Search Results (87)

Recent studies support the concept of a bidirectional lung–brain axis. While neural, immune, and microbial pathways are increasingly recognized in lung-to-brain communication, the role of matrikines—bioactive peptides generated by extracellular matrix (ECM) proteolysis during remodeling—in this inter-organ communication remains underexplored. This review highlights matrikines originating from the lung, particularly the collagen-derived tripeptide Pro-Gly-Pro (PGP) and the elastin-derived hexapeptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG), as potential mediators linking pulmonary pathology with neurological outcomes. The lung is rich in ECM proteins, and inflammatory conditions such as chronic obstructive pulmonary disease (COPD) and emphysema trigger proteolytic activity by matrix metalloproteinases (MMPs) and neutrophil elastase, releasing matrikines into circulation. Under conditions of blood–brain barrier (BBB) dysfunction, they may access the central nervous system (CNS), where they influence neurons, microglia, and astrocytes, modulating neuroinflammation, autophagy, and synaptic integrity. While PGP can exhibit context-dependent neuroprotective effects, its acetylated form and VGVAPG are associated with neurotoxicity, Tau hyperphosphorylation, and microglial activation. Additional matrikines, including Gly-His-Lys (GHK) and endorepellin, may further modulate CNS homeostasis. Collectively, these findings support lung-derived matrikines as circulating mediators of lung-to-brain signaling, providing a novel mechanistic framework linking chronic pulmonary inflammation to neuropathologies, such as stroke and neurodegenerative disorders, and highlighting potential targets for therapeutic intervention. Full article

Glioblastoma, with a 5-year survival rate of just under 7.0%, is the most common form of brain cancer in adults. In this study, we evaluated the antiproliferative activity of the biopolymer p21-ELP1-Bac, a p21-derived peptide delivered via an elastin-like polypeptide (ELP1) carrier and a cell-penetrating peptide (CPP), across three glioblastoma cell lines: U87, GBM43, and GBM6. We assessed proliferation, cell cycle progression, and apoptosis to determine whether ELP-mediated intracellular delivery of p21-ELP1-Bac suppresses glioblastoma growth through cytostatic mechanisms rather than inducing apoptosis. Treatment with the modified protein effectively inhibited proliferation across all three lines, with U87 cells showing the greatest sensitivity and GBM6 cells demonstrating the greatest drug tolerance. Although apoptotic responses were generally low, they appeared more pronounced in GBM6 cells. Confocal microscopy revealed sustained cellular uptake and signal observed in both the cytoplasm and in proximity to the nucleus in all cell lines. Collectively, these findings indicate that p21-ELP1-Bac is efficiently internalized and capable of modulating proliferation across all three glioblastoma cell lines, supporting its further evaluation as a cytostatic delivery platform. Full article

Background: No Fourier transform infrared (FTIR) spectroscopy studies have directly evaluated adrenalectomy vessels, the technique’s established ability to probe collagen/elastin-associated spectral features and lipid peroxidation-related signatures, and protein structural damage. Stable gastric pentadecapeptide BPC 157 therapy was found to maintain the vascular function under severe stress, as FTIR spectroscopy recently demonstrated rapid peptide-induced molecular changes in healthy rat blood vessels, particularly in lipid content and protein secondary structure. Methods: To extend these findings and highlight the BPC 157 vascular background in the special circumstances of the course following unilateral adrenalectomy, abdominal aortas were collected at 15 min, 5 h, and 24 h after unilateral adrenalectomy for the FTIR spectroscopy assessment. Results: FTIR spectra were acquired, preprocessed, and analyzed using principal component analysis (PCA), support vector machine discriminant analysis (SVMDA), and band-specific statistics. BPC 157 (10 ng/kg intragatrically immediately after unilateral adrenalectomy) produced a clear, reproducible separation of aortic spectra from control samples at all time points. The main discriminatory spectral signatures were observed in three regions, including amide I and amide II (protein-related bands, consistent with collagen/elastin contributions) and lipid C–H stretching bands. These spectral signatures are consistent with early extracellular matrix reinforcement and membrane preservation in the vascular wall and align with the recovering effect on the lesions in counteraction of the severe vascular and multiorgan failure, attenuation/elimination of thrombosis and blood pressure disturbances in various occlusion/occlusion-like syndromes. Conclusions: Together, after unilateral adrenalectomy, the FTIR data provide molecular-level spectral signatures consistent with rapid remodeling of the aortic wall toward a more structurally stable and functionally favorable state. Full article

Chitosan oligosaccharides (COSs) with defined degrees of polymerization (DP) exhibit distinct bioactivities with promising applications in food, pharmaceutical, and agricultural industries. However, the specific and sustainable production of COSs remains challenging due to the broad product distribution of wild-type chitosanases and the difficulties in enzyme recovery and reuse. In this study, we employed rational design to engineer a GH46 chitosanase (CsnB) from Bacillus sp. BY01 for chitobiose production. Through homology modeling and molecular docking analysis, 15 mutants were designed by targeting key residues structurally critical for substrate stabilization, product release, and active-site geometry in the substrate-binding subsites. The D78Y mutant exhibited exclusive specificity for chitobiose, demonstrating a specific activity of 102.4 U/mg and yielding chitobiose with a purity exceeding 98%, thereby surpassing the previously reported enzymes for chitobiose production. To address the challenges of enzyme stability, purification costs, and product separation, we developed a ReELP system by integrating elastin-like polypeptides (ELPs) with a ReverseCatcher/ReverseTag peptide pair. This system enabled one-step purification and co-immobilization of CsnB-D78Y directly from cell lysate onto biomimetic silica nanoparticles, achieving 96.8% immobilization efficiency and 90.7% activity recovery. The immobilized enzyme exhibited enhanced thermal and pH stability, retaining approximately 50% activity after 12 h at 40 °C compared to only 5.7% for the free enzyme. In reusability assays, the immobilized CsnB-D78Y maintained efficient chitobiose production over 5 consecutive cycles. This work provides a green and cost-effective strategy for the specific and sustainable production of chitobiose, offering new insights into enzyme engineering and immobilization for industrial COS production. 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

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

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

Precise control of protein translocation is essential for synthetic biology and protein engineering. Here, we present a temperature-responsive system using elastin-like polypeptides (ELPs) to regulate the translocation of a conditionally lethal enzyme in Escherichia coli. The enzyme, levansucrase, whose activity becomes lethal in the presence of sucrose, was engineered with an N-terminal signal peptide and a C-terminal ELP tag. At 37 °C, the ELP tag induced intracellular aggregation of the fusion protein, preventing its secretion and allowing cell survival, as indicated by translucent colony formation. In contrast, at 16 °C, the ELP remained soluble, permitting levansucrase secretion into the medium. The resulting conversion of sucrose into levan by the secreted enzyme led to host cell death. These findings highlight ELP-mediated aggregation as a reversible and tunable strategy for regulating protein localization and secretion in E. coli, with potential applications in synthetic biology, metabolic engineering, and biocontainment systems. Full article

Chrono Control Penta is a novel plant derived multifunctional bioactive peptide, which offer a tailored targeted approach to skin health by addressing both pigmentation and aging. Chrono Control Penta inhibits tyrosinase with an IC₅₀ value of 202.8 µM. Additionally, it significantly increased collagen (+87.53%) and elastin (+61.29%) production and secretion (+66.29% and +69.74%, respectively) and decreased the Matrix metalloproteinase-9 (MMP-9) and MMP-2 secretion in aged human dermal fibroblasts, vs. aging condition. At the clinical level, Chrono Control Penta was demonstrated to be already active after 2 weeks, promoting a 9.3% reduction in pigmentation after 6 weeks of use, showing its efficacy in promoting skin complexion. Furthermore, it exhibited significant moisturizing (13.05%), anti-wrinkle (11.55%), and purifying effects (12.45%), as well as firming effects (6.35%), after 6 weeks. The peptide was also well tolerated, with no adverse effects reported in clinical patch tests. This timely study presents novel research on a plant derived peptide, Chrono Control Penta, a significantly contribution to the burgeoning cosmetic peptide market. Our rigorous findings make it a new powerful ingredient, offering a comprehensive solution for skin health, and establishing a strong foundation for future research and application. Full article

Emergent phenomena arise from the interaction of competing forces at multiple scale levels, resulting in complex outcomes that are not readily apparent from analyzing the individual components. Regarding biological systems, when a critical threshold is reached, a phase transition occurs, producing a spontaneous system reorganization characterized by recognizable molecular, microscopic, and macroscopic changes. The current paper explores the emergent phenomena underlying the pathogenesis of pulmonary emphysema, a disease characterized by progressive airspace enlargement. The competitive relationship between mechanical strain imposed on alveolar walls and a countervailing increase in elastin crosslinking to prevent alveolar wall rupture leads to airspace enlargement as the balance between these two processes shifts toward increasing lung injury. This phase transition is also accompanied by an accelerated release of peptide-free elastin-specific desmosine crosslinks as the mean alveolar wall diameter begins to increase, suggesting their potential use as a biomarker for the molecular changes that precede the development of pulmonary emphysema. Early detection of the disease would allow more timely therapeutic intervention involving multiple agents that address the complexities of emergent phenomena at different scale levels. Full article

Collagen products are widely marketed for skin improvement. This study evaluated the efficacy of VERISOL B in relation to key skin aging parameters. In a double-blind, placebo-controlled trial, 66 women (aged 35–55) were randomized to receive either 2.5 g of bovine-derived bioactive collagen peptides (SCPs) (n = 33) or a placebo (n = 33) daily for 8 weeks. Their eye wrinkle volume, skin elasticity, and hydration were objectively measured at baseline (X₀), 4 weeks (X₄), and 8 weeks (X₈). Additionally, the SCPs’ impact on type I collagen, elastin, and proteoglycan biosynthesis was assessed in human dermal fibroblasts. The SCP supplementation significantly (p < 0.05) reduced their eye wrinkle volume and improved their skin elasticity and hydration within 4 weeks. After 8 weeks of treatment, the positive effects were even more pronounced for all of the clinical parameters measured (p < 0.05). The fibroblast experiments confirmed the SCPs’ stimulatory impact on dermal metabolism (p < 0.05). In conclusion, oral SCP supplementation effectively reduced wrinkles and enhanced skin elasticity and hydration, likely by promoting extracellular matrix biosynthesis. Full article

Background/Objectives: Previous studies have shown varying efficacy of high-fiber diets containing different ingredients in abdominal aortic aneurysms (AAAs). This study aimed to identify which high-fiber diet protects against AAA in mice and elucidate the underlying mechanisms. Methods: This study compared inulin, cellulose, and chow diets in terms of their impact on aneurysm enlargement, elastin degradation, matrix metalloproteinase 2 and 9 expressions, CD3+ T cell and CD68+ macrophage infiltration, and macrophage differentiation. It also examined gut microbiota composition, focusing on Akkermansia, and evaluated intestinal barrier function and systemic inflammatory response. Results: The inulin diet, but not the cellulose diet, compared with the chow diet, reduced aneurysm enlargement, elastin degradation, matrix metalloproteinase 2 and 9 expressions, CD3+ T cell and CD68+ macrophage infiltration, and skewed macrophage towards M2 differentiation. The inulin diet enriched Akkermansia in both the small and large intestine. The inulin diet also enhanced the intestinal barrier by augmenting goblet cells, upregulating the gene related to the epithelial barrier and antibacterial peptides in the small intestine, and reducing circulating lipopolysaccharide and interleukin-1β levels. The inulin diet lowered the proportion of Ly6Chi monocytes and C-C chemokine receptor 2 expression on these cells in the bone marrow, reducing aneurysm infiltration. Administering Akkermansia to AAA mice decreased intestinal permeability and mitigated AAA. Conclusions: A diet rich in fermentable fiber inulin, as opposed to cellulose, alleviates AAA in mice. This beneficial effect is attributed to the enhanced presence of Akkermansia bacteria and improvement of the intestinal barrier. Full article

The degradation of elastic fibers is a fundamental characteristic of pulmonary emphysema, resulting in the release of proinflammatory elastin peptides. The findings discussed in this paper support the hypothesis that these peptides act as carriers of disease, interacting with elastin receptor complexes that promote inflammation, elastic fiber damage, and airspace enlargement. Studies from our laboratory show that the breakdown of these fibers is significantly enhanced by intratracheal instillation of elastin peptides in a lipopolysaccharide-induced model of acute lung injury. This result is consistent with a mechanism of elastic fiber injury in which an expanding pool of elastin peptides generates further elastolysis. The accelerating release of the peptides results in a self-perpetuating disease process with the features of an epidemic, where self-replicating agents spread disease. As in the case of an epidemic, elastin peptides resemble disease vectors that transmit alveolar wall injury throughout the lung. This concept may provide a framework for developing novel therapeutic approaches specifically designed to protect elastic fibers from various enzymatic and oxidative insults, thereby slowing the progression of a disease with no robust treatment options. Full article

Arterial stiffening is a significant risk factor for the development of cardiovascular diseases, including hypertension, atherosclerosis, and arteriopathy. The destruction of elastic fibers, accompanied by vascular inflammatory remodeling, is a key process in the progression of arterial stiffening and related pathologies. In young, healthy arteries, intact elastic fibers create a resilient microenvironment that maintains the quiescence of arterial cells. However, with advancing age, these elastic fibers undergo post-translational modifications, such as oxidation, glycosylation, and calcification, leading to their eventual degeneration. This degeneration results in the release of degraded peptides and the formation of an inflammatory, stiffened niche. Elastic fiber degeneration profoundly impacts the proinflammatory phenotypes and behaviors of various arterial cells, including endothelial cells, smooth muscle cells, macrophages, fibroblasts, and mast cells. Notably, the degraded elastic fibers release elastin-derived peptides (EDPs), which act as potent inflammatory molecules. EDPs activate various arterial cellular processes, including inflammatory secretion, cell migration, proliferation, and calcification, by interacting with the elastin receptor complex (ERC). These elastin-related cellular events are commonly observed with aging and in diseased arteries. These findings suggest that the degeneration of the elastic fiber meshwork is a primary event driving arterial inflammation, stiffening, and adverse remodeling with advancing age. Therefore, preserving elastic fibers and blocking the EDP/ERC signaling pathways may offer promising therapeutic strategies for mitigating age-related arterial remodeling and related arterial diseases. Full article