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Objectives To investigate the effects of FGF2 on the proliferation and collagen production of hypoxia-induced scleral fibroblasts(SF) and explore the downstream signaling pathways it regulates. Methods 5% O2 was used to stimulate the SF to induce myopia SF model for 24 hours. RT-qPCR was used to detect FGF2 mRNA expression, and Western blot analysis was used to check FGF2 protein expression. The Cell Counting Kit-8(CCK8), flow cytometry, and Western blot were used to assess cell proliferation vitality, cell apoptosis, and the expression of collagen metabolism-related proteins collagen I, MMP2, and pathway proteins PERK, p-PERK, EIF2α, EIF2α, and ATF4. Results Hypoxia increased FGF2 mRNA and protein expression(P < 0.01), activated the PERK/EIF2α/ATF4 pathway(P < 0.001), inhibited SF cell proliferation(P < 0.001) and collagen I expression(P < 0.001), while induced MMP2 expression(P < 0.001) and apoptosis(P < 0.001). Knocking down FGF2 or treating with PERK inhibitor GSK2606414 reversed the effect of hypoxia on SF cells, increased cell proliferation( P < 0.001) and collagen Ⅰ expression( P < 0.01), and suppressed cell apoptosis( P < 0.01) . Mechanism study revealed that FGF2 knockdown dampened the activation of PERK/EIF2α/ATF4 pathway. Conclusion FGF2 affects hypoxia-induced SF proliferation and collagen metabolism by regulating the activation of PERK/EIF2α/ATF4 signaling pathway. [ABSTRACT FROM AUTHOR]

To investigate the effects of 21 days of bed rest immobilization (with and without exercise and nutrition interventions) on type II collagen biomarker concentrations in healthy individuals. Twelve healthy male participants (age 34.2 ± 8.3 years; body mass index 22.4 ± 1.7 kg/m²) were exposed to 6 days ambulatory baseline data collection (BDC), 21 days head-down-tilt bed rest (HDT, CON) + interventions (HDT + resistive vibration exercise (2 times/week, 25 minutes): RVE; HDT + RVE + whey protein (0.6 g/kg body weight/day) and bicarbonate supplementation (90 mmol KHCO 3 /day: NeX), and 6 days of re-ambulation (R) in a cross-over designed study. The starting HDT condition was randomized (CON-RVE-NEX, RVE-NEX-CON, NEX-CON-RVE). Blood and urine samples were collected before, during, and after HDT. Serum concentrations (s) of CPII, C2C, C1,2C, and urinary concentrations (u) of CTX-II and Coll2–1NO2 were measured. Twenty-one days of HDT resulted in increased sCPII (p < 0.001), sC2C (p < 0.001), and sC1,2C (p = 0.001) (highest increases: sCPII (+24.2% - HDT5), sC2C (+24.4% - HDT7), sC1,2C (+13.5% - HDT2). sC2C remained elevated at R+1 (p = 0.002) and R+6 (p < 0.001) compared to baseline. NeX led to lower sCPII (p < 0.001) and sC1,2C (p = 0.003) compared to CON. uCTX-II (second void and 24-hour urine) increased during HDT (p < 0.001, highest increase on HDT21: second void +82.8% (p < 0.001); 24-hour urine + 77.8% (p < 0.001). NeX resulted in lower uCTX-II concentrations in 24-hour urine (p = 0.012) compared to CON. Twenty-one days of bed rest immobilization results in type II collagen degradation that does not recover within 6 days of resuming ambulation. The combination of resistive vibration exercise and protein/bicarbonate supplementation minimally counteracted this effect. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lumbar disc degeneration is a common disease that causes lower back pain and lower limb neurological symptoms. The balance of collagen metabolism plays an important role in maintaining the stability of the intervertebral discs. OBJECTIVE: To review the research progress in the imbalance of collagen metabolism in intervertebral disc degeneration. METHODS: The first author searched for relevant literature published before May 2024 in CNKI, PubMed and Web of Science databases. Search terms were “degenerative disc disease,” “collagen metabolism,” “collagenase family,” “collagen synthesis related factors,” and “collagen breakdown related factors” in Chinese and English. Seventy-six articles were finally included for review. RESULTS AND CONCLUSION: In the process of intervertebral disc degeneration, the balance of collagen metabolism plays a crucial role in maintaining the stability of the normal intervertebral disc. When intervertebral disc degeneration occurs, a large amount of pro-inflammatory factors, collagenase, and oxidative stress reactions occur in the intervertebral disc, which increases the breakdown of collagen in the intervertebral disc. At the same time, it inhibits the generation of growth factors, collagen synthase, and collagen synthesis-related factors, resulting in a decrease in collagen synthesis in the intervertebral disc. The combined effect of the above two conditions disrupts the balance of collagen metabolism in the intervertebral disc, further exacerbating the process of intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]

Aim. To study the relationship of biomarkers of collagen metabolism and systemic inflammation with left ventricular (LV) remodeling in patients with stable coronary artery disease (CAD) and obstructive sleep apnea (OSA).Material and methods. The study included 195 patients with stable CAD, of which 63 without OSA and 132 patients with combination of CAD and OSA. The mean age of patients was 63,4±3,7 years. Biomarkers of collagen metabolism and systemic inflammation were assessed by determining the concentration of matrix metalloproteinase (MMP)-9, tissue inhibitor of matrix metalloproteinase-1, monocyte chemoattractant protein-1 (MCP-1) and calculating the neutrophil-to-lymphocyte (NLR) and platelet-tolymphocyte ratio (PLR). Echocardiography was performed according to a standard protocol.Results. There were no significant differences in systemic inflammation parameters (MCP-1, NLR, PLR) between the group of patients with CAD and CAD with mild OSA and a significantly higher level of MCP-1, NLR, PLR in more severe OSA. In patients with CAD and severe OSA, the eccentric LV remodeling was diagnosed in 75% of individuals, while the concentric type was diagnosed in only 25%.Conclusion. In patients with stable CAD, the more severe the OSA, the more pronounced systemic inflammation (MCP-1, NLR, PLR), and there are higher proportion of eccentric LV hypertrophy, which may be associated with an imbalance of fibrosis markers (high concentration of MMP-9 with an almost unchanged level of tissue inhibitor of MMP-1).

The review summarizes information on possibilities of plant preparations use for collagen structure and metabolism disturbances correction. Biologically active compounds of plant origin can both stimulate and inhibit the biosynthesis of various types collagens, accelerate or slower down their catabolism, regulate the activity of enzymes involved in the collagen's metabolism. Most of the studied compounds realize their effects simultaneously by several mechanisms. Among them, the most common are the direct influence of the substance on the processes of collagen genes expression and indirect influence via TGF-beta1- pathway. In addition, a fairly common are effects on collagen synthesis by changing organism's pools of free amino acids (as the starting compounds for this protein synthesis) and by regulation of hydroxylases (performing collagen post-translational modifications and crosslinking). Besides TGF-beta1 others cytokines can also be involved in the processes of collagen metabolism regulation by compounds of plant origin. In particular, this is characteristic of triterpenes and phytoestrogens. Such a variety of methods for collagens metabolism regulation creates a wide range of possibilities for developing new preparations based on extracts or pure plant compounds able to correct connective tissue collagen structure and metabolic disorders with minimal adverse effects. Fundamentally different possibilities for the influence of plant organisms on collagens are opened with the use of genetically modified plants. Recombinant collagens allow to obtain proteins with new programmed features, making it possible to synthesize proteins with predetermined properties for medical use.

Skin photoaging is primarily caused by ultraviolet radiation and can lead to the degradation of skin extracellular matrix components, resulting in hyperpigmentation and skin elasticity loss. In this area, polyphenols have become of great interest because of their antioxidant, anti-inflammatory and antiaging properties. Here, we evaluated the effects of the pomegranate natural extract Pomanox® on skin health-related parameters in normal and UV-induced photoaging conditions in human fibroblast Hs68 cells. Moreover, the inhibitory effects of Pomanox® on tyrosinase activity were assessed. In normal conditions, Pomanox® significantly modulated collagen and hyaluronic acid metabolisms. In UV-exposed cells, both preventive and regenerative treatments with Pomanox® positively modulated hyaluronic acid metabolism and decreased ROS levels. However, only the preventive treatment modulated collagen metabolism. Finally, Pomanox® showed a marked inhibitory capacity of tyrosinase activity (IC50 = 394.7 μg/mL). The modulation of skin health-related parameters exhibited by Pomanox® open a wide range of potential applications of this product. [ABSTRACT FROM AUTHOR]

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Heart failure is a common and deadly disease requiring new treatments. The neuregulin-1/ERBB4 pathway offers cardioprotective benefits, but using recombinant neuregulin-1 as therapy has limitations due to the need for intravenous delivery and lack of receptor specificity. We hypothesize that small-molecule activation of ERBB4 could protect against heart damage and fibrosis. To test this, we conduct a screening of 10,240 compounds and identify eight structurally similar ones (EF-1 to EF-8) that induce ERBB4 dimerization, with EF-1 being the most effective. EF-1 reduces cell death and hypertrophy in cardiomyocytes and decreases collagen production in cardiac fibroblasts in an ERBB4-dependent manner. In wild-type mice, EF-1 inhibits angiotensin-II-induced fibrosis in males and females and reduces heart damage caused by doxorubicin and myocardial infarction in females, but not in Erbb4-null mice. This study shows that small-molecule ERBB4 activation is feasible and may lead to a novel class of drugs for treating heart failure., Competing Interests: Competing interests: Patent “MODULATORS OF ERBB4 IN THE TREATMENT OF DISEASES”; EP20210160742; Inventors: V.F.M.S., G.W.D.K., E.F., H.D.W., (© 2025. The Author(s).)

A hallmark of chronic and inflammatory diseases is the formation of a fibrotic and stiff extracellular matrix (ECM), typically associated with abnormal, leaky microvascular capillaries. Mechanisms explaining how the microvasculature responds to ECM alterations remain unknown. Here, we used a microphysiological model of capillaries on a chip mimicking the characteristics of healthy or fibrotic collagen to test the hypothesis that perivascular cells mediate the response of vascular capillaries to mechanical and structural changes in the human ECM. Capillaries engineered in altered fibrotic collagen had abnormal migration of perivascular cells, reduced pericyte differentiation, increased leakage, and higher regulation of inflammatory/remodeling genes, all regulated via NOTCH3 , a known mediator of endothelial-perivascular cell communication. Capillaries engineered either with endothelial cells alone or with perivascular cells silenced for NOTCH3 expression showed a minimal response to ECM alterations. These findings reveal a previously unknown mechanism of vascular response to changes in the ECM in health and disease.

Infective endocarditis (IE) represents a significant concern among hospital-acquired infections, frequently caused by the Gram-positive bacterium Staphylococcus aureus . Nuclear imaging is emerging as a noninvasive and precise diagnostic tool. However, the gold standard radiotracer [ 18 F]-FDG cannot distinguish between infection and inflammation, resulting in false positives. Based on the presence of collagen-binding proteins in the cell wall of S. aureus , we propose the radiolabeling of collagen for its evaluation in IE animal models by single-photon emission computed tomography (SPECT) imaging. We radiolabeled rat tail collagen I using DTPA chelator and [ 99m Tc]NaTcO 4 . Selectivity was evaluated in vitro using 3 Gram-positive bacteria, 1 Gram-negative bacteria and 1 yeast. In vivo SPECT/computed tomography (CT) imaging was conducted on 8 SD rat models of IE and 8 sterile sham model as controls. Ex vivo biodistribution and autoradiography were performed following imaging. Diagnosis of IE was confirmed through microbiological studies and H&E histopathology. [ 99m Tc]-DTPA-Collagen was synthesized successfully with a yield of 42.86 ± 6.35%, a purity of 95.84 ± 1.85% and a stability higher than 90% after 50 h postincubation. In vitro uptake demonstrated the selectivity for Gram-positive bacteria (63.85 ± 15.15%). Ex vivo analysis confirmed hepato-splenic excretion. In vivo SPECT/CT imaging revealed highly localized uptake within the aortic valve with a sensitivity of 62.5% and specificity of 87.5%. We successfully synthesized and characterized a new SPECT radiotracer based on [ 99m Tc]Tc-radiolabeled collagen. In vitro studies demonstrated the selectivity of the radiotracer for Gram-positive bacteria. In vivo SPECT/CT-based assessment in an IE model confirmed the potential of this approach to detect active IE.

Crohn's Disease and Ulcerative Colitis, the main types of Inflammatory Bowel Disease (IBD), are life-threatening gastrointestinal disorders with no definitive cure. The establishment of biorelevant in vitro models that closely recapitulate the IBD microenvironment is of utmost importance to validate newly developed IBD therapies. To address the existing flaws in the current representation of the IBD microenvironment, we propose a novel three-dimensional (3D) in vitro model comprising a multi-layered gastrointestinal tissue with functional immune responses under inflammatory conditions. The multi-layered architecture consists of a lamina propria-like hydrogel with human intestinal fibroblasts (HIF), supporting an epithelial layer composed of Caco-2 and HT29-MTX cells, along with an endothelial layer surrogating the absorptive capillary network. A collagen-alginate composite matrix was optimized for the lamina propria-like hydrogel, preserving HIF metabolic activity and morphology over time. To achieve immune competence, pre-differentiated THP-1-derived macrophages were incorporated into the epithelial barrier. Inflammation was induced through the optimization of an inflammatory cocktail consisting of E. coli O111:B4 lipopolysaccharide combined with a specialized cytokine array (tumor necrosis factor-α, interferon-γ, and interleukin-1β). This inflammation-inducing stimulus led to a significant upregulation of pro-inflammatory cytokines commonly associated with IBD onset, including CCL20, IL-6, CXCL9 and CXCL10. Altogether, this 3D in vitro model has the potential to accelerate the drug development pipeline by providing reliable permeability and efficacy outputs for emerging therapies, reducing unnecessary animal experiments. Moreover, it offers a valuable in vitro platform for studying IBD pathophysiology and cell interplay dynamics., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Form-function relationships often have tradeoffs: if a material is tough, it is often inflexible, and vice versa. This is particularly relevant for the elephant trunk, where the skin should be protective yet elastic. To investigate how this is achieved, we used classical histochemical staining and second harmonic generation microscopy to describe the morphology and composition of elephant trunk skin. We report structure at the macro and micro scales, from the thickness of the dermis to the interaction of 10 μm thick collagen fibers. We analyzed several sites along the length of the trunk to compare and contrast the dorsal-ventral and proximal-distal skin morphologies and compositions. We find the dorsal skin of the elephant trunk can have keratin armor layers over 2 mm thick, which is nearly 100 times the thickness of the equivalent layer in human skin. We also found that the structural support layer (the dermis) of the elephant trunk contains a distribution of collagen-I (COL1) fibers in both perpendicular and parallel arrangement. The bimodal distribution of collagen is seen across all portions of the trunk, and is dissimilar from that of human skin where one orientation dominates within a body site. We hypothesize that this distribution of COL1 in the elephant trunk allows both flexibility and load-bearing capabilities. Additionally, when viewing individual fiber interactions of 10 μm thick collagen, we find the fiber crossings per unit volume are five times more common than in human skin, suggesting that the fibers are entangled. We surmise that these intriguing structures permit both flexibility and strength in the elephant trunk. The complex nature of the elephant skin may inspire the design of materials that can combine strength and flexibility., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Species reintroductions are increasingly seen as important methods of biodiversity restoration. Reintroductions of red kites Milvus milvus and white-tailed eagles Halieaeetus albicilla to Britain, which were extirpated in the late 19th and early 20th centuries, represent major conservation successes. Here, we measured stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) in feather keratin and bone collagen of museum specimens of red kites and white-tailed eagles, which were collected from across Scotland between the 1800s and 2010s. Our objectives were to investigate dietary differences between species and between the pre- and post- reintroduction periods. Among reintroduced birds, δ13C values were significantly less negative and δ15N values higher in feather keratin and bone collagen of white-tailed eagles compared to red kites, likely reflecting a greater reliance on marine resources by the former. Our stable isotope data showed a wide range, confirming the dietary diversity observed in conventional diet studies of both taxa, with white-tailed eagles, in particular, having wide dietary niches and a considerable degree of inter-individual variability. Isotopic data from pre-introduction red kites mostly fell within the range of post-reintroduction birds, suggesting they had similar diets to the pre-reintroduction birds, or the prey base for modern birds is isotopically indistinguishable from that of their historic counterparts. For white-tailed eagles, several pre-reintroduction birds were isotopically distinct from the post-reintroduction population. These differences may indicate a changing prey base, although these conclusions are complicated by shifting distributions and small population samples. Overall, our study demonstrates the utility of natural history collections in examining changes in diet, environment, and interactions with humans in reintroduced species compared with pre-extirpation indigenous populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Waterman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Levels of tissue oxygenation and collagen regeneration are critical indicators in the early evaluation of wound healing. Traditionally, these factors have been assessed using separate instruments and different methodologies. Here, we adopt the spatially averaged phosphorescence lifetime approach using Re I -diimine complexes (Re I -probe) to enable simultaneous quantification of these two critical factors in healing wounds. The topically applied, biocompatible Re I -probe penetrates wound tissue effectively and selectively binds to collagen fibers. During collagen regeneration, the phosphorescence lifetimes of the collagen-bound probe significantly extend from an initial range of 4.5-6.5 μs on day 0 to 5.5-8.5 μs by day 7. Concurrently, unbound probes in the tissue interstitial spaces exhibit a phosphorescence lifetime of 4.5-5.2 μs, revealing the oxygenation states. Using phosphorescence lifetime imaging microscopy (PLIM) and a frequency domain phosphorescence lifetime measurement (FD-PLM) system, we validated the dual-functionality of this Re I -probe in differentiating healing stages in chronic wounds. With its noninvasive, quantitative measurement capabilities for cutaneous wounds, this Re I -probe-based approach offers promising potential for early wound healing diagnosis.

Matrigel ® /BME ® , a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells [T. Sato et al. , Nature 459 , 262-265 (2009); T. Sato et al. , Gastroenterology 141 , 1762-1772 (2011)]. Here, we show that interaction between Matrigel's major component laminin-111 with epithelial α6β1-integrin is crucial for this process. The outer membrane protein Invasin of Yersinia is known to activate multiple integrin-β1 complexes, including integrin α6β1. A C-terminal integrin-binding fragment of Invasin, coated on culture plates, mediated gut epithelial cell adhesion. Addition of organoid growth factors allowed multipassage expansion in 2D. Polarization, junction formation, and generation of enterocytes, goblet cells, Paneth cells, and enteroendocrine cells were stable over time. Sustained expansion of other human, mouse, and even snake epithelia was accomplished under comparable conditions. The 2D "organoid sheet" format holds advantages over the 3D "in gel" format in terms of imaging, accessibility of basal and apical domains, and automation for high-throughput screening. Invasin represents a fully defined, affordable, versatile, and animal-free complement to Matrigel ® /BME ® ., Competing Interests: Competing interests statement:H.C. is an inventor on patents held by the Royal Netherlands Academy of Arts and Sciences that cover organoid technology and a co-founder of Xilis, Duke University (NC). He is currently Head of pharma Research and Early Development (pRED) at Roche, Basel Switzerland. J.J.A.P.M.W., W.d.L., and H.C. are inventors on a patent application directly related to this study. The other authors declare no conflicts of interest., Yes, the authors have research support to disclose, Supported by the Gravitation project Material Driven Regeneration (024.003.013 ZWK MDR) from the Netherlands Organization for Scientific Research (NWO) funded by the Ministry of Education, Culture and Science of the government of the Netherlands (J.J.A.P.M.W., W.d.L., D.K., H.C.) and the Oncode Institute (partly financed by the Dutch Cancer Society (H.C.). H.C. is currently head of Pharma Research and Early development at Roche.

The use of collagen in cell cultures promotes cell proliferation and differentiation, and it has been commercialized. In this study, we separated and purified collagen from adipose tissue discarded during liposuction and prepared collagen-coated dishes. After collagen was identified from human adipose tissue, type identification and quantification were performed using SDS-PAGE and FPLC. Collagen type I was used to coat culture dishes. Human skin fibroblasts and human adipose tissue-derived stem cells were seeded at a density of 2.5 × 105 cells/ml on prepared dishes at a collagen concentration of 3 mg/ml and cultured for 7 days. Cell viability was then measured and analyzed. The WST-1 assay was used to evaluate the results. The amount of collagen in 300 g of adipose tissue was 25.5 mg for type I, 41.4 mg for type III, 10.6 mg for type IV, 6.5 mg for type V and 15 mg for type VI. The highest rates were observed for adipose stem cells cultured on human adipose tissue-derived collagen-coated dishes. In cell cultures, cell affinity was higher when cells and the substrate used were of the same origin, and affinity was stronger when the tissue of origin was the same., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Fourier transform infrared spectroscopy (FTIRS) can provide rich information on the composition and content of samples, enabling the detection of subtle changes in tissue composition and structure. This study represents the first application of FTIRS to investigate cartilage under microgravity. Simulated microgravity cartilage model was firstly established by tail-suspension (TS) for 7, 14 and 21 days, which would be compared to control samples. A self-developed hollow optical fiber attenuated total reflection (HOF-ATR) probe coupled with a FTIR spectrometer was used for the spectral acquisition of cartilage samples in situ, and one-way analysis of variance (ANOVA) was employed to analyze the changes in the contents of cartilage matrix at different stages. The results indicate that cartilage degenerates in microgravity, the collagen content gradually decreases with the TS time, and the structure of collagen fibers changes. The trends of proteoglycan content and collagen integrity show an initial decrease followed by an increase, ultimately significantly decreasing. The findings provide the basis for the cartilage degeneration in microgravity with TS time, which must be of real significance for space science and health detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The extracellular matrix (ECM) is a complex structure involved in many biological processes with collagen being the most abundant protein. Density of collagen fibers in the matrix is a factor influencing cell motility and migration speed. In cancer, this affects the ability of cells to migrate and invade distant tissues which is relevant for designing new therapies. Furthermore, increased cancer cell migration and invasion have been observed in hypoxic conditions. Interestingly, it has been revealed that the Hypoxia Inducible Factor (HIF) can not only impact the levels of metabolic genes but several collagen remodeling genes as well. The goal of this paper is to explore the impact of the HIF protein on both the tumour metabolism and the cancer cell migration with a focus on the Warburg effect and collagen remodelling processes. Therefore, we present an agent-based model (ABM) of tumour growth combining genetic regulations with metabolic and collagen-related processes involved in HIF pathways. Cancer cell migration is influenced by the extra-cellular collagen through a biphasic response dependant on collagen density. Results of the model showed that extra-cellular collagen within the tumour was mainly influenced by the local cellular density while collagen also influenced the shape of the tumour. In our simulations, proliferation was reduced with higher extra-cellular collagen levels or with lower oxygen levels but reached a maximum in the absence of cell-cell adhesion. Interestingly, combining lower levels of oxygen with higher levels of collagen further reduced the proliferation of the tumour. Since HIF impacts the metabolism and may affect the appearance of the Warburg Effect, we investigated whether different collagen conditions could lead to the adoption of the Warburg phenotype. We found that this was not the case, results suggested that adoption of the Warburg phenotype seemed mainly controlled by inhibition of oxidative metabolism by HIF combined with oscillations of oxygen., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s).)

Equine endometrosis is a major cause of infertility in mares and is characterized by degenerative, functional and fibrotic changes in the endometrium with increased collagen (COL) deposition. Transforming growth factor (TGF)-β1 is one of the major pro-fibrotic factors involved in the excessive deposition of extracellular matrix (ECM) components in the equine endometrium. It has been demonstrated that ovarian steroids, specifically 17β-estradiol (E2) and progesterone (P4), not only regulate the cyclicity of the estrous cycle, but also have been implicated as anti- or pro-fibrotic factors. This study aimed to evaluate (i) the effect of E2 and P4 on the expression of ECM-associated genes including COL1A1, COL3A1, matrix metalloproteases (MMPs): MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13, and tissue inhibitors of MMPs (TIMPs): TIMP-1 and TIMP-2 in equine endometrial fibroblasts, and (ii) the effect of ovarian steroids on TGF-β1-induced COL1 expression in equine endometrial explants from the follicular and mid-luteal phases of the estrous cycle. The mRNA expression of ECM-associated genes in endometrial fibroblasts and TGF-β1-induced COL1 expression in endometrial explants was modulated by ovarian steroids, with variations depending on the type of steroid and the duration of treatment. Moreover, P4 decreased TGF-β1-induced COL1 protein abundance in the mid-luteal phase of the estrous cycle after 48 h (p < 0.05). The results of our study indicate that during the estrous cycle, the ovarian steroids E2 or P4 may act directly on endometrial fibroblasts, thereby affecting the expression of genes involved in tissue remodeling, namely MMPs and TIMPs. Furthermore, P4 appears to affect not only the ECM-associated genes in endometrial fibroblasts, but also to attenuate the pro-fibrotic action of TGF-β1 in the mid-luteal stage of the estrous cycle., Competing Interests: Declarations. Competing interests: No conflict of interest. Ethics approval and consent to participate: The samples were collected according to the European mandates (EFSA, AHAW/04–027). The materials collected were reviewed and accepted following the guidelines of the Local Ethics Committee for Experiments on Animals in Olsztyn, Poland (Agreements 51/2011). Consent for publication: Not applicable., (© 2024. The Author(s).)

Ultraviolet (UV) irradiation is a major factor contributing to skin photoaging, including the formation of reactive oxygen species (ROS), collagen breakdown, and overall skin damage. Insulin-like growth factor-I (IGF-1) is a polypeptide hormone that regulates dermal survival and collagen synthesis. Echinacoside (Ech), a natural phenylethanoid glycoside, is the most abundant active compound in Cistanches. However, its potential benefits for the skin and the underlying molecular mechanisms remain unclear. The objective of this research is to investigate the protective effect of Ech on human dermal fibroblast cells (HDFs) against UVB-induced skin photodamage. In this study, we demonstrated that Ech promotes IGF-1/IGF-1R/ERK-mediated collagen synthesis and IGF-1/IGF-1R/PI3K-mediated survival pathways, as well as induces IGF-1 secretion to counteract UVB-induced aging in HDFs. Furthermore, UVB-induced accumulation of SA-β-gal-positive cells, ROS, and impaired collagen synthesis were attenuated following Ech treatment. However, the protective effects of Ech were significantly diminished when IGF-1 and IGF-1R expression was silenced using small interfering RNA, indicating that Ech exerts its antiaging effects primarily by activating the IGF-1/IGF-1R signaling pathway. Our findings provide evidence of the antiaging effects of Ech on UVB-induced skin photodamage and suggest its potential development as a supplement in cosmetic dermal protective products., (© 2025 International Union of Biochemistry and Molecular Biology.)

Body wall of sea cucumber Bohadschia bivittate contains a protein consisting of highly insoluble collagen fibers. We aimed to evaluate the biocompatibility and cytotoxicity of nonirradiated or γ-irradiated pepsin soluble collagen (PSC) extracted from Bohadschia bivittata on human periodontal ligament fibroblasts cells. The MTT assay showed significant increase in the cell viability values indicating that PSC is noncytotoxic. Further, nonirradiated PSC showed higher cell viabilities values than γ-irradiated PSC at all concentration, especially at an optimal dilution of 25% (p < 0.05). This exploratory study suggests that PSC from Bohadschia bivittata could be utilized as a novel biomaterial in periodontal regenerative therapies., (© 2024 John Wiley & Sons Ltd.)

Background: Multiple factors, such as muscle fatty infiltration (FI), tendon collagen content, and collagen arrangement, determine bone-tendon interface (BTI) healing after rotator cuff (RC) repair., Purpose: To evaluate the effects of systemic administration of ezetimibe-atorvastatin (EZE/ATZ) combination on muscle FI and tendon collagen density and arrangement in an RC repair rat model., Study Design: Controlled laboratory study., Methods: A total of 26 male Sprague-Dawley rats were randomly divided equally into control and EZE/ATZ groups and subjected to RC tendon repair surgery. Postoperatively, the EZE/ATZ group rats received a combination of EZE (10 mg/kg/d) and ATZ (20 mg/kg/d) for 4 weeks, after which they were sacrificed. Oil Red O staining was used to assess FI in the supraspinatus muscle. The expression of biomarkers related to muscle atrophy and FI was measured using quantitative real-time polymerase chain reaction. For the qualitative and quantitative analysis of FI-related biomarkers, immunohistochemical staining was performed. Biomechanical and histological analyses were performed to evaluate the quality of BTI healing after RC repair., Results: The EZE/ATZ group showed significantly lower FI compared with the control group ( P < .001) and significantly downregulated expression of gene markers related to muscle atrophy and FI. On histological analysis, the EZE/ATZ group exhibited increased collagen type I contents, consistent collagen arrangement ( P = .005), and significantly higher collagen density ( P = .003) compared with the control group. Biomechanical analysis of the BTI healing revealed that the EZE/ATZ group had significantly increased ultimate strength ( P = .006) compared with the control group., Conclusion: Systemic EZE/ATZ administration suppressed supraspinatus FI by downregulating muscle atrophy-related and FI-related genes after RC repair. Additionally, EZE/ATZ use improved collagen biosynthesis, density, and arrangement at the BTI and significantly increased tensile strength., Clinical Relevance: The results of the current study strongly advocate the use of EZE/ATZ to improve shoulder function and tendon healing after RC repair., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by a grant from the National Research Foundation of Korea (NRF), funded by the Republic of Korea government (MSIT) (NRF-2022R1A2C1005374). This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant No. HR22C1832). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. All animal procedures were approved by the Institutional Animal Care and Use Committee of Kyungpook National University, Daegu, Republic of Korea (IACUC No. KNU 2023-0210).

First introduced over 20 years ago as a treatment for progressive keratoconus, the original "Dresden" corneal cross-linking (CXL) protocol involved riboflavin saturation of the stroma, followed by 30 min of 3 mW/cm 2 -intensity ultraviolet-A (UV-A) irradiation. This procedure generates reactive oxygen species (ROS) that cross-link stromal molecules, thereby stiffening the cornea and counteracting the ectasia-induced weakening. Due to their large size, riboflavin molecules cannot readily pass through the corneal epithelial cell tight junctions; thus, epithelial debridement was performed. Moreover, the Dresden protocol necessitates a minimal corneal thickness of 400 μm to protect the endothelium from UV-induced damage. While the Dresden protocol is highly effective at enhancing corneal biomechanical strength, there was a strong desire for CXL procedures that would deliver Dresden-like strengthening in a shorter time, in corneas thinner than 400 μm, and without requiring epithelial debridement. This review explores the advancements and scientific discoveries that have enabled such improvements. Accelerated CXL protocols, utilizing our increased knowledge about the role of oxygen and photochemical reactions in the cornea have shortened and simplified the procedure duration while maintaining efficacy and safety, improving clinical workflow and patient compliance. CXL is not confined to improving biomechanics in corneal ectasia, but rather represents a technique that modulates corneal physiology and biochemistry on multiple levels. Accordingly, CXL indications have expanded to include treating other corneal ectasias, corneal neovascularization, corneal sterile melting, inflammatory dry eye and importantly, infectious keratitis in a procedure termed photoactivated chromophore for keratitis-CXL (PACK-CXL). In PACK-CXL, ROS have a direct pathogen-killing effect, and cross-linking enhances the cornea's resistance to pathogen-produced protease digestion through steric hindrance. The distinct requirements of PACK-CXL compared to ectasia treatment have led to the development of different CXL protocols, including higher UV fluences and other chromophore/light combinations, specifically rose bengal and green light. Additionally, combining CXL with vision-enhancing procedures like individualized wavefront- or topographically-guided excimer ablation can regularize a biomechanically stable cornea, improve visual acuity, and potentially eliminate the need for corneal transplantation, leading to long-term improvements in quality of life., (Copyright © 2024. Published by Elsevier Ltd.)

Amniote integumentary appendages constitute a diverse group of micro-organs, including feathers, hair and scales. These structures typically develop as genetically controlled units 1 , the spatial patterning of which emerges from a self-organized chemical Turing system 2,3 with integrated mechanical feedback 4,5 . The seemingly purely mechanical patterning of polygonal crocodile head scales provides an exception to this paradigm 6 . However, the nature and origin of the mechanical stress field driving this patterning remain unclear. Here, using precise in ovo intravenous injections of epidermal growth factor protein, we generate Nile crocodile embryos with substantially convoluted head skin, as well as hatchlings with smaller polygonal head scales resembling those of caimans. We then use light-sheet fluorescence microscopy to quantify embryonic tissue-layer geometry, collagen architecture and the spatial distribution of proliferating cells. Using these data, we build a phenomenological three-dimensional mechanical growth model that recapitulates both normal and experimentally modified patterning of crocodile head scales. Our experiments and numerical simulations demonstrate that crocodile head scales self-organize through compressive folding, originating from near-homogeneous skin growth with differential stiffness of the dermis versus the epidermis. Our experiments and theoretical morphospace analyses indicate that variation in embryonic growth and material properties of skin layers provides a simple evolutionary mechanism that produces a diversity of head-scale patterns among crocodilian species., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Platelet-derived growth factor-AA (PDGFA) is known to play an important role in hair loss and hair growth by involving in the anagen phase of the hair follicle growth cycle. In this study, we synthesized skin-permeable recombinant low-molecular-weight protamine (LMWP)-conjugated PDGFA (LMWP-PDGFA) by linking LMWP to the N terminus of PDGFA. We evaluated the hair loss improvement effect, wound healing efficacy, and skin permeability of LMWP-PDGFA. LMWP-PDGFA showed higher cell proliferation, cell permeability, 5α-reductase inhibition activity and IGF-1 activity than PDGFA in human hair follicle dermal papilla cells (HFDPC). We also found that LMWP-PDGFA increased cell migration and collagen synthesis better than PDGFA. These results indicate that LMWP-PDGFA can be a good candidate as a hair treatment agent with superior cell permeability than PDGFA. Additionally, it is expected that the efficacy of the protein can be maximized by combining LMWP with other functional proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We examined the role of myofibroblasts in regulating Cx43 and collagen structure in iatrogenic preterm amniotic membrane (AM) defects subjected to mechanical stimulation., Method: Preterm AM specimens were collected from women undergoing planned preterm caesarean section after in utero intervention for correction of spina bifida by open fetal surgery (n = 4 patients; preterm delivery at 34 + 0 weeks to 35 + 0 weeks). Control specimens taken 5 cm away from the open fetal surgery defect site were compared with wound edge AM. In separate experiments, the effects of mechanical stimulation and co-treatment with Cx43 antisense on matrix and repair proteins were examined. Specimens were immunostained to detect αSMA and Cx43 in myofibroblasts and counterstained with DAPI to quantify nuclei shape. The direction of collagen fibrils in the wound edge region was examined by SHG imaging. Markers for matrix (collagen, elastin, GAG), inflammation (PGE 2 ) and repair (TGFβ 1 ) were examined by RT-qPCR and biochemical assays., Results: In iatrogenic preterm AM specimens, the diameter of the open fetal surgery defect ranged between 3.5 and 7.5 cm. At the wound edge of the open fetal surgery defect, αSMA positive myofibroblasts had deformed nuclei and showed abundant Cx43 localized in the cell bodies or formed plaques. In the fibroblast layer, collagen had degenerated in some regions or had polarity near the wound edge. In preterm AM defects, mechanical stimulation and Cx43 antisense increased the levels of collagen and elastin but not GAG or PGE 2 release. Mechanical stimulation increased Cx43 and TGFβ 1 gene expression., Conclusion: In open fetal surgery defects, myofibroblasts were elongated with collagen fibrils that either degenerated or had polarity. Whilst cells produced substantially higher Cx43 in the fibroblast than in the epithelial layer, they formed plaques, which may prevent migration and delay healing. Mechanical stimulation of preterm AM enhanced matrix repair proteins and the mechanotransduction should be explored to understand how Cx43 contributes to membrane integrity., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Different concentrations and infiltration times of rose bengal (Rb) were assessed for their impact on penetration depth and crosslinking efficacy in rabbit sclera. Fresh rabbit eyes were used. Rb solution with concentrations of 0.1%-0.9% were applied for 5-30 min to infiltrate the sclera. The penetration depth of Rb was observed with confocal microscopy. After infiltration, the sclera was irradiated by green light for crosslinking. The sclera's biomechanical stiffness and the resistance to enzyme digestion post-treatment were evaluated. Histopathological analysis and transmission electron microscopy were performed to observe the morphology. As the infiltration time increased, the penetration depth and the fluorescence intensity of the Rb in sclera increased. After 32 h, 48.6% of the scleral tissue was undissolved in the 0.5% Rb-10min group, followed by the 0.1% Rb-20min group (13.8%) and 0.05% Rb-30min group (7.7%). At 8% strain, the Young's modulus of the 0.05%Rb-30min, the 0.1% Rb-20min and the 0.5% Rb-10min group were respectively 1.77, 2.45 and 3.19 times greater than that of the untreated group. There were no morphological differences between the experimental group and the untreated group. RG-SXL significantly increased the diameter of large collagen fibers in the middle and inner layers of the sclera. Ultimately, 0.5% Rb infiltration for 10 min achieves an appropriate infiltration depth and crosslinking effect, and may thus be a feasible schedule for scleral crosslinking., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

By developing a 3D X-ray modeling and spatially correlative imaging method for fibrous collagenous tissues, this study provides a comprehensive mapping of nanoscale deformation in the collagen fibril network across the intact bone-cartilage unit (BCU), whose healthy functioning is critical for joint function and preventing degeneration. Extracting the 3D fibril structure from 2D small-angle X-ray scattering before and during physiological compression reveals of dominant deformation modes, including crystallinity transitions, lateral fibril compression, and reorientation, which vary in a coupled, nonlinear, and correlated manner across the cartilage-bone interface. A distinct intermolecular arrangement of collagen molecules, and enhanced molecular-level disorder, is found in the cartilage (sliding) surface region. Just below, fibrils accommodate tissue strain by reorientation, which transitions molecular-level kinking or loss of crystallinity in the deep zone. Crystalline fibrils laterally shrink far more (20×) than they contract, possibly by water loss from between tropocollagen molecules. With the calcified plate acting as an anchor for surrounding tissue, a qualitative switch occurs in fibrillar deformation between the articular cartilage and calcified regions. These findings significantly advance this understanding of the complex, nonlinear ultrastructural dynamics at this critical interface, and opens avenues for developing targeted diagnostic and therapeutic strategies for musculoskeletal disorders., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Damage to the human heart is an irreparable process that results in a permanent impairment in cardiac function. There are, however, a number of vertebrate species including zebrafish (Danio rerio) that can regenerate their hearts following significant injury. In contrast to these regenerative species, mammals are known to have high levels of thyroid hormones, which has been proposed to play a role in this difference in regenerative capacity. However, the mechanisms through which thyroid hormones effect heart regeneration are not fully understood. Here, zebrafish were exposed to exogenous triiodothyronine (T 3 ) for two weeks and then their hearts were damaged through cryoinjury to investigate the effect of thyroid hormones on ECM remodeling and the components of the immune response during heart regeneration. Additionally, cardiac fibroblasts derived from trout, another species of fish known to display cardiac regenerative capacity, were exposed to T 3 in vitro to analyze any direct effects of T 3 on collagen deposition. It was found that cryoinjury induction results in an increase in myocardial stiffness, but this response was muted in T 3 exposed zebrafish. The measurement of relevant marker gene transcripts suggests that T 3 exposure reduces the recruitment of macrophages to the damaged zebrafish heart immediately following injury but had no effect on the regulation of collagen deposition by cultured trout fibroblasts. These results suggest that T 3 effects both the immune response and ECM remodeling in zebrafish following cardiac injury., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Progressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, fibrosis is increasingly linked with catecholamines such as adrenaline (AD) and noradrenaline (NA) and hormones such as aldosterone (ALD). The essential functions of the adrenal glands include the production of catecholamines and numerous hormones, but the contribution of adrenal glands to lung fibrosis remains less well studied. Here, we characterized the impact of surgical adrenal ablation in the bleomycin model of lung fibrosis. Wild-type mice underwent surgical adrenalectomy or sham surgery followed by bleomycin administration. We found that although bleomycin-induced collagen overdeposition in the lung was not affected by adrenalectomy, histologic indices of lung remodeling were ameliorated. These findings were accompanied by a decrease of lymphocytes in bronchoalveolar lavage (BAL) and macrophages in lung tissues, along with concomitant reductions in alpha-smooth muscle actin (αSMA) and fibronectin. Surgical adrenalectomy completely abrogated AD, not NA, detection in all compartments. Systemic ALD levels were reduced after adrenalectomy, whereas ALD levels in lung tissues remained unaffected. Taken together, these results support the presence of a pulmonary-adrenal axis in lung fibrosis and suggest that adrenalectomy is protective in this disease. Further investigation will be needed to better understand this observation and aid in the development of novel therapeutic strategies. NEW & NOTEWORTHY The lung-adrenal axis plays a significant role in pulmonary fibrosis. Adrenalectomy provides protection against lung fibrotic ECM remodeling and lung inflammation by reducing the levels of lymphocytes in BAL and macrophages in lung of bleomycin-treated mice. Although compared with sham surgery, adrenalectomy raised collagen concentration in uninjured mice, there was no discernible difference in bleomycin-induced collagen accumulation. However, adrenalectomy significantly reversed the enhanced expression and colocalization of αSMA and fibronectin induced by bleomycin.

Damage-accumulation failure models are broadly used to examine tissue property changes caused by mechanical loading. However, damage accumulation models are purely phenomenological. The underlying justification in using this type of model is often that damage occurs to the extracellular fibers and/or cells which changes the fundamental mechanical behavior of the system. In this work, we seek to align damage accumulation models with microstructural models to predict alterations in the mechanical behavior of biological materials that arise from structural heterogeneity associated with nonuniform remodeling of tissues. Further, we seek to extend this multiscale model toward assessing catastrophic failure events such as cerebral aneurysm rupture. First, we demonstrate that a model made up of linear elastin and actin and nonlinear collagen fibers can replicate bot the pre-failure and failure tissue-scale mechanics of uniaxially-stretched cerebral aneurysms. Next, we investigate how mechanical heterogeneities, like those observed in cerebral aneurysms, influence fiber and tissue failure. Notably, we find that failure occurs and the interface between regions of high and low material stiffness, suggesting that spatial mechanical heterogeneity influences aneurysm failure behavior. This model system is a step toward linking structural changes in growth and remodeling to failure properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Joint injury can lead to articular cartilage damage, excessive inflammation, and post-traumatic osteoarthritis (PTOA). Collagen is an essential component for cartilage function, yet current literature has limited understanding of how biochemical and biomechanical factors contribute to collagen loss in injured cartilage. Our aim was to investigate spatially dependent changes in collagen content and collagen integrity of injured cartilage, with an explant model of early-stage PTOA. We subjected calf knee cartilage explants to combinations of injurious loading (INJ), interleukin-1α-challenge (IL) and physiological cyclic loading (CL). Using Fourier transform infrared microspectroscopy, collagen content (Amide I band) and collagen integrity (Amide II/1338 cm -1 ratio) were estimated on days 0 and 12 post-injury. We found that INJ led to lower collagen content near lesions compared to intact regions on day 0 (p < 0.001). On day 12, near-lesion collagen content was lower compared to day 0 (p < 0.05). Additionally, on day 12, INJ, IL, and INJ + IL groups exhibited lower collagen content along most of tissue depth compared to free-swelling control group (p < 0.05). CL groups showed higher collagen content along most of tissue depth compared to corresponding groups without CL (p < 0.05). Immunohistochemical analysis revealed higher MMP-1 and MMP-3 staining intensities localized within cell lacunae in INJ group compared to CTRL group on day 0. Our results suggest that INJ causes rapid loss of collagen content near lesions, which is intensified on day 12. Additionally, CL could mitigate the loss of collagen content at intact regions after 12 days., (© 2024 The Author(s). Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Collagen cross-linking (CXL) is considered as a successful therapeutic approach for corneal conditions like keratoconus and corneal ectasia. Despite its efficacy in stabilizing these conditions, the occurrence of post-CXL scars remains a concern. Keratoconus and other corneal ectasias are characterized by structural weaknesses in the cornea. This weakness contributes to the vulnerability of corneal scar formation. In addition, corneal biomechanics and tissue properties play a significant role in scar development. Procedural factors during CXL, including duration and intensity of ultraviolet light exposure, the concentration and type of riboflavin, and the precise application of treatment, have been identified as potential causes of scar formation. Individual patient factors such as variations in healing response and genetic predispositions, associated ocular allergy, and chronic contact lens wear can also impact scar development post-CXL. Understanding these variables is essential for risk stratification and personalized treatment approaches, ultimately optimizing patient outcomes. In addition, regular follow-up visits and patient education are essential to ensure optimal healing and minimize scar related complications. We have tried to explain the numerous reasons of scarring following epithelium-off CXL by conducting a thorough Medline search and reviewing our clinical images. This review serves as a concise overview of the causes and risk factors associated with scar formation after epithelium-off CXL., (Copyright © 2024 Indian Journal of Ophthalmology.)

Objectives: This study aimed to investigate the effects of cathepsin K (catK) on proteoglycans (PGs) and the subsequent impacts on dentin collagen degradation., Materials and Methods: Demineralized dentin samples were prepared and divided into the following groups: deionized water (DW), 0.1 U/mL chondroitinase ABC (C-ABC), and 1 μM odanacatib (ODN). Then, they were immersed for 48 h and then incubated in 1 mL of PBS (pH=5.5) at 37 °C for 5 d. Glycosaminoglycan (GAG) were examined to explore the degradation of PGs by catK. To determine the effect of catK-mediated PGs on dentin collagen degradation, hydroxyproline (HYP) assays, assessment of the degree of dentin crosslinking, and scanning electron microscopy (SEM) were assessed. Statistical analysis was conducted using one-way ANOVA followed by Tukey's tests or Welch's ANOVA followed by Dunnett's tests at a significance level of 0.05., Results: The production of GAG was significantly lower in the ODN group than in the DW group (P < 0.05), revealing that PG degradation was reduced in dentin after ODN treatment. Additionally, ODN treatment minimized the gaps in collagen fibers, improved fiber arrangement, and significantly increased the degree of collagen crosslinking, subsequently reducing the total amount of collagen fiber degradation in the dentin (P < 0.05)., Conclusions: CatK-mediated degradation of PGs negatively impacted the stability of collagen fibers, promoted gaps, led to a less organized arrangement of dentin collagen fibers, ultimately increasing collagen degradation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate changes in corneal backscattering after collagen cross-linking (CXL) for progressive keratoconus and compare its course with different techniques - standard epithelium-off CXL (SCXL), contact lens-assisted CXL (CACXL), and transepithelial CXL (TECXL)., Setting: Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India., Design: Retrospective comparative study., Methods: Ninety-four eyes (SCXL: 47, CACXL: 30, and TECXL: 17) were compared. Corneal haze was quantified using Scheimpflug tomography, pre- and post-CXL at 1, 3, 6, and 12 months., Results: The baseline mean density score of the central anterior stromal layer was 16.14 ± 7.07, 15.85 ± 7.89 and 15.89 ± 7.21 in SCXL, CACXL, and TECXL groups, respectively ( P 0.93). After SCXL, the score increased to 28.83 and 31.34 at 1 and 3 months, respectively (both P < 0.001) and dropped at 6 months (28.66, P < 0.001) and 12 months (23.72, P 0.003). Post-CACXL, the mean densitometry peaked at 3 months (20.35, P 0.14) and returned toward baseline at 6 months (18.82, P 0.15). After TECXL, it increased slightly at 1 month (18.47, P 0.17), decreased at 3 months (14.88, P 0.7), and plateaued over 1 year. No correlation with visual acuity was seen., Conclusion: Corneal haze increased significantly after SCXL, peaking at 3 months, declining over 6-12 months, and returning to baseline at 12 months. In contrast, post-TECXL and -CACXL, there was an insignificant increase in anterior corneal haze, which returned to baseline within 3-6 months., (Copyright © 2024 Indian Journal of Ophthalmology.)

Thoracic aortic aneurysms (TAA) represent a critical health issue for which computational models can significantly contribute to better understand the physiopathology. Among different computational frameworks, the Homogenized Constrained Mixture Theory has shown to be a computationally efficient option, allowing the inclusion of several mechanically significant constituents into a layer-specific mixture. Different patient-specific Growth and Remodeling (G&R) models correctly predicted TAA progression, although simplifications such as the inclusion of a limited number of collagen fibers and imposed boundary conditions might limit extensive analyses. The current study aims to enhance existing models by incorporating several discrete collagen fibers and to remove restrictive boundary conditions of the previous models. The implementation of discretized fiber dispersion presents a more realistic description of the vessel, while the removal of boundary conditions was addressed by including cross-links in the model to provide a supplemental stiffness against through-thickness shearing, a feature that was previously absent, and by the development of a non-local framework that ensures the stable deposition and degradation of collagen fibers. With these improvements, the current model represents a step forward towards more robust and comprehensive simulations of TAA growth., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Experimental investigation in human eyelids to confirm that exposing excised tarsal plates to ultraviolet-A radiation can induce a stiffening effect through the riboflavin-photosensitized crosslinking of tarsal collagen., Methods: Thirteen tarsal plates excised from nonfrozen human cadavers were irradiated with ultraviolet-A rays (365 nm wavelength) at an irradiance of 75 mW/cm 2 for 3 minutes, equivalent to a radiation fluence of 13.5 J/cm 2 , in the presence of a riboflavin derivative as a photosensitizer. The tensile stress (strength) and Young's modulus (stiffness) of both nonirradiated and irradiated specimens were measured with the BioTester 5000 in the uniaxial mode at a strain of 10% and analyzed statistically. Individual specimens excised from 2 cadavers were also examined by routine histopathologic protocols to assess the effect of radiation on the Meibomian glands and collagen organization., Results: The irradiation enhanced both stiffness and strength of the human tarsal specimens, the difference between the test samples and controls being statistically significant ( p < 0.0002 for n = 13). Histology indicated no damage to tarsal connective tissue or to Meibomian glands, and revealed a more compact packing of the collagen network located around the glands, which may be beneficial. The existence of collagen compaction was also supported by the reduction of samples' thickness after irradiation ( p = 0.0645)., Conclusions: The irradiation of tarsal tissue with ultraviolet-A light of tarsus appears to be a safe and effective method for reducing eyelid laxity in human patients., Competing Interests: U.S. Patent No. 11420073 (B2) and Australian Patent No. AU 2018201200 B2 have been granted for the method related to this research, and have been assigned to the Queensland Eye Institute Foundation by the authors S.S. and T.V.C. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Skeletal muscle (SkM) is a plastic and dynamic tissue, essential in energy metabolism. Growing evidence suggests a close relationship between intramuscular fat accumulation, oxidative stress (OS), extracellular matrix (ECM) remodeling, and metabolic deregulation in SkM. Nowadays natural products emerge as promising alternatives for the treatment of metabolic disorders. We have previously shown that chia seed administration reverts SkM lipotoxicity and whole-body insulin resistant (IR) in sucrose-rich diet (SRD) fed rats. The purpose of the present study was to assess the involvement of OS and fibrosis in SkM metabolic impairment of insulin-resistant rats fed a long-term SRD and the effects of chia seed upon these mechanisms as therapeutic strategy. Results showed that insulin-resistant SRD-fed rats exhibited sarcopenia, increase in lipid peroxidation, altered redox state, and ECM remodeling-increased collagen deposition and lower activity of the metalloproteinase 2 (MMP-2) in SkM. Chia seed increased ferric ion reducing antioxidant power and glutathione reduced form levels, and the activities of glutathione peroxidase and glutathione reductase enzymes. Moreover, chia seed reversed fibrosis and restored the MMP-2 activity. This work reveals a participation of the OS and ECM remodeling in the metabolic alterations of SkM in our experimental model. Moreover, current data show novel properties of chia seed with the potential to attenuate SkM OS and fibrosis, hallmark of insulin-resistant muscle., (© 2024 International Union of Biochemistry and Molecular Biology.)

Purpose: Corneal cross-linking (CXL) is the standard of care in patients with keratoconus but presents unique challenges in children and developmentally delayed patients. We present our clinical decision-making algorithm, CXL surgical technique, and outcomes in these groups., Methods: A retrospective chart review was undertaken at a tertiary referral center of all patients who underwent CXL for keratoconus at University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between October 1, 2017, and April 1, 2021. Demographic information along with preoperative, intraoperative, and postoperative ophthalmic examination findings were collected. The main outcome measures were indications of CXL, postoperative complications, and visual acuity (VA)., Results: Forty-eight eyes of 34 patients [21 patients (30 eyes) with developmental delay (DD) and 13 patients (18 eyes) with no DD (NDD)] underwent epithelium-off, standard CXL. General anesthesia was used for CXL in all patients except for 3 with NDD. A temporary central tarsorrhaphy was performed in all patients with DD and 7 patients with NDD. The remaining got a bandage contact lens. There were no immediate postoperative complications. A trend toward improvement in VA was noted postoperatively. The mean logMAR VA (with habitual correction) was 0.67 preoperatively and 0.57 postoperatively ( P = 0.3) in DD and 0.52 and 0.36, respectively ( P = 0.13), in NDD., Conclusions: This retrospective review presents a technique for assessment and treatment of keratoconus in children and those with DD. Our technique ensures timely diagnosis and provides a safe method for CXL in these groups. Temporary central tarsorrhaphy is a well-tolerated option to reduce postoperative pain., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To comparatively evaluate the influence of different riboflavin formulations and soaking durations on the anterior segment optical coherence tomography (AS-OCT) findings following accelerated corneal crosslinking (ACXL) at 9 mW/cm 2 for in progressive keratoconus., Methods: In this prospective study, consecutive patients with progressive keratoconus were randomized into 4 groups. Group 1: hydroxypropyl methylcellulose (HPMC)-based riboflavin for 10 min; Group 2: HPMC-based riboflavin for 20 min; Group 3: dextran-based riboflavin (0.1%) for 30 min. Riboflavin soaking was followed by ultraviolet-A irradiation at 9 mW/cm 2 for 10 min in all three groups. Group 4 underwent conventional CXL (CCXL) using Dresden protocol. The AS-OCT features of the crosslinked cornea were evaluated at postoperative month 1 and correlated to the clinical outcomes at postoperative month 12., Results: The study enrolled 26 eyes of 26 patients in each group. In groups 1 and 2, the AS-OCT findings were similar ( p  > .05) and the demarcation lines depth (DLD) were deep as obtained following CCXL. The DLD was significantly shallower in group 3 compared to the other groups ( p  < .01). There were no between-group differences in regards to the visual, refractive, keratometric, and tomographic outcomes at postoperative month 12. No significant endothelial cell loss or any other clinically significant adverse event was encountered in any patient's eye at 12 months follow-up., Conclusion: Although structural variations were noted in the crosslinked cornea, DLDs observed following ACXL (9 mW/cm 2 ) using HPMC-based solution for 10 or 20 min were similar to those observed following CCXL. Whereas, ACXL (9 mW/cm 2 ) using dextran-based solution for 30 min resulted in the shallowest DLD. Despite these remodeling differences, the visual, refractive and tomographic outcomes of all groups were comparable at postoperative 1-year follow-up. Studies with a greater number of patients and longer follow-ups are required to establish any relation between AS-OCT characteristics of crosslinked cornea and ACXL efficacy.

The albino northern snakehead (Channa argus) is an aquaculture species characterized by heritable albino body color, in contrast to the typical coloration. Additionally, there are gray- and golden-finned individuals, which exhibit distinct coloration in their caudal fins. We performed RNA-seq to profile the transcriptome of caudal fin tissues in albino gray-finned and golden-finned C. argus, contrasting these with normal morphs to elucidate the differences between the two groups. A total of 137,130 unigenes were identified in this study. Gene Ontology (GO) analysis showed that the identified DEGs were significantly enriched in cellular components related to cytoplasm. So far, 379 common DEGs have been identified in all three groups. Notably, we observed more DEGs in golden-finned individuals compared to gray-finned individuals. We also revealed that golden-finned individuals were enriched in collagen-related pathways compared with normal individuals. The enriched DEGs of collagen components include collagen I of COL1A1 and COL1A2, collagen II of COL2A1, collagen V of COL5A1 and COL5A2, collagen VI of COL6A1 and COL6A3, collagen IX of COL9A3, collagen X of COL10A1, collagen XI of COL11A2, collagen XII of COL12A1, collagen XVI of COL16A1, collagen XVIII of COL18A1 and decorin (DCN), all of which play a role in modulating the collagen matrix. In golden-finned albino fish, collagen-related genes were downregulated, suggesting that despite the abundance of collagen types in their caudal fin cells, gene expression was slightly limited. This work provides valuable genetic insights into collagen variation in albino C. argus, lays the foundation for research on collagen genes and is crucial for the development and utilization of fish-derived collagen as a biomaterial for tissue engineering and biomedical applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Orthodontic tooth movement (OTM) relies on the remodeling of periodontal tissues, including the periodontal ligament (PDL) and alveolar bone. Collagen remodeling plays a crucial role during this process, allowing for the necessary changes in the PDL's structure and function. Endo180, an urokinase plasminogen activator receptor-associated protein, is a transmembrane receptor regulated collagen remodeling. This study aims to investigate whether and how Endo180 participates in collagen remodeling within the PDL during OTM., Materials and Methods: A mechanical force-induced OTM rat model was established using a closed coiled spring to mesially move the right maxillary first molar. The distance of OTM was examined by micro-computed tomography (micro-CT). The collagen remodeling within the PDL was assessed using atomic force microscope (AFM), Hematoxylin-Eosin (HE) staining and Masson staining. Protein expressions of Endo180, collagen I (COL I) and collagen III (COL III) were analyzed via immunofluorescence staining. Additionally, the mRNA expressions of Endo180, COL I, and COL III in force-induced PDL cells were examined by RT-qPCR in vitro. To further illustrate the role of Endo180 in regulating COL I and COL III expressions, Endo180 siRNA (siEndo) was applied to force-stimulated PDL cells., Results: Force application increased OTM distance and disrupted collagen fiber organization, with a greater decrease in collagen elastic modulus on the mesial side than on the distal side of the PDL. After 7 days of force application, Endo180 and COL III expressions significantly increased in PDL tissues, while COL I expression decreased in PDL tissues. Compressive force loading in vitro upregulated the mRNA expressions of Endo180 and COL III, but downregulated COL I mRNA expression. Notably, Endo180 knockdown using siRNA suppressed force-induced COL III expression while restoring the downregulated COL I expression under compressive force stimuli., Conclusion: Force-induced Endo180 expression modulates collagen remodeling in PDL during OTM by upregulating COL III and downregulating COL I. This collagen reorganization facilitates efficient tooth movement, highlighting Endo180 as a potential therapeutic target to optimize orthodontic treatment outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Peking University Ethical Committee (LA2013-92 and PKUSSIRB-201311103), following ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) and the National Research Council’s Guide for the Care and Use of Laboratory Animals. To obtain the PDL cells, the individuals who provided tooth were provided with a detailed explanation of the entire research protocol and had signed the informed consent document. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The tumor microenvironment features dynamic biomechanical interactions between extracellular matrix physics and tumor progression. Tumor growth compresses the supportive matrix, and the stiffness-gradient guides tumor invasion. From the mechanical perspective, the complexity of the matrix topology involving durotaxis-driven metastasis remains lacking in a comprehensive description. In this study, A549 adenocarcinoma spheroids were exposed to a stiffness-and fiber-adjusted collagen matrix to examine the influence of collective motility. Centrifugated compression on the collagen constructs was adopted to mimic the matrix deformation in response to solid tumor development. Centrifugated compression physically stiffened and condensed collagen constructs simultaneously. Cultured with A549 spheroids for 7 days, compressed collagen constructs disadvantaged spheroid expansion without the effect of tumor proliferation potency but promoted matrix metalloproteinase activity corresponding to softened rigidity. Results suggested that the fibrous structure may counterbalance the matrix stiffness-induced motility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rotatory devices are essential in clinical surgical practice, however, depending on the different systems available, their function can impact bone repair and postoperative responses on varying scales. This impact underscores the need to explore new techniques aiming to enhance bone repair. This study aimed to assess the immediate and delayed effects on bone healing in subcritical bone defects using both air turbine and an electric handpiece. For this purpose, 40 male Wistar rats were allocated into two groups. The Control Group (CG) had bone defect made using an air turbine device, while the Experimental Group (EG) had defects made using an electric handpiece. Ten animals were sacrificed for each time of evaluation. Bone neoformation, microstructure, and collagen organization were assessed ate 7, 15 and 30 days postoperative. Inflammatory profiling was conducted at 7 and 15 days. Immediate thermal osteonecrosis were evaluated after the use of rotary systems. Multivariate analysis was used to access statistical differences. The EG exhibited enhanced parameters of bone neoformation in all analyses, with statistical difference between 15 and 30 days (P = .0002) and in comparison with CG in 30 days (P = .0009). A reduced number of inflammatory cells and increased angiogenesis in the initial periods was seen in EG, corroborating the consistent values of collagen type 1 and a decrease of collagen type 3 over times. Immediate thermal osteonecrosis was statistically higher for the CG (P < .05), which showed adequate neoformation of subcritical defects but consistently lower values than those found in the EG. These data suggest that the electric handpiece demonstrated more bone repair area, proving to be an excellent alternative to surgical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sol et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Idiopathic pulmonary fibrosis (IPF) is a fatal disease defined by a progressive decline in lung function due to scarring and accumulation of extracellular matrix (ECM) proteins. The SOCS (Suppressor Of Cytokine Signaling) domain is a 40 amino acid conserved domain known to form a functional ubiquitin ligase complex targeting the Von Hippel Lindau (VHL) protein for proteasomal degradation. Here we show that the SOCS conserved domain operates as a molecular tool, to disrupt collagen and fibronectin fibrils in the ECM associated with fibrotic lung myofibroblasts. Our results demonstrate that fibroblasts differentiated using TGFβ, followed by transduction with the SOCS domain, exhibit significantly reduced levels of the contractile myofibroblast-marker, α-SMA. Furthermore, in support of its role to retard differentiation, we find that lung fibroblasts expressing the SOCS domain present with significantly reduced levels of α-SMA and fibrillar fibronectin after differentiation with TGFβ. We show that adenoviral delivery of the SOCS domain in the fibrotic phase of experimental lung fibrosis in mice, significantly reduces collagen accumulation in disease lungs. These data underscore a novel function for the SOCS domain and its potential in ameliorating pathologic matrix deposition in lung fibroblasts and experimental lung fibrosis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Articular cartilage is distinguished by the unique alignment of type II collagen, a feature crucial for its mechanical properties and function. This characteristic organization is established during postnatal development of the tissue, yet the underlying mechanisms remain poorly understood. In this study, a potential mechanism for type II collagen alignment by cartilage-specific growth from within the tissue was investigated. Bovine chondrocyte-derived cartilage organoids were cultured in a transwell system, subjecting the created tissue to transforming growth factor β1 stimulation from either the bottom (bottom-up) or the top (top-down) compartment to induce interstitial growth and appositional growth, respectively. The results demonstrate that interstitial growth within the tissue, stimulated from underneath, successfully produced aligned type II collagen parallel to the direction of this growth. In contrast, appositional growth did not yield such alignment. These findings underscore the critical role of the direction of growth in recreating the characteristic collagen organization of articular cartilage, offering valuable insights for the advancement of creating functional tissue in tissue engineering strategies., Competing Interests: Declarations. Competing interests: J.P., M.H., F.A., S.C. and J.F. declare no competing interests. K.I. is contracted as CSO of NC Biomatrix BV., (© 2024. The Author(s).)

The importance of collagen and elastin remains incompletely understood concerning tumor immunity in cancer tissues. This study explored the clinical significance of collagen and elastin deposition on tumor immunity in advanced colorectal cancer patients. The collagen and elastin contents were assessed simultaneously using elastic van Gieson (EVG) histochemical staining. Immunohistochemical staining was performed to measure the immune cell markers CD3, CD8, CD86, and CD163 in surgically resected primary tumors from 78 pT4 colorectal cancer patients. High collagen, elastin, and EVG scores are associated with aggressive characteristics and short disease-free survival. A high EVG score was identified as an independent predictor of poor disease-free survival. Furthermore, tumors with high collagen and EVG scores exhibited significantly fewer intratumoral CD3 + and CD8 + cells. Evaluating tumor fibrosis using the classical and straightforward EVG staining method could be a reliable predictor of recurrence in high-risk colorectal cancer patients with tumor immune tolerance., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Thoracoabdominal aortic aneurysms (TAAAs) are rare but serious conditions characterized by dilation of the aorta characterized by remodeling of the vessel wall, with changes in the elastin and collagen content. Individuals with Marfan syndrome have a genetic predisposition for elastic fiber fragmentation and elastin degradation and are prone to early aneurysm formation and progression. Our objective was to analyze the medial collagen characteristics through histological, polarized light microscopy, and electron microscopy methods across the thoracic and abdominal aorta in twenty-five patients undergoing open surgical repair, including nine with Marfan syndrome. While age at surgery differed significantly between the groups, maximum aortic diameter and aneurysm extent did not. Collagen content increased from thoracic to infrarenal segments in both cohorts, with non-Marfan patients exhibiting higher collagen percentages, notably in the infrarenal aorta (729.3 nm vs. 1068.3 nm, p = 0.02). Both groups predominantly displayed mature collagen fibers, with the suprarenal segment containing the highest proportion of less mature fibers. Electron microscopy revealed comparable collagen fibril diameters across segments irrespective of Marfan status. Our findings underscore non-uniform histological patterns in TAAAs and suggest that ECM remodeling involves mature collagen deposition, albeit with lower collagen content observed in the infrarenal aorta of Marfan patients.

Aim: To study the relationship between laboratory markers and echocardiography (EchoCG) parameters in heart failure with preserved ejection fraction (HFpEF) depending on the results of the diastolic stress test (DST)., Material and Methods: The diagnostic algorithm provided by the current guidelines for the assessment of left ventricular (LV) diastolic function was used to select patients. If there were not enough criteria to make a conclusion about increased LV filling pressure (FP) based on standard resting echocardiography data in patients with arterial hypertension and ischemic heart disease, DST was performed to detect HFpEF. 80 patients (50.0% men, mean age 66.3±5.4 years) were included. Group 1 consisted of 41 patients with a positive DST, and group 2 included 39 patients with a negative DST. Concentrations of the markers of immune inflammation, endothelial dysfunction, collagen homeostasis, and myocardial stress were measured., Results: The DST showed significant differences in the E/e' ratio (15.1 [13.4; 15.9] in group 1 and 9.5 [7.9; 10.3] in group 2, respectively, p&lt;0.001) and the diastolic functional reserve index (DFRI) (9.8 [6.8; 14.0] and 21.0 [13.0; 29.0], p &lt; 0.001). Resting EchoCG revealed significant differences in the left atrial reservoir strain (LASr) (22.8 [19.6; 25.6]% and 28.0 [24.8; 30.2]%, p&lt;0.001) and the left atrial stiffness index (LASI) (0.50 [0.40; 0.57] and 0.34 [0.27; 0.41], p&lt;0.001). In patients with HFpEF, the laboratory parameters of collagen regulation had the greatest number of relationships. Correlations were found between the concentrations of matrix metalloproteinase-9 and other biomarkers, including interleukin-10 (IL-10) (r=0.311; p=0.048), myeloperoxidase (r=0.382; p=0.014), N-terminal propeptide of procollagen type I (procollagen I N-terminal propeptide, PINP) (r=0.722; p&lt;0.001) and type III (r=0.591; p&lt;0.001), C-terminal propeptide of procollagen type I (r=0.330; p=0.035), tissue inhibitor of metalloproteinases type 1 (r=0.410; p=0.008), EchoCG parameters, including left atrial volume index (LAVI) (r=0.414; p=0.007) and DFRI (r=0.354; p=0.025). In addition, correlations were found for the concentrations of PINP with IL-10 (r=0.401; p=0.009) and endothelin-1 (r= -0.337; p=0.031); PINP with LAVI (r=0.498; p=0.001) and DFRI (r=0.420; p=0.007)., Conclusion: Patients with HFpEF have a greater number of relationships between markers of collagen homeostasis disorders and EchoCG parameters characterizing an increase in LV FP.