Elastin Synthesis Research Articles

NCOR1 maintains the homeostasis of vascular smooth muscle cells and protects against aortic aneurysm.

Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays critical roles in the pathogenesis of aortic aneurysm (AA). The function of nuclear receptor corepressor1 (NCOR1) in regulation of VSMC phenotype and AA is unclear. Herein, using smooth muscle NCOR1 knockout mice, we demonstrated that smooth muscle NCOR1 deficiency decreased both mRNA and protein levels of contractile genes, impaired stress fibers formation and RhoA pathway activation, reduced synthesis of elastin and collagens, and induced the expression and activity of MMPs, manifesting a switch from contractile to degradative phenotype of VSMCs. NCOR1 modulated VSMC phenotype through 3 different mechanisms. First, NCOR1 deficiency increased acetylated FOXO3a to inhibit the expression of Myocd, which downregulated contractile genes. Second, deletion of NCOR1 derepressed NFAT5 to induce the expression of Rgs1, thus impeding RhoA activation. Third, NCOR1 deficiency increased the expression of Mmp12 and Mmp13 by derepressing ATF3. Finally, a mouse model combined apoE knockout mice with angiotensin II was used to study the role of smooth muscle NCOR1 in the development of AA. The results showed that smooth muscle NCOR1 deficiency increased the incidence of aortic aneurysms and exacerbated medial degeneration in angiotensin II-induced AA mouse model. Collectively, our data illustrated that NCOR1 interacts with FOXO3a, NFAT5, and ATF3 to maintain contractile phenotype of VSMCs and suppress AA development. Manipulation of smooth muscle NCOR1 may be a potential approach for AA treatment.

Facial skin ageing: Key concepts and overview of processes.

IntroductionThe face is a cosmetically sensitive region where the process of ageing is most clearly manifested. With increased focus on anti‐ageing and longevity, more anti‐senescent treatments are being proposed despite limited evidence. This study outlines the pathways and mechanisms underpinning the biological process of ageing in the face.MethodsComprehensive searches of MEDLINE, EMBASE, Cochrane Library and CINAHL from inception to 2020. Inclusion criteria included all empirical human research studies specific to facial ageing features, written in the English language.ResultsA total of 65 papers met inclusion criteria for analysis. Pathways were subdivided into intrinsic and extrinsic senescence mechanisms. Intrinsic pathways included genetics, generation of reactive oxygen species and hormonal changes. Extrinsic pathways included photoageing and damage to skin layers. The combined intrinsic and extrinsic pathway alterations result in wrinkles, higher laxity, slackness and thinning of the skin. Skin functions such as barrier immune function, wound healing, thermoregulation and sensory function are also impaired.ConclusionThe ageing process is unique to the individual and depends on the interplay between an individual's genetics and external environmental factors. Through understanding the molecular and cellular mechanisms, an appreciation of the consequent structural and functional changes can be achieved. Based on this knowledge, further research can focus on how to slow or impede the ageing process and identify specific targets to develop and evolve new treatment strategies.

The brown alga Laminaria ochroleuca: Charming shell pickers of the strait of Messina, fanciful sirens, and treating war wounds and scars in prostitutes

Sir, In one of his precious masterpieces, Portuguese novelist José Saramago narrates in detail the lives of the rice weeders who used to work in this land and, after a day of work, soak their bare feet in a bath with hot water, salt, mallow, and chamomile in order to restore their ankles, swollen and inflated for the alga native to these particular paddy fields, Laminaria ochroleuca (Bachelot de la Pylaie), extremely rich in fucose and alginates, provoking an accelerated and paroxistic synthesis of elastin, fibronectin, and collagen. This brown alga may be retrieved from the waters of France, Spain, Scotland, and the Shetland Islands, yet even in the Azores Islands and Morocco (Alboran Sea) [1–4]. The authors of this paper selected a special Laminaria from the Strait of Messina (Nereocystis luetkeana), a heterokont that is able to grow half a meter per day reaching the surprising and amazing height of 260 ft.). The legend has it that shell collectors, chiefly young girls, day after day, saw their legs together to create the tail of a siren, a cartilaginous appendage rich in collagen and elastin becoming scaly and squamous owing to the seawater. The authors created a dermocosmetic emulsion with high concentrations of acetolyte from Laminaria ochroleuca (12%) and other nourishing active ingredients (obviously, the chief components were petrolatum and lanolin, as per the pharmaceutical art of preparing the cold cream of Galenus). Hence, this golden alga is able to support the skin by providing antioxidants to fight free radicals, supporting the health of collagen and elastin, which helps the skin retain elasticity and radiance, reducing fine lines and wrinkles and helping to moisturize the skin while boosting its barrier. Some researchers [5] claimed that this alga could be useful to build a skin equivalent, as fucoidan significantly stimulates the proliferation of CCD-25Sk human fibroblasts. Also, western blot analysis demonstrates that fucoidan markedly increases the expression of cyclin D1 and decreases the expression of p27. Fucoidan was practically used to reconstruct SE. Immunohistochemical staining reveals that the addition of fucoidan to dermal equivalents increases the expression of proliferating cell nuclear antigen (PCNA) and p63. In addition, the expression of a6-integrin is significantly increased by fucoidan, whereas the expression of b1-integrin, type 1 collagen, elastin, and fibronectin does not markedly change. In the light of the above, the authors may assert that fucoidan shows positive effects on epidermal reconstruction and is, therefore, beneficial in the reconstruction of all types of skin damage. The authors recruited a panel of eight people: 2 veterans from Iraq and Afghanistan (a-b) presenting old war wounds with no chance to cure these after years of treatments and a myriad of surgical operations; 2 elders (one male and one female, 87 and 89 yrs. old, respectively, c-d) presenting severe bedsores; 2 older ladies (e-f) who, in the past, underwent unsuccessful aesthetical operations, presenting puckers, seams, furrows and deep wrinkles; 2 girls (two ex-prostitutes, one black and one white, g-h) who were scarred with a razor by their enemies.

Abstract 558: De Novo Synthesis Of Elastic Fibers In Dissected Aortas Of β-aminopropionitrile-administered Mice

Introduction: Elastin, a major component of extracellular matrix, is vital for aortic development and maintenance of integrity. It assumed that elastin synthesis does not occur in aortas of adults, as elastin fibers are stable molecule that may have a half-life as long as ~70 years. However, there is no direct evidence to verify this speculation. In addition, it remains unclear whether and how age-dependent alteration of elastin synthesis impacts the integrity of aortic wall. Methods and Results: First, elastin mRNA abundance was assessed in the aorta of male C57BL/6J mice at different ages (0, 2, 4, 10, 20 and 40-week-old, n=6/group). qPCR revealed that elastin mRNA was more abundant in the aorta at 2 weeks than 0 week of age, and decreased drastically at 4 weeks of age. Of note, elastin mRNA was barely detectable after 10 weeks of age. Lysyl oxidase, a key regulator in crosslinking of elastic fibers during aortic development, were also examined. Consistent with the temporal changes in elastin mRNA abundance, both molecules peaked at 2 weeks of age, and were much less abundant after 10 weeks of age. These results indicate that elastin synthesis and crosslinking were highly activated in the juvenile phase, but diminished in the adult phase. We next investigated the impact of age-dependent deletion of elastin synthesis and crosslinking on aortic integrity. β-aminopropionitrile (BAPN, 0.5% wt/vol) was administered for 12 weeks to induce aortic aneurysms and dissections in juvenile and adult male C57BL/6J mice (4, 24 weeks of age, n=15, 37/group). Corresponding to elastin mRNA abundance, development of aortic aneurysms and dissections were observed only in mice with BAPN started at juvenile, but not adult, phase. It is noteworthy that multiple laminas of fragmented elastic fibers were detected adjacent to the false lumen of dissected aortas. Since our time course study revealed that elastin synthesis was diminished after 10 weeks of age, elastic fibers observed around the false lumen was considered to be synthesized in response to aortopathy formation. Conclusion: Elastin mRNA synthesis is suppressed in the aorta of adult mice. However, its synthesis is reactivated in dissected aortas of BAPN-administered mice.

Semisolid formulations based on solid-in-oil-in-water systems containing proteins

In recent years, improvements have been made, through biotechnological processes, in the production and development of peptides capable of increasing collagen and elastin synthesis for anti-aging skin care. However, proteins have many limitations due to their structural, chemical and physical fragility to external aggressions, which may cause conformational changes, leading to loss of biological activity. Therefore, it is important to create delivery systems that protect these biomolecules from damage, allowing them to reach their target. This work aimed to develop a system able to carry bovine serum albumin (BSA), used as a model of a protein, and to incorporate this system in a semisolid formulation suitable for skin application. A microemulgel based on a solid-in-oil-in-water (S/O/W) microemulsion was prepared. Firstly, the association efficiency (AE) of lyophilized BSA-sucrose ester complex and the size of S/O nanodispersion were assessed; then, the characterization and stability evaluation of the final semisolid formulation through evaluation of pH, texture and rheological behavior were performed. The average value of AE was 54.74% ± 2.17. It was possible to develop an S/O/W microemulsion, which allowed the subsequent development of an S/O/W microemulgel that assured suitable pH, texture and rheological characteristics for skin application.

Elastin Structure, Synthesis, Regulatory Mechanism and Relationship With Cardiovascular Diseases.

As the primary component of elastic fibers, elastin plays an important role in maintaining the elasticity and tensile ability of cardiovascular, pulmonary and many other tissues and organs. Studies have shown that elastin expression is regulated by a variety of molecules that have positive and negative regulatory effects. However, the specific mechanism is unclear. Moreover, elastin is reportedly involved in the development and progression of many cardiovascular diseases through changes in its expression and structural modifications once deposited in the extracellular matrix. This review article summarizes the role of elastin in myocardial ischemia-reperfusion, atherosclerosis, and atrial fibrillation, with emphasis on the potential molecular regulatory mechanisms.

Structural Remodeling of the Extracellular Matrix in Arteriogenesis: A Review.

Lower extremity arterial occlusive disease (AOD) results in significant morbidity and mortality for the population, with up to 10% of patients ultimately requiring amputation. An alternative method for non-surgical revascularization which is yet to be fully understood is the optimization of the body's own natural collateral arterial network in a process known as arteriogenesis. Under conditions of conductance vessel stenosis or occlusion resulting in increased flow, shear forces, and pressure gradients within collaterals, positive remodeling occurs to increase the diameter and capacity of these vessels. The creation of a distal arteriovenous fistula (AVF) will drive increased arteriogenesis as compared to collateral formation with the occlusion of a conductance vessel alone by further increasing flow through these arterioles, demonstrating the capacity for arteriogenesis to form larger, more efficient collaterals beyond what is spontaneously achieved after arterial occlusion. Arteries rely on an extracellular matrix (ECM) composed of elastic fibers and collagens that provide stability under hemodynamic stress, and ECM remodeling is necessary to allow for increased diameter and flow conductance in mature arterial structures. When positive remodeling occurs, digestion of lamella and the internal elastic lamina (IEL) by matrix metalloproteinases (MMPs) and other elastases results in the rearrangement and thinning of elastic structures and may be replaced with disordered elastin synthesis without recovery of elastic function. This results in transmission of wall strain to collagen and potential for aneurysmal degeneration along collateral networks, as is seen in the pancreaticoduodenal artery (PDA) after celiac occlusion and inferior mesenteric artery (IMA) with concurrent celiac and superior mesenteric artery (SMA) occlusions. Further understanding into the development of collaterals is required to both better understand aneurysmal degeneration and optimize collateral formation in AOD.

Dermal extracellular matrix response to facetem implant: a randomised controlled experimental study

Background. A leading concept in modern regenerative medicine is the perspective of using own body resources to remodel organs and tissues via the formation of “living scaffold”. A pivotal role in the formation of dermal scaffold is played by fibroblasts that produce extracellular matrix (ECM).Aim. A study of the fibroblast activation mechanism mediating synthesis of the dermal ECM fibrillar component under the Facetem filler administration.Methods. The experimental trial was conducted in Wistar male rats (72 animals). Animals had 0.05 mL Facetem (Korea) injections subdermally. The filler is a calcium-containing product featuring gradual degradation delivered through structural microspheric properties of the Lattice-pore technology. Biological material was sampled at weeks 1 and 2 of months 1, 2, 3 and 5. Tissues were paraffin-embedded in standard histological assays and stained with Mallory’s trichrome, Picrosirius red in polarisation microscopy and immunohistochemistry with collagen types I, III and elastin antibodies (Abcam).Results. Collagen distribution in dermis and the filling zone suggests that collagen production occurs by week 2 of the Facetem filler placement followed by an increase in synthesised matrix volume to 4.39 ± 0.7 for collagen type I and 3.9 ± 0.2 for collagen type III (p < 0.05). The synthetic activity of fi broblasts reduces by month 3, albeit with collagen production remaining above control even by the end of month 5. Elastin synthesis also initiates by week 2 of the filler injection in dermis and grows by month 3.Conclusion. The presence of Facetem filler triggers a foreign body inflammatory response in dermis. This multifactorial process initiates with protein adsorption proceeding to dermal cell recruitment and modulation of fibroblasts and macrophages. Activation of these cell types induces neocollagenesis entailing the extracellular matrix synthesis and expansion in dermis.

Evaluation of Anti-Photoaging Effects of a Novel Cosmeceutical Containing a Retinoids Mixture Using In Vitro Cell Models

Physiological ageing due to the passing of time and prolonged exposure to harmful sun rays generate wrinkles and reduce skin elasticity. These visible and clinical signs can be prevented or reversed by known strategies, such as the daily use of cosmetic products with antioxidant combinations or retinoids. A new dermocosmetic formulation enriched with a complex of retinoids, called RETINOIDS SERUM, was investigated through in vitro assays using human skin cells. The experiments were carried out to assess the anti-ageing activity in normal human dermal fibroblasts (NHDF) and epidermal keratinocytes (HaCaT). After the preliminary MTT assay, the proliferation together with the synthesis of collagen and elastin fibers was performed on NHDF cells after 24 h treatment with the two non-cytotoxic concentrations. Using UVB-irradiated HaCaT cells, the measurement of matrix metalloproteinase-1 (MMP-1) levels was also investigated. In vitro studies show that the dermocosmetic product improves collagen and elastin synthesis and the renewal of dermal fibroblasts. Moreover, a reduction in the MMP-1 secretion was also highlighted in UVB-irradiated HaCaT cells. These results suggest that the cosmetic formulation containing functional compounds such as retinoids can be useful to prevent the natural sign of ageing.

Exaggerated elastin turnover in childhood and adolescence in Marfan syndrome – correlation with age – new insights from the AIMS trial

Abstract Background Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the Fibrillin1 gene (FBN1) that leads to impaired elastin formation and extra-cellular matrix homeostasis. Elastin synthesis and related lamellae formation in the aorta is completed in the newborn. Thereafter further elastin turnover is thought to be minimal during life. Elastin homeostasis is little studied in patients with MFS who have been reported to have reduced elastin in their aorta and are at risk of aortic dilatation and consequent life-threatening dissection. It is not clear if elastin loss is due to reduced elastin formation in utero or accelerated degradation during life. However, aortopathy develops early in MFS with 70% of patients developing aortic dilatation by the age of 20 years. Therefore, the longitudinal and circumferential aortic growth that occurs in childhood may involve elastic lamellae remodelling that is impaired in MFS. Desmosine is the cross-link component in the elastin molecule and is exclusively released from mature elastin breakdown, thus is a physiologically relevant biomarker of elastin turnover. We hypothesise that physiologic aortic growth is associated with elastic lamellae remodelling and increased elastin turnover, detected by elevated plasma desmosine (pDES), and that elastin turnover is exaggerated during the fast-growing period in MFS. Purpose The aims of this study were 1. To investigate the relationship between elastin turnover and age in the control subjects, and 2. To compare the elastin turnover in MFS with control subjects. Methods pDES was measured by stable isotope dilution LC-MS/MS in 113 MFS subjects (48% male, mean age 18.2±9.4 (SD) years), mean aortic root 33.8±2.1mm and Z-score 3.4±2.1 in the AIMS trial at baseline before intervention, and in 109 healthy controls (46% male, mean age 26.1±9.5 years). Results pDES levels were associated positively with age, body surface area and negatively with diastolic BP in the control group (p=0.05 and 0.21 respectively after correcting for age). In MFS subjects pDES also positively correlated with age and male sex (p<0.05). Interestingly, the age-dependent association with pDES showed a peak distribution in both control and MFS groups (Figure 1) where teenage children expressed the highest pDES levels. MFS subjects had significantly higher pDES compared to controls before the age of 20 (p=0.01) but in adulthood, there was no difference (Figure 2). Conclusion Elastin turnover is highly dynamic before early adulthood, and peaks in adolescence and is exaggerated in MFS, suggesting that this period of growth is critical in developing aortopathy. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart FoundationTENOVUS Scotland Figure 1Figure 2

Extracellular matrix: paving the way to the newest trends in atherosclerosis.

Purpose of reviewThe extracellular matrix (ECM) is critical for all aspects of vascular pathobiology. In vascular disease the balance of its structural components is shifted. In atherosclerotic plaques there is in fact a dynamic battle between stabilizing and proinflammatory responses. This review explores the most recent strides that have been made to detail the active role of the ECM – and its main binding partners – in driving atherosclerotic plaque development and destabilization.Recent findingsProteoglycans-glycosaminoglycans (PGs-GAGs) synthesis and remodelling, as well as elastin synthesis, cross-linking, degradation and its elastokines potentially affect disease progression, providing multiple steps for potential therapeutic intervention and diagnostic targeted imaging. Of note, GAGs biosynthetic enzymes modulate the phenotype of vascular resident and infiltrating cells. In addition, while plaque collagen structure exerts very palpable effects on its immediate surroundings, a new role for collagen is also emerging on a more systemic level as a biomarker for cardiovascular disease as well as a target for selective drug-delivery.SummaryThe importance of studying the ECM in atherosclerosis is more and more acknowledged and various systems are being developed to visualize, target and mimic it.

Assessment of the dynamics of indicators of morphological and functional characteristics of the skin in patients with the combined subtype of rosacea under the influence of complex phototherapy

Rosacea is a common chronic inflammatory dermatosis of vascular origin, characterized by a lesion of the face skin in the form of erythema and papulopustular elements. Taking into account the new research devoted to the treatment of rosacea, it is of scientific and practical interest to develop new methods for the treatment of this dermatosis using complex physiotherapy approaches and their synergy, for example, IPL radiation (without the use of photo filters) and submilisecond neodymium 1,064nm laser radiation. Material and methods. The study included 130patients with the combined subtype of rosacea (CSR) with varying degrees of severity of ETR and PPR. In order to study the effectiveness of complex photo- and laser therapy of CSR, all patients were divided into 4groups by simple randomization (envelope method). The treatment of the patients in each separate group included: group I — laser therapy and 1% metronidazole cream; group II — phototherapy and 1% metronidazole cream; group III — complex photo-laser therapy and 1% metronidazole cream; group IV — comparison group, patients received only 1% metronidazole cream. This work takes into account the synergism of both physiotherapeutic effects provided by non-truncated (without the use of photo filters) IPL radiation and submilisecond neodymium 1,064 nm laser radiation, as well as the increased destruction of pathologically altered vessels observed during the sequential use of both procedures, and the developed original method of treating patients with CSR. Conclusion. Based on the obtained results, it was concluded that the maximum improvement in the morphofunctional parameters of the skin was in the third group of patients with CSR. The increase in the hydration index of the skin exceeded the indicators of the other groups of patients with CSR. Also, the intensity of sebum production decreased most significantly. There was a maximum narrowing of the excretory ducts of the sebaceous glands, while in the other groups, the narrowing of the excretory ducts of the sebaceous glands occurred to a lesser and equal extent. Such changes reflect the pronounced effect of complex phototherapy on the tone of the sphincter of the excretory duct, the intensity of sebum production, as well as on the synthesis of collagen and elastin, which is reflected in the maximum approximation to the indicators of the group of healthy volunteers of such characteristics as «hydration» and «smoothness».

EFFECT OF CU(II)2 (3,5-DIPS)4 (H2 O)3 ON SURVIVAL, AVERAGE LIFE AND HEMATOLOGICAL INDICATORS IN ANIMALS WITH BURNS III DEGREE

Taking into account the properties of copper: normalization of the endocrine system, participation in the process of hematopoiesis, participation in the synthesis of collagen and elastin, neutralization of toxins, reduction of inflammatory reactions — we used a number of copper chelates to treat burn injuries under experimental conditions. Before discovering possible healing properties for burns, we quantified the toxicological properties of the substance. For this, the average lethal dose LD50/7LD50/7 which is the dose of a substance at which 50% of animals die within 7 days (after subcutaneous injection of the substance), was calculated by the integration method of H. Behrens in experiments on rats. In the second series, we caused grade III burn lesions on the backs of epilated animals, 30% of the body surface. The organometallic complex Cu(II)2 (3,5-DIPS)4 (H2 O)3 was injected into the animals intraperitoneally 30 min after the burn injury (for the first time at a dose of 50 mg/kg). From day 2, chelate was administered at a dose of 20 mg/kg. The injection was done once every 2 days for 10 days until the scab falls off. According to the experimental results, the Cu(II)2 (3,5-DIPS)4 (H2 O)3 metal complex is a compound with low toxicity. When administered subcutaneously in the dose range from 100 mg/kg to 300 mg/kg, behavioral disturbances and death of animals were not observed within 24 hours. We studied 5 hematological indicators: blood clotting time (BCT), the number of leukocytes, erythrocytes, the level of hemoglobin and platelets. Survival and average life expectancy in the group (burn) were, respectively, 40% and 18.8 days, and in the group burn + metal complex — 60% and 19.2 days, which indicates a positive effect of this metal complex on the body. There was a significant difference in clotting time, leukocyte count and platelet count compared to the control group (p<0.05), which indicates the healing properties of the Cu complex in case of burns.

Analysis of immediate use of sunscreen after microneedling

Microneedling promotes skin microlesions that lead to an inflammatory process, increasing cell proliferation, cell metabolism, and synthesis of collagen and elastin, therefore restoring skin integrity. This study aims to investigate the differences between the physical and the physical-chemical sunscreen application after microneedling, assessed through histological analysis. This was a two-phase study. The first phase investigated the physical and physical-chemical sunscreen penetration mixed with India ink through histological analysis. The sunscreens were applied after the microleakagein vivoon the skin of a volunteer who underwent abdominoplasty 24hours after the procedure. Histological analyses were carried out using optical and electron microscopy. The second phase analysed the skin reactions with the use of physical sunscreen after different microneedling treatments. The sample consisted of 30 volunteers distributed into three groups: G1 received the "Roller" microneedling, G2 received pen micropuncture treatment, and G3 received the fractional radiofrequency treatment. The histological analyses of the first phase indicated that the physical-chemical protection sunscreen penetrated more deeply, and pigment was found among the collagen fibres and the dermal fibroblast cytoplasm in comparison to the physical protection sunscreen, which had the pigment confined exclusively in the superficial epidermis layer. The second phase results demonstrated that the use of the physical protection sunscreen after the different microneedling techniques showed no adverse reactions such as itching, pain or soreness, and the hyperaemia. The proposed intervention showed that the use of physical protection sunscreen after different microneedling procedures is safe.

Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes.

Lack of adult cells’ ability to produce sufficient amounts of elastin and assemble functional elastic fibers is an issue for creating skin substitutes that closely match native skin properties. The effects of female sex hormones, primarily estrogen, have been studied due to the known effects on elastin post-menopause, thus have primarily included older mostly female populations. In this study, we examined the effects of female sex hormones on the synthesis of elastin by female and male human dermal fibroblasts in engineered dermal substitutes. Differences between the sexes were observed with 17β-estradiol treatment alone stimulating elastin synthesis in female substitutes but not male. TGF-β levels were significantly higher in male dermal substitutes than female dermal substitutes and the levels did not change with 17β-estradiol treatment. The male dermal substitutes had a 1.5-fold increase in cAMP concentration in the presence of 17β-estradiol compared to no hormone controls, while cAMP concentrations remained constant in the female substitutes. When cAMP was added in addition to 17β-estradiol and progesterone in the culture medium, the sex differences were eliminated, and elastin synthesis was upregulated by 2-fold in both male and female dermal substitutes. These conditions alone did not result in functionally significant amounts of elastin or complete elastic fibers. The findings presented provide insights into differences between male and female cells in response to female sex steroid hormones and the involvement of the cAMP pathway in elastin synthesis. Further explorations into the signaling pathways may identify better targets to promote elastic fiber synthesis in skin substitutes.

Assessment of the dynamics of indicators of morphological and functional characteristics of the skin in patients with the combined subtype of rosacea under the influence of complex phototherapy

Rosacea is a common chronic inflammatory dermatosis of vascular origin, characterized by a lesion of the face skin in the form of erythema and papulopustular elements. Taking into account the new research devoted to the treatment of rosacea, it is of scientific and practical interest to develop new methods for the treatment of this dermatosis using complex physiotherapy approaches and their synergy, for example, IPL radiation (without the use of photo filters) and submilisecond neodymium 1,064 nm laser radiation. Material and methods: The study included 130 patients with the combined subtype of rosacea (CSR) with varying degrees of severity of ETR and PPR. In order to study the effectiveness of complex photo- and laser therapy of CSR, all patients were divided into 4 groups by simple randomization (envelope method). The treatment of the patients in each separate group included: group I — laser therapy and 1% metronidazole cream; group II — phototherapy and 1% metronidazole cream; group III — complex photo-laser therapy and 1% metronidazole cream; group IV — comparison group, patients received only 1% metronidazole cream. This work takes into account the synergism of both physiotherapeutic effects provided by non-truncated (without the use of photo filters) IPL radiation and submilisecond neodymium 1,064 nm laser radiation, as well as the increased destruction of pathologically altered vessels observed during the sequential use of both procedures, and the developed original method of treating patients with CSR. Conclusion: Based on the obtained results, it was concluded that the maximum improvement in the morphofunctional parameters of the skin was in the third group of patients with CSR. The increase in the hydration index of the skin exceeded the indicators of the other groups of patients with CSR. Also, the intensity of sebum production decreased most significantly. There was a maximum narrowing of the excretory ducts of the sebaceous glands, while in the other groups, the narrowing of the excretory ducts of the sebaceous glands occurred to a lesser and equal extent. Such changes reflect the pronounced effect of complex phototherapy on the tone of the sphincter of the excretory duct, the intensity of sebum production, as well as on the synthesis of collagen and elastin, which is reflected in the maximum approximation to the indicators of the group of healthy volunteers of such characteristics as «hydration» and «smoothness».

The role of dietary supplements in cosmetology therapy based on deep chemical peels

Treatments based on deep chemical peels are aimed at cell renewal, accelerating the synthesis of collagen, elastin and glycosaminoglycans, and consequently improving skin firmness, reducing wrinkles and scars. Due to the small molecule and low pH, chemical peels interact at the level of the living layers of the epidermis and dermis. They lead to controlled skin damage and initiate regeneration and remodeling processes. The consequence of using peels at the level of the dermis is the formation of new cells capable of synthesizing more collagen, elastin and hyaluronic acid. During treatments aimed at cell exchange and stimulation of fibroblasts, the demand for amino acids, microelements and vitamins increases. Their supply is complemented by dietary supplements. The aim of the study was to show the role of dietary supplements in cosmetology treatments based on chemical peels acting at the level of the dermis. The synergy of simultaneous use of dietary supplements and chemical peels as well as the positive effect of supplementation on the effects visible on the skin was indicated.

Synergistic effect of copper and amino acid mixtures on the production of extracellular matrix proteins in skin fibroblasts.

The stimulation of extracellular matrix (ECM) protein production is an interesting target to maintain normal skin structure and delay skin aging. Copper has been shown to stimulate ECM protein synthesis by activating lysyl oxidase. Although copper increases elastin and collagen synthesis, the effect of copper and amino acid mixtures on gene expression and protein synthesis changes relating to the ECM have not been fully investigated. In this study, we showed that copper ions (Cu2+) and amino acid mixtures significantly increased the expression of genes and proteins related to the ECM in human dermal fibroblasts. The expression of genes involved in ECM production was evaluated through quantitative polymerase chain reaction in the presence of amino acid mixtures containing different Cu2+ concentrations. Cu2+ dose-dependently increased the gene expression of elastin and collagen I. In addition, a mixture of amino acids and Cu2+ increased the protein expression of elastin and collagen I. We further evaluated the effect of Cu2+ with or without amino acids. Although Cu2+ treatment increased the expression of genes encoding ECM proteins, the Cu2+ treatment without amino acids did not increase protein expression in the ECM. Our results demonstrated the synergistic effects of amino acids and a Cu2+ mixture on ECM protein synthesis in dermal fibroblasts.

Control Delivery of Multiple Growth Factors to Actively Steer Differentiation and Extracellular Matrix Protein Production.

In tissue engineering, biomaterials have been used to steer the host response. This determines the outcome of tissue regeneration, which is modulated by multiple growth factors (GFs). Hence, a sustainable delivery system for GFs is necessary to control tissue regeneration actively. A delivery technique of single and multiple GF combinations, using a layer-by-layer (LBL) procedure to improve tissue remodeling, is developed. TGF-β1, PDGF-ββ, and IGF-1 are incorporated on tailor-made polymeric rods, which could be used as a tool for potential tissue engineering applications, such as templates to induce the formation of in situ tissue engineered blood vessels (TEBVs). Cell response is analyzed in vitro using rat and human dermal fibroblasts for cellular proliferation, fibroblast differentiation, and extracellular matrix (ECM) protein synthesis. Results revealed a higher loading efficiency and control release of GFs incorporated on chloroform and oxygen plasma-activated (COX) rods. Single PDGF-ββ and IGF-1 release, and dual release with TGF-β1 from COX rods, showed higher cell proliferation when compared to COX rods alone. A substantial increase in α-smooth muscle actin (α-SMA) is also observed in GF releasing COX rods, with TGF-β1 COX rods providing the most pronounced differentiation. A significant increase in collagen and elastin synthesis is observed on all GF releasing COX rods compared to control, with COX rods releasing TGF-β1 and IGF-1 providing the highest secretion. TGF-β1 and IGF-1 releasing COX rods induced higher Glycosaminoglycan (GAG)/DNA amounts than the other GF releasing COX rods. As PDGF-ββ and TGF-β1/PDGF-ββ COX rods displayed the highest fibroblast attachment, these rods provided the highest total collagen and elastin production. The attractive results from efficiently incorporating single and multiple GFs on COX rods and their sustainable release to steer cellular behavior suggest a promising route to enrich the formation of in situ engineered tissues.

Immunohistochemistry analysis reveals lysyl oxidase-like 3 as a novel prognostic marker for primary melanoma.

Lysyl oxidase-like 3 (LOXL3) is an extracellular enzyme involved in the synthesis of collagen and elastin, and it has been reported to promote melanoma cell proliferation and invasion in vitro. However, the expression level of LOXL3 at different stages of melanocytic lesions and the role of LOXL3 in melanoma pathogenesis remain unknown. Immunohistochemical staining of LOXL3 in a tissue microarray of 373 biopsies at different melanocytic stages was conducted. The correlation between LOXL3 expression and patient survival was examined using Kaplan-Meier survival analysis. Univariate and multivariate Cox regression analyses were conducted to study the hazard ratios. The tissue microarray study revealed that stronger expression of LOXL3 protein was found at more advanced melanocytic stages (P < 0.0001; χ2 test). Increased LOXL3 expression was associated with enhanced tumor thickness and mitosis. Survival analysis showed significantly worsened prognosis in primary melanoma patients when the LOXL3 expression level was higher (P = 0.043; log-rank test). Multivariate Cox regression analysis further showed that LOXL3 expression is a prognostic factor for primary melanoma patient survival (P = 0.04). LOXL3 expression is positively correlated with tumor progression and invasion, and its overexpression is associated with worse prognosis of primary melanoma patients. LOXL3 can serve as a prognostic marker to help identify primary melanoma patients at higher risks of death.