Figure - available from: Archives of Dermatological Research
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Histologic images of hypertrophic scars and keloids. a 5 × 10, hematoxylin and eosin (H&E), The section shows a hypertrophic scar with nodular fibrosis. The overlying epidermis shows prurigo nodularis changes. b 10 × 10, H&E, keloid formation within the hypertrophic scar after a wide local excision procedure. c 10 × 10, H&E, keloid on ear followed by ear piercing trauma: swollen and eosinophilic collagen and scattered fibroblasts with thin overlying epidermis. Dilated blood vessels are present. d 20 × 10, H&E, Keloid: haphazard bundles of eosinophilic (bubble gum pink) collagen with bland fibroblasts and hyalinized collagen
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![PRISMA flow diagram [45]](publication/368473360/figure/fig2/AS:11431281176726953@1690249936203/PRISMA-flow-diagram-45_Q320.jpg)
Exaggerated healing and remodeling after skin injury may cause hypertrophic and keloidal scars, which are associated with functional and quality of life impairment. There is limited guidance available regarding the relative effectiveness of therapies for hypertrophic scars and keloids. In this review, we aim to compare the effectiveness of treatmen...
Citations
... In recent years, there has been a significant advance in understanding molecular mechanisms underlying keloid pathogenesis (2, [19][20][21][22][23]. While these advances have shed light on the proliferation of mesenchymal fibroblasts (FBs) driven by fibrogenic growth factors such as TGF-b signaling and their association with the pathological accumulation of extracellular matrix components, the broader landscape of keloid development remains complex (3,9,24,25). It is critical to recognize the multifactorial nature of keloid pathogenesis, which includes genetic predisposition, environmental influences, and molecular mechanisms. ...
Background
Mast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored.
Objectives
To elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity.
Methods
Keloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids.
Results
The scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples.
Conclusions
scRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions.
... In addition to the fact that the event that led to the formation of the scar is strongly fixed in the memory, relatives and loved ones can relate precisely when and how the traumatic event happened. In this way, scars can be used to identify people, both living and dead [1,2]. ...
The purpose of this narrative review is to analyze surgical techniques for removing scar tissue and minimizing them. A considerable proportion of the population have scars that are related to a traumatic event that they remember accurately, this being especially true for scars on the face, but also on the rest of the body if they are of significant size. The negative consequences of the esthetic damage are felt mainly in the family and at professional level, without losing sight of the fact that any person suffers as a result of the awareness of unsightly wounds or scars. To be successful, an aesthetic intervention must represent the optimal balance between science, the art of plastic surgery and the patient’s expectations. Good communication between surgeon and patient is also needed. We must state that there is no method of total removal of scars; even in the case of complex surgical techniques, the scar cannot be completely excised, but a much more aesthetic appearance can be obtained. Scars cannot be completely removed from the skin, they can improve their appearance by fading or thinning, initially by conservative treatment, later, if necessary, by surgical scar reduction techniques. Improving the appearance of a scar depends on the type of scar, its severity, its surface and location, the causing factors, the time elapsed from production to the application of specialized treatment.
... Pathological scars are defined as such when they negatively affect a person's health and quality of life (psychic, social, working) [28,29]. We can recognize different pathological scars, such as hypertrophic scars, keloids, atrophic scars, and striae distensae (SD) or stretch marks. ...
The skin is a complex organ, a system that influences and is influenced by the body system, with different skin layers always mechano-biologically active. In the presence of a lesion that damages the dermis, the skin undergoes sensory, morphological, and functional alterations. The subsequent adaptation is the formation of scar tissue, following distinct and overlapping biological phases. For reasons not yet fully elucidated, some healing processes lead to pathological scars, from which symptoms such as pain, itching, and functional limitations are derived. Currently, there is no gold standard treatment that fully meets the needs of different scars and can eliminate any symptoms that the patient suffers. One such treatment is manual medicine, which involves direct manual approaches to the site of injury. Reviewing the phases that allow the skin to be remodeled following an injury, this article reflects on the usefulness of resorting to these procedures, highlighting erroneous concepts on which the manual approach is based, compared to what the current literature highlights the cicatricial processes. Considering pathological scar adaptations, it would be better to follow a gentle manual approach.
Background
Keloid is a chronic proliferative fibrotic disease caused by abnormal fibroblasts proliferation and excessive extracellular matrix (ECM) production. Numerous fibrotic disorders are significantly influenced by ferroptosis, and targeting ferroptosis can effectively mitigate fibrosis development. This study aimed to investigate the role and mechanism of ferroptosis in keloid development.
Methods
Keloid tissues from keloid patients and normal skin tissues from healthy controls were collected. Iron content, lipid peroxidation (LPO) level, and the mRNA and protein expression of ferroptosis-related genes including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined. Mitochondrial morphology was observed using transmission electron microscopy (TEM). Keloid fibroblasts (KFs) were isolated from keloid tissues, and treated with ferroptosis inhibitor ferrostatin-1 (fer-1) or ferroptosis activator erastin. Iron content, ferroptosis-related marker levels, LPO level, mitochondrial membrane potential, ATP content, and mitochondrial morphology in KFs were detected. Furthermore, the protein levels of α-smooth muscle actin (α-SMA), collagen I, and collagen III were measured to investigate whether ferroptosis affect fibrosis in KFs.
Results
We found that iron content and LPO level were substantially elevated in keloid tissues and KFs. SLC7A11, GPX4, and Nrf2 were downregulated and TFRC was upregulated in keloid tissues and KFs. Mitochondria in keloid tissues and KFs exhibited ferroptosis-related pathology. Fer-1 treatment reduced iron content, restrained ferroptosis and mitochondrial dysfunction in KFs, Moreover, ferrostatin-1 restrained the protein expression of α-SMA, collagen I, and collagen III in KFs. Whereas erastin treatment showed the opposite results.
Conclusion
Ferroptosis exists in keloid. Ferrostatin-1 restrained ECM deposition and fibrosis in keloid through inhibiting ferroptosis, and erastin induced ECM deposition and fibrosis through intensifying ferroptosis.
Based on engineered cell/exosome technology and various skin-related animal models, exosomal microRNA (miRNA)-based therapies derived from natural exosomes have shown good therapeutic effects on nine skin diseases, including full-thickness skin defects, diabetic ulcers, skin burns, hypertrophic scars, psoriasis, systemic sclerosis, atopic dermatitis, skin aging, and hair loss. Comparative experimental research showed that the therapeutic effect of miRNA-overexpressing exosomes was better than that of their natural exosomes. Using a dual-luciferase reporter assay, the targets of all therapeutic miRNAs in skin cells have been screened and confirmed. For these nine types of skin diseases, a total of 11 animal models and 21 exosomal miRNA-based therapies have been developed. This review provides a detailed description of the animal models, miRNA therapies, disease evaluation indicators, and treatment results of exosomal miRNA therapies, with the aim of providing a reference and guidance for future clinical trials. There is currently no literature on the merits or drawbacks of miRNA therapies compared with standard treatments.
Actinic keratosis (AK) is a common precancerous skin lesion that can develop into cutaneous squamous cell carcinoma (CSCC). AK is characterized by atypical keratinocytes in the skin’s outer layer and is commonly found in sun-exposed areas. Like many precancerous lesions, the development of AK is closely associated with genetic mutations. The molecular biology and transcriptional mechanisms underlying AK development are not well understood. Ultraviolet (UV) light exposure, especially UVA and UVB radiation, is a significant risk factor for AK, causing DNA damage and mutagenic effects. Besides UV exposure, comorbidities like diabetes, rheumatoid arthritis, and psoriasis may also influence AK development. AK patients have shown associations with various internal malignancies, indicating potential vulnerability in cancer-associated genes. Treatment for AK includes cryosurgery, electrodesiccation and curettage, chemotherapeutic creams, photodynamic therapy, or topical immune-modulators. Genomic studies have identified genetic aberrations in AK, with common mutations found in genes like TP53, NOTCH1, and NOTCH2. The progression from AK to CSCC involves chromosomal aberrations and alterations in oncogenes and tumor-suppressor genes. The functional relationships among these genes are not fully understood, but network analysis provides insights into their potential mechanisms. Further research is needed to enhance our understanding of AK’s pathogenesis and develop novel therapeutic approaches.
