Search Results (477)

Introduction: This study was conducted to question the findings of a prior study published in Journal of Drugs in Dermatology (JDD) in September 2023, which reported that a topical firming and toning body lotion (FTB—SkinMedica^®, Allergan Aesthetics, an AbbVie Company, Irvine, CA, USA) upregulated several genes in a UV-irradiated 3D full-thickness human skin model, outperforming other products, including TransFORM Body Treatment with TriHex Technology^® (ATF—Alastin Skincare^®, a Galderma company, Fort Worth, TX, USA). Given the unique response reported for FTB, we conducted this study to assess the reproducibility of these results and explore gene expression at multiple time points, along with validating protein expression in an ex vivo model. Materials and Methods: Experiments were conducted using an ex vivo model with photodamaged skin from facelift patients, under an Institutional Review Board-approved study. Skin samples were processed, cultured in transwells with Skin Media, and treated daily with either TransFORM or FTB for 7 days. A control group was left untreated. Gene expression was assessed using RT-PCR on days 1 and 3 and using immunofluorescence after 3 and 7 days of treatment. Skin samples were fixed, paraffin-embedded, sectioned, and stained with an anti-tropoelastin antibody. Fluorescence detection and imaging were conducted to assess protein expression changes. Results: Gene expression data from our study and the initial study showed a few similarities but multiple discrepancies. As opposed to results previously reported at only the 24 h time point, our study was completed at multiple time points and showed a complete reversal of many of these results. For example, COL1A1 expression at 24 h was similar for FTB in both studies but differed for TransFORM, which showed higher levels at 24 h in our study. At day 3, COL1A1 expression decreased markedly for FTB and was sustained for TransFORM. Other genes, such as COL3A1, COL5, ELN, VEGFC, ATG7, ATG12, BECN1, POMP, PSMB5, and PSMB6, exhibited varying expression patterns between the two studies and across different time points. From a translational perspective, histological analysis showed that TransFORM enhanced elastin fiber presence in the dermal–epidermal junction (DEJ) more effectively than FTB at both days 3 and 7. FTB-treated samples maintained a gap in the DEJ, while TransFORM-treated samples exhibited increased cellular proliferation and DEJ undulation, indicative of a healthier regenerative response. Conclusion: This study highlights the problems of examining data and drawing conclusions using a single point of examination. In addition, when a study reports positive results for only one product among a range of eight competitive products, further questioning is essential to exclude the possibility of the experimental model favoring that product. The additional 3-day time point and further translational examination of histological changes paint a completely different picture to that reported in the prior publication. TransFORM outperformed FTB in most gene expressions and histological parameters when assessed over multiple time points in a physiologically relevant ex vivo model. Full article

Mechanical mismatch between native aortas and aortic grafts can induce graft failure. This study aims to compare the mechanical and microstructural properties of different graft materials used in aortic repair surgeries with those of normal and dissected human ascending aortas. Five types of materials including normal aorta (n = 10), dissected aorta (n = 6), human pericardium (n = 8), bovine pericardium (n = 8) and Dacron graft (n = 5) were collected to perform uniaxial tensile testing to determine their material stiffness, and ultimate strength/stretch. The elastin and collagen contents in four tissue groups except for Dacron were quantified by histological examinations, while the material ultrastructure of five material groups was visualized by scanning electron microscope. Statistical results showed that three graft materials including Dacron, human pericardium and bovine pericardium had significantly higher ultimate strength and stiffness than both normal and dissected aortas. Human and bovine pericardia had significantly lower ultimate stretch than native aortas. Histological examinations revealed that normal and diseased aortic tissues had a significantly higher content of elastic fiber than two pericardial tissues, but less collagen fiber content. All four tissue groups exhibited lamellar fiber ultrastructure, with aortic tissues possessing thinner lamella. Dacron was composed of densely coalesced polyethylene terephthalate fibers in thick bundles. Aortic graft materials with denser fiber ultrastructure and/or higher content of collagen fiber than native aortic tissues, exhibited higher ultimate strength and stiffness. This information provides a basis to understand the mechanical failure of aortic grafts, and inspire the design of biomimetic aortic grafts. Full article

For centuries, mushrooms have been used as a component of skincare formulations. Environmental stresses and a modern lifestyle expose the skin to accelerated aging. To slow down this process, natural anti-aging skincare ingredients are being sought. In this review, 52 scientific publications about the effects of chemical compounds extracted from the fruiting bodies of macrofungi on skin cells were selected. The effects of extracts from nine species that are tested for anti-aging effects have been described. According to available literature data, macrofungi contain many polysaccharides, phenolic compounds, polysaccharide peptides, free amino acids, sterols, proteins, glycosides, triterpenes, alkaloids, which can have an anti-aging effect on the skin by acting as antioxidants, photoprotective, skin whitening, moisturizing, anti-inflammatory and stabilizing collagen, elastin and hyaluronic acid levels in the skin. Full article

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. Full article

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. Full article

Skin radiance is crucial for enhancing facial attractiveness and is negatively affected by factors like hyperpigmentation and aging-related changes. Current treatments often lack comprehensive solutions for improving skin radiance. This study aimed to develop a cosmetic formula that enhances skin radiance by reducing hyperpigmentation and improving skin regeneration by targeting specific receptors—the endothelin receptor type B (EDNRB) for hyperpigmentation and the adiponectin receptor 1 (ADIPOR1) for sagging and wrinkles. To achieve this, we used artificial intelligence technologies to screen and select ingredients with an affinity for EDNRB and ADIPOR1. Vitamin B12 (VitB12) was identified as a molecule that targets EDNRB, which is involved in melanogenesis. Adenosine triphosphate (ATP) targets ADIPOR1, which is associated with skin regeneration. VitB12 successfully inhibited intracellular calcium elevation and melanogenesis induced by endothelin-1. In contrast, ATP increased the mRNA expression of collagen and elastin and promoted wound healing. Moreover, the VitB12 and ATP complex significantly increased the expression of hyaluronan synthases, which are crucial for skin hydration. Furthermore, in human participants, the application of the VitB12 and ATP complex to one-half of the face significantly improved skin radiance, elasticity, and texture. Our findings provide valuable insights for the development of skincare formulations. Full article

Coronary artery bypass grafting (CABG) utilizing saphenous vein grafts (SVGs) stands as a fundamental approach to surgically treating coronary artery disease. However, the long-term success of CABG is often compromised by the development of intimal hyperplasia (IH) and subsequent graft failure. Understanding the mechanisms underlying this pathophysiology is crucial for improving graft patency and patient outcomes. Objectives: This study aims to explore the potential of an ex vivo model utilizing SVG to investigate IH and re-endothelialization. Methods: A thorough histological examination of 15 surplus SVG procured from CABG procedures at Hospital Canselor Tuanku Muhriz, Malaysia, was conducted to establish their baseline characteristics. Results: SVGs exhibited a mean diameter of 2.65 ± 0.93 mm with pre-existing IH averaging 0.42 ± 0.13 mm in thickness, alongside an observable lack of luminal endothelial cell lining. Analysis of extracellular matrix components, including collagen, elastin, and glycosaminoglycans, at baseline and after 7 days of ex vivo culture revealed no significant changes in collagen but demonstrated increased percentages of elastin and glycosaminoglycans. Despite unsuccessful attempts at re-endothelialization with blood outgrowth endothelial cells, the established ex vivo SVG IH model underscores the multifaceted nature of graft functionality and patency, characterized by IH presence, endothelial impairment, and extracellular matrix alterations post-CABG. Conclusions: The optimized ex vivo IH model provides a valuable platform for delving into the underlying mechanisms of IH formation and re-endothelialization of SVG. Further refinements are warranted, yet this model holds promise for future research aimed at enhancing graft durability and outcomes for CAD patients undergoing CABG. Full article

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. Full article

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 RiboScreen^TM, a technology for identifying molecules that enhance the production of specific proteins, to target the production of tropoelastin. We make use of RiboScreen^TM 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 RiboScreen^TM, 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 RiboScreen^TM 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. Full article

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. Full article

The importance of decellularized extracellular matrix (dECM) as a natural biomaterial in tissue engineering and regenerative medicine is rapidly growing. The core objective of the decellularization process is to eliminate cellular components while maximizing the preservation of the ECM’s primary structure and components. Establishing a rapid, effective, and minimally destructive decellularization technique is essential for obtaining high-quality dECM to construct regenerative organs. This study focused on human umbilical cord tissue, designing different reagent combinations for decellularization protocols while maintaining a consistent processing time. The impact of these protocols on the decellularization efficiency of human umbilical cord tissue was evaluated. The results suggested that the composite decellularization strategy utilizing trypsin/EDTA + Triton X-100 + sodium deoxycholate was the optimal approach in this study for preparing decellularized human umbilical cord dECM. After 5 h of decellularization treatment, most cellular components were eliminated, confirmed through dsDNA quantitative detection, hematoxylin and eosin (HE) staining, and DAPI staining. Meanwhile, Masson staining, periodic acid-silver methenamine (PASM) staining, periodic acid-Schiff (PAS) staining, and immunofluorescent tissue section staining results revealed that the decellularized scaffold retained extracellular matrix components, including collagen and glycosaminoglycans (GAGs). Compared to native umbilical cord tissue, electron microscopy results demonstrated that the microstructure of the extracellular matrix was well preserved after decellularization. Furthermore, Fourier-transform infrared spectroscopy (FTIR) findings indicated that the decellularization process successfully retained the main functional group structures of extracellular matrix (ECM) components. The quantitative analysis of collagen, elastin, and GAG content validated the advantages of this decellularization process in preserving and purifying ECM components. Additionally, it was confirmed that this decellularized matrix exhibited no cytotoxicity in vitro. This study achieved short-term decellularization preparation for umbilical cord tissue through a combined decellularization strategy. Full article

There is a pressing need for alternative medical treatments for abdominal aortic aneurysms (AAAs). Mesenchymal regenerative cells derived from adipose tissue (ADRCs) have shown potential in modulating the inflammation and immune responses that drive AAA progression. We hypothesized that ADRCs could reduce inflammation and preserve vascular integrity, potentially slowing the progression of AAA. In our study, subcutaneous adipose tissue was harvested from male Sprague Dawley rats, from which ADRCs were isolated. AAA was induced in these rats using intraluminal porcine pancreatic elastase, followed by intravenous administration of either ADRCs (10⁶ cells) or saline (0.1 mL). We monitored the progression of AAA through weekly ultrasound, and the rats were sacrificed on day 28 for histological analysis. Our results showed no significant difference in the inner abdominal aortic diameter at day 28 between the control group (172% ± 73%, n = 17) and the ADRC-treated group (181% ± 75%, n = 15). Histological analyses of AAA cross-sections also revealed no significant difference in the infiltration of neutrophils or macrophages between the two groups. Furthermore, the integrity and content of elastin in the tunica media were similar between groups. These findings indicate that a single injection of ADRCs does not inhibit the development of AAA in rats in a randomized blinded study. Full article

The sophisticated, elegant protein-polymers designed by nature can serve as inspiration to redesign and biomanufacture protein-based materials using synthetic biology. Historically, petro-based polymeric materials have dominated industrial activities, consequently transforming our way of living. While this benefits humans, the fabrication and disposal of these materials causes environmental sustainability challenges. Fortunately, protein-based biopolymers can compete with and potentially surpass the performance of petro-based polymers because they can be biologically produced and degraded in an environmentally friendly fashion. This paper reviews four groups of protein-based polymers, including fibrous proteins (collagen, silk fibroin, fibrillin, and keratin), elastomeric proteins (elastin, resilin, and wheat glutenin), adhesive/matrix proteins (spongin and conchiolin), and cyanophycin. We discuss the connection between protein sequence, structure, function, and biomimetic applications. Protein engineering techniques, such as directed evolution and rational design, can be used to improve the functionality of natural protein-based materials. For example, the inclusion of specific protein domains, particularly those observed in structural proteins, such as silk and collagen, enables the creation of novel biomimetic materials with exceptional mechanical properties and adaptability. This review also discusses recent advancements in the production and application of new protein-based materials through the approach of synthetic biology combined biomimetics, providing insight for future research and development of cutting-edge bio-inspired products. Protein-based polymers that utilize nature’s designs as a base, then modified by advancements at the intersection of biology and engineering, may provide mankind with more sustainable products. Full article

Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of treatment with the gasdermin D inhibitor necrosulfonamide on experimental AAAs. AAAs were induced in male apolipoprotein E-deficient mice by subcutaneous angiotensin II infusion (1000 ng/kg body weight/min), with daily administration of necrosulfonamide (5 mg/kg body weight) or vehicle starting 3 days prior to angiotensin II infusion for 30 days. Necrosulfonamide treatment remarkably suppressed AAA enlargement, as indicated by reduced suprarenal maximal external diameter and surface area, and lowered the incidence and reduced the severity of experimental AAAs. Histologically, necrosulfonamide treatment attenuated medial elastin breaks, smooth muscle cell depletion, and aortic wall collagen deposition. Macrophages, CD4⁺ T cells, CD8⁺ T cells, and neovessels were reduced in the aneurysmal aortas of necrosulfonamide- as compared to vehicle-treated angiotensin II-infused mice. Atherosclerosis and intimal macrophages were also substantially reduced in suprarenal aortas from angiotensin II-infused mice following necrosulfonamide treatment. Additionally, the levels of serum interleukin-1β and interleukin-18 were significantly lower in necrosulfonamide- than in vehicle-treated mice without affecting body weight gain, lipid levels, or blood pressure. Our findings indicate that necrosulfonamide reduced experimental AAAs by preserving aortic structural integrity as well as reducing mural leukocyte accumulation, neovessel formation, and systemic levels of interleukin-1β and interleukin-18. Thus, pharmacologically inhibiting gasdermin D activity may lead to the establishment of nonsurgical therapies for clinical AAA disease. Full article

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. Full article