositions of AsEO were analyzed via gas chromatography–mass spectrometry (GC–MS). A total of 42 compounds were detected. 1,8-cineole, trans-caryophyllene, (1R,4S)-1,7,7-trimethylbicyclo [2.2.1] heptan-2-yl acetate, (±)-camphor, and β-myrcene were identified as the five main constituents. Moreover, the antifungal activity of AsEO was assessed against black spot on Yanbian Pingguoli pear in China. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were determined as 0.10% (v/v) and 0.12% (v/v), respectively. Scanning electron microscopy (SEM) analysis revealed that treatment with AsEO induced significant morphological aberrations in A. alternata and A. tenuissima mycelia, including surface roughening, hyphal collapse, and loss of structural integrity. Concurrently, a marked increase in alkaline phosphatase (AKP) enzyme activity and electrical conductivity was observed, a key indicator of cell wall and plasma membrane permeabilization and damage. When the concentration of AsEO was less than 120 µg/mL, there was no toxicity to keratinocytes (HaCaTs) and skin fibroblasts (NHSFs). In summary, this study provides a theoretical basis for the development of AsEO as a fungicide against black spot disease on Pingguoli pear in China. Full article

Despite antiretroviral therapy, HIV proteins, such as Tat, persist in tissues, driving chronic inflammation. Cervical inflammation in females not only accelerates HIV progression but also increases the risk of other STIs; hence, understanding the underlying factors/regulators is vital. However, Tat-induced cervical inflammation and its regulation are hitherto poorly understood, which we investigated using TZM-bl cells. Tat stimulation in these cervical epithelial cells significantly increased the expression of various inflammatory mediators, including cytokines (IL-1β, TNF-α, IL-6, IL-17a, GM-CSF), chemokines (MIP-1α, MIP-1β), adhesion molecules (ICAM-1, P-Selectin, E-Selectin), and ROS. Further upregulation of inflammatory mediators (NF-κB, IRAK-4) along with TLR7 was observed in Tat-stimulated cells. Interestingly, Tat stimulation decreased miR-204-5p expression in these cells, suggesting a role in regulating Tat-mediated inflammatory processes. Using a gain-of-function approach, we further observed that the overexpression of miR-204-5p reduced the expression of IL-1β, TNF-α, IL-6, MIP-1α, MIP-1β, ICAM-1, P-Selectin, and ROS in the Tat-stimulated TZM-bl cells, along with NF-κB, IRAK-1, and IRAK-4. Using Western blotting and luciferase assays, miR-204-5p was further shown to directly target NF-κB. Here, we report that HIV-1 Tat stimulation in cervical epithelial cells downregulates hsa-miR-204-5p, thereby activating the pro-inflammatory TLR7/NF-κB axis, highlighting its relevance to understanding mechanisms underlying cervical inflammation. Full article

Polydopamine (PDA) surface coatings are widely used in biomedical engineering to enhance cell–substrate interactions; however, their effects on cancer-cell behavior remain unclear. In this study, we investigated how PDA-coated two-dimensional (2D) culture surfaces influence oncogenic traits of human prostate cancer (PC) cells in vitro. Using LNCaP, DU145, and PC3 cell lines, we found that PDA-coated substrates markedly increased the adhesion, migration, invasion, proliferation, and colony formation in a dose- and time-dependent manner. PDA exposure also induced epithelial–mesenchymal transition (EMT), upregulated cancer stem cell markers (CD44, CD117, CD133, Sox2, Oct4, and Nanog), and elevated expression of metastasis- and chemoresistance-associated molecules (MMP-2, MMP-9, MDR1, and MRP1). Mechanistically, PDA coatings enhanced integrin α₂β₁-associated cell adhesion, accompanied by increased focal adhesion kinase (FAK) phosphorylation and downstream activation of JNK signaling. Pharmacological inhibition of integrin α₂β₁ (BTT-3033), FAK (PF573228) and JNK (SP600125) effectively abrogated PDA-induced malignant phenotypes and restored chemosensitivity to cabazitaxel, cisplatin, docetaxel, curcumin, and enzalutamide. Collectively, these findings identify PDA-coated surfaces as a simple, efficient, and reductionist in vitro platform for studying adhesion-mediated signaling and phenotypic plasticity in PC cells, while acknowledging that further validation in three-dimensional (3D) and patient-derived models will be required to establish in vivo relevance. Full article

Osteoarthritis (OA) is the most common multifactorial joint disease characterized by progressive cartilage degradation and impaired tissue repair. Osteochondral defects represent a major clinical challenge within OA, as damage to cartilage and underlying bone can initiate degenerative changes and contribute to joint deterioration. The Wnt/β-catenin signaling pathway plays an important role in OA pathogenesis, and its dysregulation contributes to chondrocyte catabolism and cartilage loss. NOTUM, an extracellular Wnt inhibitor, has emerged as a potential therapeutic modulator capable of restoring signaling balance and promoting cartilage homeostasis. This study aimed to evaluate the efficacy of NOTUM compared with hyaluronic acid (HA), human adipose-derived mesenchymal stromal cells (hAd-MSCs), and Colchicine in a rabbit osteochondral defect model relevant to osteoarthritis. Twenty-seven New Zealand White rabbits underwent standardized femoral condyle injury and received single-dose treatments. Serum levels of cartilage biomarkers—Procollagen Type IIA N-terminal Propeptide (PIIANP) and Cartilage Oligomeric Matrix Protein (COMP)—were measured by ELISA at 4, 6, and 8 weeks post-surgery, and histological repair at week 12 was assessed using the modified O’Driscoll scoring system. NOTUM treatment significantly increased PIIANP and decreased COMP levels compared with HA, indicating enhanced cartilage synthesis and reduced degradation. Histological scores confirmed superior surface morphology and tissue composition in NOTUM-treated joints. These findings suggest that NOTUM performs a protective and regenerative effect through Wnt/β-catenin modulation, supporting the conclusion that it enhances osteochondral defect repair and motivating further studies of NOTUM as an OA therapy. Full article

New nano-biomaterials for specific dentistry applications have been developed thanks to contributions from materials science. The present work aims to characterize the physicochemical properties of a composite nanomaterial scaffold in block form for maxillofacial bone regeneration applications. The scaffold was composed of block-shaped elements and consisted of a mixture of nano-hydroxyapatite, β-tricalcium phosphate, and type I collagen of bovine origin. Collagen I molecule is biodegradable, biocompatible, easily available, and a natural bone matrix component. The biomaterial was analyzed using a range of methods, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), chemical composition microanalysis, and X-Ray diffractometry (XRD). The wettability was measured. This was carried out by measuring the contact angle of a 0.9% NaCl solution on the surface. Differential scanning calorimetry (DSC) was used to measure the phase transformation temperatures. In the SEM and TEM analyses, it was possible to identify the layers of the materials and, with microanalysis, quantify their chemical composition. The XRD spectra showed the presence of nano-hydroxyapatite and ß-TCP. Wettability testing revealed that the material is highly hydrophilic, and BM-MSC culture analyses demonstrated that the biomaterial can promotes cell adhesion and interaction. The higher wettability is due to the higher density of the porous material observed in the SEM analysis. The results of the DSC testing showed that the sample analyzed undergoes endothermic transitions and transformation between 25 and 150 °C. The first phase transformation during heating occurs at 61.1 °C, which is above body temperature. The findings demonstrated that the composite was devoid of any contamination arising from manufacturing processes. It can be concluded that the n-HA/β-TCP and type 1 collagen are free of manufacturing contaminants. They also have high wettability, which increases the spreading of body fluids on the biomaterial’s surface and its interactions with cells and proteins. This makes them suitable for clinical application. Full article

Neurodegeneration—driven by oxidative stress, chronic inflammation, and protein aggregation—underlies disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and stroke. Current pharmacological treatments are largely symptomatic and do not restore lost neural circuitry, motivating regenerative approaches. Mesenchymal stem cells (MSCs) provide neurotrophic and immunomodulatory benefits and can support synaptic repair, yet robust conversion into mature, electrophysiologically functional neurons remain challenging and often depends on complex inducer cocktails with translational limitations. Crocin, a saffron-derived carotenoid, is reported to enhance neurogenesis and neuroprotection in preclinical models through pathways including Wnt/β-catenin, Notch1, CREB/BDNF, and modulation of GSK-3β, while reducing apoptosis and inflammatory signaling. Here, we synthesize evidence supporting crocin’s neuroprotective and proneurogenic activity and propose a testable hypothesis that crocin-based or crocin-modified formulations could be evaluated as adjuncts to guide MSC neuronal lineage commitment. Importantly, direct evidence that crocin alone can drive MSC trans-differentiation into fully functional neurons is currently insufficient; future work should define functional benchmarks (electrophysiology, synaptogenesis, and phenotypic stability) and rigorously validate safety, dosing, and delivery strategies for neuroregenerative translation. Full article

Sinensetin, a polymethoxylated flavone abundant in citrus fruits, has been recognized for its broad biological activities and wide use in traditional medicine around the world. Emerging clinical evidence from flavonoid-enriched orange juice interventions indicates antioxidant and anti-inflammatory effects, aligning with extensive preclinical data. In this review, we explored in vitro and in vivo findings on the anti-inflammatory and anticancer actions of sinensetin and delineated the underlying cellular pathways, especially in terms of proposed targets for sinensetin. In inflammatory settings, sinensetin attenuates NF-κB activation, lowers pro-inflammatory cytokines (e.g., TNF-α, IL-6), and enhances antioxidant defenses, supporting its reported antioxidant, anti-bacterial, anti-viral, and anti-obesity properties. Across multiple tumor models, sinensetin suppresses oncogenic signaling—including β-catenin, PI3K/AKT, VEGF, NRF2, P53, and MKK6—concomitant with reduced proliferation, migration, and survival signaling. We further discuss emerging immunological effects, including modulation of innate immune cell activation and cytokine production, which may contribute to tumor microenvironment reprogramming and inflammation resolution. Together, these mechanistic insights position sinensetin as a promising lead for chemopreventive and adjunct therapeutic strategies. Our efforts aim to provide insights into the future translational development and clinical evaluation of sinensetin and its derivatives. Full article

Atherosclerosis is a chronic, multifactorial vascular disease and the leading global cause of cardiovascular morbidity. Its development reflects interconnected disturbances in lipid metabolism, endothelial function, inflammation, smooth muscle cell (SMC) phenotypic switching, and extracellular matrix remodeling. Genetic predisposition, including monogenic disorders such as familial hypercholesterolemia and polygenic risk variants, modulates disease susceptibility by altering lipid homeostasis as well as inflammatory and thrombotic pathways. Epigenetic regulators and noncoding RNAs, such as histone modifications, microRNAs, and long noncoding RNAs, further shape gene expression and link environmental cues to vascular pathology. Endothelial injury promotes lipoprotein retention and oxidation, triggering monocyte recruitment and macrophage-driven foam cell formation, cytokine secretion, and necrotic core development. Persistent inflammation, macrophage heterogeneity, and SMC plasticity collectively drive plaque growth and destabilization. Emerging insights into immune cell metabolism, intracellular signaling networks, and novel regulatory RNAs are expanding therapeutic possibilities beyond lipid-lowering. Current and evolving treatments include statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, anti-inflammatory agents targeting interleukin-1 beta (IL-1β) or NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), and advanced approaches such as gene editing, siRNA, and nanoparticle-based delivery. Integrating multi-omics, biomarker-guided therapy, and precision medicine promises improved risk stratification and next-generation targeted interventions. This review summarizes recent molecular advances and highlights translational opportunities for enhancing atherosclerosis prevention and treatment. Full article