A Retrospective Pragmatic Longitudinal Case-Series Clinical Study to Evaluate the Clinical Outcome of Triple-Frequency Ultrasound in Treatment of Cellulite.

Objective: In this single-centre, retrospective, pragmatic, longitudinal case-series clinical study triple-frequency LDM (TF-LDM) technology with frequencies of 1/3/10 MHz and 3/10/19 MHz was applied for treatment of cellulite to reveal the effect of these waves on the cellulite skin and assess the sustainability of treatment outcomes during the long-term follow-up controls.

Methods: Twenty Caucasian females with mild-to-severe gynoid lipodystrophy aged 27-53 years who received cellulite monotherapy with TF-LDM were included in this study. All participants were evaluated at three time points: baseline (T1), on the day of the last treatment (T2), and during the last follow-up (T3).

A Retrospective Pragmatic Two-Center Clinical Study to Evaluate the Clinical Outcome of Triple-Frequency Ultrasound in the Treatment of Mild-to-Severe Acne Vulgaris.

Objectives: Earlier, quickly alternating dual-frequency ultrasound waves (LDM technology) were successfully applied for the treatment of different inflammatory skin conditions such as rosacea and acne. In this retrospective pragmatic two-center clinical study, we applied the triple-frequency LDM (TF-LDM) technology with frequencies of 1/3/10 and 3/10/19 MHz for the treatment of mild-to-severe acne skin to assess the effectivity and sustainability of the treatment outcomes.

Methods: Twenty-two patients with mild-to-severe acne were included in this study: 11 patients were treated with TF-LDM (1/3/10 MHz), and other 11 patients-with TF-LDM (3/10/19 MHz).

Is the endotoxin-complement cascade the major driver in lipedema?

Lipedema is a poorly understood disorder of adipose tissue characterized by abnormal but symmetrical deposition of subcutaneous white adipose tissue (WAT) in proximal extremities. Here, we propose that the underlying cause for lipedema could be triggered by a selective accumulation of bacterial lipopolysaccharides (LPS; also known as endotoxin) in gluteofemoral WAT. Together with a malfunctioning complement system, this induces low-grade inflammation in the depot and raises its uncontrollable expansion.

Pathophysiology of cellulite: Possible involvement of selective endotoxemia.

The most relevant hallmarks of cellulite include a massive protrusion of superficial adipose tissue into the dermis, reduced expression of the extracellular glycoprotein fibulin-3, and an unusually high presence of MUSE cells in gluteofemoral white adipose tissue (gfWAT) that displays cellulite. Also typical for this condition is the hypertrophic nature of the underlying adipose tissue, the interaction of adipocytes with sweat glands, and dysfunctional lymph and blood circulation as well as a low-grade inflammation in the areas of gfWAT affected by cellulite. Here, we propose a new pathophysiology of cellulite, which connects this skin condition with selective accumulation of endogenous lipopolysaccharides (LPS) in gfWAT.

Phenotypical Conversions of Dermal Adipocytes as Pathophysiological Steps in Inflammatory Cutaneous Disorders.

Adipocytes from the superficial layer of subcutaneous adipose tissue undergo cyclic de- and re-differentiation, which can significantly influence the development of skin inflammation under different cutaneous conditions. This inflammation can be connected with local loading of the reticular dermis with lipids released due to de-differentiation of adipocytes during the catagen phase of the hair follicle cycle. Alternatively, the inflammation parallels a widespread release of cathelicidin, which typically takes place in the anagen phase (especially in the presence of pathogens).

Skin aging: Dermal adipocytes metabolically reprogram dermal fibroblasts.

Emerging data connects the aging process in dermal fibroblasts with metabolic reprogramming, provided by enhanced fatty acid oxidation and reduced glycolysis. This switch may be caused by a significant expansion of the dermal white adipose tissue (dWAT) layer in aged, hair-covered skin. Dermal adipocytes cycle through de-differentiation and re-differentiation.

Assessment of Mechanical Stress Induced by Radiofrequency Currents on Skin Interfaces.

The epidermal-dermal (ED) and dermal-subcutaneous (DS) junctions are the most prominent skin interfaces, which are known to be of primary importance in different dermatological and aesthetic conditions. These interfaces are strongly modified in aging skin, and their effective targeting can lead to improvement of skin appearance in aging and by cellulite. Application of radiofrequency (RF) currents to the skin can selectively produce mechanical stress on these interfaces.

Acoustic Waves in Axonal Membrane and Caveolins are the New Targets for Pain Treatment with High Frequency Ultrasound.

Reciprocal interaction between electrical and mechanical waves observed in axonal membrane during its excitation leads to a paradigm shift in pain research making the uncoupling of electro-mechanical signals an interesting target in pain treatment. This uncoupling can be realized either through direct disturbance of the mechanical surface waves in axonal membrane or through shifting of the thermodynamic state of this membrane far from its phase transition point. Both effects can be effectively realized through application of the very high frequency ultrasound waves.

Obesity and diabetes as comorbidities for COVID-19: Underlying mechanisms and the role of viral-bacterial interactions.

Obesity and diabetes are established comorbidities for COVID-19. Adipose tissue demonstrates high expression of ACE2 which SARS- CoV-2 exploits to enter host cells. This makes adipose tissue a reservoir for SARS-CoV-2 viruses and thus increases the integral viral load.

Dermal adipocytes contribute to the metabolic regulation of dermal fibroblasts.

Dermal fibroblasts are an essential population of skin cells. They are not only responsible for synthesis and remodelling of the extracellular matrix of the dermis, but also communicate with other skin cells via autocrine and paracrine interactions. Skin-associated dermal adipocytes reside below the reticular dermis.

The MMP14-caveolin axis and its potential relevance for lipoedema.

Lipoedema is associated with widespread adipose tissue expansion, particularly in the proximal extremities. The mechanisms that drive the development of lipoedema are unclear. In this Perspective article, we propose a new model for the pathophysiology of lipoedema.

The Role of Adipocytes and Adipocyte-Like Cells in the Severity of COVID-19 Infections.

Coronavirus disease-2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis. In this Perspective, we argue that adipocytes and adipocyte-like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to SARS-CoV-2. Expression of angiotensin-converting enzyme 2 (the functional receptor for SARS-CoV) is upregulated in adipocytes of patients with obesity and diabetes, which turns adipose tissue into a potential target and viral reservoir.

Caveolin as a Universal Target in Dermatology.

Caveolin-1 is strongly expressed in different dermal and subdermal cells and physically interacts with signaling molecules and receptors, among them with transforming growth factor beta (TGF-β), matrix metalloproteinases, heat shock proteins, toll-like and glucocorticoid receptors. It should therefore be heavily involved in the regulation of cellular signaling in various hyperproliferative and inflammatory skin conditions. We provide an overview of the role of the caveolin-1 expression in different hyperproliferative and inflammatory skin diseases and discuss its possible active involvement in the therapeutic effects of different well-known drugs widely applied in dermatology.

Caveolin-1 as a possible target in the treatment for acne.

Expression of caveolin-1 (Cav-1) is an important pathophysiological factor in acne. Cav-1 strongly interacts with such well-recognized etiopathogenic factors such as hyperseborrhea, follicular hyperkeratinization and pathogenicity of Cutibacterium acnes. Cav-1 is a strong negative regulator of transforming growth factor beta (TGF-β) expression.

Dermal adipose tissue has high plasticity and undergoes reversible dedifferentiation in mice.

Dermal adipose tissue (also known as dermal white adipose tissue and herein referred to as dWAT) has been the focus of much discussion in recent years. However, dWAT remains poorly characterized. The fate of the mature dermal adipocytes and the origin of the rapidly reappearing dermal adipocytes at different stages remain unclear.

Caveolin-1 in skin aging - From innocent bystander to major contributor.

Caveolin-1 (Cav-1) appears to be both a pathophysiological contributor and a target in different inflammatory and hyperproliferative skin conditions as well as in skin aging. Skin fibroblasts demonstrate an up-regulation of Cav-1 expression both in chronological and UV-induced aging, and such an up-regulation was observed both in vitro and in vivo. Typical alterations in aging skin involve a reduction of the dermis thickness, a significant expansion of the dermal white adipose tissue as well as modifications of the content and distribution of hyaluronan, impairment of autophagic flux, a reduction of collagen expression and an increase in tissue inflammation.

Caveolin-1 as a target in prevention and treatment of hypertrophic scarring.

Reduced expression of caveolin-1 (Cav-1) is an important pathogenic factor in hypertrophic scarring (HTS). Such a reduction can be found in connection with the main known risk factors for HTS, including dark skin, female gender, young age, burn site and severity of the injury. The degree of overexpression of Cav-1 associated with different therapeutic options for HTS correlates with clinical improvements in HTS.

Caveolin-1 as a pathophysiological factor and target in psoriasis.

Low expression of caveolin-1 (Cav-1) is typical in psoriatic lesions and overexpression of Cav-1 leads to a reduction of inflammation and suppression of epidermal hyperproliferation, thus ameliorating these two well-known hallmarks of psoriasis. At the same time, the interfacial layers of the white adipose tissue (WAT) adjacent to psoriatic lesions demonstrate much higher stiffness, which also points to a modification of Cav-1 expression in this tissue. These processes are connected with each other and regulated via exosomal exchange.

The Role of Immature and Mature Adipocytes in Hair Cycling.

Hair follicles (HFs) strongly interact with adipocytes within the dermal white adipose tissue (dWAT), suggesting a strong physiological dependence on the content of immature and mature adipocytes in this layer. This content is regulated by the proliferation and differentiation of adipocyte precursors, as well as by dedifferentiation of mature existing adipocytes. Spatially, long-range interactions between HFs and dWAT involve the exchange of extracellular vesicles which are differentially released by precursors, preadipocytes, and mature adipocytes.

Skin aging as a mechanical phenomenon: The main weak links.

From a mechanical point of view, human skin appears as a layered composite containing the stiff thin cover layer presented by the stratum corneum, below which are the more compliant layers of viable epidermis and dermis and further below the much more compliant adjacent layer of subcutaneous white adipose tissue (sWAT). Upon exposure to a strain, such a multi-layer system demonstrates structural instabilities in its stiffer layers, which in its simplest form is the wrinkling. These instabilities appear hierarchically when the mechanical strain in the skin exceeds some critical values.

Hyaluronan in adipogenesis, adipose tissue physiology and systemic metabolism.

Hyaluronic acid (HA, also known as hyaluronan), is a non-sulfated linear glycosaminoglycan polymer consisting of repeating disaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine abundantly present in the extracellular matrix. The sizes of hyaluronic acid polymers range from 5000 to 20,000,000 Da in vivo, and the functions of HA are largely dictated by its size. Due to its high biocompatibility, HA has been commonly used as soft tissue filler as well as a major component of biomaterial scaffolds in tissue engineering.

Local effects of adipose tissue in psoriasis and psoriatic arthritis.

The structure and physiological state of the local white adipose tissue (WAT) located underneath the lesional psoriatic skin and inside of the joints affected by psoriatic arthritis play an important role in the pathophysiology of these diseases. WAT pads associated with inflammatory sites in psoriasis and psoriatic arthritis are, correspondingly, dermal WAT and articular adipose tissue; these pads demonstrate inflammatory phenotypes in both diseases. Such local WAT inflammation could be the primary effect in the pathophysiology of psoriasis leading to the modification of the local expression of adipokines, a change in the structure of the basement membrane and the release of keratinocytes with consequent epidermal hyperproliferation during psoriasis.

Role of adipose tissue in facial aging.

Age-dependent modification of the facial subcutaneous white adipose tissue (sWAT) connected with reduction of its volume, modification of collagen content and adhesion between dermal and adipose layers can significantly influence mechanical stability of the skin and cause the development of aging symptoms such as wrinkles. Typical aging appearance in facial skin is at least partly connected with special phenotypical features of facial preadipocytes and mature adipocytes. In this paper, we have discussed the possible roles of local inflammation, compartmental structure of facial sWAT and trans-differentiation processes such as beiging of white adipocytes and adipocyte-myofibroblast transition in facial skin aging.