IL-13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation.

Keloids are considered the manifestation of a fibroproliferative disease characterized by chronic inflammation that is induced following skin injury. Deciphering the underlying mechanism of keloid formation is essential for improving treatment outcomes. Here, we found that more macrophages were activated toward the M2 subtype in keloid dermis when compared with normal dermis. Western blotting revealed that the level of phosphorylated STAT6 (p-STAT6), a known inducer of M2 polarization, was higher in keloid fibroblasts as opposed to fibroblasts from normal dermis. Moreover, keloid fibrosis was shown to be positively correlated with the level of p-STAT6. Further, we identified downregulation of IL-13RA2, a decoy receptor for IL-13, in keloid fibroblasts compared with fibroblasts from normal dermis. Ectopic expression of IL-13RA2 in keloid fibroblasts resulted in inhibition of STAT6 phosphorylation, cell proliferation, migration, invasion, extracellular matrix secretion, and myofibroblast marker expression, as well as an increase in apoptosis. Consistently, knockdown of IL-13RA2 in normal fibroblasts induced a keloidal status. Furthermore, both in vitro application and intratumoral injection of p-STAT6 inhibitor AS1517499 in a patient-derived xenograft keloid-implantation mouse model resulted in proliferation inhibition and tissue necrosis, apoptosis, and myofibroblast marker reduction. Collectively, this study elucidates the key role of IL-13RA2 in keloid pathology and inspires further translational research of keloid treatment concerning JAK/STAT6 inhibition.

Secondary analysis of existing microarray data reveals potential gene drivers of cutaneous squamous cell carcinoma.

Cutaneous squamous-cell carcinoma (cSCC) is the second most common skin cancer, with an increasing incidence in recent years. To define the molecular basis that drive cSCC development and progression, this study aimed at identifying potential novel molecular targets for the diagnosis and therapy of patients with cSCC. Two data sets with the accession number GSE45164 and GSE66359 were downloaded from Gene Expression Omnibus (GEO) database. After the identification of differentially expressed genes (DEGs) from these two data sets, respectively, between cSCC samples and controls, a combination of DEGs from these two data sets were subjected to the following analyses, including functional annotation, protein-protein interaction (PPI) network and module construction, transcription factor (TF)-target regulation prediction, and drug-gene interaction predictive analysis. A total of 204 upregulated genes and 213 downregulated genes were found in two data sets which were used for the follow-up analysis. Upregulated and downregulated genes were mainly involved in the functions such as cell division, mitotic nuclear division, cell cycle, and p53 signaling pathway. Interferon induced protein family members and proteasome subunit members were involved in the TF-target regulatory network, such as PSMB8, CXCL10, and IFIT3. Eight upregulated genes ( TOP2A, CXCL8, RRM2, PSMB8, PSMB9, PBK, CXCL10, and ISG15) that were hub genes in the PPI network and significant modules were identified in the predicted drug-gene interaction. In conclusion, TOP2A, CXCL8, RRM2, PSMB8, PSMB9, PBK, CXCL10, and ISG15 may be potential targets for the diagnosis and therapy of patients with cSCC.

Computed Tomography and Magnetic Resonance Imaging-aided Diagnosis of Primary Essential Cutis Verticis Gyrata: A Case Report with 5-year Follow-up and Review of the Literature.

BACKGROUND: Cutis Verticis Gyrata (CVG) is a rare skin disease caused by overgrowth of the scalp, presenting as cerebriform folds and wrinkles. CVG can be classified into two forms: primary (essential and non-essential) and secondary. The primary non-essential form is often associated with neurological and ophthalmological abnormalities, while the primary essential form occurs without associated comorbidities. DISCUSSION: We report on a rare case of primary essential CVG with a 4-year history of normal-colored scalp skin mass in the parietal-occipital region without symptom in a 34-year-old male patient, retrospectively summarizing his pathological and Computer Tomography (CT) and magnetic resonance imaging (MRI) findings. The major clinical observations on the CT and MR sectional images include a thickened dermis and excessive growth of the scalp, forming the characteristic scalp folds. With the help of CT and MRI Three-dimensional (3D) reconstruction techniques, the characteristic skin changes could be displayed intuitively, providing more evidence for a diagnosis of CVG. At the 5-year followup, there were no obvious changes in the lesion. CONCLUSION: Based on our observations, we propose that not all patients with primary essential CVG need surgical intervention, and continuous clinical observation should be an appropriate therapy for those in stable condition.

Analysis of transcriptome sequencing of sciatic nerves in Sprague-Dawley rats of different ages.

An aging-induced decrease in Schwann cell viability can affect regeneration following peripheral nerve injury in mammals. It is therefore necessary to investigate possible age-related changes in gene expression that may affect the biological function of peripheral nerves. Ten 1-week-old and ten 12-month-old healthy male Sprague-Dawley rats were divided into young (1 week old) and adult (12 months old) groups according to their ages. mRNA expression in the sciatic nerve was compared between young and adult rats using next-generation sequencing (NGS) and bioinformatics (n = 4/group). The 18 groups of differentially expressed mRNA (DEmRNAs) were also tested by quantitative reverse transcription polymerase chain reaction (n = 6/group). Results revealed that (1) compared with young rats, adult rats had 3608 groups of DEmRNAs. Of these, 2684 were groups of upregulated genes, and 924 were groups of downregulated genes. Their functions mainly involved cell viability, proliferation, differentiation, regeneration, and myelination. (2) The gene with the most obvious increase of all DEmRNAs in adult rats was Thrsp (log2FC = 9.01, P < 0.05), and the gene with the most obvious reduction was Col2a1 (log2FC = -8.89, P < 0.05). (3) Gene Ontology analysis showed that DEmRNAs were mainly concentrated in oligosaccharide binding, nucleotide-binding oligomerization domain containing one signaling pathway, and peptide-transporting ATPase activity. (4) Analysis using the Kyoto Encyclopedia of Genes and Genomes showed that, with increased age, DEmRNAs were mainly enriched in steroid biosynthesis, Staphylococcus aureus infection, and graft-versus-host disease. (5) Spearman's correlation coefficient method for evaluating NGS accuracy showed that the NGS results and quantitative reverse transcription polymerase chain reaction results were positively correlated (rs = 0.74, P < 0.05). These findings confirm a difference in sciatic nerve gene expression between adult and young rats, suggesting that, in peripheral nerves, cells and the microenvironment change with age, thus influencing the function and repair of peripheral nerves.

Can we predict the outcome of 595-nm wavelength pulsed dye laser therapy on capillary vascular malformations from the first beginning: a pilot study of efficacy co-related factors in 686 Chinese patients.

Currently, there are no standardized, objective, and clinically applicable methods to predict the outcome of pulsed dye laser (PDL) therapy on capillary vascular malformation (CVM) patients. The introduction of a method that can predict the outcome prior to treatment will be valuable for both the patients and the doctors. In this study, the authors treated CVM with 595-nm wavelength PDL in Chinese patients (n = 686) and analyzed the efficacy of treatment and complications retrospectively in a 5-year period. Nearly 18 % of patients (n = 122) had 76 % or more clearing of lesions; over 52 % of patients (n = 360) had more than 50 % of clearing. The lesions in head and neck region had the best effective rate (58.3 %), followed by trunk (42.9 %) and extremities (35.6 %). The efficacy of PDL therapy is related to age, type, and location of lesions. Fifty-seven patients (8.3 %) had complications, including 2.0 % blistering (n = 14), 4.5 % hyperpigmentation (n = 31), 1.3 % hypopigmentation (n = 9), and 0.4 % hypertrophic scarring (n = 3). Based on these preliminary data, the authors established a standardized, objective, and clinically applicable equation that may be applied to predict the efficacy of 595 nm PDL therapy on a newly diagnosed Chinese CVM patients based on the age, type, and location of lesions.

[Histopathology and ultrastructural characteristics of acellular allogenic dermal matrix engrafted with thin split-thickness skin autograft: mid- and long-term results].

OBJECTIVE: To observe mid- and long-term changes in the histopathology and electron microscopic characteristics of the acellular dermal matrix engrafted with thin split-thickness skin autograft. METHODS: Twenty-three biopsy samples were collected from 17 patients undergoing extremity scar resection, who received subsequent grafting using allogenic dermal matrix dressed with thin split-thickness skin autografts. Six months to 2 years after the grafting, the grafts were sampled for histopathological and electron microscopic observations of the layer of the epidermis, thickness of the basal membrane, structural components of the dermis, and infiltration of fibroblasts and revascularization. The data were compared with those of the normal skin samples from the patients. RESULTS: Only the number of epidermal layers showed statistically significant difference between the skin grafts and the normal skin (16.33-/+5.89 vs 26.57-/+3.46, P=0.007). The thickness of the basal membrane of the skin grafts was similar to that of normal skin, and no significant difference was found in the number of fibroblasts and newly generated capillaries between them. CONCLUSION: The mid- and long-term histopathology and ultrastructures of the composite skin graft in the extremities are similar to those of normal skin, suggesting satisfactory effect of the skin grafts.