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Fibroelastolytic papulosis (FEP) is an acquired cutaneous disorder of elastin that encompasses both white fibrous papulosis of the neck (WFPN) and pseudoxanthoma elasticum (PXE)-like papillary dermal elastolysis (PDE). Although FEP is a benign acquired disorder, it shares overlapping clinical features with pseudoxanthoma elasticum (PXE), a genetic disorder with systemic manifestations. We report two cases of FEP, including the WFPN and PXE-like PDE variants, in elderly women. In one case, a woman in her 70s with hyperlipidemia and chronic kidney disease presented with white-to-yellow, smooth, monomorphic papules coalescing into plaques on the posterior neck and bilateral antecubital fossa. A punch biopsy and elastic stain revealed a loss of elastic fibers in the papillary dermis. Based on these findings, we diagnosed our patient with PXE-like PDE. In another case, a woman in her 60s with no significant medical history similarly presented with skin-colored, smooth monomorphic papules on the posterior and anterior neck. A punch biopsy was also performed and an elastic stain showed a loss of elastic fibers in the papillary dermis, confirming the diagnosis of WFPN. Although rare, FEP is an important entity for dermatologists to recognize and differentiate from PXE given the potential for systemic complications in PXE.

Pulmonary emphysema involves progressive destruction of alveolar walls, leading to enlarged air spaces and impaired gas exchange. While the precise mechanisms responsible for these changes remain unclear, there is growing evidence that the extracellular matrix plays a critical role in the process. An essential feature of pulmonary emphysema is damage to the elastic fiber network surrounding the airspaces, which stores the energy needed to expel air from the lungs. The degradation of these fibers disrupts the mechanical forces involved in respiration, resulting in distension and rupture of alveolar walls. While the initial repair process mainly consists of elastin degradation and resynthesis, continued alveolar wall injury may be associated with increased collagen deposition, resulting in a mixed pattern of emphysema and interstitial fibrosis. Due to the critical role of elastic fiber injury in pulmonary emphysema, preventing damage to this matrix component has emerged as a potential therapeutic strategy. One treatment approach involves the intratracheal administration of hyaluronan, a polysaccharide that prevents elastin breakdown by binding to lung elastic fibers. In clinical trials, inhalation of aerosolized HA decreased elastic fiber injury, as measured by the release of the elastin-specific cross-linking amino acids, desmosine, and isodesmosine. By protecting elastic fibers from enzymatic and oxidative damage, aerosolized HA could alter the natural history of pulmonary emphysema, thereby reducing the risk of respiratory failure. [ABSTRACT FROM AUTHOR]

Objective: The structure of elastic fibres changes with ageing. Elastin microfibril interface–located protein 1 (EMILIN‐1) is known to contribute to structural changes in elastic fibres. EMILIN‐1 is one of the components of elastic fibres and also colocalizes with oxytalan fibres near the epidermis. Therefore, EMILIN‐1 may be affected by epidermal–dermal interactions. The purpose of this study is to identify the key factors involved in epidermal–dermal interactions during the structural degeneration of elastic fibres. Methods: Keratinocytes and fibroblasts were co‐cultured, and changes in elastic fibre‐related proteins were evaluated. Additionally, cytokine arrays were used to identify the factors involved in epidermal–dermal interactions. Results: EMILIN‐1 expression in fibroblasts was increased in the presence of keratinocytes, and its expression decreased when keratinocytes were stressed. Amphiregulin (AREG) and interleukin‐1α (IL‐1α) were identified as the keratinocyte‐derived cytokines that influence the production of EMILIN‐1, which is secreted by the fibroblasts. EMILIN‐1 expression was promoted by AREG and decreased by IL‐1α via an increase in cathepsin K (a catabolic enzyme). AREG and IL‐1α were associated with changes in EMILIN‐1 levels in fibroblasts. Conclusion: The findings suggest that the suppression of IL‐1α expression and promotion of AREG expression in the epidermis could be a new approach that prevents the wrinkles and sagging caused by the structural changes in elastic fibres. [ABSTRACT FROM AUTHOR]

Background: Cutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear. Case presentation: A 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in pulmonary function tests (expiratory volume in one second (FEV1)/forced vital capacity (FVC): 34.85%; %residual volume [RV]: 186.5%; %total lung capacity [TLC]: 129.2%). Pulmonary function tests also indicated small airway disease (%FEF50%, 7.9%; %FEF75%, 5.7%; and %FEF25–75%, 6.8%). Computed tomography (CT) revealed the lack of normal increase in lung attenuation on expiratory CT scan, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD) from 37.84% to 46.61% over the 8-year follow-up, despite the absence of overt changes in CT findings, specifically the lack of normal increase in lung attenuation on expiratory CT scan. Over the same follow-up interval, there was a modest reduction of 25.6 mL/year in FEV1 coupled with a significant increase in %RV. Pulmonary function test metrics, reflective of small airway disease, exhibited a continual decline; specifically, %FEF50%, %FEF75%, and %FEF25–75% diminished from 7.9% to 7.0%, 5.7% to 4.6%, and 6.8% to 5.4%, respectively. Conclusions: This case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a mild reduction in FEV1. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion Skin elasticity, which is vital for a youthful appearance, depends on the elastic fibres in the dermis. However, these fibres deteriorate with ageing, resulting in wrinkles and sagging. Changes that occur in the elastic fibres in living human skin and the relationship between elastic fibres and the state of the skin surface remain unclear. Therefore, it is necessary to verify the relationship between elastic fibres and skin elasticity. In this study, we investigated the association of the elastic fibre structure with skin elasticity and stratum corneum protein content in living human skin.Thirty‐five female volunteers aged 25–66 years were included in this study. Elastic fibres were observed using a multiphoton scanning laser biomicroscope. Skin elasticity was measured using a Cutometer, and stratum corneum proteins (Heat‐shock protein 27 [HSP27] and galectin‐7 [Gal‐7]) in tape‐stripped samples were analysed using an enzyme‐linked immunosorbent assay.Elastic fibres exhibited increased curvature and thickness with increased age, with fragmentation observed in women aged >60 years. Elastin scores, which reflect thinness and curvature, were negatively correlated with age, whereas they were positively correlated with R7 elasticity (recovery ability). In individuals aged 20–30 years, higher levels of inflammatory markers (HSP27 and Gal‐7) correlated with lower elastin scores; however, this trend was not observed in older participants.Elastic fibre deterioration worsened after 40 years of age, and this effect correlated with reduced skin recovery and increased wrinkles. In younger individuals, inflammatory markers affected elastic fibres. These findings can guide anti‐ageing strategies that focus on elastic fibre preservation and inflammation control. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions To elucidate the anti‐ageing mechanism of the combination of eight ingredients on the skin from a multidimensional view of the skin.The target pathway mechanisms of composition to delay skin ageing were investigated by a network pharmacology approach and experimentally validated at three levels: epidermal, dermal, and tissue.We identified 24 statistically significant skin ageing‐related pathways, encompassing crucial processes such as epidermal barrier repair, dermal collagen and elastin production, inhibition of reactive oxygen species (ROS), as well as modulation of acetylcholine and acetylcholine receptor binding. Furthermore, our in vitro experimental findings exhibited the following outcomes: the composition promotes fibroblast proliferation and the expression of barrier‐related genes in the epidermis; it also stimulated the expression of collagen I, collagen III, and elastic fibre while inhibiting ROS and β‐Gal levels in HDF cells within the dermis. Additionally, Spilanthol in the Acmella oleracea extract contained in the composition demonstrated neuro‐relaxing activity in Zebrafish embryo, suggesting its potential as an anti‐wrinkle ingredient at the hypodermis level.In vitro experiments validated the anti‐ageing mechanism of composition at multiple skin levels. This framework can be extended to unravel the functional mechanisms of other clinically validated compositions, including traditional folk recipes utilized in cosmeceuticals. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory condition of the arteries and represents the primary cause of various cardiovascular diseases. Despite ongoing progress, finding effective anti-inflammatory therapeutic strategies for atherosclerosis remains a challenge. Here, we assessed the potential of molecular magnetic resonance imaging (MRI) to visualize the effects of 01BSUR, an anti-interleukin-1β monoclonal antibody, for treating atherosclerosis in a murine model. Male apolipoprotein E-deficient mice were divided into a therapy group (01BSUR, 2 × 0.3 mg/kg subcutaneously, n = 10) and control group (no treatment, n = 10) and received a high-fat diet for eight weeks. The plaque burden was assessed using an elastin-targeted gadolinium-based contrast probe (0.2 mmol/kg intravenously) on a 3 T MRI scanner. T1-weighted imaging showed a significantly lower contrast-to-noise (CNR) ratio in the 01BSUR group (pre: 3.93042664; post: 8.4007067) compared to the control group (pre: 3.70679168; post: 13.2982156) following administration of the elastin-specific MRI probe (p < 0.05). Histological examinations demonstrated a significant reduction in plaque size (p < 0.05) and a significant decrease in plaque elastin content (p < 0.05) in the treatment group compared to control animals. This study demonstrated that 01BSUR hinders the progression of atherosclerosis in a mouse model. Using an elastin-targeted MRI probe, we could quantify these therapeutic effects in MRI. [ABSTRACT FROM AUTHOR]

The article describes the groundbreaking new ingredient Shiloxome ™, developed by Provital, which counteracts signs of aging and protects the skin in a multi-omic way. The ingredient is derived from the endophytic yeast Kwoniella mangroviensis and acts as a protective shield for the skin. Provital has developed a technology that allows them to isolate endophytic strains and investigate their bioactivity. The first developed ingredient, Shiloxome ™, comes from the endophytic yeast species Kwoniella mangroviensis found in the bark of the cork oak. This ingredient protects the skin and gives it the ability to adapt and survive. Provital has also conducted a study on the effectiveness of the ingredient, which has shown that it protects the skin from environmental stressors and improves the integrity of the skin barrier. The active ingredient has a positive effect on the overall chain length of the lipidome and strengthens the permeability barrier of the skin. Signal pathways related to the structure and organization of the extracellular matrix have been identified. The active ingredient also has a significant effect on the remodeling and overall condition of the skin structure and function. An improvement in elastin and collagen I levels has been observed. The results show that the active ingredient strengthens the lipid barrier and contributes to the restoration of youthful and healthy skin. The article describes a new active ingredient called Shiloxome ™, developed by Provital. The active ingredient is based on endophytes and is produced using the Triplobiome ™ technology. Shiloxome ™ offers benefits in the fight against skin aging and restructures the skin barrier. It has been shown that the active ingredient reduces lipid oxidation and provides comprehensive skin protection. Shiloxome ™ is recommended as a powerful ally for resilient, youthful skin. [Extracted from the article]

Objective(s): To study the anti-aging effect of (-)-α-bisabolol ((-)-α-bis) on the skin and preliminarily clarify its mechanism. Materials and Methods: Human skin fibroblasts (HSF) were induced senescence by D-Galactose. Senescence β-galactosidase staining was utilized to evaluate the senescence of HSF. TNF-α, IL6, IL-8, IL-1β, CCL-2, CCL-5, and MMP-9 in senescence-as-sociated secretory phenotype (SASP) were detected by RT-qPCR. Meanwhile, aged BALB/c mice were applied topically with 0.5% and 2%(-)-α-bis gel for 30 days continuously to evaluate anti-aging parameters on the skin such as surface measurement, the Trans Epidermal Water Loss (TEWL), and skin barrier index of dorsal skin. Then, HE staining, Masson staining, and IHC were applied to measure epidermal thickness, collagen fiber content in the dermis, and content of dermal collagen I, respectively. Last, SOD, MDA, and HYP contents of the back skin tissue of mice were also detected. Results: (-)-α-Bis reduced the expression of senescence-associated β-galactosidase (SA-β-gal) and expression levels of SASP in HSF cells stimulated by D-Gal (P<0.05). Mice aged 9 months were applied locally with (-)-α-bis gel to improve skin aging, the TEWL and skin barrier index of dorsal skin, and ameliorate the epidermal thickness and contents of dermal collagen fibers and collagen I (P<0.05). Furthermore, (-)-α-bis up-regulated the mRNA expression levels of elastin and collagen III effectively (P<0.05). Conclusion: (-)-α-Bis can delay the senescence of HSF cells by reducing the expression of SA-β-gal and SASP factors in vitro. Improved skin barrier function as well as SASP is responsible for the delay of skin aging in vivo. [ABSTRACT FROM AUTHOR]

Excessive UV exposure can lead to skin roughness, wrinkles, pigmentation, and reduced elasticity, with severe cases potentially causing skin cancer. Nowadays, various anti-photoaging strategies have been developed to maintain skin health. Among them, dietary supplements with anti-photoaging properties are gaining increasing attention. Yak whey protein (YWP) possesses multiple benefits, including anti-inflammatory, antioxidant, and immune-boosting properties, effectively protecting the skin. This study used a mixed UVA and UVB light source to irradiate a nude mouse model, exploring the advantages of YWP in anti-photoaging and regulating gut microbiota. The results indicated that YWP alleviated UV-induced skin damage, wrinkles, dryness, and reduced elasticity by inhibiting oxidative stress, inflammatory factors (IL-1α, IL-6, and TNF-α), and matrix metalloproteinases (MMP-1, MMP-3, and MMP-12), thereby increasing the levels of elastin, type I collagen, and type III collagen in the extracellular matrix (ECM). Additionally, YWP significantly improved the abundance of Firmicutes and Bacteroidota in the gut microbiota of mice, promoting the growth of beneficial bacteria such as Lachnospiraceae_NK4A136_group, Ruminococcus_torques_group, and Clostridia_UCG_014, mitigating the dysbiosis caused by photoaging. These findings underscore the potential of YWP in anti-photoaging and gut microbiota improvement, highlighting it as a promising functional food for enhancing skin and gut health. [ABSTRACT FROM AUTHOR]

BACKGROUND: The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment. Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament, but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE: To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS: Elastase solution and control buffer were prepared. The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0, 0.1, 1.0, 2.0, 5.0, and 10.0 U/mL elastase solution for 6 hours, and other small samples of the same size were soaked in 2 U/mL elastase solution for 0, 1, 3, 6, 9, and 12 hours. To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect, histological staining was used to compare the effects of enzyme treatment on tissue structure and composition. The ligament samples were randomly divided into elastase-treated group and PBS group, and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours, respectively. A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION: (1) The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%, and had no significant effect on other mechanical-related components in the tissue. (2) The histological results showed that elastase was able to penetrate the tissue, and the loose degree of tissue increased after treatment. (3) In the mechanical results before and after treatment, the mechanical properties of the PBS group decreased significantly, only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group. (4) The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment, but the low-tension elastic modulus, initial slopes, saturated slopes, and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group. (5) These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to examine the aging process of fibrous elements in the dermis of male volunteers over a 10-year period (47–57 years). It was observed that the aging process included visible changes in the content and organization of type I collagen fibers, resulting in changes in fibroblast morphology, and changes in type III collagen and elastic fibers. For the first time, this study presents a comparison of the dynamics of changes in morphology of the dermis in the same volunteer over a time interval of 10 years. Skin aging is a complex phenomenon influenced by multiple internal and external factors that can lead to significant changes in skin structure, particularly the degradation of key extracellular matrix (ECM) components such as collagen and elastic fibers in the dermis. In this study, we aimed to meticulously assess the morphological changes within these critical fibrous ECM elements in the dermis of the same volunteer at age 47 and 10 years later (2012 to 2022). Using advanced histological staining techniques, we examined the distribution and characteristics of ECM components, including type I collagen, type III collagen, and elastic fibers. Morphological analysis, facilitated by hematoxylin and eosin staining, allowed for an accurate assessment of fiber bundle thickness and a quantification of collagen and elastic fiber areas. In addition, we used the generalized Pareto distribution for histogram modeling to refine our statistical analyses. This research represents a pioneering effort to examine changes in ECM fiber material, specifically within the male dermis over a decade-long period. Our findings reveal substantial changes in the organization of type I collagen within the ECM, providing insight into the dynamic processes underlying skin aging. [ABSTRACT FROM AUTHOR]

BACKGROUND: Skin aging as a continuous and irreversible process is mainly the result of alterations of function and structure of the dermis. Among the modalities used for treating skin aging, carboxytherapy has been introduced as a safe minimally-invasive method for rejuvenation, reparation, and reconditioning of the skin. OBJECTIVE: We assessed the efficacy of carboxytherapy for the treatment of intrinsic skin aging through pathological and immunohistochemical (IHC) investigations. METHODS: Our study was a split-body, randomized clinical trial on 15 female patients with intrinsic skin aging of the abdomen. Carboxytherapy was performed on one side of the abdomen, weekly for 10 sessions, while the other side was left untreated. Two weeks after the last session, skin biopsies were taken from both sides of the abdomen. Staining with hematoxylineosin, Masson-trichrome, and Orcein Giemsa was performed for the assessment of epidermal and dermal thickness, collagen, and elastin organization, respectively. IHC examination was performed for investigation of TGF-β1 and VEGF. RESULTS: Pathological examination showed a significant increase in epidermal and dermal thickness and re-organization of collagens and elastic fibers with carboxytherapy. IHC examinations revealed a significantly increased expression of TGF-β1 and VEGF with carboxytherapy. CONCLUSION: Our study demonstrated the effectiveness of carboxytherapy in treating and reversing intrinsic aging skin through pathological and IHC studies. [ABSTRACT FROM AUTHOR]

The mechanical resilience of the knee meniscus is provided by a group of structural proteins in the extracellular matrix. Aging can alter the quantity and molecular structure of these proteins making the meniscus more susceptible to debilitating tears. In this study, we determined the effect of aging on the quantity of structural proteins and collagen crosslinks in human lateral meniscus, and examined whether the quantity of these molecules was predictive of tensile toughness (area under the stress‐strain curve). Two age groups were tested: a young group under 40 and an older group over 65 years old. Using mass spectrometry, we quantified the abundance of proteins and collagen crosslinks in meniscal tissue that was adjacent to the dumbbell‐shaped specimens used to measure uniaxial tensile toughness parallel or perpendicular to the circumferential fiber orientation. We found that the enzymatic collagen crosslink deoxypyridinoline had a significant positive correlation with toughness, and reductions in the quantity of this crosslink with aging were associated with a loss of toughness in the ground substance and fibers. The non‐enzymatic collagen crosslink carboxymethyl‐lysine increased in quantity with aging, and these increases corresponded to reductions in ground substance toughness. For the collagenous (Types I, II, IV, VI, VIII) and non‐collagenous structural proteins (elastin, decorin, biglycan, prolargin) analyzed in this study, only the quantity of collagen VIII was predictive of toughness. This study provides valuable insights on the structure‐function relationships of the human meniscus, and how aging causes structural adaptations that weaken the tissue's mechanical integrity. [ABSTRACT FROM AUTHOR]

Elastin, a key structural protein essential for the elasticity of the skin and elastogenic tissues, degrades with age. Replenishing elastin holds promise for anti-aging cosmetics and the supplementation of elastic activities of the cardiovascular system. We employed RiboScreenTM, a technology for identifying molecules that enhance the production of specific proteins, to target the production of tropoelastin. We make use of RiboScreenTM in two crucial steps: first, to pinpoint a target ribosomal protein (TRP), which acts as a switch to increase the production of the protein of interest (POI), and second, to identify small molecules that activate this ribosomal protein switch. Using RiboScreenTM, we identified ribosomal protein L40, henceforth eL40, as a TRP switch to boost tropoelastin production. Drug discovery identified a small-molecule hit that binds to eL40. In-cell treatment demonstrated activity of the eL40 ligand and delivered increased tropoelastin production levels in a dose-dependent manner. Thus, we demonstrate that RiboScreenTM can successfully identify a small-molecule hit capable of selectively enhancing tropoelastin production. This compound has the potential to be developed for topical or systemic applications to promote skin rejuvenation and to supplement elastic functionality within the cardiovascular system. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cells (VSMCs) play a critical role in maintaining vascular integrity. VSMC dysfunction leads to numerous vascular diseases. Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, has shown both RNA editing and non-editing functions. Global deletion of ADAR1 causes embryonic lethality, but the phenotype of homozygous ADAR1 deletion specifically in SMCs (ADAR1sm-/-) remains to be determined. By crossing ADAR1fl/fl mice with Myh11-CreERT2 mice followed by Tamoxifen induction, we found that ADAR1sm-/- leads to lethality in adult mice 14 days after the induction. Gross examination revealed extensive hemorrhage and detrimental vascular damage in different organs. Histological analyses revealed destruction of artery structural integrity with detachment of elastin laminae from VSMCs in ADAR1sm-/- aortas. Furthermore, ADAR1sm-/- resulted in severe VSMC apoptosis and mitochondrial dysfunction. RNA sequencing analyses of ADAR1sm-/- aorta segments demonstrated profound transcriptional alteration of genes impacting vascular health including a decrease in fibrillin-1 expression. More importantly, ADAR1sm-/- disrupts the elastin and fibrillin-1 interaction, a molecular event essential for artery structure. Our results indicate that ADAR1 plays a critical role in maintaining SMC survival and vascular stability and resilience. [ABSTRACT FROM AUTHOR]

In this study, bioengineered and biosynthesized elastin-like polypeptide (ELP) was adopted for a non-volatile memory resistive switching device or a memristor. The ELP mimicked from elastin of mammal was synthetically produced in polypeptide by Escherichia coli gene recombination. They were composed of a repeating pentapeptide sequence having [Val-Pro-Gly-Val-Gly]32 sequence for bioelectronic devices with ELP showing multiple electrical resistance states between a high resistance state and a low resistance state through an applied electrical field. In addition, the ELP-coated 5-nm gold nanoparticles (Au NPs) layer was also to be biomaterials used for nanobiohybrid memristive devices. Simple metal–insulator–metal device structure and lateral electrode device with ELP layer on 5-nm Au NPs could show neuromorphic adaptive current–voltage (I–V) behavior and electrical stimulus-induced potentiation and depression in a hydrogel state. In addition, with an introduction of a neurotransmitter cortisol's specific antibody, a preliminary sensing protocol was also examined with the nanobiohybrid device. Therefore, the introduction of ELP into neuromorphic device is regarded as the cornerstone for the development of biocompatible bioelectronic devices that can be integrated into human bionics for future artificial neuromorphic format. [ABSTRACT FROM AUTHOR]

A peptide-based hydrogel sequence was computationally predicted from the Ala-rich cross-linked domains of elastin. Three candidate peptides were subsequently synthesised and characterised as potential drug delivery vehicles. The elastin-derived peptides are Fmoc-FFAAAAKAA-NH2, Fmoc-FFAAAKAA-NH2, and Fmoc-FFAAAKAAA-NH2. All three peptide sequences were able to self-assemble into nanofibers. However, only the first two could form hydrogels, which are preferred as delivery systems compared to solutions. Both of these peptides also exhibited favourable nanofiber lengths of at least 1.86 and 4.57 µm, respectively, which are beneficial for the successful delivery and stability of drugs. The shorter fibre lengths of the third peptide (maximum 0.649 µm) could have inhibited their self-assembly into the three-dimensional networks crucial to hydrogel formation. [ABSTRACT FROM AUTHOR]

Abstract Tendon healing involves mechanosensitive cells that adapt to mechanical stimuli through mechanotransduction, resulting in increased tissue strength. However, detailed insights into this process in response to different loads remain limited. We aimed to investigate how different loading regimes impact the spatial composition of elastin and collagens during Achilles tendon healing. Histological analysis was conducted on healing rat Achilles tendons exposed to (1) full loading, (2) reduced loading, or (3) minimal loading. Histological analysis included Hematoxylin & Eosin and immunohistochemical staining targeting elastin, Collagen 1, Collagen 3, and CD31. Our results showed that the impact of mechanical stimuli on healing tendons varied with the degree of loading. Unexpectedly, minimal loading led to higher staining intensity for collagens and elastin. However, tendons exposed to minimal loading appeared thinner and exhibited a less organized matrix structure, with fewer, less aligned, and more rounded cells. Additionally, our findings indicated an inverse correlation between angiogenesis and load level, with more blood vessels in tendons subjected to less loading. Tissue integrity improved by 12 weeks post-injury, but the healing process continued and did not regain the structure seen in intact tendons even after 20 weeks. This study reveals a load-dependent effect on matrix alignment, cell density, and cell alignment.

Abstract Background Cutis laxa constitutes a diverse group of connective tissue diseases, both inherited and acquired, characterized by loose skin and varying systemic involvement, including pulmonary lesions. While cutis laxa has been linked to conditions like emphysema, asthma, and bronchiectasis, the specific pathological and radiological characteristics underlying pulmonary complications related to cutis laxa remain unclear. Case presentation A 36-year-old woman, diagnosed with cutis laxa at birth, presented to our outpatient clinic with severe obstructive ventilatory impairment, evident in pulmonary function tests (expiratory volume in one second (FEV1)/forced vital capacity (FVC): 34.85%; %residual volume [RV]: 186.5%; %total lung capacity [TLC]: 129.2%). Pulmonary function tests also indicated small airway disease (%FEF50%, 7.9%; %FEF75%, 5.7%; and %FEF25–75%, 6.8%). Computed tomography (CT) revealed the lack of normal increase in lung attenuation on expiratory CT scan, with no discernible emphysematous changes. Exome sequencing was performed to confirm the association between the pulmonary lesions and cutis laxa, revealing a frameshift variant in exon 30 of the elastin gene (ELN). Further analysis employing a parametric response map revealed a longitudinal increase in the percentage of functional small airway disease (fSAD) from 37.84% to 46.61% over the 8-year follow-up, despite the absence of overt changes in CT findings, specifically the lack of normal increase in lung attenuation on expiratory CT scan. Over the same follow-up interval, there was a modest reduction of 25.6 mL/year in FEV1 coupled with a significant increase in %RV. Pulmonary function test metrics, reflective of small airway disease, exhibited a continual decline; specifically, %FEF50%, %FEF75%, and %FEF25–75% diminished from 7.9% to 7.0%, 5.7% to 4.6%, and 6.8% to 5.4%, respectively. Conclusions This case highlighted an instance of autosomal dominant cutis laxa arising from a frameshift variant in exon 30 of ELN, accompanied by small airway disease. Comprehensive investigation, utilizing quantitative CT analysis, revealed a longitudinal increase in fSAD percentage with a mild reduction in FEV1. These findings indicate that elastin deficiency may not only diminish elastic fibers in the skin but also be implicated in small airway disease by impacting components of the extracellular matrix in the lungs.

Abstract Atherosclerosis is a chronic inflammatory condition of the arteries and represents the primary cause of various cardiovascular diseases. Despite ongoing progress, finding effective anti-inflammatory therapeutic strategies for atherosclerosis remains a challenge. Here, we assessed the potential of molecular magnetic resonance imaging (MRI) to visualize the effects of 01BSUR, an anti-interleukin-1β monoclonal antibody, for treating atherosclerosis in a murine model. Male apolipoprotein E-deficient mice were divided into a therapy group (01BSUR, 2 × 0.3 mg/kg subcutaneously, n = 10) and control group (no treatment, n = 10) and received a high-fat diet for eight weeks. The plaque burden was assessed using an elastin-targeted gadolinium-based contrast probe (0.2 mmol/kg intravenously) on a 3 T MRI scanner. T1-weighted imaging showed a significantly lower contrast-to-noise (CNR) ratio in the 01BSUR group (pre: 3.93042664; post: 8.4007067) compared to the control group (pre: 3.70679168; post: 13.2982156) following administration of the elastin-specific MRI probe (p

Background: Nanotechnology has the potential to produce innovations in drug formulation and drug delivery systems. Nanocosmetics and nanocosmeceuticals containing natural ingredients have been proven to overcome the weaknesses of traditional cosmetics and also add value to their formulations. Objective: This study aims to analyze the application of nanocosmeceutical technology based on ethanol extract of butterfly pea flower (Clitoria Ternatea L) in the preparation of nanoemulsion spray as a skin antiaging agent for the growth of collagen, elastin and extracellular matrix. Methods Method used true experimental design with posttest control group with random allocation to model mice given UVB radiation. The levels of collagen, elastin, and cellular matrix extract were assessed using Verhoef staining and observed by two experts, Results: The results of this research show that a nanoemulsion spray preparation of ethanol extract of butterfly pea flower (Clitoria Ternatea L) improves skin damage in aging model mice by increasing the production of extra cellular matrix, collagen and elastin. Conclusion: The preparation of butterfly pea flower flower extract nanoemulsion sprey (Clitoria Ternate L) has antiaging, collagen and elastin formation activities

Abstract Large bone defects are a significant health problem today with various origins, including extensive trauma, tumours, or congenital musculoskeletal disorders. Tissue engineering, and in particular bone tissue engineering, aims to respond to this demand. As such, we propose a specific model based on Elastin-Like Recombinamers-based click-chemistry hydrogels given their high biocompatibility and their potent on bone regeneration effect conferred by different bioactive sequences. In this work we demonstrate, using biochemistry, histology, histomorphometry and imaging techniques, the biocompatibility of our matrix and its potent effect on bone regeneration in a model of bone parietal lesion in female New Zealand rabbits.

Global demand for the water monitor's skin, Varanus salvator, has made it a valuable wildlife commodity. Leathercraft manufacturing must consider not only beauty but also the strength and flexibility of the leather, which is determined by its structure in the skin. Therefore, this study analyzed and evaluated the fiber type characteristic of the water monitor's skin. Skin samples were collected from 10 Sumatra water monitors with a Snout-Vent Length size of 39-89 cm and were divided into small (39-59 cm) and large (60-89 cm) groups. The skins from the dorsocervical, lumbosacral, and ventral regions were proceeded for histological sections. Histochemical approaches utilized were Hematoxylin Eosin, Picrosirius Red, and Elastin Verhoeff's Hematoxylin staining methods. Thick fibers are the main component in the skin, ranging from 69-73%, respectively, while thin fibers varied greatly and were observed predominantly in the reticular dermis. Fiber size in the reticular dermis of small lizards was lower than that of larger ones. Elastic fibers were observed abundantly at the border of the reticular dermis and subcutaneous layer in both small and large lizards. Moreover, the skin of the small-sized lizard also has a lower morphometric than that of a large-sized lizard, both in thickness and fiber type percentage. Therefore, the skin of small-sized lizards was considered less tough than that of large-sized lizards. [ABSTRACT FROM AUTHOR]

Background: Indonesia is a tropical country that is exposed to sunlight throughout the year. Due to this exposure, Indonesians are more susceptible to aging. It has been demonstrated that the antioxidative chemicals in Aceh nilam and Arabica Gayo coffee peel extract can prevent the aging process of the skin. Purpose: To observe the effect of combination cream patchouli extract and arabica Gayo coffee peel extract on aging skin, focusing on collagen and elastin. Methods: This is an exploratory study using a randomized post-test only design. The rats were divided into two control groups and three experimental treatments, each with a different active ingredient concentration (10%, 12.5%, and 15% of patchouli and coffee peel extract). For six weeks, each group is exposed to UVB light three times a week, for a total dose of 1020 mJ/cm2. The macroscopic morphology, density, and thickness of collagen and elastin in rat skin were observed and assessed. Result: There were noteworthy variations observed in collagen density, collagen thickness, and elastin density, whereas no significant difference was found in elastin thickness. The macroscopic skin morphology exhibited absence of inflammation across all experimental groups. Conclusions: This study suggests that cream containing Aceh patchouli extract and 15% of Arabica Gayo coffee peel extract exhibits potential in enhancing the quantity and quality of collagen while preserving elastin levels and it is safe for rat skin.

Abstract Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.

In this in vivo study on hairless mice, we examined the effects of light-emitting diode (LED) treatment applied prior to ultraviolet B (UVB) irradiation. We found that pre-treating with LED improved skin morphological and histopathological conditions compared to those only exposed to UVB irradiation. In our study, histological evaluation of collagen and elastic fibers after LED treatment prior to UVB irradiation showed that this pretreatment significantly enhanced the quality of fibers, which were otherwise poor in density and irregularly arranged due to UV exposure alone. This suggests that LED treatment promotes collagen and elastin production, leading to improved skin properties. Additionally, we observed an increase in Claudin-1 expression and a reduction in nuclear factor-erythroid 2-related factor 2 (Nrf-2) and heme-oxygenase 1 (HO-1) expression within the LED-treated skin tissues, suggesting that LED therapy may modulate key skin barrier proteins and oxidative stress markers. These results demonstrate that pretreatment with LED light can enhance the skin’s resistance to UVB-induced damage by modulating gene regulation associated with skin protection. Further investigations are needed to explore the broader biological effects of LED therapy on other tissues such as blood vessels. This study underscores the potential of LED therapy as a non-invasive approach to enhance skin repair and counteract the effects of photoaging caused by UV exposure.

It is well known that the acidity of the microenvironment has a significant impact on the functional activity of cells involved in tissue repair. To date, the effect of biomaterials containing components of the human dermis intercellular matrix on fibroblasts under acidosis has not been fully studied.The aim of the study. To evaluate the effect of a composite hydrogel containing dermal components on the functional activity of intact fibroblasts and fibroblasts with acid-induced dysfunction.Materials and methods. To simulate the physicochemical conditions of acute inflammation, human fibroblasts were incubated for an hour at 39 °C in a nutrient medium overacidified to pH = 6. The morphometric characteristics of human skin fibroblasts were assessed using light and fluorescence microscopy methods. The number of apoptotic cells and proliferation index were assessed using flow cytometry.Results. It has been established that exposure of fibroblasts to an acidic medium inhibits their adhesive properties and reduces the rate of cell growth. The introduction of hydrogel into a cell suspension with damaged cells restores adhesive properties and cell growth. In the fibroblast population, after acid exposure, the number of living cells decreases, and the number of apoptotic cells increases. Cultivation of damaged fibroblasts in the presence of a composite hydrogel increases the number of living cells in the population and reduces the number of apoptotic cells. Acid-induced fibroblast damage reduces the proliferative activity index. It was revealed that the introduction of hydrogel into the culture medium stimulates the proliferative activity of both intact and damaged fibroblasts. The results obtained indicate that a composite hydrogel consisting of extracellular matrix components is capable of restoring the functional activity of fibroblasts damaged as a result of exposure to an acidic medium. The results obtained can be used to create biomaterials that increase the efficiency of skin regeneration in cases of excessively intense acute inflammation.

Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC. [ABSTRACT FROM AUTHOR]

Background: The delicate periorbital region is susceptible to skin dehydration, wrinkles, and loss of elasticity. Thus, targeted and effective anti‐aging interventions are necessary for the periorbital area. Aim: To evaluate the efficacy and safety of a new anti‐aging eye cream formulated with the active complex (Yeast/rice fermentation filtrate, N‐acetylneuraminic acid, palmityl tripeptide‐1, and palmitoyl tetrapeptide‐7). Methods: The cell viability and expressions of key extracellular matrix (ECM) components of the active complex were evaluated using a human skin fibroblast model. In the 12‐week clinical trial, skin hydration, elasticity, facial photographs, and collagen density following eye cream application were assessed using Corneometer, Cutometer, VISIA, and ultrasound device, respectively. Dermatologists and participants evaluated clinical efficacy and safety at baseline, and after 4, 8, and 12 weeks. Results: PCR and immunofluorescent analyses revealed that the active complex significantly stimulated fibroblast proliferation (p < 0.05) and markedly promote the synthesis of collagen and elastin. Clinical findings exhibited a substantial enhancement in skin hydration (28.12%), elasticity (18.81%), and collagen production (54.99%) following 12 weeks of eye cream application. Dermatological evaluations and participants' assessments reported a significant improvement in skin moisture, roughness, elasticity, as well as fine lines and wrinkles by week 8. Conclusion: The new anti‐aging eye cream, enriched with the active complex, demonstrates comprehensive rejuvenating effects, effectively addressing aging concerns in the periorbital area, coupled with a high safety profile. [ABSTRACT FROM AUTHOR]

Background: The negative effects of skin aging are primarily related to the destruction of dermal architectural structure. More specifically, this includes changes in the spatial arrangement of collagen, elastin fibers, mucopolysaccharides, proteoglycans, and ground substances. Aims: The purpose of this study is to investigate the histologic effects of dermal and subdermal tissue after a controlled single treatment with radiofrequency (RF) macroneedling. This therapy provides a controlled, localized, thermal effect on the dermis whereby triggering the body's own healing processes of extracellular matrix remodeling. Clinically benefits include skin tightening. Methods: Biopsies were obtained for histologic evaluation from four patients (n = 4), 4 weeks after completing a single RF macroneedling facial treatment. Results: Age‐related changes of the dermal and subdermal architecture were observed at baseline. After treatment, all biopsies demonstrated an increase in epidermal cells, collagen, elastin, fibroblasts, vasculature, and a decrease in inflammatory cells. Conclusions: The results of this histologic study confirm a significant "subsurfacing" thermal effect from the noncoagulative ascendant thermal injury. The obtained results characterize RF macroneedling therapy as an effective method for correcting age‐related changes in facial skin. [ABSTRACT FROM AUTHOR]

Tremella polysaccharide is the main active substance in Tremella, possessing various functions such as anti- oxidant and anti-aging effects. The widely occurring chemical contaminant in the environment, benzo[a]pyrene (BaP), can be absorbed through the skin and metabolized, thereby posing a risk of carcinogenicity. In this experiment, the antioxidant activity of crude Tremella polysaccharide was measured in vitro, and then cellular assays were conducted to determine the changes in mRNA expression of collagen (Collagen I, Collagen III), Elastin and matrix metalloproteinases-1 (MMP-1) in fibroblasts under the combined effect of BaP and Tremella polysaccharide, along with the protein content of Collagen I. The anti-aging effect of polysaccharides was also determined. It was found that Tremella polysaccharide had good in vitro antioxidant activity with the highest superoxide anion radical scavenging rate of 70.28%, DPPH scavenging rate of 50.10% and hydroxyl radical scavenging rate of 32.69%. Tremella polysaccharide only at 0.1 µg/mL could effectively inhibit the stimulation of related gene expression by BaP at 20 µmol/L (P<0.05). The expression of Collagen I, Collagen III and Elastin genes increased in a polysaccharide concentration-dependent manner. Under BaP exposure, although collagen gene expression increased to 1.26-fold, the heavily expressed MMP-1 caused the degradation of collagen, therefore, under the effect of Tremella polysaccharide, the content of Collagen-1 decreased to 3.06 µg/L (which was lower than the value of the blank control: 3.48 µg/L). The results indicated that Tremella polysaccharide could effectively inhibit the BaP-induced damage to cells and promote the expression of cell genes (on which the concentration had an important influence). [ABSTRACT FROM AUTHOR]

Native tissues feature unique hierarchical designs, in which fiber units are arranged from the bottom up in anisotropic patterns. The processing of biomaterials into fibers, followed by their textile‐like assembly into complex patterns, is therefore a promising avenue to engineer native‐like tissue replacements. Here it is shown for the first time the fabrication of meter‐long hydrogel fibers prepared from engineered elastin using a microinjection system and exploiting the catalyst‐free click chemistry. Given their similarity to native elastin, the fabricated elastin‐like fibers achieved excellent stretching (500%) and recoiling performance. Moreover, the fabrication scheme is compatible with the implementation of a salt‐leaching gas‐foaming approach, resulting in highly porous elastin‐like fibers (the first of their kind). From the translation perspective, the fibers can be autoclaved, which allows for sterilization and long‐term storage. Human umbilical vein endothelial cells cultured on autoclaved fibers produced a confluent endothelial layer lining the fiber surface, in which the cells became aligned in response to physiological fiber stretching. It is also shown that these functional fibers can be assembled by weaving, braiding and knitting, with various spatial patterns. Overall, the elastin‐like fibers can be used as building blocks for the reconstruction of functional tissues using the principles of textile technology. [ABSTRACT FROM AUTHOR]

Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male ApoE−/− mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin, and mice were randomized into four groups: (1) control/COG: no intervention; (2) ΒOG: bosentan 100 mg/kg/day per os; (3) ATG: atorvastatin 20 mg/kg/day per os; and (4) BO + ATG: combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix metalloproteinases (MMP-2, -3, -9), and TIMP-1 were determined. The percentage of lumen stenosis was significantly lower across all treated groups: BOG: 19.5 ± 2.2%, ATG: 12.8 ± 4.8%, and BO + ATG: 9.1 ± 2.7% compared to controls (24.6 ± 4.8%, p < 0.001). The administration of both atorvastatin and bosentan resulted in significantly higher collagen content and thicker fibrous cap versus COG (p < 0.01). All intervention groups showed lower relative intra-plaque concentrations of MCP-1, MMP-3, and MMP-9 and a higher TIMP-1concentration compared to COG (p < 0.001). Importantly, latter parameters presented lower levels when bosentan was combined with atorvastatin compared to COG (p < 0.05). Bosentan treatment in diabetic, atherosclerotic ApoE−/− mice delayed the atherosclerosis progression and enhanced plaques' stability, showing modest but additive effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Aneurysms pose life-threatening risks due to the dilatation of the arteries and carry a high risk of rupture. Despite continuous research efforts, there are still no satisfactory or clinically effective pharmaceutical treatments for this condition. Accelerated inflammatory processes during aneurysm development lead to increased levels of matrix metalloproteinases (MMPs) and destabilization of the vessel wall through the degradation of the structural components of the extracellular matrix (ECM), mainly collagen and elastin. Tissue inhibitors of metalloproteinases (TIMPs) directly regulate MMP activity and consequently inhibit ECM proteolysis. In this work, the synthesis of TIMP-1 protein was increased by the exogenous delivery of synthetic TIMP-1 encoding mRNA into aortic vessel tissue in an attempt to inhibit MMP-9. In vitro, TIMP-1 mRNA transfection resulted in significantly increased TIMP-1 protein expression in various cells. The functionality of the expressed protein was evaluated in an appropriate ex vivo aortic vessel model. Decreased MMP-9 activity was detected using in situ zymography 24 h and 48 h post microinjection of 5 µg TIMP-1 mRNA into the aortic vessel wall. These results suggest that TIMP-1 mRNA administration is a promising approach for the treatment of aneurysms. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) is critical to biological architecture and determines cellular properties, function and activity. In many situations it is highly abundant, with collagens and elastin being some of the most abundant proteins in mammals. The ECM comprises of multiple different protein species and sugar polymers, with both different isoforms and post-translational modifications (PTMs) providing a large variety of microenvironments that play a key role in determining tissue structure and health. A number of the PTMs (e.g. cross-links) present in the ECM are critical to integrity and function, whereas others are deleterious to both ECM structure and associated cells. Modifications induced by reactive oxidants and electrophiles have been reported to accumulate in some ECM with increasing age. This accumulation can be exacerbated by disease, and in particular those associated with acute or chronic inflammation, obesity and diabetes. This is likely to be due to higher fluxes of modifying agents in these conditions. In this focused review, the role and effects of oxidants and other electrophiles on ECM are discussed, with a particular focus on the artery wall and atherosclerotic cardiovascular disease. Modifications generated on ECM components are reviewed, together with the effects of these species on cellular properties including adhesion, proliferation, migration, viability, metabolic activity, gene expression and phenotype. Increasing data indicates that ECM modifications are both prevalent in human and mammalian tissues and play an important role in disease development and progression. [ABSTRACT FROM AUTHOR]

Despite recent advances in extrusion bioprinting of cell‐laden hydrogels, using naturally derived bioinks to biofabricate complex elastic tissues with both satisfying biological functionalities and superior mechanical properties is hitherto an unmet challenge. Here, we address this challenge with precisely designed biological tough hydrogel bioinks featuring a double‐network structure. The tough hydrogels consisted of energy‐dissipative dynamically crosslinked glycosaminoglycan hyaluronic acid (o‐nitrobenzyl‐grafted hyaluronic acid) and elastin through Schiff's base reaction, and free‐radically polymerized gelatin methacryloyl. The incorporation of elastin further improved the elasticity, stretchability (∼170% strain), and toughness (∼45 kJ m−3) of the hydrogels due to the random coiling structure. We used this novel class of hydrogel bioinks to bioprint several complex elastic tissues with good shape retention. Furthermore, in vitro and in vivo experiments also demonstrated that the existence of elastin in the biocompatible bioinks facilitated improved cell behaviors and biological functions of bioprinted tissues, such as cell spreading and phenotype maintenance as well as tissue regeneration. The results confirmed the potential of the elastin‐containing tough hydrogel bioinks for bioprinting of 3D complex elastic tissues with biological functionalities, which may find widespread applications in elastic tissue regeneration. [ABSTRACT FROM AUTHOR]

Background. Proliferative diabetic retinopathy (PDR) is a major cause of irreversible blindness in the working age population. The dysfunction of retinal vascular endothelial cells (RVECs) is the primary cause of PDR. Extracellular matrix (ECM) accumulation promotes intracellular signaling required for RVEC proliferation, migration, survival, and tube morphogenesis. Objectives. This study aimed to investigate the role of lysyl oxidase (LOX) in the cellular function of RVECs and PDR pathogenesis and to identify the underlying mechanisms. Materials and methods: Protein expression was determined with western blot. The interaction between LOX and elastin (ELN) was detected using a co-immunoprecipitation (Co-IP) assay, and the Cell Counting Kit-8 (CCK-8) assay evaluated cell viability. A colony formation assay was employed to assess the proliferation of human RVECs (hRVECs), and a transwell assay to determine their migration ability. Streptozotocin was used to establish PDR in mice in vivo. A histological analysis was conducted using hematoxylin and eosin (H&E) staining. Results: The results showed that LOX was overexpressed in PDR patients. The LOX knockdown suppressed ECM formation and hRVEC proliferation and migration. Additionally, LOX upregulated ELN expression. However, overexpressed ELN promoted hRVEC proliferation and migration. In vivo experiments showed that curcuminmediated LOX deficiency restored retinal tissue structure. Conclusions. The LOX-knockdown suppressed ECM formation and hRVEC proliferation and migration by inactivating ELN. Therefore, LOX/ELN signaling may be a potential PDR biomarker. [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum (PXE) is a rare disease characterized by ectopic calcification, however, despite the widely spread effect of pro/anti-calcifying systemic factors associated with this genetic metabolic condition, it is not known why elastic fibers in the same patient are mainly fragmented or highly mineralized in clinically unaffected (CUS) and affected (CAS) skin, respectively. Cellular morphology and secretome are investigated in vitro in CUS and CAS fibroblasts. Here we show that, compared to CUS, CAS fibroblasts exhibit: a) differently distributed and organized focal adhesions and stress fibers; b) modified cell-matrix interactions (i.e., collagen gel retraction); c) imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases; d) differentially expressed pro- and anti-calcifying proteoglycans and elastic-fibers associated glycoproteins. These data emphasize that in the development of pathologic mineral deposition fibroblasts play an active role altering the stability of elastic fibers and of the extracellular matrix milieu creating a local microenvironment guiding the level of matrix remodeling at an extent that may lead to degradation (in CUS) or to degradation and calcification (in CAS) of the elastic component. In conclusion, this study contributes to a better understanding of the mechanisms of the mineral deposition that can be also associated with several inherited or age-related diseases (e.g., diabetes, atherosclerosis, chronic kidney diseases). An in vitro study on fibroblasts from clinically affected or unaffected skin of patients with Pseudoxanthoma elasticum indicates that local microenvironment guides the level of matrix remodeling and the extent of elastic fiber calcification. [ABSTRACT FROM AUTHOR]

Lysyl oxidase-like 2 (LOXL2) is a Cu2+-dependent amine oxidase, and it catalyzes the oxidative deamination of the ε-amino group of Lys residues on elastin and collagen, which is critical for extracellular matrix modeling. Stability is an important property for protein and it directly affects the dynamics and function of protein, which strongly relates to the human health and disease. However, the stability of LOXL2 is not well defined, i.e., which residues are important for its stability is unclear. In this paper, protein stability of LOXL2 was calculated by four methods, viz. mCSM, PremPS, DeepDDG and FoldX. Our results indicate that 95 residues (key residues) are important for the stability of LOXL2, with the amount of 14, 13, 8, 11, 26 in domain 1, 2, 3, 4, 5, respectively, while 23 in the linker between domains. Among these key residues, the types (numbers) are Leu (24), Val (20), Ile (12), Trp (11), Phe (11), Tyr (6), Cys (6), Met (4) and Arg (1). Most of the key residues are hydrophobic (88 in 95), which is consistent with the fact that hydrophobic interaction is the main force in protein folding. Cys residues are paired to constitute disulfide bonds, which play an important role in the structure and function of LOXL2. In the discussion, we compare the results with experimental data, and use the free energy perturbation for verification, which prove the reliability of this work. Thus, this study provides important insight for the research of disease treatment targeting LOXL2. [ABSTRACT FROM AUTHOR]

Background: Skin's exposure to intrinsic and extrinsic factors causes age‐related changes, leading to a lower amount of dermal collagen and elastin. Aim: This study investigated the effects of a novel facial muscle stimulation technology combined with radiofrequency (RF) heating on dermal collagen and elastin content for the treatment of facial wrinkles and skin laxity. Methods: The active group subjects (N = 6) received four 20‐min facial treatments with simultaneous RF and facial muscle stimulation, once weekly. The control subject (N = 1) was untreated. Skin biopsies obtained at baseline, 1‐month and 3‐month follow‐up were evaluated histologically to determine collagen and elastin fibers content. A group of independent aestheticians evaluated facial skin appearance and wrinkle severity. Patient safety was followed. Results: In the active group, collagen‐occupied area reached 11.91 ± 1.80 × 106 μm2 (+25.32%, p < 0.05) and 12.35 ± 1.44 × 105 μm2 (+30.00%, p < 0.05) at 1‐month and 3‐month follow‐up visits. Elastin‐occupied area at 1‐month and 3‐month follow‐up was 1.64 ± 0.14 × 105 μm2 (+67.23%, p < 0.05), and 1.99 ± 0.21 × 105 μm2 (+102.80%, p < 0.05). In the control group, there was no significant difference (p > 0.05) in collagen and elastin fibers. Active group wrinkle scores decreased from 5 (moderate, class II) to 3 (mild, class I). All subjects, except the control, improved in appearance posttreatment. No adverse events or side effects occurred. Conclusion: Decreased dermal collagen and elastin levels contributes to a gradual decline in skin elasticity, leading to facial wrinkles and unfirm skin. Study results showed noticeable improvement in facial appearance and increased dermal collagen and elastin content subsequent to simultaneous, noninvasive RF, and facial muscle stimulation treatments. [ABSTRACT FROM AUTHOR]

AimCompared with the C57BL/6N substrain, the C57BL/6J substrain is more susceptible to the angiotensin II (Ang II)-induced development of dissected abdominal aortic aneurysms (AAAs). The aim of this study was to elucidate whether the widely used C57BL/6N mouse substrain is as susceptible as the C57BL/6J mouse substrain to porcine pancreatic elastase (PPE) infusion-induced experimental nondissected AAA development.MethodsExperimental nondissected AAAs were induced in C57BL/6J and C57BL/6N mice via transient aortic luminal infusion of PPE. On Day 0 (baseline) and Day 14 after PPE infusion, the abdominal aortic diameter was directly measured. Aortic aneurysmal segment samples were collected, and histopathological analysis was performed.ResultsOn Day 14 after PPE infusion, aortic diameters were significantly increased in both mouse substrains (from approximately 0.51 to 1.24 mm in C57BL/6J mice and from 0.51 to 1.18 mm in C57BL/6N mice). The increase in diameter of all the mice exceeded 50% and met the criteria for AAA model establishment (143% and 135% in C57BL/6J mice and C57BL/6N mice, respectively). PPE infusion also induced obvious local aortic wall macrophage and T-cell infiltration, elastin degradation, smooth muscle cell depletion and high metallopeptidase (MMP)-2 and MMP-9 expression levels in C57BL/6N mice, but these differences were not significant compared with those in C57BL/6J mice. However, PPE infusion led to the recruitment of more B cells and the sprouting of more neovessels at the aneurysmal lesion site in C57BL/6J mice than in C57BL/6N mice.ConclusionThe C57BL/6N mouse substrain is suitable for establishing a model of AAA via elastase infusion.

Natural biomaterials, particularly fibrous proteins, are extensively utilized in skin tissue engineering. However, their application is impeded by batch-to-batch variance, limited chemical or physical versatility, and environmental concerns. Recent advancements in gene editing and fermentation technology have catalyzed the emergence of recombinant fibrous protein biomaterials, which are gaining traction in skin tissue engineering. The modular and highly customizable nature of recombinant synthesis enables precise control over biomaterial design, facilitating the incorporation of multiple functional motifs. Additionally, recombinant synthesis allows for a transition from animal-derived sources to microbial sources, thereby reducing endotoxin content and rendering recombinant fibrous protein biomaterials more amenable to scalable production and clinical use. In this review, we provide an overview of prevalent recombinant fibrous protein biomaterials (collagens, elastin, silk proteins and their chimeric derivatives) used in skin tissue engineering (STE) and compare them with their animal-derived counterparts. Furthermore, we discuss their applications in STE, along with the associated challenges and future prospects.

Marfan syndrome is a connective tissue disorder that affects multiple organs, with the most serious complications occurring in the cardiovascular system. Aortic root dilatation and dissection are particularly concerning. While the prevalence of Marfan syndrome is equal between genders, male patients have a higher risk of developing thoracic aortic aneurysm and dissection compared to females. A recent study using a mouse model of severe Marfan syndrome found that male mice had poorer survival rates and exhibited lower elastin content and more fragmented elastic fibers compared to female mice. The study suggests that material properties, aortic size, and wall integrity may be connected to dissection risk. Further research is needed to understand how age and sex contribute to dissection risk in Marfan syndrome. [Extracted from the article]