The myotendinous junction (MTJ) is a critical interface connecting skeletal muscle and tendon, responsible for transmitting contractile forces and ultimately enabling musculoskeletal movement. Due to its complex architecture, the MTJ is particularly susceptible to injury under conditions of excessive stretching, high-impact loading, aging and neuromuscular disorders such as muscular dystrophies. Despite its significant physiological role, research on the MTJ remains limited, primarily due to the challenges associated with obtaining human tissue samples. This limitation underscores the urgent need for advancedin vitromodels that can accurately replicate tissue-specific features. In this work, we developed a human-derived 3D MTJ-like model using the rotary wet-spinning technology. Human primary pericytes and human tendon derived stem cells were spatially patterned within the extruded hydrogel fibers in a consecutive manner to form highly integrated and anisotropically aligned biomimetic multicellular tissue constructs. Upon maturation, immunofluorescence analysis confirmed the presence of tendon and muscle-tissue specific markers including collagen type I, collagen type III, tenascin, tenomodulin and myosin heavy chain, respectively. Specifically, cellular organization recapitulated the interdigitated architecture typical of the MTJ native microenvironment. Moreover, the expression of collagen type VI, thrombospondin 4, and collagen type XXII, along with the polarized localization of paxillin and neural cell adhesion molecule 1 at the myotube-tendon interface, confirmed the establishment of a highly specialized junctional niche characterized by active cell-matrix interactions and cytoskeletal anchorage. Collectively, our biomimetic 3D model could offer a promising platform for the in-depth investigation of musculoskeletal development, pathophysiological processes, and the advancement of targeted therapeutic strategies.

Introduction: Established differences between young versus adult dermal fibroblasts characteristics and functions have been previously reported, which are due to various changes in skin cells with aging such as cellular senescence, etc. However, a comparison of human neonatal versus adult dermal fibroblasts has not been investigated in the production of collagen type I along with testing estrogenic stimulatory compounds like phytoestrogens (equol and its isomers) or the primary natural steroid hormone, 17β-estradiol in short-term cultures. Methods: Experiment 1 tested neonatal human dermal fibroblasts exposed to R-equol, racemic equol, S-equol or 17β-estradiol at 10 nM for 48 hours. Experiment 2 tested adult skin cells in tri-culture (epidermal keratinocytes; dermal fibroblasts and epidermal melanocytes in a 1:1:1 ratio) exposed to R-equol, racemic equol, S-equol or 17β-estradiol at 10 nM or 50 nM for 48 hours. Results: Collagen type I levels in neonatal fibroblasts (in controls and under estrogenic stimulation) displayed a significantly greater robust response compared to the adult tri-cultured cells with the same estrogenic treatments. In general, the neonatal cells compared to adult cells showed more than a seven-fold increase in controls levels and more than an eight-fold increase in the various treatments, however, there were no significant differences among the treatments. Conclusion: The findings of this study should encourage investigators to clearly state the age of human fibroblasts that are utilized in experimental reports, since evidently the results are dependent upon the age of the donor tissue/cells or age range of the derived human dermal cells.

Males with chronic kidney disease (CKD) experience worse outcomes than females, a difference not fully explain ed by comorbidities or sociocultural factors. We explored whether sex-based differences in biomarkers could account for this difference in risk. Our study included 1,680 male and 1,204 female participants with non-dialysis-dependent CKD and 84 controls from NURTuRE-CKD, a prospective multicentre cohort study. Twenty-one biomarkers relating to kidney injury and fibrosis, inflammation, and cardiovascular stress were measured. Outcomes were kidney failure (estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2 or kidney replacement therapy) and all-cause mortality. Multivariable Cox and Fine and Gray models assessed outcomes by sex. ANCOVA compared biomarker values between males and females adjusted for eGFR and urine albumin to creatinine ratio (UACR). Sex differences in biomarker concentrations were observed in both controls and CKD participants. In male controls, higher levels of urinary Vascular Endothelial Growth Factor, Tissue Inhibitor of Metalloproteinases-1 and blood Neutrophil Gelatinase-Associated Lipocalin, soluble Cluster of Differentiation 40, soluble Cluster of Differentiation 40 Ligand, soluble Tumour Necrosis Factor Receptor 1, Monocyte Chemoattractant Protein-1, and High-Sensitivity Cardiac Troponin T were observed. In males with CKD, additionally higher levels of urine Collagen Type I Alpha 1, blood Kidney Injury Molecule-1, Growth Differentiation Factor-15, and N-terminal pro-B-type Natriuretic Peptide. were noted, while females with CKD showed higher urinary Osteoactivin, KIM-1, Matrix Metalloproteinase-9 and blood Fibroblast Growth Factor-23, concentrations. In Cox proportional hazards models adjusted for demographics, kidney function, comorbidities, social factors, and medications, male sex was associated with a higher risk of kidney failure (hazard ratio (HR) 1.28, 95% confidence interval (CI): 1.09-1.50) and mortality (HR 1.29, 95% CI: 1.05-1.60). Male sex was no longer associated with higher risk after adjustment for biomarker differences, kidney failure (HR 1.18, 95% CI: 0.97, 1.43) and mortality (HR 1.17, 95% CI: 0.98, 1.58). Male sex was associated with a higher risk of kidney failure and mortality, despite adjustment for demographic, clinical, and treatment factors. Males had higher levels of inflammatory and extracellular matrix deposition biomarkers. In contrast, females showed higher levels of matrix turnover and degradation markers. After adjustment for these biomarker differences, the elevated risk associated with male sex was eliminated, suggesting a biological basis for the observed sex difference in outcomes.

Collagen is a protein that helps maintain the structural integrity and functionality of connective tissue. Collagen hydrolysate, which has recently gained popularity due to its high bioavailability, has attracted attention due to its reported benefits, such as improving skin health, relieving joint pain, and reducing signs of ageing. This review aims to compile and categorize 28 well-researched and well-known, as well as less popular, types of collagens, and investigate their relationship with physiological processes and diseases. It also examines how collagen affects ageing and its potential impact on various health conditions. Collagen hydrolysate is a food ingredient known for its support of collagen synthesis and a wide range of health benefits, such as antioxidant, anti-inflammatory, and antihypertensive effects. Types I, II, and III collagen constitute 80–90 % of the human body. Collagen Types I through VII are most commonly associated with skin health, with other collagen types also playing a variety of roles in health and disease. Dietary supplements containing collagen hydrolysate have been shown to have positive effects, including reducing signs of ageing, maintaining skin health, reducing symptoms of joint disorders, and improving overall quality of life.

Background Dizziness/vertigo is a multifactorial neurological disorder with complex ge-netic and cellular bases, yet its molecular mechanisms remain unclear. Understanding how gene regulation contributes to dizziness/vertigo may reveal novel neurobiological and therapeutic insights. Methods We established a multi-omics integrative framework combining genome-wide association study (GWAS) data with expression quantitative trait loci (eQTL) from brain single-cell types, CD4+ T cells, oneK1K immune cells, and plasma. Two-sample Mendelian randomization (MR) and colocalization analyses were applied to identify causal genes. Single-cell RNA sequencing (scRNA-seq) of the auditory nerve was used to as-sess cell type–specific expression, intercellular communication, and pseudotime dynam-ics. Gene–gene interaction and drug–target networks were further constructed to identify potential therapeutic candidates. Results Six key genes—Activin A Receptor Type 2A (ACVR2A), Phospholipid Transfer Protein (PLTP), Androgen Dependent TFPI Regulating Protein (ADTRP), Methylenetetrahydrofolate Dehydrogenase (NADP + Dependent) 1 Like (MTHFD1L), Collagen Type VII Alpha 1 Chain (COL7A1), and Pantothenate Kinase 4 (PANK4)—showed strong causal and colocalization evidence for dizziness/vertigo. Single-cell analysis revealed distinct cell type–specific expression, with fibroblasts and adipocytes playing central roles in signaling and gene regulation. Pseudo-time trajectories indicated coordinated upregulation of ACVR2A, MTHFD1L, PANK4, and PLTP during later developmental stages. Interaction network analysis positioned these genes as major hubs, and DrugBank screening identified Sotatercept as a promising candidate targeting ACVR2A. Conclusion This integrative analysis links gene expres-sion regulation to dizziness/vertigo across neuroimmune and metabolic systems. The findings uncover coordinated molecular pathways underlying disease susceptibility and highlight novel therapeutic targets, providing a foundation for precision treatment strate-gies.

Application of Adipose-Derived Mesenchymal Stem Cell 3D Spheroid, Microblock, as a Skin Regeneration Therapy.

Inflammation plays a pivotal role in neonatal lung injury and is closely associated with the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants, although the underlying molecular mechanisms remain incompletely understood. Our study detected elevated serum levels of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in preterm neonates as early as postnatal day 1 among those who later developed moderate-to-severe BPD. In pulmonary fibroblasts, co-treatment. with IFN-γ and TNF-α significantly downregulated α-smooth muscle actin (α-SMA) and disrupted extracellular matrix (ECM) homeostasis, evidenced by reduced collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and elastin expression, but elevated fibronectin 1 (FN1) and matrix metalloproteinase-1. Furthermore, dual-cytokine exposure attenuated SMAD2/3 phosphorylation and nuclear translocation, while upregulating SMAD7. Parallel experiments using E19.5 fetal mouse lung explants recapitulated these changes, showing decreased COL1A1, elevated SMAD7, and BPD-like histopathological alterations, including alveolar simplification and enlarged airspaces. Mechanistically, IFN-γ and TNF-α synergistically promoted SMAD7 overexpression, which competitively bound to SMAD2/3 and suppressed TGF-β signaling, ultimately leading to ECM dysregulation. These data delineate a novel inflammatory axis impairing lung development, highlighting SMAD7 and TGF-β pathways as promising intervention targets.

This article addresses the unmet clinical need of scaffolds for bone regeneration that can combine osteogenic properties, such as the promotion of bone marrow stem cell differentiation into osteoblasts, with the ability to withstand cyclic loading. In our previous study, we demonstrated that discs of SiO2-CaOCME/poly(tetrahydrofuran)/poly(caprolactone) hybrids or their dissolution products can drive terminal osteogenic differentiation of human bone marrow stromal cells (h-BMSCs) in vitro. The current study shows that the 3D-printed hybrid scaffolds with physiologically relevant 3D architecture further promote h-BMSC osteogenesis. The 3D-printed scaffolds support spatially organized cell behavior in an environment mirroring conditions relevant to off-the-shelf implant applications. Primary cellular functions, including viability, adhesion, and proliferation, were maintained across 3D scaffold surfaces and within inter-strut regions. osteogenic commitment was evidenced by the upregulation of lineage-specific transcripts, hydroxyapatite deposition, and the organized assembly of extracellular matrix (ECM)proteins. Our results demonstrate that 3D-printed scaffolds drive osteogenesis by modulating cell metabolism, inducing osteogenic morphological transitions, and promoting the expression of osteocalcin and collagen type I alpha 1 chain, alongside hydroxyapatite matrix mineralization. Collectively, our findings highlight the SiO2-CaOCME/poly(tetrahydrofuran)/poly(caprolactone) scaffold's strong osteogenic properties-driven by composition, surface architecture, and ion release - and its promise for clinical bone regeneration.

Background/Objectives: Indocyanine green (ICG) is an FDA-approved, near-infrared fluorescent dye widely used for tumor imaging. This study aimed to evaluate the photodynamic efficacy and selectivity of ICG as a photosensitizer in photodynamic therapy (PDT) against MCF-7 breast cancer cells in 2D monolayers and 3D collagen-embedded cell cultures that simulate ECM diffusion, and to confirm direct generation of singlet oxygen (1O2) as the primary cytotoxic species. Methods: MCF-7 breast adenocarcinoma cells and HMEC normal mammary epithelial cells were cultured in 2D monolayers, with MCF-7 cells additionally grown in 3D collagen type I matrices to mimic tumor environments. Cells were incubated with 50 µM ICG for 30 min, washed, and irradiated with a 780 nm diode laser at 39.8 mW/cm2. Cell viability was quantified using the Muse® Count &amp; Viability assay at multiple time points, while ICG uptake and penetration were assessed via flow cytometry, fluorescence microscopy, and confocal imaging. Direct 1O2 production was measured through its characteristic 1270 nm phosphorescence using time-resolved near-infrared spectrometry. Results: ICG-PDT reduced MCF-7 viability to 58.3 ± 7.4% in 2D cultures (41.7% cell kill, p &lt; 0.0001) and 70.2 ± 10.7% in 3D cultures (29.8% cell kill, p = 0.0002). In contrast, normal HMECs maintained 91.0 ± 1.3% viability (only 9% reduction, p = 0.08), resulting in a therapeutic index of approximately 4.6. IC50 values in 2D MCF-7 cultures decreased over time from 51.4 ± 3.0 µM at 24 h to 27.3 ± 3.0 µM at 72 h. ICG uptake was higher in 2D (78%) than in 3D (65%) MCF-7 cultures, with diffusion in 3D collagen exhibiting linear depth-dependent penetration. Notably, the singlet-oxygen phosphorescence signal, though weak and requiring highly sensitive detectors, provided direct evidence of efficient 1O2 generation. Conclusions: ICG as a photosensitizer in photodynamic therapy using clinically compatible parameters is highly cytotoxic to MCF-7 breast cancer cells while largely sparing HMECs in 2D cell culture. Direct spectroscopic evidence confirms efficient 1O2 generation, which contributes significantly to the cytotoxicity. The reduced efficacy in 3D versus 2D models highlights the importance of penetration barriers also present in solid tumors. These results support further preclinical and clinical investigation of ICG as a dual imaging-and-therapy (theragnostic) agent for selective photodynamic treatment of breast cancer.

Submandibular saliva from male rats modulates osteogenic differentiation of bone marrow progenitor cells In Vitro.

Differential effects of type I, III, and V collagens on mammary epithelial development in vitro.

Microneedling accelerates burn wound healing and promotes collagen remodeling: Insights from a rodent model.

Exploring the relationship between gut microbiota-metabolite axis and Jiawei Danxuan Koukang's therapeutic effects in male rats with oral submucous fibrosis: A multi-omics analysis.

Escitalopram exposure compromises osteogenic potential of human osteoblastic cells.

Establishment of an animal model of shaft femoral pseudoarthrosis in rabbits.

Paeoniflorin suppresses cardiomyocyte pyroptosis and ameliorates diabetic cardiomyopathy by AMPK/Nrf2/NLRP3 pathway.

Abdominal aortic aneurysm: characteristics of extracellular matrix abnormalities caused by disorders of collagen types I and III and elastin.

Identification of collagen types in moon jellyfish and fabrication of fibrous hydrogels incorporating Ag nanoparticles

Soufeng Sanjie formula and its active ingredient formononetin alleviate osteoarthritis via PPARG-AKT-ERK1/2 promoted cartilage extracellular matrix anabolism.

PurposeTo investigate the longitudinal relationships between serum biomarkers of joint metabolism, knee injury, and Knee Injury and Osteoarthritis Outcome Score (KOOS) using novel methodologies.MethodsData were collected from military officers who enrolled as cadets between 2004–2009, with follow-up conducted between 2015–2017. Analyses included 234 officers who had no history of knee ligament/meniscal injury at the time of military academy matriculation, had serum biomarker measurements at matriculation and graduation, demographic data, and KOOS assessment at follow-up. Biomarkers included Collagen Type II (C2C) and Type I and II (C1,2C) collagenase-generated cleavage epitopes, C-terminal propeptide of Type II collagen (CPII), and C- and N-terminal telopeptides of type I collagen (CTX and NTX). Angle-based Joint and Individual Variation Explained (AJIVE) was used to determine demographic determinants of biomarker levels and individual modes of variation specific to biomarker levels at matriculation and graduation, stratified by sex.ResultsWe confirmed known associations of joint metabolism biomarkers with age in both sexes and with smoking in males. Matriculation biomarker data in males suggested a protective biomarker profile characterized by high cartilage synthesis and low cleavage of type I and II collagen in association with healthy KOOS scores at follow-up. CPII measured at matriculation was negatively associated with incident injuries after adjustment for smoking status (p = 0.03, logistic regression), confirming results from AJIVE.ConclusionThese exploratory analyses suggest that CPII alone, or in combination with other joint metabolism biomarkers, may help identify individual risk of knee injury.