Search Results (2,885)

Purpose: The reversible deviant in epigenomic modulations is the highlight of developing new anti-cancer drugs, necessitating the use of fisetin as an epigenetic modifier in the study. Methods: In silico and molecular studies were performed to analyze the modulatory effect of fisetin on various writers and erasers. Further, whole genome DNA methylation sequencing and expression studies were performed. Global DNA methylation-LINE 1 kit was used to check global DNA methylation. Additionally, the effect of fisetin on migration was evaluated by colony, scratch, and invasion assays and qPCR and protein expression studies of migration-related genes were carried out on HeLa cells. Results: In silico studies have supported that fisetin interacts with writers and erasers in their catalytic site and the simulation studies showed minimum fluctuations in energy and temperature over a 10 ns timescale indicating that these complexes are likely to remain stable. Fisetin (20–50 µM) dose-dependently inhibited DNA methyltransferases (DNMT), histone deacetyl transferases (HDAC), histone acetyl transferases (HAT), and histone methyltransferases (HMT) activities at 48 h, with inhibition ranging from 24 to 72% compared to the control. The expression and enzymatic activity of these proteins, along with various H4 and H3 modification marks, were observed to be altered following fisetin treatment at 48 h. Fisetin treatment reduced promoter methylation in various tumor suppressor genes ranging from 15.29% to 76.23% and leading to the corresponding reactivation of important tumor suppressor genes; however, it did not lead to any alteration in the global DNA methylation compared to untreated controls linked with the anti-migratory properties of fisetin as the percentage of migrated cells dropped from ~40% to ~8%. Conclusions: This study gives a mechanistic insight of fisetin as a potential epigenetic modifier in HeLa cells. Full article

Atractylenolides (ATs; mainly AT-I, II, and III), as one of the primary active components of the traditional Chinese medicine Atractylodes macrocephala, have demonstrated significant antitumorigenic effects against various cancer cells in both in vitro and in vivo studies. This review aims to systematically review the antitumorigenic effects, mechanisms, pharmacokinetics, and safety profile of ATs, aiming to contribute to clinical research and applications. To achieve this, a systematic literature search was conducted across multiple databases, and findings were synthesized narratively to provide a comprehensive overview of the current evidence. This review comprehensively discusses the antitumorigenic effects and mechanisms of ATs, including arresting tumor cell cycle progression, inducing programmed cell death (apoptosis, autophagy, and ferroptosis), inhibiting tumor angiogenesis, suppressing tumor migration and invasion, modulating the tumor immune microenvironment, and enhancing the efficacy of combination therapies. Additionally, their pharmacokinetic properties and safety profile are summarized, with a focus on their research and application prospects. ATs appear to be safe and reliable candidate anticancer agents in preclinical models, exhibiting potent antitumor efficacy both as monotherapy and in combination regimens. Preliminary clinical data from a small pilot study also indicated no signs of toxicity, but more extensive trials are needed to confirm their safety profile in humans. Further studies on their mechanisms are warranted to facilitate their development into clinically effective antitumor agents. Full article

As energy exploration and development continue to advance into deep and ultradeep formations, systematic studies of rock mechanical properties face significant challenges due to high core acquisition costs and sample damage under extreme conditions. To overcome these challenges, high-precision, minimally invasive, or non-destructive testing methods are urgently needed. This study systematically characterizes the microstructural features and mechanical heterogeneity of deep carbonate rocks from the Shunbei area by integrating XRD, SEM-EDS, and nanoindentation techniques. The results show that these rocks are primarily composed of a continuous calcite phase, with quartz as the secondary phase occurring in regional aggregates embedded within the calcite matrix. The two phases commonly exhibit an intergrown texture, and mineral distribution displays notable spatial heterogeneity and sample-to-sample variation. Nanoindentation tests reveal that the quartz phase exhibits excellent mechanical stability, with elastic moduli ranging from 70.6 to 101.8 GPa and hardness values between 10.8 and 13.5 GPa. The data are tightly clustered, indicating structural homogeneity and strong resistance to deformation. In contrast, the calcite phase shows lower and more scattered mechanical parameters, with elastic moduli of 27.4~76.0 GPa and hardnesses of 0.7~2.3 GPa, reflecting pronounced microscale heterogeneity. Furthermore, a strong negative correlation exists between hardness and maximum indentation depth, further confirming the dominant influence of mineral composition on local mechanical response. Notably, despite similar mineralogical compositions among samples A13, A15, and A18, their micromechanical performance follows the order A15 > A18 > A13, indicating that subtle differences in diagenetic history, crystal development, and local stress conditions can significantly affect rock mechanical behavior. Full article

This study presents a multifunctional theranostic platform based on anisotropic gold nanostars (AuNSs) functionalized with 2-thiouracil (2-TU) for cancer diagnostics and photothermal therapy (PTT). The unique plasmonic properties of AuNSs, combined with the anticancer and photothermal potential of 2-TU, were harnessed to create a system capable of simultaneous colorimetric biosensing and therapeutic action. Under dual-wavelength irradiation (660 nm and 525 nm), the AuNSs–2-TU conjugate demonstrated enhanced photothermal conversion efficiency, selective cancer cell targeting, and signal amplification, resulting in a significant reduction in the IC₅₀ for MCF-7 breast cancer cells. The system exhibited minimal cytotoxicity to normal fibroblasts (WS1), ensuring therapeutic precision. Compared to conventional spherical gold nanoparticles, this platform provides superior multifunctionality, including real-time biosensing with simple, naked-eye colorimetric readouts. These results highlight the potential of the AuNSs–2-TU conjugate as an innovative, minimally invasive nanotheranostic platform suitable for integrated cancer detection and treatment, particularly in resource-constrained settings. Full article

Background/Objectives: Empagliflozin (EMPA) was repurposed for Alzheimer’s disease (AD) treatment via buccal delivery, exploiting novel nanofibers (NFs) integrating chitosan (Cs), silk fibroin (Fb), and poly(lactic acid) (PLA). Methods: EMPA-loaded Cs/Fb/PLA NFs were electrospun in different formulations to optimize the formulation parameters. The optimized formulation was then investigated for its enhanced in vivo effect. Results: Optimized nanofiber diameters ranged from 459 ± 173 to 668 ± 148 nm, possessing bead-free morphology confirmed by SEM and satisfactory mechanical properties. EMPA was successfully well-dispersed in the polymer matrix as evidenced by FTIR, XRD, and drug content. The optimized NFs displayed a hydrophilic surface (contact angle < 90°), and biphasic drug release with sustained EMPA liberation (84.98% over 24 h). In vivo, buccal EMPA-Cs/Fb/PLA NFs in an AlCl₃-induced AD rat model significantly reduced brain-amyloid-β, phosphorylated tau, IL-1β, and AGER expression by 2.88-, 2.64-, 2.87-, and 2.50-fold, respectively, compared to positive controls, and improved locomotor activity (1.86-fold) and cognitive performance (T-maze) (4.17-fold). Compared to pure EMPA, the nanofiber formulation achieved further reductions in amyloid-β (1.78-fold), p-tau (1.42-fold), IL-1β (1.89-fold), and AGER (1.38-fold), with efficacy comparable to memantine. Histopathological examination revealed preservation of the hippocampal neuronal structure. Conclusions: The findings suggest EMPA-loaded Cs/Fb/PLA NFs as a promising non-invasive, sustained-release buccal delivery platform for AD therapy, offering multimodal neuroprotection through modulation of the Aβ–AGER–p-tau axis. Full article

Background: White spot lesions (WSLs) are characterized by enamel demineralization. Minimally invasive treatments using infiltrating resins, such as the commercially available Icon^®, are recommended. The need for such treatments justifies ongoing research into developing materials that can address existing limitations regarding strength, durability, and biocompatibility. Objectives: This study aimed to synthesize and characterize four novel nanobiomaterials by evaluating their physicochemical properties and biocompatibility compared to the commercial material Icon^®. Materials and methods: The recipes for the experimental nanobiomaterials NB3, NB6, NB3F, and NB6F contain varying proportions of TEGDMA, UDMA, HEMA, Bis-GMA, and HAF-BaF2 glass. Mechanical and physicochemical characteristics were evaluated, such as flexural strength, measured using the three-point test; water absorption and solubility; fluoride release; polymerization conversion; and residual monomers, assessed using High-Performance Liquid Chromatography (HPLC). In vitro cell viability was assessed via colorimetry using human dysplastic oral keratinocytes (DOKs). Results: NB6 and NB6F demonstrated the greatest polymerization potential. NB3 exhibited the lowest water absorption and solubility due to its hydrophobic nature. Additionally, the inclusion of UDMA enhanced the strength and elasticity of NB3 when compared to NB6. Among the samples with fluoride additives (NB3F and NB6F), the highest fluoride release on day 7 occurred with the material lacking UDMA. In contrast, the NB3F sample containing UDMA released the least amount of fluoride on the same day. In quantitative terms, NB3 and NB6F exhibited the lowest levels of residual monomers, whereas NB6 showed the highest levels. Both NB3 and NB6 were significantly better tolerated by the cells, showing higher cell viability compared to the commercial material Icon^®. Conclusions: The materials’ mechanical and physicochemical properties varied with component proportions, enabling identification of a suitable formulation for targeted clinical applications. Biocompatibility tests showed that the experimental NB3 and NB6 were better tolerated than Icon^®. Furthermore, the incorporation of filler particles improved the mechanical strength of the experimental nanobiomaterials. Full article

This article describes the microbiome of the outer ear and the earwax in the ear canal, which performs various protective functions against bacterial infections. This article is based on an analysis of literature gathered from databases including PubMed, Google Scholar, Web of Science, and Scopus, primarily from the last 15 years. The search strategy included MeSH terms: ear canal, microbiome, earwax, cerumen, antibacterial peptides, ear infections, biofilm. Only peer-reviewed articles were included. The natural ear canal microbiota provides so-called colonization resistance, which protects against invasion by pathogenic microorganisms. Earwax is composed primarily of keratin secreted by epithelial cells and substances secreted by sweat and apocrine glands. It plays a key role in the physiology of the ear canal, maintaining a low pH, limiting moisture, and exhibiting antimicrobial properties. Both an excess and a deficiency of earwax can lead to dysbiosis of the outer ear, and consequently to the development of various infections. In an era of increasing antibiotic resistance and the search for new solutions in the fight against pathogenic microorganisms, understanding the natural properties of earwax is becoming increasingly important. Full article

Glioblastoma (GBM), the most common, invasive, and chemoresistant form of adult primary brain cancer, is characterized by rapid cell proliferation, local invasiveness, and resistance to chemotherapy (e.g., temozolomide (TMZ)) and radiation therapy. Curcumin, a bioactive polyphenol derived from Curcuma longa, has exhibited exceptional anti-cancer properties, including anti-proliferative, pro-apoptotic, anti-inflammatory, and anti-angiogenic activities in a wide range of cancer models, including GBM. However, the clinical application of curcumin has been seriously limited by several challenges, including low water solubility, low bioavailability, rapid systemic clearance, and poor blood–brain barrier (BBB) penetration. To overcome these challenges, several nanocarrier systems to produce nanocurcumin have been developed, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, and micelles. These nanoformulations improve the solubility, stability, systemic circulation, and target-directed delivery of curcumin to glioma cells, thereby resulting in a high level of accumulation in the glioma microenvironment. On the other hand, this work is devoted to the potential of curcumin and nanocurcumin for the treatment of GBM. The article provides a detailed review of the major molecular targets of curcumin, such as NF-κB, STAT3, PI3K/AKT/mTOR, and p53 signaling pathways, as well as recent advancements in nanotechnology-based delivery platforms that improve drug delivery across the BBB and their possible clinical translation. We also include a thorough examination of the issues, limitations, and potential opportunities associated with the clinical advancement of curcumin-based therapeutics for GBM. Full article

Osteoarthritis (OA) is a prevalent chronic pain syndrome and a leading cause of disability worldwide, characterized by progressive deterioration of articular cartilage. This degradation leads to pain, swelling, inflammation, and eventual stiffness as the cartilage wears down, causing bone-on-bone friction. Current medical treatments primarily aim at pain relief; however, many interventions, especially invasive or surgical ones, carry risks of adverse outcomes. Consequently, intra-articular (IA) therapy, particularly hyaluronic acid (HA) injections, is widely adopted as a conservative treatment option. HA plays a crucial role in maintaining joint homeostasis by supporting proteoglycan synthesis and scaffolding, restoring optimal HA concentrations in synovial fluid, and providing chondroprotective and anti-inflammatory effects. In recent years, hydrogels composed of natural and synthetic materials have emerged as promising candidates for OA treatment. Our research focuses on the biosynthesis and characterization of novel hydrogel composites combining short peptide hydrogelators with aminated graphene oxide (a-GO) nanosheets functionalized with HA (a-GO-HA@Hgel). These a-GO-HA@Hgel nanocomposites are designed to facilitate the controlled release of HA into the extracellular matrix, aiming to promote cartilage regeneration and mitigate inflammation. The strategy is to exploit the oxygen-containing functional groups of GO nanosheets to enable covalent coupling or physical adsorption of HA molecules through various chemical approaches. The resulting a-GO-HA are incorporated within hydrogel matrices to achieve sustained and controlled HA release. We study the influence of a-GO-HA on the native hydrogel structure and its viscoelastic properties, which are critical for mimicking the mechanical environment of native cartilage tissue. Through this multidisciplinary approach combining advanced materials science and cellular biology, this work aims to develop innovative nanocomposite hydrogels capable of delivering HA in a controlled manner, enhancing cartilage repair and providing a potential therapeutic strategy for OA management. Full article

Saline water intrusion poses a major threat to groundwater security in arid and semi-arid regions, reducing freshwater availability and challenging sustainable water resource management. Accurate delineation of the fresh-saline water interface is therefore essential; however, conventional hydrochemical and laboratory-based assessments remain costly, invasive, and spatially limited. Resistivity methods have long been used to infer subsurface salinity, as low resistivity typically reflects clay-rich saline water and higher resistivity reflects freshwater-bearing sand or gravel. Yet, resistivity values for similar lithologies frequently overlap, causing ambiguity in distinguishing fresh and saline aquifers. To overcome this limitation, Dar–Zarrouk (D–Z) parameters are often applied to enhance hydrogeophysical discrimination, but previous studies have relied exclusively on one-dimensional (1D) D–Z derivations using vertical electrical sounding (VES), which cannot resolve the lateral complexity of alluvial aquifers. This study presents the first application of electrical resistivity tomography (ERT) to derive two- and three-dimensional D–Z parameters for detailed mapping of the fresh-saline water interface in the alluvial aquifers of Punjab, Pakistan. ERT provides non-invasive, continuous, and high-resolution subsurface imaging, enabling volumetric assessment of aquifer electrical properties and salinity structure. The resulting 2D/3D models reveal the geometry, depth, and spatial continuity of salinity transitions with far greater clarity than VES-based or purely hydrochemical methods. Physicochemical analyses from boreholes along the ERT profiles independently verify the geophysical interpretations. The findings demonstrate that ERT-derived 2D/3D D–Z modeling offers a cost-effective, scalable, and significantly more accurate framework for assessing fresh-saline water boundaries. This approach provides a transformative pathway for sustainable groundwater monitoring, improved well siting, and long-term aquifer protection in salinity-stressed alluvial regions. Full article

Inflammation is the body’s natural immune response to invasion by foreign pathogens and is closely linked to many diseases. Chronic inflammation, if not properly controlled, can pose serious health risks and even threaten life. Currently, the main anti-inflammatory drugs are classified into steroidal and non-steroidal anti-inflammatory drugs, but both have significant side effects that limit their clinical applications. α-Hederin, a pentacyclic triterpenoid saponin, is derived from various plants, including Pulsatilla chinensis, Hedera helix, and Nigella sativa. It has been reported that α-hederin can be used to treat both acute and chronic inflammatory diseases. However, it has poor water solubility and low bioavailability. This study shows that α-hederin can directly self-assemble into a hydrogel through hydrogen bonds and van der Waals forces, called He-Gel. The mechanical properties of He-Gel were further characterized using rheological and microrheological methods. Its self-assembly mechanism was comprehensively elucidated through a combination of spectroscopic analyses and computational chemistry. Furthermore, in vitro experiments showed that He-Gel exhibits lower cytotoxicity and more excellent anti-inflammatory activity compared to free α-hederin. In conclusion, this research provides a solution for the further development of α-hederin. Unlike conventional approaches that rely on polymers as drug carriers, this preparation method is both green and economical. More importantly, it highlights that direct self-assembly of natural small molecules represents a promising strategy for anti-inflammatory therapy. Full article

Heracleum sosnowskyi Manden., or H. sosnowskyi, of the Apiaceae was first cultivated in the USSR in 1947 as a potential fodder plant. Due to the development of cold-resistant cultivars and the characteristics of H. sosnowskyi, it quickly became feral. As a result, H. sosnowskyi began to spread as an aggressive invasive species in the 1970s and 1980s. By the 90s it had become an ecological disaster. As well as forming monocultures and displacing native species, H. sosnowskyi contains furanocoumarins, photosensitizing compounds that increase skin sensitivity to ultraviolet rays and cause severe burns. In addition, furanocoumarins have cytotoxic, genotoxic, mutagenic and estrogenic effects. H. sosnowskyi also contains essential oils, which are particularly active during flowering and can irritate the mucous membranes of the eyes and respiratory tract, as well as cause allergic reactions in the form of bronchospasm in people with asthma and hypersensitivity. When released in high concentrations, these biologically active compounds have an allelopathic effect on native plant species, displacing them and reducing biodiversity. As H. sosnowskyi is not native; the biologically active compounds it secretes have a xenobiotic effect, causing serious damage to the ecosystems it occupies. However, in parallel with these negative properties, furanocoumarins have been found to be effective in the treatment of cancer and skin diseases. Furanocoumarins possess antimicrobial antioxidant osteo- and neuroprotective properties. Essential oils containing octyl acetate, carboxylic acid esters, and terpenes can be used in the pharmaceutical industry as antiseptic and anti-inflammatory agents. Additionally, essential oils can be used as biofumigants and natural herbicides. A comprehensive approach allows H. sosnowskyi to be viewed in two ways. On the one hand, it is an aggressive alien species that causes significant damage to ecosystems and poses a threat to human health. On the other hand, it is a potentially valuable natural resource whose biomass can be used within the principles of the circular economy. It is hoped that the use of H. sosnowskyi for economic interests can be a partial compensation for the problem of its aggressive invasion, which is of anthropogenic origin. Full article

This study presents the development of a smart packaging material utilizing garlic-derived nitrogen-doped carbon dots (CDs) integrated into a whey protein–starch (WP-S) emulsion. The research aimed to create a real-time, non-invasive biosensor capable of detecting microbial spoilage. The synthesized CDs demonstrated strong pH-sensitive photoluminescence, exhibiting distinct changes in CIE coordinates and fluorescence intensity in response to varying pH values. The WP-S-CDs emulsion was tested against E. coli, S. aureus, and C. albicans. The results showed that the composite film provided a clear colorimetric shift and fluorescence quenching, both of which are directly correlated with microbial metabolic activity. The physical and electronic properties of the composite were investigated to understand the sensing mechanism. Scanning electron microscopy (SEM) of the dried film revealed that the WP-S-CDs system formed a more porous structure with larger pore sizes (3.63–8.18 µm) compared to the control WP-S film (1.62–6.52 µm), which facilitated the rapid diffusion of microbial metabolites. Additionally, density functional theory (DFT) calculations demonstrated that the incorporation of CDs significantly enhanced the composite’s electronic properties by reducing its band gap and increasing its dipole moment, thereby heightening its reactivity and sensitivity to spoilage byproducts. In a practical application on apples, the WP-S-CDs coating produced a visible red spot, confirming its function as a dynamic sensor. The material also showed a dual-action antimicrobial effect, synergistically inhibiting C. albicans while exhibiting an antagonistic effect against bacteria. These findings validate the potential of the WP-S-CDs emulsion as a powerful, multi-faceted intelligent packaging system for food quality monitoring. Full article

Chronic diabetic wounds are often characterized by persistent hypoxia and poor healing outcomes, highlighting the need for regenerative grafts that not only promote tissue repair but also provide insights into the wound microenvironment. In this study, we introduce a novel strategy for diabetic ulcer treatment through the development of a structurally personalized skin graft. The graft is fabricated via 3D bioprinting of natural porcine skin extracellular matrix (psECM) and integrated with microsensors for oxygen monitoring. We established a porcine skin decellularization protocol that efficiently removed cellular components, while preserving the integrity of the ECM, as verified by DNA quantification and scanning electron microscopy. The resulting psECM bioink demonstrated rheological properties suitable for 3D printing, which depended on psECM concentration and exhibited temperature-responsive gelation behavior. Incorporation of LiNC-BuO oxygen microsensors into the bioink enabled real-time, non-invasive oxygen level monitoring within the printed constructs. Both in vitro and in vivo studies confirmed the cytocompatibility and low immunogenicity of the psECM-based grafts with embedded microsensors. Moreover, the 3D bioprinting technology enabled the manufacturing of grafts tailored to match individual wound geometries. The technological proof of concept presented herein for this multifunctional platform, which integrates the regenerative benefits of ECM scaffolds with advanced biosensing capabilities, represents a promising approach for enhancing future therapeutic outcomes in the management of diabetic ulcers. Full article

The glioblastoma multiforme (GBM) microenvironment, characterized by hypoxia and inflammation, is a principal driver of therapeutic resistance. Although natural compounds such as Caffeic Acid Phenethyl Ester (CAPE) are investigated for their anti-neoplastic properties, their bioactivity within the distinct metabolic landscape of the tumor core remains to be fully elucidated. Taking advantage of the recognized immunomodulatory properties of CAPE and its ability to cross the blood–brain barrier, we hypothesized that hypoxia is a key factor determining its effect on glioma-associated inflammation. To test this hypothesis, we investigated the immunomodulatory effects of CAPE on the human astrocytoma cell line CCF-STTG1. Cells were cultured under normoxic and hypoxic conditions, stimulated with lipopolysaccharide (LPS) and interferon-alpha (IFN-α) to induce an inflammatory phenotype, and subsequently treated with CAPE. The secretion profiles of key cytokines (IL-8, IL-10, IL-26) and matrix metalloproteinases (MMPs) as well as pentraxin-3 (PTX-3) were then quantified using a multiplex immunoassay. Our results revealed a striking functional dichotomy. Under normoxic conditions, CAPE suppressed the secretion of key pro-inflammatory mediators. Conversely, under hypoxic conditions, CAPE significantly amplified the release of pro-tumorigenic factors, including the mediator facilitating tumor cell migration, invasion, and angiogenesis such as IL-8 and the invasion-associated metalloproteinase MMP-2. These findings suggesting that hypoxia may fundamentally reprograms the immunomodulatory potential of CAPE. However, due to limitations of study requires further validation in a broader panel of glioblastoma models. Full article