Keloids are fibroproliferative skin disorder caused by abnormal healing of injured or irritated skin and are characterized by excessive extracellular matrix (ECM) synthesis and deposition, which results in excessive collagen disorders and calcinosis, increasing the remodeling and stiffness of keloid matrix. The pathogenesis of keloid is very complex, and may include changes in cell function, genetics, inflammation, and other factors. In this review, we aim to discuss the role of biomechanical factors in keloid formation. Mechanical stimulation can lead to excessive proliferation of wound fibroblasts, deposition of ECM, secretion of more pro-fibrosis factors, and continuous increase of keloid matrix stiffness. Matrix mechanics resulting from increased matrix stiffness further activates the fibrotic phenotype of keloid fibroblasts, thus forming a loop that continuously invades the surrounding normal tissue. In this process, mechanical force is one of the initial factors of keloid formation, and matrix mechanics leads to further keloid development. Next, we summarized the mechanotransduction pathways involved in the formation of keloids, such as TGF-β/Smad signaling pathway, integrin signaling pathway, YAP/TAZ signaling pathway, and calcium ion pathway. Finally, some potential biomechanics-based therapeutic concepts and strategies are described in detail. Taken together, these findings underscore the importance of biomechanical factors in the formation and progression of keloids and highlight their regulatory value. These findings may help facilitate the development of pharmacological interventions that can ultimately prevent and reduce keloid formation and progression.

The periodic growth of hair follicles is regulated by the balance of activators and inhibitors. The BMP signaling pathway plays an important role during hair follicle regeneration, but the exact BMP protein that controls this process has not been revealed. The expression of BMP6 was determined via in situ hybridization and immunofluorescence. The in vivo effect of BMP6 overexpression was studied by using a previously established adenovirus injection model. The hair follicle regeneration was assessed by gross observation, H&E staining and 5-bromo-2-deoxyuridine (BrdU) tracing. The expression patterns of BMP6 signaling and Wnt10b signaling in both AdBMP6-treated and AdWnt10b-treated skins were determined by in situ hybridization and immunofluorescence. BMP6 was expressed differently in the stages of hair follicle cycle. The telogen-anagen transition of hair follicles was inhibited by adenovirus-mediated overexpression of BMP6. In the in vivo model, the BMP6 signaling was inhibited by Wnt10b and the Wnt10b signaling was inhibited by BMP6. The activation of hair follicle stem cells (HFSCs) was also competitively regulated by Wnt10b and BMP6. Combined with previously reported data of Wnt10b, our findings indicate that BMP6 and Wnt10b are major inhibitors and activators respectively and their balance regulates the telogen-anagen transition of hair follicles. To the best of our knowledge, our data provide previously unreported insights into the regulation of hair follicle cycling and provide new clues for the diagnosis and therapies of hair loss.

Wound infections may disrupt the normal wound-healing process. Large amounts of antibiotics are frequently used to prevent pathogenic infections; however, this can lead to resistance development. Biomaterials possessing antimicrobial properties have promising applications for reducing antibiotic usage and promoting wound healing. Silk sericin (SS) has been increasingly explored for skin wound healing applications owing to its excellent biocompatibility and antioxidant, antimicrobial, and ultraviolet-resistant properties. In recent years, SS-based composite biomaterials with a broader antimicrobial spectrum have been extensively investigated and demonstrated favorable efficacy in promoting wound healing. This review summarizes various antimicrobial agents, including metal nanoparticles, natural extracts, and antibiotics, that have been incorporated into SS composites for wound healing and elucidates their mechanisms of action. It has been revealed that SS-based biomaterials can achieve sustained antimicrobial activity by slow-release-loaded antimicrobial agents. The antimicrobial-loaded SS composites may promote wound healing through anti-infection, anti-inflammation, hemostasis, angiogenesis, and collagen deposition. The manufacturing methods, benefits, and limitations of antimicrobial-loaded SS materials are briefly discussed. This review aims to enhance the understanding of new advances and directions in SS-based antimicrobial composites and guide future biomedical research.

Despite therapeutic advancements (e.g. B-RAF inhibitors) targeting cutaneous melanoma, many cellular processes, including inducible heme oxygenase 1 (HO-1), counteract treatments for malignancies. So there is an urgent need to find biological treatment targets, develop new therapeutic approaches and achieve longer responses. This study aimed to explore the relationship of HO-1 and B-Raf via mediating ERK1/2 signaling on cell cycle in melanoma. Immunohistochemistry was applied to evaluate the levels of HO-1 and B-Raf expression in melanoma tissues and adjacent healthy tissues. Co-immunoprecipitation (Co-IP) assessed the interaction of HO-1 with B-Raf. Further study overexpression and knock-down of HO-1 in A375 cell lines, especially knockout HO-1 using CRISPR-Cas9, verified HO-1 regulate cell proliferation in vivo and in vitro. Finally, Western blot analysis and qRT-PCR were performed to investigate the mechanisms by which HO-1 mediates cell cycle by B-RAF-ERK1/2 signaling. First, histology and Co-IP show that HO-1 interacts with B-Raf directly in melanoma tissue. Further study illustrated that HO-1 overexpression promotes melanoma cell proliferation while HO-1 reduction represses melanoma cell proliferation because of HO-1 affects cell cycle. Mechanistic studies revealed that HO-1 was associated with a marked activation of B-RAF-ERK1/2 signaling and led to CDK2/cyclin E activation, thereby promoting melanoma proliferation. Our result reveals a previously unknown mechanism that the HO-1-B-RAF-ERK axis plays an important role in melanoma cell proliferation. Therapeutic target on HO-1 could be a novel method for treating melanoma.

Background: Extrinsic injury can evoke intrinsic stimulation subquently initiate physiological repair process. Several kinds of injury have been studied to promote hair growth and skin pigmentation. In this study, we ask if proper injury could be employed to create local stimuli subsquently to induce hair regeneration and vitiligo repigmentation.Methods: We firstly manufactured a novel designed device to precisely control all micro-injury parameters. Then the most appropriate micro-injury extent was evaluated without over-damage to skin. The effects of micro-injury on hair regeneration and vitiligo repigmentation were examined by macroscopical observation, histological staining, gene and protein expression analysis.Results: We discover that proper micro-injury effectively induces hair regeneration by activating the hair follicle stem cell proliferation and migration downwards to hair matrix, finally shifting the hair follicle stage from telogen into anagen. On vitiligo model mice, micro-injury also induces the hair follicle melanocyte stem cell migrate upwards to interfollicular epidermis, activate and give rise to melanocytes to repopulate vitiligo lesion. Mechanism analysis indicates that the canonical Wnt/b-catenin pathway plays a key role in the micro-injury induced regeneration process. Conclusions: The present study demonstrates that micro-injury has great potential in inducing hair regeneration and vitiligo repigmentation, laid a foundation to develop micro-injury based treatment method in alopecia and vitiligo.

Background: Psoriasis vulgaris (PV) is one of the most common chronic inflammatory skin diseases, but its exact etiology and pathological mechanism are not fully understood. The regulation of tryptophan metabolism by gut microbiota-host co-metabolism has been confirmed to significantly affect the pathogenesis of various chronic inflammatory and autoimmune diseases. Tryptophan and its main metabolites are partly involved in the pathogenesis and progression of psoriasis, but its specific regulatory mechanism has not yet been clarified. The purpose of this study is to explore the changes in the intestinal flora and its metabolic characteristics in PV patients. Methods: 16S rRNA sequencing combined with metabolomics was used to explore changes in gut microbiota and its metabolic characteristics. Alpha, Beta diversity and LEfSe (Linear Discriminant Analysis Effect Size) analyses were used to analyze the changes in the intestinal flora and to screen biomarkers. PCA (Principal Component Analysis) and OPLS-DA (Orthogonal Partial Least Squares-Discriminant Analysis) methods were used to analyze the differences in metabolite composition. PICRUS (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) software was used to predict metabolic function. Results: The result revealed differences in the tract microbiota composition between normal and psoriasis patients, suggesting that microbial populations may mediate the development of psoriasis. Fecal metabolite profiles revealed distinct metabolites associated with the psoriasis samples group (PSG). These products of metabolism primarily participated in metabolic pathways including amino acid biosynthesis, carbohydrate degradation and glycolysis. There is a positive/negative correlation between these gut microbes and metabolites. Conclusions: The results suggest that the gut microbiota and its metabolites may play a crucial role in the development of PSG, which may provide a potential biomarker for the treatment of PSG.