Search Results (7,544)

Background: Diabetic wound healing has always been a clinical challenge with minimal response or efficacy to standard treatment. This study aims to assess the therapeutic potential of hypoxia-induced extracellular vesicles (hy-EVs) produced by human umbilical cord mesenchymal stem cells (HUCMSCs) to treat diabetic wounds. Methods: HUCMSCs were isolated from umbilical cord tissue, cultured under hypoxic conditions to induce the release of extracellular vesicles (EVs) and compared with normoxia-induced extracellular vesicles (n-EVs). We assessed the functions of hy-EVs on human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs) in vitro. Simultaneously, we analyzed the pro-angiogenic effects of hy-EVs, their effects on macrophage polarization, and their ability to scavenge endogenous reactive oxygen species (ROS). In addition, a diabetic wound model was established to assess the curative effect of hy-EVs in diabetic wound healing. Results: We found by in vitro study that hy-EVs markedly improved the functional activities of HSFs, thus significantly promoting wound repair. Remarkably, it was determined that hy-EVs greatly enhanced the proliferation and migration ability as well as the angiogenic ability of HUVECs, while promoting the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial-generation-associated factor A (VEGFA), and platelet endothelial adhesion molecule (CD31), which suggested that hy-EVs can effectively activate the HIF-1α pathway to promote angiogenesis. Above all, we found that hy-EVs promoted the expression of CD206 while decreasing the expression of CD86, suggesting that hy-EVs could induce macrophages to shift from M1-type (pro-inflammatory) to M2-type (anti-inflammatory), thereby modulating the inflammatory response. Additionally, hy-EVs inhibited ROS production in both HSFs and HUVECs to reduce oxidative stress. In vivo results showed that hy-EVs enhanced collagen deposition and angiogenesis, modulated macrophage polarization, and inhibited immune response at the wound spot, which significantly enhanced diabetic wound healing. Conclusions: Our study shows that hy-EVs significantly promote angiogenesis through activation of the HIF-1α pathway, modulate macrophage polarization and attenuate cellular oxidative stress, possibly through delivery of specific miRNAs and proteins. Our discoveries offer a key theoretical basis and potential application to develop novel therapeutic strategies against diabetes-related tissue injury. Full article

Snail mucus has shown promise in promoting wound healing; however, its active components and their mechanisms of action are poorly understood. In the present study snail mucus was isolated and hydrolyzed using trypsin to obtain snail mucus active peptides (SMAPs). SMAPs were analyzed using liquid chromatography–mass spectrometry, and bioinformatics screening. Among the screened peptides, an active 12-amino-acid peptide, EK-12 (molecular weight: 1366.2 Da), was identified and synthesized using a solid-phase peptide synthesis approach. In vitro functional verification showed that EK-12 significantly promoted endothelial cell proliferation, migration, and tube formation. An in vivo experiment demonstrated that EK-12 significantly accelerated wound healing in mouse models. Pathological examination revealed a significantly upregulated expression of CD31 and vascular endothelial growth factors in wound tissues, suggesting that this is the mechanism by which the active peptide promotes angiogenesis and wound healing. Thus, snail mucus-derived peptides hold strong potential for development as therapeutic agents for wound healing. Full article

Cholangiocarcinoma (CCA), an aggressive biliary tract cancer whose prevalence is rising, particularly in Thailand, is marked by elevated oxidative stress driven by chronic inflammation, parasitic infections, and dysregulated redox signaling. This study investigates the anticancer potential of tiliacorinine using a silico approach, including drug-likeness, ADMET, network pharmacology, molecular docking, and dynamics simulations. Tiliacorinine and 216 predicted targets were identified, with 79 overlapping CCA-related genes from GeneCards. GO and KEGG analyses revealed involvement in cell migration, membrane structure, kinase activity, and cancer-associated pathways. Network and PPI analyses identified ten key targets, including SRC, HIF1A, HSP90AA1, NFKB1, MTOR, MMP9, MMP2, PIK3CA, ICAM1, and MAPK1. Tiliacorinine showed the strongest affinity for MTOR (−10.78 kcal/mol, K_i = 12.62 nM), binding at the same site as known inhibitors with superior energy and specificity, supported by hydrogen bonding at ASP950 and hydrophobic interactions. Tiliacorinine also demonstrated strong binding to SRC, MMP9, and MAPK1. Molecular dynamics simulations revealed stable binding of tiliacorinine to MTOR, particularly at residues ASP950, TRP1086, and PHE1087. Comparative analysis with the MTOR–GDC-0980 complex confirmed consistent interaction patterns, reinforcing the structural stability and specificity of tiliacorinine. These results highlight its strong pharmacological potential and support its candidacy as a promising lead compound for cholangiocarcinoma therapy. Full article

C1q/TNF-related protein 6 (CTRP6) is emerging as a critical regulator of cancer biology with direct implications for clinical outcomes. Across a wide spectrum of malignancies, CTRP6 plays a central role in coordinating key oncogenic processes and linking metabolic, inflammatory, and signaling pathways that drive tumor progression. While CTRP6 generally promotes oncogenic behavior in cancers such as hepatocellular carcinoma, lung cancer, and clear cell renal cell carcinoma, conflicting findings have been reported in gastric cancer and oral or head and neck squamous cell carcinoma, where its tumor-promoting versus tumor-suppressive roles remain unresolved. CTRP6 has been shown to modulate fundamental processes including angiogenesis, ferroptosis, proliferation, apoptosis, migration, invasion, and inflammation. These effects are primarily mediated through activation of the PI3K/AKT and MEK/ERK signaling pathways, which are central to tumor growth, metastasis, and therapeutic resistance. Beyond its mechanistic roles, CTRP6 demonstrates potential as a diagnostic and prognostic biomarker, with altered expression patterns linked to cancer initiation, progression, and patient survival. Inhibition of CTRP6 in preclinical models enhances ferroptotic cell death and suppresses tumor progression, highlighting its promise as a therapeutic target. By consolidating current evidence from multiple cancer models, this review provides a comprehensive overview of CTRP6’s contributions to oncogenesis and underscores its dual potential as both a biomarker and a therapeutic target. Advancing a deeper understanding of CTRP6 in specific tumor contexts will be critical for unlocking its clinical utility and may open new opportunities to improve diagnosis, optimize therapeutic strategies, and ultimately enhance patient outcomes. Full article

The railway architectural heritage in Jilin Province, as a significant component of Northeast China’s modern railway network, demonstrates how construction techniques, cultural integration, and social transformation have evolved throughout different historical periods. In this study, we conducted a systematic survey of 474 railway heritage buildings along the province’s main line. In order to quantitatively classify the spatiotemporal distribution characteristics of the heritage sites, we used five key Geographic Information System (GIS) methods—kernel density estimation, nearest neighbour index, spatial autocorrelation, standard deviational ellipses, and mean centre analysis—along with information entropy, relative richness, and the Bray–Curtis dissimilarity index. We continued our binary logistic regression using four prerequisite parameters—location, structure, architecture, and function—which contribute to the prerequisite, fundamental, and driving factors of architectural heritage. We concluded that local culture shapes geopolitics, population migration triggers economic conservation, and design trends carry ideology. These three factors intertwine to influence architecture and spatial patterns. Compared with previous studies, this research fills the gap concerning the architectural characteristics of towns at various lower-and mid-level stations, as well as the construction activities during the affiliated land period. This study provides a systematic framework for analysing railway heritage corridors and supports their sustainable conservation and reuse. Full article

Fibroblasts determine repair quality during skin-wound healing. Our previous study found that Activin B promotes keratinocyte proliferation and migration, facilitating re-epithelialization. However, specific mechanisms governing fibroblast function during wound healing remain unclear. Here, we aimed to elucidate the mechanism by which Activin B regulates fibroblast activity during skin-wound healing. Using a murine skin-wound model, we performed hematoxylin-eosin, immunohistochemical, and Masson’s trichrome staining to evaluate Activin B’s effects on granulation tissue formation, angiogenesis, and collagen fiber synthesis. We assessed Activin B’s effects on fibroblast proliferation, migration, and collagen protein synthesis and investigated signaling pathway mechanisms in vitro. Animal experiments showed that Activin B accelerated wound healing by promoting granulation tissue regeneration and angiogenesis without affecting collagen fibers and Type I collagen synthesis. In vitro experiments demonstrated that Activin B modulates fibroblast proliferation and migration by activating JNK and ERK signaling pathways. Activin B may enhance angiogenesis by stimulating fibroblasts to secrete vascular endothelial growth factor, which induces dermal microvascular endothelial cell proliferation, promoting angiogenesis. Thus, we elucidated the dual regulatory paradigm of Activin B in fibroblasts; Activin B drives proliferation and migration via JNK/ERK signaling but does not directly regulate collagen synthesis. Full article

In response to escalating environmental concerns, the construction industry is under growing pressure to adopt sustainable practices. As a major consumer of natural resources and a significant emitter of greenhouse gases, it paradoxically holds the potential to become a leader in green transformation. This study investigates the development of innovative, fire-resistant, and alkali-activated hybrid binder foams incorporating recycled materials: fly ash, coal slag, and ground brick waste, as sustainable alternatives to traditional building materials. The fire resistance performance at a technical scale and the thermal behavior of fiber-reinforced, alkali-activated hybrid binder foams synthesized from recycled aluminosilicate precursors were determined. The properties of unreinforced composite were compared with the composites reinforced with merino wool, basalt fibers, polypropylene fibers, and coconut fiber. Small-scale fire-resistance tests revealed that merino wool-reinforced composites exhibited the best thermal insulation performance, maintaining structural integrity, that is, retaining shape and continuity without delamination or collapse for 83 min under fire exposure. Analyses combining chemical characterization (X-ray fluorescence) with microstructural methods (computed tomography and colorimetry) confirmed that fire performance is strongly influenced not only by fiber type but also by pore distribution, phase composition, and oxide migration under thermal loading. These findings demonstrate the potential of fiber-reinforced foamed, alkali-activated hybrid binder as eco-efficient, printable materials for fire-safe and thermally demanding construction applications. Full article

Anthropogenic activity seriously damages the environment. Cadmium, lead, and thallium are toxic elements that are especially hazardous for nature. In polluted air, they are present in the form of microparticles 2–3 μm in size and belong to the PM_2.5 fraction. Such particles can be transported over long distances, penetrate into water and dissolve, and then enter the food chain. This poses a severe threat to human and animal health due to the bioaccumulation of metals. Therefore, it is important to study the properties of toxic metals of this size. In this work, we developed a radiation–chemical method for obtaining microparticles of cadmium, lead, and thallium corresponding to the PM_2.5 fraction and studied their properties in aqueous solutions. In the absence of oxygen, the metals do not dissolve. Over time, they agglomerate and settle. When exposed to air, the particles quickly dissolve in water, usually within a few minutes. This process involves the disappearance of small particles and a decrease in the size of larger ones. The rate of dissolution increases in the Pb-Cd-Tl series. Cadmium dissolves approximately 4–5 times faster than lead, and thallium more than 10 times faster. Acidification of water accelerates this process. Studying the properties of microparticles of heavy metals is important for assessing their migration in the environment, health risks, and developing methods for preventing pollution. Full article

Background/Objectives: Endometrial cancer (EC), a malignancy arising from the uterine lining, is a leading gynecological cancer in developed countries. Syringic acid (SA), a naturally occurring phenolic compound, possesses various bioactivities including antioxidant, anti-inflammatory, chemoprotective, and anti-angiogenic properties. This study aimed to investigate the effects of SA on the proliferation and migration of RL95-2 EC cells, its protective role in normal endometrial stromal cells (HESCs), and the underlying molecular mechanisms. Furthermore, the potential synergistic anticancer effects of SA in combination with chemotherapeutic agents against EC were evaluated. Methods: Cell viability was assessed using nuclear fluorescence staining, the MTT assay, and clonogenic survival assay. Cell migration was evaluated through wound closure and Transwell migration assays. Gene expression levels were analyzed by the RT-PCR method. Results: SA significantly inhibited the proliferation of RL95-2 EC cells, with an IC₅₀ value of 27.22 μM. Co-treatment with SA and the chemotherapeutic agent doxorubicin (Dox) demonstrated an additive inhibitory effect. Mechanistically, both SA and the SA-Dox combination induced apoptosis by upregulating the expression of caspases-3, -8, and -9, increasing the expression of pro-apoptotic genes (Bax and Bad), and downregulating anti-apoptotic genes (Bcl-XL and Bcl-2). Cell cycle analysis revealed the downregulation of cyclin D and the upregulation of tumor suppressors p21 and p27, contributing to growth arrest. In addition, both SA and the combination treatment effectively suppressed cell migration by downregulating matrix metalloproteinases (MMPs) and β-catenin. SA treatment also induced the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and activated NF-κB signaling, leading to an elevated expression of inflammatory mediators such as COX-2 and iNOS. Furthermore, SA promoted oxidative stress in RL95-2 cells by inhibiting the Nrf2 pathway and reducing the expression and activities of antioxidant enzymes including catalase, glutathione peroxidase, and superoxide dismutase, thereby enhancing reactive oxygen species (ROS) accumulation. In contrast, in lipopolysaccharide-stimulated HESC cells, SA attenuated inflammation and ROS generation, indicating its selective cytoprotective role in normal endometrial cells. Conclusions: SA may serve as a promising adjuvant candidate to enhance chemotherapeutic efficacy while protecting normal cells by mitigating inflammation and oxidative stress. Full article

Artificial light at night (ALAN) is impacting sea turtle nesting around the globe by decreasing the nesting attempts, disorienting the sea turtle hatchlings while trying to find the sea, and disrupting hatchlings’ offshore migration. In the Mediterranean Sea, the shoreline of Kyparissia Bay is considered the most important nesting site for loggerhead sea turtles (Caretta caretta), with several thousand nests on an annual basis. The current study reports for the first time the exposure of the core 10 km of nesting area to ALAN pollution, evaluates the potential impact on sea turtle conservation, and discusses mitigation measures as coastal urbanization and touristic activity increase rapidly in the region. Our findings demonstrate that most of the core area was not impacted by ALAN pollution, although a specific region (Kalo Nero) was subjected to high illumination at night, leading to reduced sea turtle nests and potential threats to hatchlings. Full article

Pathological vascular remodeling—central to restenosis, atherosclerosis, and vasculo-proliferative diseases—depends on the phenotypic switching of vascular smooth muscle cells (VSMCs) from a quiescent, contractile state to a synthetic, proliferative program. Although the receptor tyrosine kinase c-Kit is implicated in proliferation, migration, and tissue repair, its role in VSMC plasticity has yet to be fully understood. Using c-Kit haploinsufficient mice subjected to right carotid artery ligation (CAL) and primary aortic VSMC cultures, we show that c-Kit is required for the contractile-to-synthetic transition. In vitro, c-Kit haploinsufficiency halved c-Kit expression, reduced 5-bromo-2′-deoxyuridine (BrdU) incorporation, and blunted platelet-derived growth factor BB (PDGF-BB)-induced repression of contractile genes. c-Kit–deficient VSMCs exhibited a senescence program with increased p16^INK4a/p21 expression and upregulated senescence-associated secretory phenotype (SASP) mediators. RNA-Seq of carotid arteries 7 days post-ligation revealed that wild-type arteries activated cell-cycle pathways and suppressed contractile signatures, whereas c-Kit-deficient carotid arteries failed to fully engage proliferative programs and instead maintained contractile gene expression. At 28 days post CAL in vivo, c-Kit haploinsufficiency produced markedly reduced neointima, fewer Ki67+ VSMCs, more p16^INK4a+ cells, and impaired re-endothelialization. Because progenitor-to-VSMC differentiation contributes to remodeling, we tested adult cardiac stem/progenitor cells (CSCs) as a model system of adult progenitor differentiation. Wild-type CSCs efficiently generated induced VSMCs (iVSMCs) with appropriate smooth-muscle gene upregulation; c-Kit–deficient rarely did so. Restoring c-Kit with a BAC transgene rescued both the smooth-muscle differentiation and proliferative competence of c-Kit-deficient iVSMCs. Collectively, our data identified c-Kit as a gatekeeper of reparative VSMC plasticity. Adequate c-Kit enables progenitor-to-VSMC commitment and the expansion of newly formed VSMCs while permitting injury-induced proliferation and matrix synthesis; reduced c-Kit locks cells in a hypercontractile, senescence-prone state and limits neointima formation. Modulating the c-Kit axis may therefore offer a strategy to fine-tune vascular repair while mitigating pathological remodeling. Full article

The volatile organic compounds (VOCs) are the main flavor constituents of different pig breeds, which have positive effects on the quality evaluation of pork. This study aimed to clarify the effects of lipid oxidation on characteristic VOCs in different breeds of pigs. The fatty acid composition and antioxidant characteristics of the Ningxiang (NX) pig, Rongchang (RC) pig, Duroc × Wujin (DW) pig, and Duroc × Landrace × Yorkshire (DLY) pig were determined. The VOCs from these four pig breeds were analyzed by gas chromatography–ion migration spectrometry (GC-IMS) and solid-phase micro-extraction–gas chromatography–olfactory mass spectrometry (SPME-GC-O-MS). A total of 49 volatile compounds were identified by GC-IMS, whereas GC-O-MS detected 97 volatile components, including aldehydes, alcohols, ketones, acids, and esters. Among these, aldehydes and alcohols were the predominant categories. The results showed that RC breed pork had the highest fatty acid content, whereas NX breed pork exhibited the highest antioxidant activity. Among the VOCs from these four pig breeds, tridecanal showed a strong positive correlation with antioxidant capacity (T-AOC) and vitamin E, which was mainly reflected in NX. Furthermore, the key VOCs across the different pig breeds were mainly related to unsaturated fatty acids, such as C20:3n6, C18:1n9c, and C18:2n6c. In conclusion, the antioxidant characteristics of NX pigs are closely associated with their unique volatile flavor profile, while the characteristic flavor compounds across different pig breeds are primarily influenced by the composition and oxidation of unsaturated fatty acids. Full article

Food-derived bioactive peptides are known to possess immunomodulatory properties, although their molecular mechanisms remain incompletely characterized. In this study, we investigated the immunoregulatory effects and underlying mechanisms of YPFPGPIH, a peptide derived from bovine β-casein, using the RAW264.7 macrophage model. Our results demonstrate that YPFPGPIH enhanced macrophage proliferation and phagocytosis in a dose-dependent manner and promoted chemotactic migration through the upregulation of monocyte chemoattractant proteins MCP-1 and MCP-3. Under lipopolysaccharide (LPS)-induced inflammatory conditions, YPFPGPIH significantly reduced the levels of pro-inflammatory mediators, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), while increasing the production of the anti-inflammatory cytokine interleukin-10 (IL-10), thereby reestablishing cytokine balance. Mechanistic studies revealed that YPFPGPIH inhibited LPS-induced activation of the NF-κB and MAPK pathways, as indicated by reduced nuclear translocation of p65 and decreased phosphorylation of ERK, JNK, and p38. Molecular docking analysis indicated strong binding affinities between YPFPGPIH and Toll-like receptors TLR2 and TLR4, suggesting the involvement of TLR-mediated signaling. Notably, YPFPGPIH downregulated inducible nitric oxide synthase (iNOS) expression and upregulated chemokine mRNA levels, reflecting its dual role in modulating inflammatory and migratory responses. These findings highlight YPFPGPIH as a multifunctional immunomodulatory peptide that fine-tunes macrophage activity through crosstalk between TLR, NF-κB, and MAPK signaling pathways. This study provides new insights for developing peptide-based therapeutics and functional foods aimed at managing inflammatory diseases. Full article

The availability of key precursors of alkali-activated binder (AAB) systems is declining, requiring sources. Calcined clays (CCs) stand out as a promising alternative due to their widespread accessibility. Although the properties of CC and blast furnace slag (BFS)-based two-part AABs have been well reported in the literature, the effect of minor additives on the properties of a one-part AAB system composed of CC and BFS remains unexplored. In this research, calcined magnesia (CM), aerial lime (AL), hydraulic lime (NHL), quicklime (QL), borax (BR), and zeolite (ZP) have been used as minor additives and incorporated into the AAB system at between 2% and 15%. The specimens were activated with sodium–metasilicate, and the fresh, physical, mechanical, durability and microstructural properties of mortars have been investigated. Key findings indicate that all minor additives, except for BR, enhanced the early- and later-age mechanical properties. Notably, 10% QL addition significantly increased compressive strength by up to 55% at 28 days (50.9 MPa), compared to the reference. BR and ZP usage eliminated the efflorescence formation without compromising other properties. Furthermore, incorporating QL, AL, CM, and BR markedly reduced the chloride permeability of the mortars and decreased D_nssm value by as much as 81%, compared to the reference. Full article

A corneal abrasion results from the disruption or loss of cells in the corneal epithelium. If inadequately treated, it can compromise visual clarity. The wound healing process of a corneal abrasion involves epithelial migration, proliferation and adhesion. Clitoria ternatea flower extract (CTE) is rich in flavonoids, anthocyanins and other bioactive compounds. It has antioxidant, anti-inflammatory and wound-healing properties. This study explores the potential of CTE to be used as a natural supplement to improve corneal wound healing. Phytochemical profiling via LC–MS identified a total of 51 distinct bioactive constituents. The anthocyanin content, quantified in terms of cyanidin-3-glucoside equivalent, was quantified at 33.06 mg per gram of extract. The extract exhibited 33.8% DPPH radical scavenging activity and a total polyphenol content equivalent to 24.14 mg/g gallic acid. Human telomerase-immortalized corneal epithelial (hTCEpi) cells maintained in keratinocyte basal medium were utilized to determine cytotoxicity and wound-healing effects. The optimal extract concentration of 0.08 mg/mL, quantified via MTT assay, resulting in enhanced cell viability. Scratch assays demonstrated a higher percentage of wound closure in the CTE-treated group at 6 and 12 h relative to the untreated group, with statistical significance (p < 0.05). The gene expressions of CK3 and Cx43, quantified via qRT-PCR, showed no significant differences between groups. However, within the CTE-treated group, CK3 expression increased at 12 h relative to 0 h and 6 h, and Cx43 expression rose significantly at 12 h compared with 0 h (p < 0.05). Immunofluorescence confirmed positive protein expression of both markers. These findings suggest that CTE possesses potent antioxidant properties and promotes corneal epithelial wound healing through upregulation of CK3 and Cx43 in vitro. Full article