The browning and mobilization of subcutaneous white adipose tissue supports efficient skin repair.

Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage-tracing mouse studies revealed that sWAT would enter into the large wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested that beige adipocytes in sWAT abundantly express neuregulin 4 (NRG4), which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.

Clinical, Histologic, and Transcriptomic Evaluation of Sequential Fat Grafting for Morphea: A Nonrandomized Controlled Trial.

Importance: Morphea is a rare disease of unknown etiology without satisfactory treatment for skin sclerosis and soft tissue atrophy. Objective: To provide clinical, histologic, and transcriptome evidence of the antisclerotic and regenerative effects of sequential fat grafting with fresh fat and cryopreserved stromal vascular fraction gel (SVF gel) for morphea. Design, Setting, and Participants: This single-center, nonrandomized controlled trial was conducted between January 2022 and March 2023 in the Department of Plastic and Reconstructive Surgery of Nanfang Hospital, Southern Medical University and included adult participants with early-onset or late-onset morphea who presented with varying degrees of skin sclerosis and soft tissue defect. Interventions: Group 1 received sequential grafting of fresh fat and cryopreserved SVF gel (at 1 and 2 months postoperation). Group 2 received single autologous fat grafting. All patients were included in a 12-month follow-up. Main Outcome and Measures: The primary outcome included changes in the modified Localized Scleroderma Skin Severity Index (mLoSSI) and Localized Scleroderma Skin Damage Index (LoSDI) scores as evaluated by 2 independent blinded dermatologists. The histologic and transcriptome changes of morphea skin lesions were also evaluated. Results: Of 44 patients (median [IQR] age, 26 [23-33] years; 36 women [81.8%]) enrolled, 24 (54.5%) were assigned to group 1 and 20 (45.5%) to group 2. No serious adverse events were noted. The mean (SD) mLoSSI scores at 12 months showed a 1.6 (1.50) decrease in group 1 and 0.9 (1.46) in group 2 (P = .13), whereas the mean (SD) LoSDI scores at 12 months showed a 4.3 (1.34) decrease in group 1 and 2.1 (1.07) in group 2 (P < .001), indicating that group 1 had more significant improvement in morphea skin damage but not disease activity compared with group 2. Histologic analysis showed improved skin regeneration and reduced skin sclerosis in group 1, whereas skin biopsy specimens of group 2 patients did not show significant change. Transcriptome analysis of skin biopsy specimens from group 1 patients suggested that tumor necrosis factor α signaling via NFκB might contribute to the immunosuppressive and antifibrotic effect of sequential fat grafting. A total of 15 hub genes were captured, among which many associated with morphea pathogenesis were downregulated and validated by immunohistochemistry, such as EDN1, PAI-1, and CTGF. Conclusions and Relevance: The results of this nonrandomized trial suggest that sequential fat grafting with fresh fat and cryopreserved SVF gel was safe and its therapeutic effect was superior to that of single autologous fat grafting with improved mLoSSI and LoSDI scores. Histological and transcriptomic changes further support the effectiveness after treatment. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2200058003.

Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma.

Adipose tissue transplantation shows great therapeutic potential in reversing localized scleroderma-associated skin fibrosis. Brown adipose tissue (BAT) can specifically secrete various cytokines against fibrosis, but its therapeutic potential in improving skin fibrosis has not yet been demonstrated. In this study, we have demonstrated the superior therapeutic efficacy of BAT transplantation for sclerotic skin by transplanting two distinct types of adipose tissue. In comparison to the white adipose tissue (WAT) group, mice treated with BAT transplantation exhibited a significant reduction in dermal thickness. BAT transplantation effectively reverses skin sclerosis through mechanisms involving inflammation reduction, promotion of angiogenesis, inhibition of myofibroblast accumulation, and collagen deposition. This therapeutic effect can be attributed to its unique paracrine effects. Furthermore, transcriptome sequencing (RNA-Seq) revealed upregulation of pathways associated with lipogenesis and fatty acid metabolism in BAT while downregulating pathways are related to transforming growth factor ß(TGF-ß), epithelial-mesenchymal transition (EMT), and inflammatory response. These findings suggest that BAT transplantation holds great promise as a novel approach for localized scleroderma treatment.

Comparison of radius of anterior lens surface curvature measurements in vivo using the anterior segment optical coherence tomography and Scheimpflug imaging.

BACKGROUND: To assess the radius of anterior lens surface curvature (RAL) measurements with anterior segment optical coherence tomography (AS-OCT) in comparison with Scheimpflug imaging. METHODS: This prospective, cross-sectional study was carried out at Zhongshan Ophthalmic Center, Guangzhou, China. We enrolled 59 eyes, including 30 eyes from 30 cataractous volunteers (59 to 87 years) and 29 eyes from 29 young participants (19 to 49 years). After mydriasis, the RAL was measured automatically by the built-in software in the AS-OCT (CASIA 2). The Scheimpflug images were measured with the build-in caliper tool of the Scheimpflug camera (Pentacam), and RAL were further calculated with the principle of best-fitted circle. Intraobserver and interobserver reproducibility of RAL measurement using Scheimpflug camera were evaluated with limit of agreement (LoA) and intraclass correlation coefficient (ICC). Consistency between RAL measurement of Scheimpflug camera and AS-OCT were assessed with LoA, correlation analysis and linear regression. RESULTS: For all subjects, intraobserver (LoA: -0.25 to 0.23 mm, ICC: 0.996) and interobserver reproducibility (LoA: -0.85 to 0.92 mm, ICC: 0.947) of RAL were good using Scheimpflug imaging. Both AS-OCT and Scheimpflug imaging found that the age-related cataract participants had smaller RAL (P=0.010, P=0.001 respectively). LoA of RAL measurement between AS-OCT and Scheimpflug imaging was -3.83 to -0.79 mm, and the Pearson correlation efficient was 0.909 (P<0.001). The RAL values measured by AS-OCT were significantly greater than that by Scheimpflug camera with a mean difference of 2.31 mm for all participants (P<0.001). The RAL measurement could be converted using the equation: YCASIA 2 =1.155 × XPentacam + 1.060. CONCLUSIONS: Both Scheimpflug camera system with internal caliper tool and the AS-OCT are fast and non-contact tools that could measure RAL successfully. The two measurement results are highly correlated and interchangeable through linear regression equation.