Search Results (580)

Pulmonary emphysema is a progressive and debilitating lung disease characterized by the destruction of alveolar walls and enlargement of airspaces, resulting in impaired gas exchange and reduced lung function. Central to this pathology is the degradation of the extracellular matrix (ECM), particularly the elastic fiber network containing elastin protein responsible for storing and releasing the energy that expels air from the lung. Both intrinsic and extrinsic mechanical stress play a pivotal role in ECM remodeling, influencing elastin degradation and the structural integrity of alveolar walls. This paper explores the interactions between mechanical forces and ECM components, emphasizing the role of increased elastin crosslinking in the pathogenesis and progression of emphysema. The molecular mechanisms responsible for this process are described in the context of emergent phenomena associated with alveolar wall distension and rupture, including the role of diagnostic biomarkers in the early detection of elastic fiber injury that may facilitate timely therapeutic interventions designed to preserve ECM integrity and improve patient outcomes. Full article

This review will focus on the structure and role of the ECM in physiological conditions and pathological alterations, based on a cardiological case. The patient has a particular case of connective tissue disease (CTD), specifically bicuspid aortic valve type (BAV). The presented clinical case is as follows: a 34-year-old patient has been diagnosed with BAV. The subject is concerned about how his condition may affect his daily life. The subject is worried about passing the disease on to his children. He asked experts for advice on the causes, possible consequences and treatments. BAV is a major congenital heart defect, affecting 1–2% of the global population. This review provides an overview of the structure and function of the ECM, which plays an important role in the architecture of heart valves and vascular structures associated with connective tissue disease. The BAV has been observed to affect the connective tissue, although the underlying causes remain unclear. ECM is a 3-dimensional network of macromolecules that provides structural support for cells and tissues. Extensive research has established the regulatory functions of ECM, given its role in orchestrating cell signalling, functions, properties and morphology. Extracellular and cell-bound factors represent a substantial proportion of the major constituents of the ECM. The following proteins and glycoproteins are of particular interest: collagen, elastin, laminins, tenascins, proteoglycans, glycosaminoglycans and hyaluronan. Relevant cell receptors include CD44. Full article

Hypertension, a leading factor for cardiovascular diseases (CVD), is a particularly heavy burden in women during middle age, when cardioprotective hormones begin to decline. The abnormal handling of calcium (Ca²⁺) in vascular smooth muscle cells (VSMCs) leads to increased vasoconstriction, remodeling, and altered arterial compliance during hypertension. The Spontaneously Hypertensive Rats (SHR) is a model of essential hypertension, and middle-aged females with hypertension represent a stage of disease where vascular dysfunction is prominent but understudied. Losartan, a widely prescribed angiotensin II (AngII) receptor (AT1R) blocker, exerts antihypertensive effects by affecting Ang II/Ca²⁺ signaling. However, whether it corrects the Ca²⁺ mishandling in the aorta of middle-aged female SHR has not been established. In this study, the thoracic aorta from 36-week-old female SHRs treated with losartan was assessed for Ca²⁺ mishandling using myography and biochemical assays. Meanwhile, biomechanical properties and stiffness were evaluated using Pulse Wave Velocity (PWV), Atomic Force Microscopy (AFM), and assessments of collagen and elastin contents. Compared with normotensive controls, SHR demonstrated disrupted Ca²⁺ handling, increased stiffness, and Extracellular Matrix (ECM) remodeling in middle-aged females. Treatment with losartan abrogated Ca²⁺ mishandling influx and efflux in the VSMC, decreased stiffness, and restored the aortic structural changes. These findings demonstrate that losartan abolishes Ca²⁺ mishandling and highlight a mechanistic role of AT1R blockade in restoring vascular function in the aorta of middle-aged females during hypertension. Full article

Outward remodelling of arteries is a feature of cardiovascular pathologies such as atherosclerosis and aneurysm, so a greater understanding of the processes involved in remodelling may aid the development of improved therapies for patients. As ageing increases the risk of atherosclerosis and aneurysmal disease, it was therefore hypothesised that ageing affects arterial remodelling and thereby contributes to these diseases. To test this hypothesis, we compared right carotid artery remodelling in young (2 months, n = 13) and old (18–20 months, n = 13) mice resulting from increased blood flow after ligation of the left carotid artery. The media area, thickness, collagen content and α-SM-actin content per cell of control right carotid arteries from old mice were significantly greater than observed in young mice. Positive remodelling was observed in the carotid arteries of both old and young mice 21 days after ligation of the left carotid artery. However, arteries from old mice had a significantly larger increase in lumen size and reduction in media area, thickness and α-SM-actin content per cell compared to young arteries, indicative of augmented positive remodelling in arteries from old mice. Remodelling was associated with significantly increased MMP-2 protein in arteries from young mice, but this was not observed in arteries from old mice. This study demonstrates that the extent of positive remodelling of carotid arteries is greater in old mice than in young mice and results in a potentially less resilient medial layer with decreased α-SM-actin content per cell, elastin and collagen that may promote atherosclerosis and aneurysm formation. Full article

Mesenchymal stem cells (MSCs), particularly their secreted exosomes, small microvesicles, represent a major focus in regenerative medicine due to their therapeutic potential. Exosomes exhibit growth factors and cytokines and are loaded with microRNAs (miRNA) and short interfering RNA (siRNA) that can be transferred to other cells, potentially affecting their function. Exosomes are crucial mediators of intercellular communication, are immunomodulatory, and are promoters of tissue regeneration. Despite their promise, the standardized methods for exosome isolation and characterization remain weak. This exploratory study addresses this gap by detailing an effective method for isolating exosomes from adipose tissue mesenchymal stem cells (AT-MSCs), emphasizing precipitation as a technique yielding a high efficiency and purity compared to other methods. Functionally, we aimed to confirm the AT-MSC exosomes’ ability to exert an effective protective activity on the skin and its main components, such as fibroblasts, collagen, and elastin. To achieve this goal, we had to demonstrate that AT-MSC exosomes are safe and free of toxic substances. They can express specific proteins such as CD9, CD63, and CD81, which are well-known exosome markers. These exosomes also contain key miRNAs, including miRNA-203 A, miRNA-203 B, and miRNA-3196, important for skin regeneration, as well as enhancers of cell integrity and proliferation. We eventually confirmed the ability of exosomes to exert protective and recovery effects on fibroblasts after H₂O₂-induced damage in vitro, as well as on mouse skin after UVB-induced damage in vivo. These effects were verified by measuring levels of reactive oxidative species (ROS), assessing SA-β-Galactosidase (SA-β-Gal) activity, analyzing the cell cycle, evaluating the telomere length of fibroblasts by RT-PCR, and conducting histological assessments of collagen and elastin structure in murine skin after UVB exposure. This exploratory work provides valuable insights into the isolation, characterization, and bioactive and reparative properties of exosomes from AT-MSCs, supporting their development for future studies and therapeutic applications. Full article

Reactive oxygen species (ROS) and mitochondrial dysfunction play a major role in skin aging. Due to Tropaeolum majus’ suggested protective actions against ROS, a link between T. majus extract and increased cytoglobin (CYGB) expression was evaluated for cultured skin cells. Human dermal fibroblasts and keratinocytes were treated with 0.5% v/v T. majus extract and the effect of this treatment on the expression of CYGB and on a range of cellular markers of aging were evaluated. In fibroblasts, the treatment with the extract was associated with an increase in CYGB levels. It also decreased ROS concentrations, improved the function of mitochondria, and stimulated the synthesis of collagen and elastin. Moreover, it downregulated a set of genes controlling the terminal differentiation of keratinocytes. T. majus extract activates oxygen transport within natural killer cells and thus enhances their activity, suggesting a potential senolytic effect. This extract seemed to exert a protective effect on various aging pathways such as ROS production, mitochondrial dysfunction, and collagen homeostasis, playing a promising role against skin aging. Full article

Skin aging is a complex biological process influenced by both intrinsic factors such as hormonal changes, genetic programming, and immunosenescence and extrinsic stressors including ultraviolet (UV) radiation (particularly UV-A and UV-B), pollution, and lifestyle habits. One of the most prominent manifestations of skin aging is wrinkle formation, which arises from the progressive degradation of key extracellular matrix (ECM) components like collagen and elastin. Emerging evidence highlights the skin microbiome as a critical, yet underappreciated, modulator of these structural changes. This review summarizes current understanding of how aging alters skin structure and microbial composition, and how these changes contribute to wrinkle development. Age-associated skin is characterized by reduced hydration, sebum production, and barrier integrity, accompanied by a shift in microbial communities. These microbial shifts promote local inflammation, matrix metalloproteinase (MMP) activation, and oxidative stress, all of which accelerate ECM degradation. We further discuss how commensal microbes and their bioactive products such as probiotics and postbiotics can counteract wrinkle formation. Clinical studies support the efficacy of strains such as Lactobacillus plantarum HY7714 and Bifidobacterium breve in improving skin elasticity and reducing wrinkle depth. Additionally, this review highlights the emerging role of microbiome-based interventions in skincare, including oral supplements, topical formulations, and postbiotic-enriched products. Overall, we emphasized the therapeutic potential of microbiome modulation as a novel strategy for maintaining skin health and preventing wrinkle formation during aging. Full article

Abdominal aortic aneurysms (AAAs) are progressive, life-threatening vascular disorders characterized by focal dilation of the abdominal aorta due to chronic weakening of the arterial wall. The condition often remains asymptomatic until rupture, which carries mortality rates exceeding 70–85%. Among the various etiological theories of AAA development, degradation of the extracellular matrix (ECM) has emerged as the most widely accepted paradigm, with the breakdown of elastin representing a central and irreversible hallmark event. Elastin, a highly cross-linked and durable structural protein, provides elasticity and recoil to the aortic wall. In human AAA specimens, reduced elastin content, impaired cross-linking, and extensive fiber fragmentation are consistently observed, while experimental studies across multiple animal models confirm that elastin degradation directly correlates with aneurysm initiation, expansion, and rupture risk. Elastin loss is driven by a complex interplay of proteolytic enzymes coupled with inflammatory cell infiltration and oxidative stress. Furthermore, elastin-derived peptides perpetuate immune cell recruitment and matrix degradation, creating a vicious cycle of wall injury. Genetic and epigenetic factors, including variants in ECM regulators and dysregulation of non-coding RNAs, further modulate elastin homeostasis in AAA pathobiology. Clinically, biomarkers of elastin turnover and elastin-targeted molecular imaging techniques are emerging as tools for risk stratification. Therapeutically, novel strategies aimed at stabilizing elastin fibers, enhancing cross-linking, or delivering drugs directly to sites of elastin damage have shown promise in preclinical models and early translational studies. In parallel, regenerative approaches employing stem cells, exosomes, and bioengineered elastin scaffolds are under development to restore structural integrity. Collectively, these advances underscore the pivotal roles of elastin not only as a structural determinant of aneurysm development but also as a diagnostic and therapeutic target. This review summarizes and integrates recent discoveries on elastin biology in AAA, with a particular emphasis on molecular mechanisms of elastin degradation and the translational potential of elastin-centered interventions for the prevention and treatment of AAA. Full article

Background: Type 2 diabetes (T2D) is associated with reduced cardiorespiratory fitness (CRF), a critical predictor of cardiovascular disease and all-cause mortality. CRF relies upon the coordinated action of multiple systems including the skeletal muscle where the mitochondria metabolize oxygen and substrates to sustain ATP production. Yet, previous studies have shown that impairments in muscle bioenergetics in T2D are not solely due to mitochondrial deficits. This finding indicates that factors outside the mitochondria, particularly within the local tissue microenvironment, may contribute to reduced CRF. One such factor is the extracellular matrix (ECM), which plays structural and regulatory roles in metabolic processes. Despite its potential regulatory role, the contribution of ECM remodeling to metabolic impairment in T2D remains poorly understood. We hypothesize that pathological remodeling of the skeletal muscle ECM in overweight individuals with and without T2D impairs bioenergetics and insulin sensitivity, and that exercise may help to ameliorate these effects. Methods: Participants with T2D (n = 21) and overweight controls (n = 24) completed a 10-day single-leg exercise training (SLET) intervention. Muscle samples obtained before and after the intervention were analyzed for ECM components, including collagen, elastin, hyaluronic acid, dystrophin, and proteoglycans, using second harmonic generation imaging and immunohistochemistry. Results: Positive correlations were observed with elastin content and both glucose infusion rate (p = 0.0010) and CRF (0.0363). The collagen area was elevated in participants with T2D at baseline (p = 0.0443) and showed a trend toward reduction following a 10-day SLET (p = 0.0867). Collagen mass remained unchanged, suggesting differences in density. Dystrophin levels were increased with SLET (p = 0.0256). Conclusions: These findings identify that structural proteins contribute to aerobic capacity and identify elastin as an ECM component linked to insulin sensitivity and CRF. Full article

Elastin is the principal protein found in the elastic fibers of vertebrate tissues, and the water within these fibers plays a crucial role in preserving the structure and function of this hydrophobic protein. Soluble elastin was successfully obtained by repeatedly treating insoluble elastin, extracted from pig aorta, with oxalic acid. Solid-state NMR analysis was performed on the soluble elastin, focusing on conformation-dependent chemical shifts of alanine residues. This analysis revealed that cross-linked alanine residues exhibited both α-helix and random coil structures in the dry state. In contrast, the hydrated state favored random coil structures, with some distorted helices possibly present, indicating that the cross-linked configuration is relatively unstable. Similar conformational changes were observed in insoluble elastin, mirroring those found in the soluble form. Additionally, when the soluble elastin was re-cross-linked using 1,12-dodecanedicarboxylic acid and 4-hydroxyphenyl dimethylsulfonium methylsulfate, it retained a mixture of α-helix and random coil structures in the dry state. Remarkably, in the hydrated state, α-helix structures were more prominently preserved alongside random coils. These structural changes corresponded with increased stiffness of molecular chains in the hydrophobic regions compared to their state prior to re-cross-linking, even under hydrated conditions. Full article

Cellular senescence is a major barrier to the therapeutic application of human mesenchymal stem cells (hMSCs), as it compromises their proliferative capacity, differentiation potential, and regenerative efficacy. In this study, we investigated whether FN9-10ELP, a recombinant extracellular matrix (ECM)-mimetic fusion protein composed of fibronectin type III domains 9 and 10 conjugated to elastin-like polypeptides (ELPs), could attenuate etoposide-induced senescence in human turbinate-derived MSCs (hTMSCs). Premature senescence was induced by treatment with 20 µM etoposide, and the protective effects of FN9-10ELP were evaluated in terms of cell viability (using the MTT assay), senescence-associated gene expression (by RT-qPCR analysis), nuclear morphology (after staining with 4’,6-diamidino-2-phenylindole (DAPI)), and SA-β-galactosidase activity. FN9-10ELP treatment significantly improved cell viability and reduced the expression of senescence-associated secretory phenotype (SASP) genes, including interleukin-6 (IL-6), interleukin-8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1). Furthermore, FN9-10ELP alleviated nuclear enlargement and decreased the proportion of SA-β-gal-positive cells, indicating suppression of the senescence phenotype. These findings demonstrate that FN9-10ELP effectively counteracts chemotherapy-induced senescence in hMSCs and highlight its potential as a promising biomaterial for regenerative medicine and anti-aging therapies. Full article

The revalorization of porcine meat by-products is necessary to reduce their environmental and economic impact. Porcine lungs are usually discarded or used for low-value purposes despite their richness in collagen, elastin, or phospholipids. Enzymatic hydrolysis, in combination with ultrasound pretreatment, improves the generation of hydrolyzates with biological and taste-enhancing properties. The main objective of this study was to evaluate the impact of ultrasound pretreatment and enzyme concentration in the development of functional and taste-rich porcine lung hydrolyzates. Ultrasound pretreatments significantly increased the degree of hydrolysis and the antioxidant activity in 1:100 Enzyme: Substrate (E/S) ratio hydrolyzates. On the other hand, the combination of 1:20 E/S concentration with ultrasound pretreatment significantly increased the umami free amino acids content and Equivalent Umami Concentration (EUC), being the last one comparable with other umami-rich foods and ingredients. In silico predictions showed that the use of ultrasound pretreatment enhances the percentage of potential bioactive peptides according to PeptideRanker, whereas the bioinformatics tools UMPred-FRL and BERT4Bitter showed more umami peptides than bitter in all the hydrolyzates. These results suggest the combination of ultrasound pretreatment with 1:20 E/S can be a good strategy to revalorize porcine lung by producing hydrolyzates that could be used as a functional ingredient. Full article

This article provides a comprehensive review and explores the gaps in current knowledge of lysine metabolism in humans and its potential nutritional and therapeutic indications. The first part of this study examines lysine sources, requirements, transport through the plasma membrane, lysine catabolism, and its disorders. The central part is focused on post-translational modifications of lysine in proteins, primarily desmosine formation in elastin, hydroxylation in collagen, covalent bonds with glutamine, methylation, ubiquitination, sumoylation, neddylation, acylation, lactylation, carbamylation, and glycation. Special sections are devoted to using lysine as a substrate for homoarginine and carnitine synthesis and in nutrition and medicine. It is concluded that the identification and detailed knowledge of writers, readers, and erasers of specific post-translational modifications of lysine residues in proteins is needed for a better understanding of the role of lysine in epigenetic regulation. Further research is required to explore the influence of lysine availability on homoarginine formation and how the phenomenon of lysine–arginine antagonism can be used to influence immune and cardiovascular functions and cancer development. Of unique importance is the investigation of the use of lysine in osteoporosis therapy and in reducing the resorption of harmful substances in the kidneys, as well as the therapeutic potential of polylysine and lysine analogs. Full article

Candida species commonly secrete aspartic peptidases (Saps), which are virulence factors involved in nutrient acquisition, colonization, tissue invasion, immune evasion and host adaptation. However, the regulation of Sap production remains poorly characterized in emerging, widespread and multidrug-resistant members of the Candida haemulonii clade (C. auris, C. haemulonii, C. haemulonii var. vulnera and C. duobushaemulonii). This study investigated the influence of temperature, pH and protein substrate on Sap production using bloodstream isolates of the C. haemulonii clade. Sap activity was initially assessed using the enzyme coefficient (Pz) in fungal cells grown on yeast carbon base (YCB) agar supplemented with bovine serum albumin (BSA) to determine optimal conditions for enzymatic production. C. auris and C. duobushaemulonii exhibited the highest Sap activity at 96 h, pH 4.0–5.0, and 37 °C, whereas C. haemulonii and C. haemulonii var. vulnera displayed more variable and isolate-dependent profiles. Sap production was markedly suppressed at pH 6.0. The addition of pepstatin A, an inhibitor of aspartic peptidases, abolished Sap activity and impaired fungal growth in a dose-dependent manner, confirming both the enzymatic identity and its critical role in nitrogen acquisition. Conversely, YCB supplemented with an inorganic nitrogen source (ammonium sulfate) supported fungal growth but did not induce Sap production. To explore substrate specificity, YCB was supplemented with a panel of proteins. Serum albumins (bovine and human) induced the highest Sap production, followed by globulin, gelatin, hemoglobin, collagen and immunoglobulin G, while elastin and mucin elicited the lowest Sap production. Isolate-specific preferences for protein substrates were observed. Finally, fluorometric assays using a Sap-specific fluorogenic peptide substrate confirmed the presence of Sap activity in cell-free supernatants, which was consistently and entirely blocked by pepstatin A. These findings highlight inter- and intraspecies variability in Sap regulation among C. haemulonii clade, stressing the critical roles of substrate availability, pH and temperature in shaping fungal adaptation to host environments. Full article

Background: Skin aging is mainly associated with oxidative stress and enzymatic degradation of collagen and elastin by protease activity. Peptides have antioxidant capacity and inhibitory effects on protease enzymes. Objective: The purpose of this study was to obtain peptides with in vitro anti-aging activity from the enzymatic hydrolysis of bovine casein with actinidin, a protease extracted from the green kiwi fruit (Actinidia deliciosa) Methodology: The enzyme actinidin was extracted from the pulp of the kiwi fruit, purified by ion exchange chromatography and characterized by polyacrylamide electrophoresis (SDS-PAGE). Subsequently, the extracted enzyme was used to hydrolyze commercial bovine casein at 37 °C for 30 min, precipitating the peptide fraction with trichloroacetic acid (TCA), and centrifuged. To determine the anti-aging potential of the peptides in vitro, antioxidant activity was evaluated using the ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical. Additionally, the inhibitory capacity of the peptides against collagenase and elastase enzymes was also studied. To complement the in vitro results, the enzymatic hydrolysis of casein with actinidin was simulated. The binding energy (ΔG) of each of the hydrolysates with the collagenase and elastase enzymes was calculated using molecular docking to predict the peptide sequences with the highest probability of interaction. Results: Actinidin was extracted and purified exhibiting a molecular weight close to 27 kDa. The enzyme hydrolyzed the substrate by 91.6%, and the resulting hydrolysates showed moderate in vitro anti-aging activity: antioxidant (17.5%), anticollagenase (18.55%), and antielastase (28.6%). In silico results revealed 66 peptide sequences of which 30.3% consisted of 4–8 amino acids, a suitable size to facilitate interaction with structural targets. The sequences with the highest affinity were FALPQYLK and VIPYVRYL for collagenase and elastase, respectively. Conclusions: Despite the modest inhibition values, the use of a fruit-derived enzyme and a food-grade substrate is in line with current trends in sustainable and natural cosmetics. These findings highlight the great potential for laying the groundwork for future research into actinidin-derived peptides as multifunctional and eco-conscious ingredients for the development of next-generation anti-aging formulations. Full article