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1.
J Drugs Dermatol ; 23(5): 347-352, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709700

RESUMO

This paper outlines a process undertaken by a physician to design a peptide aimed at impacting the extracellular matrix. From a position of very little expertise, a new peptide was designed with amino acid constituents based on the structural proteins collagen and elastin. Sequencing was also considered, given the periodic repetition observed in these proteins, and a peptide with reasonable molecular weight and physical characteristics was designed using available software. The sequence of events concerning intellectual property, functionality investigation, and eventual use of the peptide in new formulations is detailed. This may be of interest to physicians who consider this exercise out of the scope of the usual practice. J Drugs Dermatol. 2024;23(5):347-352.    doi:10.36849/JDD.7921.


Assuntos
Peptídeos , Humanos , Peptídeos/química , Desenho de Fármacos , Elastina/química , Colágeno/química , Matriz Extracelular , Propriedade Intelectual , Médicos
2.
Sci Rep ; 14(1): 10253, 2024 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704431

RESUMO

The tegument protein pp150 of Human Cytomegalovirus (HCMV) is known to be essential for the final stages of virus maturation and mediates its functions by interacting with capsid proteins. Our laboratory has previously identified the critical regions in pp150 important for pp150-capsid interactions and designed peptides similar in sequence to these regions, with a goal to competitively inhibit capsid maturation. Treatment with a specific peptide (PepCR2 or P10) targeted to pp150 conserved region 2 led to a significant reduction in murine CMV (MCMV) growth in cell culture, paving the way for in vivo testing in a mouse model of CMV infection. However, the general pharmacokinetic parameters of peptides, including rapid degradation and limited tissue and cell membrane permeability, pose a challenge to their successful use in vivo. Therefore, we designed a biopolymer-stabilized elastin-like polypeptide (ELP) fusion construct (ELP-P10) to enhance the bioavailability of P10. Antiviral efficacy and cytotoxic effects of ELP-P10 were studied in cell culture, and pharmacokinetics, biodistribution, and antiviral efficacy were studied in a mouse model of CMV infection. ELP-P10 maintained significant antiviral activity in cell culture, and this conjugation significantly enhanced P10 bioavailability in mouse tissues. The fluorescently labeled ELP-P10 accumulated to higher levels in mouse liver and kidneys as compared to the unconjugated P10. Moreover, viral titers from vital organs of MCMV-infected mice indicated a significant reduction of virus load upon ELP-P10 treatment. Therefore, ELP-P10 has the potential to be developed into an effective antiviral against CMV infection.


Assuntos
Antivirais , Infecções por Citomegalovirus , Elastina , Muromegalovirus , Peptídeos , Fosfoproteínas , Proteínas da Matriz Viral , Animais , Elastina/química , Elastina/metabolismo , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Camundongos , Antivirais/farmacologia , Antivirais/farmacocinética , Antivirais/química , Peptídeos/farmacologia , Peptídeos/química , Muromegalovirus/efeitos dos fármacos , Humanos , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/química , Citomegalovirus/efeitos dos fármacos , Capsídeo/metabolismo , Capsídeo/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/farmacocinética , Modelos Animais de Doenças , Polipeptídeos Semelhantes à Elastina
3.
Biomacromolecules ; 25(5): 3011-3017, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38689515

RESUMO

Stabilization against the dilution-dependent disassembly of self-assembled nanoparticles is a requirement for in vivo application. Herein, we propose a simple and biocompatible cross-linking reaction for the stabilization of a series of nanoparticles formed by the self-assembly of amphiphilic HA-b-ELP block copolymers, through the alkylation of methionine residues from the ELP block with diglycidyl ether compounds. The core-cross-linked nanoparticles retain their colloidal properties, with a spherical core-shell morphology, while maintaining thermoresponsive behavior. As such, instead of a reversible disassembly when non-cross-linked, a reversible swelling of nanoparticles' core and increase of hydrodynamic diameter are observed with lowering of the temperature.


Assuntos
Reagentes de Ligações Cruzadas , Nanopartículas , Nanopartículas/química , Reagentes de Ligações Cruzadas/química , Temperatura , Polímeros/química , Elastina/química , Tamanho da Partícula
4.
Commun Biol ; 7(1): 577, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755434

RESUMO

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).


Assuntos
Calcinose , Elastina , Fibroblastos , Pseudoxantoma Elástico , Pseudoxantoma Elástico/metabolismo , Pseudoxantoma Elástico/patologia , Pseudoxantoma Elástico/genética , Humanos , Elastina/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Calcinose/metabolismo , Calcinose/patologia , Derme/metabolismo , Derme/patologia , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Células Cultivadas , Matriz Extracelular/metabolismo , Tecido Elástico/metabolismo , Tecido Elástico/patologia
5.
Sci Rep ; 14(1): 10157, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698072

RESUMO

Extraction of nucleic acids (NAs) is critical for many methods in molecular biology and bioanalytical chemistry. NA extraction has been extensively studied and optimized for a wide range of applications and its importance to society has significantly increased. The COVID-19 pandemic highlighted the importance of early and efficient NA testing, for which NA extraction is a critical analytical step prior to the detection by methods like polymerase chain reaction. This study explores simple, new approaches to extraction using engineered smart nanomaterials, namely NA-binding, intrinsically disordered proteins (IDPs), that undergo triggered liquid-liquid phase separation (LLPS). Two types of NA-binding IDPs are studied, both based on genetically engineered elastin-like polypeptides (ELPs), model IDPs that exhibit a lower critical solution temperature in water and can be designed to exhibit LLPS at desired temperatures in a variety of biological solutions. We show that ELP fusion proteins with natural NA-binding domains can be used to extract DNA and RNA from physiologically relevant solutions. We further show that LLPS of pH responsive ELPs that incorporate histidine in their sequences can be used for both binding, extraction and release of NAs from biological solutions, and can be used to detect SARS-CoV-2 RNA in samples from COVID-positive patients.


Assuntos
COVID-19 , Elastina , Peptídeos , SARS-CoV-2 , Elastina/química , Concentração de Íons de Hidrogênio , Peptídeos/química , COVID-19/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , Humanos , Proteínas Intrinsicamente Desordenadas/química , Extração Líquido-Líquido/métodos , Ácidos Nucleicos/isolamento & purificação , Ácidos Nucleicos/química , DNA/química , DNA/isolamento & purificação , Polipeptídeos Semelhantes à Elastina , Separação de Fases
6.
Artigo em Inglês | MEDLINE | ID: mdl-38758686

RESUMO

The management of complex and severe lower-extremity injuries is challenging for the orthopedic surgeon. When the primary or secondary closure of the defect is not feasible, complex procedures with graft (split-thickness or full-thickness) or flap (pedicled or free) are required. These procedures are performed by specialized plastic surgeons and are at high risk for adverse effects, even high morbidity among both the donor and acceptor sites. Furthermore, split-thickness skin grafts (STSGs) often lead to unsatisfactory results in terms of mechanical stability, flexibility, and aesthetics due to the lack of underlying dermal tissue. Consequently, dermal substitutes, such as MatriDerm (MedSkin Solutions Dr Suwelack AG, Billerbeck, Germany), have been proposed and further developed as a treatment option addressing the management of full-thickness wound defects in conjunction with STSGs. We aimed to present a case of post-traumatic full-thickness wound defect of the left foot after traumatic amputation of the digits that was treated with MatriDerm combined with autologous STSG. In addition, we performed a systematic review of the literature to delineate the efficacy of the use of MatriDerm combined with STSGs in orthopedic cases exclusively.


Assuntos
Transplante de Pele , Humanos , Transplante de Pele/métodos , Masculino , Colágeno/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Amputação Traumática/cirurgia , Cicatrização , Adulto , Traumatismos do Pé/cirurgia , Elastina
7.
Hypertension ; 81(6): 1308-1319, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38563153

RESUMO

BACKGROUND: Abnormalities of resistance arteries may play essential roles in the pathophysiology of aging and hypertension. Deficiency of the vascular extracellular matrix protein MFAP4 (microfibrillar-associated protein 4) has previously been observed as protective against aberrant arterial remodeling. We hypothesized that MFAP4-deficiency would reduce age- and hypertension-dependent arterial changes in extracellular matrix composition and stiffening. METHODS: Mesenteric arteries were isolated from old (20-23 months) littermate Mfap4+/+ and Mfap4-/- mice, and 2-photon excitation microscopy imaging was used to quantify elastin and collagen volumes and dimensions in the vascular wall. Ten-week-old littermate Mfap4+/+ and Mfap4-/- mice were subjected to 20 days of continuous Ang II (angiotensin II) infusion and hypertension was monitored using invasive blood pressure measurements. Arterial stiffness, responses to vascular constrictors, and myogenic tone were monitored using wire- or pressure-myography. Collagen contents were assessed by Western blotting. RESULTS: MFAP4-deficiency significantly increased collagen volume and elastin fragmentation in aged mesenteric arteries without affecting arterial stiffness. MFAP4-deficient mice exhibited reduced diastolic pressure in Ang II-induced hypertension. There was no significant effect of MFAP4-deficiency on mesenteric artery structural remodeling or myogenic tone, although collagen content in mesenteric arteries was tendentially increased in hypertensive Mfap4+/+ mice relative to Mfap4-/- mice. Increased efficacy of vasoconstrictors (phenylephrine, thromboxane) and reduced stiffness were observed in Ang II-treated Mfap4-/- mouse mesenteric arteries in ex vivo myography recordings. CONCLUSIONS: MFAP4-deficiency reduces the elastin/collagen ratio in the aging resistance artery without affecting arterial stiffness. In contrast, MFAP4-deficiency reduces the stiffness of resistance arteries and ameliorates Ang II-induced hypertension.


Assuntos
Envelhecimento , Angiotensina II , Hipertensão , Artérias Mesentéricas , Resistência Vascular , Rigidez Vascular , Animais , Hipertensão/fisiopatologia , Hipertensão/metabolismo , Hipertensão/genética , Camundongos , Artérias Mesentéricas/fisiopatologia , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Rigidez Vascular/fisiologia , Rigidez Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Envelhecimento/fisiologia , Angiotensina II/farmacologia , Elastina/metabolismo , Pressão Sanguínea/fisiologia , Proteínas da Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/deficiência , Camundongos Knockout , Modelos Animais de Doenças , Masculino , Colágeno/metabolismo
8.
ACS Biomater Sci Eng ; 10(5): 2945-2955, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38669114

RESUMO

Metal-coordination bonds, a highly tunable class of dynamic noncovalent interactions, are pivotal to the function of a variety of protein-based natural materials and have emerged as binding motifs to produce strong, tough, and self-healing bioinspired materials. While natural proteins use clusters of metal-coordination bonds, synthetic materials frequently employ individual bonds, resulting in mechanically weak materials. To overcome this current limitation, we rationally designed a series of elastin-like polypeptide templates with the capability of forming an increasing number of intermolecular histidine-Ni2+ metal-coordination bonds. Using single-molecule force spectroscopy and steered molecular dynamics simulations, we show that templates with three histidine residues exhibit heterogeneous rupture pathways, including the simultaneous rupture of at least two bonds with more-than-additive rupture forces. The methodology and insights developed improve our understanding of the molecular interactions that stabilize metal-coordinated proteins and provide a general route for the design of new strong, metal-coordinated materials with a broad spectrum of dissipative time scales.


Assuntos
Histidina , Simulação de Dinâmica Molecular , Níquel , Histidina/química , Níquel/química , Elastina/química , Proteínas/química , Peptídeos/química
9.
J Med Chem ; 67(8): 6624-6637, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38588467

RESUMO

The increased remodeling of the extracellular matrix (ECM) in pulmonary fibrosis (PF) generates bioactive ECM fragments called matricryptins, which include elastin-derived peptides (EDPs). The interaction between EDPs and their receptors, including elastin-binding protein (EBP), plays a crucial role in exacerbating fibrosis. Here, we present LXJ-02 for the first time, a novel ultralong-acting inhibitor that disrupts the EDPs/EBP peptide-protein interaction, promoting macrophages to secrete matrix metalloproteinase-12 (MMP-12), and showing great promise as a stable peptide. MMP-12 has traditionally been implicated in promoting inflammation and fibrosis in various acute and chronic diseases. However, we reveal a novel role of LXJ-02 that activates the macrophage-MMP-12 axis to increase MMP-12 expression and degrade ECM components like elastin. This leads to the preventing of PF while also improving EDP-EBP interaction. LXJ-02 effectively reverses PF in mouse models with minimal side effects, holding great promise as an excellent therapeutic agent for lung fibrosis.


Assuntos
Desenho de Fármacos , Elastina , Fibrose Pulmonar , Receptores de Superfície Celular , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Animais , Camundongos , Elastina/química , Elastina/metabolismo , Humanos , Metaloproteinase 12 da Matriz/metabolismo , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/síntese química , Camundongos Endogâmicos C57BL , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino
10.
Transgenic Res ; 33(1-2): 21-33, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38573429

RESUMO

Plants can produce complex pharmaceutical and technical proteins. Spider silk proteins are one example of the latter and can be used, for example, as compounds for high-performance textiles or wound dressings. If genetically fused to elastin-like polypeptides (ELPs), the silk proteins can be reversibly precipitated from clarified plant extracts at moderate temperatures of ~ 30 °C together with salt concentrations > 1.5 M, which simplifies purification and thus reduces costs. However, the technologies developed around this mechanism rely on a repeated cycling between soluble and aggregated state to remove plant host cell impurities, which increase process time and buffer consumption. Additionally, ELPs are difficult to detect using conventional staining methods, which hinders the analysis of unit operation performance and process development. Here, we have first developed a surface plasmon resonance (SPR) spectroscopy-based assay to quantity ELP fusion proteins. Then we tested different filters to prepare clarified plant extract with > 50% recovery of spider silk ELP fusion proteins. Finally, we established a membrane-based purification method that does not require cycling between soluble and aggregated ELP state but operates similar to an ultrafiltration/diafiltration device. Using a data-driven design of experiments (DoE) approach to characterize the system of reversible ELP precipitation we found that membranes with pore sizes up to 1.2 µm and concentrations of 2-3 M sodium chloride facilitate step a recovery close to 100% and purities of > 90%. The system can thus be useful for the purification of ELP-tagged proteins produced in plants and other hosts.


Assuntos
Polipeptídeos Semelhantes à Elastina , Seda , Seda/genética , Proteínas de Artrópodes , Elastina/genética , Elastina/química , Elastina/metabolismo , Nicotiana/genética , Proteínas Recombinantes de Fusão/genética
11.
Medicina (Kaunas) ; 60(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38674297

RESUMO

Background and Objectives: Wound healing encompasses a multitude of factors and entails the establishment of interactions among components of the basement membrane. The quantification of particle concentrations can serve as valuable biomarkers for assessing biomechanical muscle properties. The objective of this study was to examine the immunoexpression and immunoconcentration of myometrial collagen type VI, elastin, alpha-smooth muscle actin, and smooth muscle myosin heavy chain, as well as the expression of platelets and clusters of differentiation 31 in the uterine scar following a cesarean section (CS). Materials and Methods: A total of 177 biopsies were procured from a cohort of pregnant women who were healthy, specifically during the surgical procedure of CS. The participants were categorized into seven distinct groups. Group 1 consisted of primiparas, with a total of 52 individuals. The subsequent groups were organized based on the duration of time that had elapsed since their previous CS. The analysis focused on the immunoexpression and immunoconcentration of the particles listed. Results: No significant variations were observed in the myometrial immunoconcentration of collagen type VI, elastin, smooth muscle myosin, and endothelial cell cluster of differentiation 31 among the analyzed groups. The concentration of alpha-smooth muscle actin in the myometrium was found to be significantly higher in patients who underwent CS within a period of less than 2 years since their previous CS, compared to those with a longer interval between procedures. Conclusions: Our findings indicate that the immunoconcentration of uterine myometrial scar collagen type VI, elastin, smooth muscle myosin heavy chain, alpha-smooth muscle actin, and endothelial cell marker cluster of differentiation 31 remains consistent regardless of the duration elapsed since the previous CS. The findings indicate that there are no significant alterations in the biomechanical properties of the uterine muscle beyond a period of 13 months following a CS.


Assuntos
Cesárea , Cicatriz , Imuno-Histoquímica , Humanos , Feminino , Cesárea/efeitos adversos , Adulto , Imuno-Histoquímica/métodos , Gravidez , Miométrio , Actinas/análise , Elastina/análise , Biomarcadores/análise , Cicatrização/fisiologia , Estudos de Coortes
12.
Acc Chem Res ; 57(9): 1227-1237, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38624000

RESUMO

ConspectusVesicles are self-assembled structures comprised of a membrane-like exterior surrounding a hollow lumen with applications in drug delivery, artificial cells, and micro-bioreactors. Lipid or polymer vesicles are the most common and are made of lipids or polymers, respectively. They are highly useful structures for many applications but it can be challenging to decorate them with proteins or encapsulate proteins in them, owing to the use of organic solvent in their formation and the large size of proteins relative to lipid or polymer molecules. By utilization of recombinant fusion proteins to make vesicles, specific protein domains can be directly incorporated while also imparting tunability and stability. Protein vesicle assembly relies on the design and use of self-assembling amphiphilic proteins. A specific protein vesicle platform made in purely aqueous conditions of a globular, functional protein fused to a glutamate-rich leucine zipper (ZE) and a thermoresponsive elastin-like polypeptide (ELP) fused to an arginine-rich leucine zipper (ZR) is discussed here. The hydrophobic conformational change of the ELP above its transition temperature drives assembly, and strong ZE/ZR binding enables incorporation of the desired functional protein. Mixing the soluble proteins on ice induces zipper binding, and then warming above the ELP transition temperature (Tt) triggers the transition to and growth of protein-rich coacervates and, finally, reorganization of proteins into vesicles. Vesicle size is tunable based on salt concentration, rate of heating, protein concentration, size of the globular protein, molar ratio of the proteins, and the ELP sequence. Increasing the salt concentration decreases vesicle size by decreasing the Tt, resulting in a shorter coacervation transition stage. Likewise, directly changing the heating rate also changes this time and increasing protein concentration increases coalescence. Increasing globular protein size decreases the size of the vesicle due to steric hindrance. By changing the ELP sequence, which consists of (VPGXG)n, through the guest residue (X) or number of repeats (n), Tt is changed, affecting size. Additionally, the chemical nature of X variation has endowed vesicles with stimuli responsiveness and stability at physiological conditions.Protein vesicles have been used for biocatalysis, biomacromolecular drug delivery, and vaccine applications. Photo-cross-linkable vesicles were used to deliver small molecule cargo to cancer cells in vitro and antigen to immune cells in vivo. pH-responsive vesicles effectively delivered functional protein cargo, including cytochrome C, to the cytosol of cancer cells in vitro, using hydrophobic ion pairing to improve cargo distribution in the vesicles and release. The globular protein used to make the vesicles can be varied to achieve different functions. For example, enzyme vesicles exhibit biocatalysis, and antigen vesicles induce antibody and cellular immune responses after vaccination in mice. Collectively, the development and engineering of the protein vesicle platform has employed amphiphilic self-assembly strategies and rational protein engineering to control physical, chemical, and biological properties for biotechnology and nanomedicine applications.


Assuntos
Elastina , Elastina/química , Humanos , Proteínas Recombinantes/química , Zíper de Leucina
13.
J Cosmet Dermatol ; 23(5): 1620-1628, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38468421

RESUMO

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.


Assuntos
Colágeno , Elastina , Músculos Faciais , Envelhecimento da Pele , Humanos , Elastina/análise , Elastina/metabolismo , Envelhecimento da Pele/efeitos da radiação , Colágeno/metabolismo , Colágeno/análise , Feminino , Pessoa de Meia-Idade , Adulto , Músculos Faciais/efeitos da radiação , Terapia por Radiofrequência/métodos , Terapia por Radiofrequência/efeitos adversos , Masculino , Terapia por Estimulação Elétrica/efeitos adversos , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Técnicas Cosméticas/efeitos adversos , Técnicas Cosméticas/instrumentação , Pele/efeitos da radiação , Pele/patologia , Face , Biópsia , Resultado do Tratamento
14.
Sci Rep ; 14(1): 7496, 2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553592

RESUMO

Intracranial arterial dolichoectasia (IADE) is associated with the interaction of hypertension and inflammation, and microcurrent can be effective in hypertension. Therefore, this study aimed to investigate the therapeutic effect of microcurrent electrical stimulation in a mouse IADE model. This study randomly categorized 20 mice into five groups: group 1-C (healthy control), group 2-D (IADE model), group 3-M + D (microcurrent administration before nephrectomy and until brain surgery), group 4-D + M (microcurrent administration for 4 weeks following brain surgery), and group 5-M (microcurrent administration for 4 weeks). Cerebral artery diameter and thickness and cerebral arterial wall extracellular matrix components were assessed. Among the five groups, group 2-D showed significantly higher cerebral arterial wall diameter (117.79 ± 17.05 µm) and proportion of collagen (42.46 ± 14.12%) and significantly lower arterial wall thickness (9.31 ± 2.26 µm) and proportion of smooth muscle cell (SMC) and elastin in the cerebral arterial wall (SMC: 38.05 ± 10.32%, elastin: 11.11 ± 6.97%). Additionally, group 4-D + M exhibited a non-significantly lower diameter (100.28 ± 25.99 µm) and higher thickness (12.82 ± 5.17 µm). Group 5-M demonstrated no evidence of toxicity in the liver and brain. The pilot study revealed that microcurrent is effective in preventing IADE development, although these beneficial effects warrant further investigation.


Assuntos
Artérias Cerebrais , Hipertensão , Animais , Camundongos , Projetos Piloto , Encéfalo , Elastina
15.
Circ Res ; 134(7): 931-949, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38547250

RESUMO

The ECM (extracellular matrix) is a major component of the vascular microenvironment that modulates vascular homeostasis. ECM proteins include collagens, elastin, noncollagen glycoproteins, and proteoglycans/glycosaminoglycans. ECM proteins form complex matrix structures, such as the basal lamina and collagen and elastin fibers, through direct interactions or lysyl oxidase-mediated cross-linking. Moreover, ECM proteins directly interact with cell surface receptors or extracellular secreted molecules, exerting matricellular and matricrine modulation, respectively. In addition, extracellular proteases degrade or cleave matrix proteins, thereby contributing to ECM turnover. These interactions constitute the ECM interactome network, which is essential for maintaining vascular homeostasis and preventing pathological vascular remodeling. The current review mainly focuses on endogenous matrix proteins in blood vessels and discusses the interaction of these matrix proteins with other ECM proteins, cell surface receptors, cytokines, complement and coagulation factors, and their potential roles in maintaining vascular homeostasis and preventing pathological remodeling.


Assuntos
Proteínas da Matriz Extracelular , Matriz Extracelular , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Colágeno/metabolismo , Elastina/metabolismo , Homeostase , Receptores de Superfície Celular/metabolismo
16.
Biomacromolecules ; 25(4): 2408-2422, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38546162

RESUMO

Elastin-collagen nanovesicles (ECnV) have emerged as a promising platform for drug delivery due to their tunable physicochemical properties and biocompatibility. The potential of nine distinct ECnVs to serve as drug-delivery vehicles was investigated in this study, and it was demonstrated that various small-molecule cargo (e.g., dexamethasone, methotrexate, doxorubicin) can be encapsulated in and released from a set of ECnVs, with extents of loading and rates of release dictated by the composition of the elastin domain of the ECnV and the type of cargo. Elastin-like peptides (ELPs) and collagen-like peptides (CLPs) of various compositions were produced; the secondary structure of the corresponding peptides was determined using CD, and the morphology and average hydrodynamic diameter (∼100 nm) of the ECnVs were determined using TEM and DLS. It was observed that hydrophobic drugs exhibited slower release kinetics than hydrophilic drugs, but higher drug loading was achieved for the more hydrophilic Dox. The collagen-binding ability of the ECnVs was demonstrated through a 2D collagen-binding assay, suggesting the potential for longer retention times in collagen-enriched tissues or matrices. Sustained release of drugs for up to 7 days was observed and, taken together with the collagen-binding data, demonstrates the potential of this set of ECnVs as a versatile drug delivery vehicle for longer-term drug release of a variety of cargo. This study provides important insights into the drug delivery potential of ECnVs and offers useful information for future development of ECnV-based drug delivery systems for the treatment of various diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Peptídeos , Preparações de Ação Retardada , Peptídeos/química , Doxorrubicina/química , Colágeno/química , Matriz Extracelular , Elastina/química
17.
Exp Cell Res ; 437(1): 113997, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508328

RESUMO

Bronchopulmonary dysplasia (BPD) is characterized by shortened secondary septa and fewer, larger alveoli. Elastin deposition to the distal tips of the secondary septa is critical for elongation of the secondary septa. Alveolar myofibroblasts, which are thought to migrate to the septal tips during alveolarization, are mainly responsible for elastin production and deposition. Antenatal exposure to inflammation induces abnormal elastin deposition, thereby increasing the risk of developing BPD. Here, we found that lipopolysaccharide (LPS) significantly increased the expression of transforming growth factor-α (TGF-α) in an LPS-induced rat model of BPD and in LPS-treated human pulmonary epithelial cells (BEAS-2B). In addition, in vitro experiments suggested that LPS upregulated TGF-α expression via toll-like receptor 4 (TLR4)/tumor necrosis factor α-converting enzyme (TACE) signaling. Increased TGF-α levels via its receptor epidermal growth factor receptor (EGFR)-induced lysyl oxidase (LOX) overactivation and cell division cycle 42 (Cdc42) activity inhibition of myofibroblasts. Similarly, in vivo LOX overactivation and inhibition of Cdc42 activity were observed in the lungs of LPS-exposed pups. LOX overactivation led to abnormal elastin deposition, and inhibition of Cdc42 activity disturbed the directional migration of myofibroblasts and disrupted elastin localization. Most importantly, the EGFR inhibitor erlotinib partially rescued LOX overactivation and Cdc42 activity inhibition, and improved elastin deposition and alveolar development in antenatal LPS-treated rats. Taken together, our data suggest that TGF-α/EGFR signaling is critically involved in the regulation of elastin deposition and represents a novel therapeutic target.


Assuntos
Displasia Broncopulmonar , Lipopolissacarídeos , Animais , Feminino , Humanos , Recém-Nascido , Gravidez , Ratos , Displasia Broncopulmonar/induzido quimicamente , Displasia Broncopulmonar/metabolismo , Elastina , Receptores ErbB/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Fator de Crescimento Transformador alfa
18.
Skin Res Technol ; 30(3): e13634, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38481080

RESUMO

BACKGROUND: Recent in vitro and in vivo studies have suggested that the elastin peptide improves the skin's biophysical properties, enhancing the proliferation of fibroblasts and elastin synthesis, resulting in anti-aging properties. Therefore, we conducted a randomized, double-blinded, placebo-controlled study to clinically evaluate the effect of elastin peptide intake on human skin. MATERIALS AND METHODS: Healthy adult participants (N = 100) were randomly assigned to receive a test product containing 100 mg of Bonito elastin peptide (VGPG Elastin® ) or placebo. In this study, all participants were Asian from Korea. The parameters of skin wrinkles, hydration, and brightening (melanin index) were measured at baseline and 4, 8, and 12 weeks after intervention. RESULTS: The average skin roughness, maximum peak-to-valley values, maximum peak height of the wrinkle, maximum valley depth of the wrinkle, average maximum height of the wrinkle, and eye wrinkle volume improved considerably in the test group compared with the placebo after 12 weeks of intervention. Skin hydration was enhanced, and the melanin index was significantly lower in the test group than in the placebo group. No participant experienced adverse events related to the test product. CONCLUSION: Oral consumption of Bonito elastin peptide (VGPG Elastin®) reduced fine wrinkles, enhanced skin moisture, and decreased melanin index without significant adverse effects and may be a promising anti-wrinkle, anti-dryness, and anti-pigmentation treatment.


Assuntos
Envelhecimento da Pele , Adulto , Animais , Humanos , Melaninas , Pele , Peptídeos/efeitos adversos , Elastina/farmacologia , Método Duplo-Cego
19.
Exp Dermatol ; 33(3): e15052, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38483134

RESUMO

Skin forms the outer barrier of the body. Upon injury, successful wound healing in normal skin restores tissue damage and counteracts the loss of extracellular matrix (ECM) proteins and cells. Collagens and elastin are the most abundant structural proteins of the ECM. In homeostasis, collagen type I is the prevalent form, but it is replaced by type III collagen upon wounding, and only later remodelled. In turn, unsuccessful healing results in scars, which tend to be inflexible and inelastic as compared to normal elastic dermis. Scar inelasticity may be due to the absence of mature elastin fibre formation and cross-linking. In this review, the available information on the process of formation of new collagen and elastic fibres during wound healing is analysed. The distinct roles of elastin and collagen proteins during healing are revisited and future research directions proposed which may help improve clinical management of open wounds and scars.


Assuntos
Cicatriz , Matriz Extracelular , Humanos , Cicatriz/metabolismo , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Pele/metabolismo , Elastina/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Cicatrização
20.
Proc Natl Acad Sci U S A ; 121(11): e2304009121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38442161

RESUMO

Elastin is an extracellular matrix material found in all vertebrates. Its reversible elasticity, robustness, and low stiffness are essential for the function of arteries, lungs, and skin. It is among the most resilient elastic materials known: During a human lifetime, arterial elastin undergoes in excess of 2 × 109 stretching/contracting cycles without replacement, and slow oxidative hardening has been identified as a limiting factor on human lifespan. For over 50 y, the mechanism of entropic recoil has been controversial. Herein, we report a combined NMR and thermomechanical study that establishes the hydrophobic effect as the primary driver of elastin function. Water ordering at the solvent:protein interface was observed as a function of stretch using double quantum 2H NMR, and the most extensive thermodynamic analysis performed to date was obtained by measuring elastin length and volume as a function of force and temperature in normal water, heavy water and with cosolvents. When stretched, elastin's heat capacity increases, water is ordered proportional to the degree of stretching, the internal energy decreases, and heat is released in excess of the work performed. These properties show that recoil in elastin under physiological conditions is primarily driven by the hydrophobic effect rather than by configurational entropy as is the case for rubber. Consistent with this conclusion are decreases in the thermodynamic signatures when cosolvents that alter the hydrophobic effect are introduced. We propose that hydrophobic effect-driven recoil, as opposed to a configurational entropy mechanism where hardening from crystallization can occur, is the origin of elastin's unusual resilience.


Assuntos
Elastina , Animais , Humanos , Artérias/química , Cristalização , Elastina/química , Termodinâmica , Água
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