Search Results (2,177)

Previous studies revealed that low expression of Selenoprotein S (SELS) could enhance osteogenic differentiation, but the underlying mechanisms remain unclear. In this study, we aimed to elucidate the role of SELS and its transcription-factor-based regulatory mechanism during osteogenic differentiation. In comparison with 12-week-old mice, which represent the stage of stable osteogenic differentiation, 3-week-old mice, representing the active ossification stage, showed significantly higher levels of SELS in the mandible. Transcriptomic analysis revealed that SELS is primarily associated with extracellular matrix organization and collagen biosynthesis during mandibular development. In bone marrow mesenchymal stem cells (BMSCs) with SELS knockdown, SP7 levels were elevated after 7 days of osteogenic induction in vitro. Consistently, immunohistochemical and immunofluorescence staining confirmed increased SP7 expression in the mandibles of 7-week-old Sels knockout mice. Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) analysis demonstrated that SP7 directly binds to the heat shock protein 47 (HSP47) promoter and negatively regulates its transcription. Consequently, upregulation of SP7 following SELS knockdown led to downregulation of HSP47 and concurrent upregulation of the SP7 downstream targets, collagen type I alpha 1 chain (COL1A1) and Secreted protein acidic and rich in cysteine (SPARC). SELS expression is upregulated during active osteogenesis. Low expression of SELS regulates osteogenic differentiation in a bidirectional and fine-tuned manner through the SP7–HSP47/COL1A1/SPARC axis. Full article

Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this study was to identify genetic variants associated with the development of osteoporosis in Korean premenopausal women. Subjects were recruited from the Anseong and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). Clinical and epidemiological characteristics were assessed, and participants were classified based on BMD values measured at the distal radius and mid-shaft tibia. Individuals with confounding risk factors such as low body weight, smoking, high alcohol consumption, steroid/hormone therapy, or relevant medical history were excluded. A total of 247 healthy controls and 57 osteoporosis patients were included. Genotyping was performed using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. Data were analyzed using the SNP and Variation Suite and PLINK, with quality control thresholds set at MAF ≥ 0.05 and HWE p ≥ 0.01. Functional annotation and protein structure predictions were performed using PolyPhen-2, SIFT, and PROVEAN. Genome-wide association analyses identified 113 single-nucleotide polymorphisms (SNPs) in 69 genes significantly associated with osteoporosis (p < 0.05) in both platforms, with 18 SNPs showing high cross-platform consistency (p < 0.01). Several of these genes were implicated in bone metabolism (e.g., ESRRG, PECAM1, COL6A5), vitamin D metabolism (e.g., NADSYN1, EFTUD1), skeletal muscle function (e.g., PACSIN2, ESRRG), and reproductive processes (e.g., CPEB1, EFCAB6, ASXL3). Notably, the CPEB1 rs783540 SNP exhibited the strongest association (p < 0.001) in both analyses. Our findings suggest that genetic polymorphisms in pathways related to bone metabolism, vitamin D signaling, muscle–bone interaction, and reproductive hormone regulation may contribute to the development of osteoporosis in Korean premenopausal women. These results provide a genetic basis for early identification of at-risk individuals and warrant further functional studies to elucidate the underlying mechanisms. Full article

Photobiomodulation (PBM) consists of applying low-level laser light to biological tissues, leading to modulation of cellular functions. PBM has recently gained much attention in the field of regenerative dentistry thanks to its powerful effect on tissue repair and regeneration. Dental pulp mesenchymal stem/stromal cells (DP-MSCs) represent the ideal targets in regenerative dentistry due to their ability to stimulate the regeneration of mineralized and soft tissues and the paracrine factors that they produce. Although there have been several studies evaluating the influence of PBM on DP-MSCs’ regenerative capacity, the results are conflicting, and there are few studies on the influence of PBM on the paracrine factors released by DP-MSCs. Therefore, the aim of this study was to investigate the effect of PBM, using different energy doses of laser irradiation, on the osteogenic capacity of DP-MSCs, focusing on changes in gene expression, mineralizing ability, and release of pro-osteogenic factors. DP-MSCs were irradiated in vitro and differentiated into an osteogenic phenotype. A cell viability assay, alizarin red staining, and TEM analysis were carried out to evaluate the effect of PBM on cell activity, morphology, and mineralization ability. The expression of the main osteogenesis-related markers Runx2, Col1A1, ALP, and BMP was measured to evaluate the influence of PBM on the ability of DP-MSCs to differentiate toward an osteogenic phenotype. The release of IL-6 and IL-8, which are mainly involved in bone remodeling processes, was investigated in the cell medium following PBM irradiation. The results showed a high level of cell viability, suggesting a lack of phototoxicity under the tested conditions. Furthermore, PBM had a significant effect on mineral deposition, IL-6 and IL-8 release, and expression of osteogenic markers. TEM analysis showed intracellular modifications linked mainly to mitochondria, the endoplasmic reticulum, and autophagic vesicles after PBM treatment. These findings demonstrated that the impact of PBM on the osteogenic potential of DP-MSCs is energy dose-dependent, supporting its potential as an effective strategy in regenerative dentistry, particularly for enhancing bone remodeling. Full article

Background: A trilayered collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HA) scaffold is used in clinical practice to treat osteochondral lesions, but the regeneration of the subchondral bone is still not satisfactory. Objective: The aim of this study was to test, in vitro, the osteoinductivity induced by the addition of bone morphogenetic protein-2 (BMP-2) or amorphous calcium phosphate granules with strontium ions (Sr-ACP), in order to improve the clinical regeneration of subchondral bone, still incomplete. Methodology: Normal human osteoblasts (NHOsts) were seeded on the scaffolds and grown for 14 days in the presence of human osteoclasts and conditioned medium of human endothelial cells. NHOst adhesion and morphology were observed with transmission electron microscopy, and metabolic activity was tested by Alamar blue assay. The expression of osteoblast- and osteoclast-typical markers was evaluated by RT-PCR on scaffolds modified by enrichment with BPM-2 or Sr-ACP, as well as on unmodified material used as a control. Results: NHOsts adhered well to all types of scaffolds, maintained their typical morphology, and secreted abundant extracellular matrix. On the modified materials, COL1A1, SPARC, SPP1, and BGLAP were more expressed than on the unmodified ones, showing the highest expression in the presence of BMP-2. On Sr-ACP-enriched scaffolds, NHOsts had a lower proliferation rate and a lower expression of RUNX2, SP7, and ALPL compared to the other materials. The modified scaffolds, particularly the one containing Sr-ACP, increased the expression of the osteoclasts’ typical markers and decreased the OPG/RANKL ratio. Both types of scaffold modification were able to increase the osteoinductivity with respect to the original scaffold used in clinical practice. BMP-2 modification seemed to be more slightly oriented to sustain NHOst activity, and Sr-ACP seemed to be more slightly oriented to sustain the osteoclast activity. These could provide a concerted action toward better regeneration of the entire osteochondral unit. Full article

Detection of defects on steel surface is crucial for industrial quality control. To address the issues of structural complexity, high parameter volume, and poor real-time performance in current detection models, this study proposes a lightweight model based on an improved YOLOv11. The model first reconstructs the backbone network by introducing a Reversible Connected Multi-Column Network (RevCol) to effectively preserve multi-level feature information. Second, the lightweight FasterNet is embedded into the C3k2 module, utilizing Partial Convolution (PConv) to reduce computational overhead. Additionally, a Group Convolution-driven EfficientDetect head is designed to maintain high-performance feature extraction while minimizing consumption of computational resources. Finally, a novel WISEPIoU loss function is developed by integrating WISE-IoU and POWERFUL-IoU to accelerate the model convergence and optimize the accuracy of bounding box regression. The experiments on the NEU-DET dataset demonstrate that the improved model achieves a parameter reduction of 39.1% from the baseline and computational complexity of 49.2% reduction in comparison with the baseline, with an mAP@0.5 of 0.758 and real-time performance of 91 FPS. On the DeepPCB dataset, the model exhibits reduction of parameters and computations by 39.1% and 49.2%, respectively, with mAP@0.5 = 0.985 and real-time performance of 64 FPS. The study validates that the proposed lightweight framework effectively balances accuracy and efficiency, and proves to be a practical solution for real-time defect detection in resource-constrained environments. Full article

The Kazakh horse, one of China’s indigenous primitive breeds, is renowned for its remarkable adaptability and distinctive physiological traits. The ovary is a vital reproductive organ in female animals, responsible for oocyte production and hormone secretion. However, limited research has been conducted on gene expression profiles in the ovarian tissue of equine species. To address this gap, the present study performed transcriptomic sequencing on ovarian tissues from 12 Kazakh horses in different physiological states. A total of 979 differentially expressed mRNAs were identified, including 619 upregulated and 360 downregulated genes. Among these, key genes such as COL1A1, LHCGR, KISS1, NTRK2, COL1A2, and THBS4 were identified as differentially expressed. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that 374 of these genes were primarily involved in ovarian steroidogenesis, the PI3K-Akt signaling pathway, and ECM-receptor interactions among 292 enriched pathways. This study provides a comprehensive transcriptomic profile of equine ovarian tissue, offering in-depth insights into differential gene expression and signal pathways associated with ovarian development in Kazakh horses, providing theoretical foundations and referential data for future research in equine ovarian development and reproductive studies. Full article

The stiffness of the extracellular matrix (ECM) plays a pivotal role in the progression of osteoarthritis (OA), particularly by promoting hypertrophic differentiation of chondrocytes, which hinders cartilage regeneration and accelerates pathological ossification. This study aimed to investigate how substrate stiffness modulates hypertrophic chondrocyte behavior and whether it can reverse their phenotype towards a more stable, chondrogenic state. A series of tunable polydimethylsiloxane (PDMS) substrates with stiffnesses ranging from 78 to 508 kPa were fabricated to simulate varying mechanical microenvironments. Hypertrophic chondrocytes were cultured on these substrates, and their morphology, nuclear architecture, gene/protein expression, and mechanotransductive signaling pathways were systematically evaluated. After 7 to 21 days of culture, the chondrocytes on stiffer matrices exhibited enlarged nuclei, increased cytoskeletal tension, and enhanced focal adhesion signaling. This corresponded with the upregulation of osteogenic and hypertrophic markers such as RUNX2, COL10A1, and COL1A1. In contrast, cells on softer substrates (78 kPa) displayed reduced nuclear YAP localization, higher levels of phosphorylated YAP, and significantly increased expression of COL2A1 and SOX9, indicating reversion to a chondrogenic phenotype. Furthermore, differential activation of Smad1/5/8 and Smad2/3 pathways was observed depending on matrix stiffness, contributing to the phenotype shift. Matrix stiffness exerts a significant regulatory effect on hypertrophic chondrocytes via YAP-mediated mechanotransduction. Soft substrates promote phenotype reversion and cartilage-specific gene expression, offering a promising biomechanical strategy for cartilage tissue engineering and OA intervention. Full article

Facial aging is a multifactorial process involving changes in bone, fat compartments, ligaments, muscles, and skin. Collagen biostimulators, including synthetic agents and autologous platelet concentrates, have gained attention for facial rejuvenation. Injectable platelet-rich fibrin (i-PRF), a second-generation autologous concentrate, has shown promising regenerative properties due to its natural composition and growth factors. Cosmetic peptides, such as palmitoyl pentapeptide-4 (Matrixyl) and Tetrapeptide-21 (GEKG), are also studied for their ability to stimulate collagen synthesis and remodel the extracellular matrix. This in vitro study examined the potential synergistic effects of i-PRF combined with Matrixyl or GEKG on human dermal fibroblast viability, proliferation, and ECM-related gene expression. Fibroblasts were cultured under six conditions: control, i-PRF alone, Matrixyl alone, GEKG alone, i-PRF + Matrixyl, and i-PRF + GEKG. Viability and proliferation were assessed via MTT, crystal violet, and RealTime-Glo™ assays. Gene expression of COL1A1, FN1, and HAS1 was measured using RT-qPCR. The combinations, especially i-PRF + GEKG, led to increased cell viability and upregulated ECM-related genes at 72 h. These effects were stronger than the individual treatments, suggesting synergistic effects, especially with GEKG. These findings highlight the clinical potential of combining autologous platelet concentrates with bioactive peptides for dermal regeneration. Further preclinical and clinical studies are warranted. Full article

Coccidioides species are thermally dimorphic fungal pathogens that cause coccidioidomycosis (Valley Fever) primarily in North and South America. Coccidioides grow as hyphae that differentiate into arthroconidia, which can be aerosolized upon soil disturbance, and inhaled by the mammalian host to cause pulmonary infections with occasional dissemination to other organs. In the context of mouse models, current methods of infection include intranasal, intravenous, and intraperitoneal delivery of the arthroconidia into mice. To explore an aerosol route of infection, we compared the intranasal method with aerosolization using the Glass-Col Inhalation Exposure System (IES). Infection with a dose of 2 × 10⁶ CFU/mL, nebulized in 5 mL of PBS, but not in water, was able to infect mice, albeit inconsistently, compared to intranasal challenge. Arthroconidia were detected inside the IES after the nebulization and decontamination cycles. These studies highlight some of the challenges with aerosolization of Coccidioides arthroconidia and serve as a reminder about biosafety considerations for use of the IES to aerosolize pathogens. Full article

Klebsiella pneumoniae is an important pathogen associated with multidrug resistance and virulence in both human and animal populations. While its prevalence and resistance patterns are well documented in clinical settings, data on K. pneumoniae in food-producing animals remain scarce. This study aimed to isolate and characterize multidrug-resistant K. pneumoniae strains from healthy rabbits raised for human consumption, with a focus on antimicrobial resistance genes, plasmid content, and associated mobile genetic elements. A total of 295 fecal samples were collected from rabbits across 20 commercial farms in northern Portugal. Isolates were confirmed using MALDI-TOF MS, tested for hypermucoviscosity, and subjected to antimicrobial susceptibility testing (EUCAST). Whole-genome sequencing (WGS) was performed to determine sequence types (STs), resistance genes, plasmids, and resistance determinants for metals and biocides. Six K. pneumoniae isolates were recovered, showing extensive antimicrobial resistance profiles, including ESBL genes such as bla_CTX-M-15, bla_SHV-28, and bla_TEM-1. The most frequent ST was ST307. Multiple genes resistant to heavy metals were identified. Plasmid analysis revealed the presence of IncFII, IncN, and ColRNAI types. Network analysis showed clusters of genetically related isolates and highlighted shared resistance mechanisms. The presence of multidrug-resistant K. pneumoniae in healthy rabbits destined for human consumption underscores the zoonotic potential of this species and the need for surveillance in the animal–food–human interface. These findings contribute to a better understanding of resistance ecology in the context of One Health. Full article

In this study, we present analysis of TESS photometry, spectral energy distribution (SED), high-resolution spectroscopy, and spot modeling of the ${\alpha }^2$ CVn-type star AL Col (HD 46462). The primary objective is to determine its fundamental physical parameters and investigate its surface activity characteristics. Using TESS short-cadence (120 s) SAP flux, we identified a rotational frequency of 0.09655 ${\mathrm{d}}^{-1}$ ($P_{\mathrm{rot}}=10.35733$ d). Wavelet analysis reveals that while the amplitudes of the harmonic components vary over time, the strength of the primary rotational frequency remains stable. A SED analysis of multi-band photometric data yields an effective temperature ($T_{\mathrm{eff}}$) of 11,750 K. High-resolution spectroscopic observations covering wavelengthrange 4500–7000 Å provide refined estimates of $T_{\mathrm{eff}}$ = 13,814 ± 400 K, $logg$ = 4.09 ± 0.08 dex, and $\upsilon sini$ = 16 ± 1 km s⁻¹. Abundance analysis shows solar-like composition of O ii, Mg ii, S ii, and Ca ii, while helium is under-abundant by 0.62 dex. Rare earth elements (REEs) exhibit over-abundances of up to 5.2 dex, classifying the star as an Ap/Bp-type star. AL Col has a radius of $R=3.74\pm 0.48{\mathrm{R}}_{\odot }$, with its H–R diagram position estimating a mass of $M=4.2\pm 0.2{\mathrm{M}}_{\odot }$ and an age of $0.12\pm 0.01$ Gyr, indicating that the star has slightly evolved from the main sequence. The TESS light curves were modeled using a three-evolving-spot configuration, suggesting the presence of differential rotation. This star is a promising candidate for future investigations of magnetic field diagnostics and the vertical stratification of chemical elements in its atmosphere. Full article

Osteoarthritis (OA) is the most common joint disorder worldwide. Autologous chondrocyte implantation (ACI) is an established treatment for articular cartilage defects of the knee, but its effectiveness in OA is still under investigation. In this study, we investigated the effects of a newly developed mammalian-derived collagen matrix, NC-Col, on the proliferation, migration, adhesion, and gene expression of human articular cartilage-derived chondrocytes from OA patients in vitro, using proliferation assays, wound healing assays, adhesion assays, RT-qPCR, and RNA sequencing, respectively. In addition, the effects of NC-Col were compared with three different commercially available collagen matrices, and the underlying molecular mechanisms through which NC-Col influences these cellular behaviours were explored. Our results showed that NC-Col, used as a coating matrix, enhances cell proliferation, maintains the phenotype, and upregulates Proteoglycan 4 (PRG4) in human articular cartilage-derived chondrocytes. Inhibition of the PI3K-Akt signalling pathway was found to be involved in some of these effects. In conclusion, our findings suggest that NC-Col collagen may offer new strategies for improving therapeutic outcomes in OA, particularly in the context of ACI. Full article

Wound healing is a complex process in which TGFβ plays a key role. Previous studies have shown that syringin, a phenylpropanoid glycoside present in lilac bark (Syringa vulgaris L.), stimulates TGFβ expression in human monocyte-derived macrophages in addition to inhibiting the secretion of pro-inflammatory cytokines. Here, we investigated the effect of syringin on migration, invasion, and TGFβ production, as well as the effect on the release of pro-inflammatory cytokines in human dermal fibroblasts (NHDF) and keratinocytes (HaCaT) and its mechanism of action. NHDF and HaCaT cells were treated with the tested compound (12.5–100 µM), and a scratch assay was performed. The effect of migration using modified Boyden chambers was analyzed. TGFβ and IL-6 release were also assessed using ELISA kits. Cell proliferation was assessed using MTT and BrdU incorporation tests, while cytotoxicity was assessed using a neutral red uptake test. Smad2 and Smad3 phosphorylation were assessed using Western Blotting. ACTA2, COL1A1, and TIMP3 expression was analyzed using qPCR. Cells treated with syringin showed an increase in invasion potential in the scratch assay. A significant increase in skin fibroblast migration through the porous membrane was also observed. Syringin increased TGFβ release and inhibited IL-6 release by NHDF and HaCaT cells. No effect of syringin on cell proliferation or cytotoxic effects was observed. Western blot analysis showed significant activation of Smad2 and Smad3 in the presence of syringin in NHDF cells, but not in HaCaT. Quantitative PCR analysis revealed a strong increase in ACTA2 and COL1A1 gene expression in fibroblast cells treated with syringin. The present study demonstrated that syringin present in S. vulgaris stem bark increased dermal fibroblasts and keratinocytes’ wound healing function through activation of cell migration. Full article

The areca nut (AN) is chewed by approximately 600 million people worldwide. Among AN chewers, ~5% develop oral submucosal fibrosis (OSF), a progressive fibrotic disorder of the oral cavity. OSF is characterized by subepithelial fibrosis and mucosal rigidity, leading to restricted mouth opening, difficulty in mastication, deglutition, and speech. These impairments severely compromise oral hygiene and routine dental care, diminishing patients’ quality of life. At least 4% of OSF patients develop oral cancer. The prevalence of OSF correlates with AN chewing, particularly when accompanied by other risk factors such as tobacco use. The International Agency for Research on Cancer has identified chronic chemical and mechanical irritation of the oral mucosa from AN chewing as a major cause of OSF. The active chemical ingredients of AN include alkaloids such as arecoline, flavonoids, and tannins. Of these, arecoline is considered the most potent fibrogenic agent. In vitro, arecoline induces cultured fibroblasts to differentiate into highly contractile α-smooth muscle actin (α-SMA)-expressing myofibroblasts, the effector cells of fibrosis, and to express profibrotic markers and mediators, including transforming growth factor-β 1 (TGF-β1) and cellular communication network factor 2 (CCN2), which is associated with malignant progression of OSF. In vivo, mice exposed to AN extract or arecoline show submucosal collagen accumulation and myofibroblast differentiation, concomitant with upregulated pro-fibrotic gene (TGF-β1, Col1A1, α-SMA) expression. Although myofibroblasts can be seen in OSF patient-derived samples, substantial disease heterogeneity exists, which has thus far hindered the generation of high-quality data necessary to gain insights into underlying mechanisms and disease progression. Consequently, treatment options for OSF are limited and primarily symptomatic. Collectively, evidence from human and animal studies establishes OSF as an AN-induced fibrotic disorder and underscores the urgent need for mechanism-focused research to identify reliable diagnostic markers and therapeutic targets to address its growing global burden. Full article

Halting liver fibrosis progression is a key goal in treating liver disease, yet effective antifibrotic drugs remain unavailable. This study explores the use of precision-cut liver slices (PCLS) as an ex vivo model to evaluate new therapies. Researchers tested how different oxygen levels affect viability, tissue integrity, and inflammatory response in PCLS from healthy and fibrotic rats. Fibrotic PCLS maintained their pathological gene signature under 40% oxygen and responded to inflammatory stimuli, indicating preserved functionality. Exposure to high oxygen levels increased oxidative stress and pro-inflammatory gene expression. Cirrhotic PCLS showed early signs of reduced viability and the upregulation of fibrosis-related genes including Col1α2, Col3α1, αSMA, Timp1, Timp2, Mmp2, Pdgfrβ, Nos2, Cox2, and Il6. Lipopolysaccharide (LPS) exposure induced the marked overexpression of Nos2 and Il1β mRNA and confirmed the model’s responsiveness to external injury. Fibrotic PCLS retained fibrogenic activity for at least 48 h. Additionally, the adenoviral delivery of a dominant-negative soluble PDGFRβ effectively blocked fibrotic signaling. Human fibrotic PCLS also remained viable for 72 h and showed an increased mRNA expression of fibrosis markers such as COL1A1, αSMA, and MMP2. These results highlight the potential of PCLS as a promising platform for future therapeutic testing, pending further validation with functional interventions. Full article