Adipose-Derived Stem Cell Exosomes Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicle Growth by Activating Wnt/ß-Catenin Pathway.

The most prevalent type of alopecia is androgenetic alopecia (AGA), which has a high prevalence but no effective treatment. Elevated dihydrotestosterone (DHT) level in the balding area was usually thought to be critical in the pathophysiology of AGA. The canonical Wnt/ß-catenin signaling pathway plays a key role in promoting hair follicle development and sustaining the hair follicle cycle. Adipose-derived stem cell exosomes (ADSC-Exos) are widely used in the field of regenerative medicine due to the advantages of being cell free and immune privileged. Still, few studies have reported the therapeutic effect on hair disorders. As a result, we sought to understand how ADSC-Exos affected hair growth and explore the possibility that ADSC-Exos could counteract the hair-growth-inhibiting effects of DHT. This research using human hair follicle organs, in vitro dermal papilla cells, and in vivo animal models showed that ADSC-Exos not only encouraged healthy hair growth but also counteracted the inhibitory effects of DHT on hair growth. Additionally, we discovered that ADSC-Exos increased Ser9 phosphorylated glycogen synthase kinase-3ß levels and facilitated nuclear translocation of ß-catenin, which may have been blocked by the specific Wnt/ß-catenin signaling pathway inhibitor dickkopf-related protein 1. Our findings suggested that ADSC-Exos are essential for hair regeneration, which is anticipated to open up new therapeutic possibilities for clinical alopecia, particularly for the treatment of AGA.

Machine learning-based radiomics analysis for predicting local recurrence of primary dermatofibrosarcoma protuberans after surgical treatment.

BACKGROUND AND PURPOSE: Dermatofibrosarcoma protuberans (DFSP) is characterized by locally invasive growth patterns and high local recurrence rates. Accurately identifying patients with high local recurrence risk may benefit patients during follow-up and has potential value for making treatment decisions. This study aimed to investigate whether machine learning-based radiomics models could accurately predict the local recurrence of primary DFSP after surgical treatment. MATERIALS AND METHODS: This retrospective study included a total of 146 patients with DFSP who underwent MRI scans between 2010 and 2016 from two different institutions: institution 1 (n = 104) for the training set and institution 2 (n = 42) for the external test set. Three radiomics random survival forest (RSF) models were developed using MRI images. Additionally, the performance of the Ki67 index was compared with the three RSF models in the external validation set. RESULTS: The average concordance index (C-index) scores of the RSF models based on fat-saturation T2W (FS-T2W) images, fat-saturation T1W with gadolinium contrast (FS-T1W + C) images, and both FS-T2W and FS-T1W + C images from 10-fold cross-validation in the training set were 0.855 (95% CI: 0.629, 1.00), 0.873 (95% CI: 0.711, 1.00), and 0.875 (95% CI: 0.688, 1.00), respectively. In the external validation set, the C-indexes of the three trained RSF models were higher than that of the Ki67 index (0.838, 0.754, and 0.866 vs. 0.601, respectively). CONCLUSION: Random survival forest models developed using radiomics features derived from MRI images were proven helpful for accurate prediction of local recurrence of primary DFSP after surgical treatment and showed better predicting performance than the Ki67 index.

Adipose Mesenchymal Stromal Cell-Derived Exosomes Carrying MiR-122-5p Antagonize the Inhibitory Effect of Dihydrotestosterone on Hair Follicles by Targeting the TGF-ß1/SMAD3 Signaling Pathway.

Androgenic alopecia (AGA) is the most common type of hair loss, where local high concentrations of dihydrotestosterone (DHT) in the scalp cause progressive shrinkage of the hair follicles, eventually contributing to hair loss. Due to the limitations of existing methods to treat AGA, the use of multi-origin mesenchymal stromal cell-derived exosomes has been proposed. However, the functions and mechanisms of action of exosomes secreted by adipose mesenchymal stromal cells (ADSCs-Exos) in AGA are still unclear. Using Cell Counting Kit-8 (CCK8) analysis, immunofluorescence staining, scratch assays, and Western blotting, it was found that ADSC-Exos contributed to the proliferation, migration, and differentiation of dermal papilla cells (DPCs) and up-regulated the expression of cyclin, ß-catenin, versican, and BMP2. ADSC-Exos also mitigated the inhibitory effects of DHT on DPCs and down-regulated transforming growth factor-beta1 (TGF-ß1) and its downstream genes. Moreover, high-throughput miRNA sequencing and bioinformatics analysis identified 225 genes that were co-expressed in ADSC-Exos; of these, miR-122-5p was highly enriched and was found by luciferase assays to target SMAD3. ADSC-Exos carrying miR-122-5p antagonized DHT inhibition of hair follicles, up-regulated the expression of ß-catenin and versican in vivo and in vitro, restored hair bulb size and dermal thickness, and promoted the normal growth of hair follicles. So, ADSC-Exos enhanced the regeneration of hair follicles in AGA through the action of miR-122-5p and the inhibition of the TGF-ß/SMAD3 axis. These results suggest a novel treatment option for the treatment of AGA.

Inhibitory effects of ursolic acid from Bushen Yijing Formula on TGF-ß1-induced human umbilical vein endothelial cell fibrosis via AKT/mTOR signaling and Snail gene.

The present study aimed to investigate the functional components from Bushen Yijing Formula and their inhibition of endothelial-mesenchymal transition (EndMT) and fibrosis in human umbilical vascular endothelial cells (HUVECs). HUVEC fibrosis was induced by treatment of transforming growth factor ß (TGF-ß) as the cellular model. Expression of EndMT biomarker gene and cofactors were determined by quantitative real-time-PCR, western blotting, and immunofluorescence. Angiogenesis capacity of vein endothelial cells was evaluated using tube formation assay. Ursolic acid and drug-contained serum ameliorated EndMT biomarker gene expression changes and angiogenesis capacity suppression induced by TGF-ß treatment. Slug, Snail, and Twist gene expression and phosphorylation of mammalian target of rapamycin (mTOR) and AKT altered by TGF-ß in HUVECs were suppressed by ursolic acid and drug-contained serum. Treatment with the mTOR signaling pathway inhibitor, rapamycin, inhibited the phosphorylation of mTOR and AKT, decreased Snail and Vimentin protein levels, and increased VE-cad protein levels. Overexpression of Snail gene promoted expression of EndMT-related genes and suppressed angiogenesis in HUVECs, which were attenuated by application of ursolic acid and drug-contained serum. Ursolic acid from Bushen Yijing Formula inhibits human umbilical vein endothelial cell EndMT and fibrosis, mediated by AKT/mTOR signaling and Snail gene expression.

Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis.

Psoriasis-specific proteins dysregulated in keratinocytes and involved in the pathophysiological process of psoriasis remains elusive. We report here that epidermal galectin-3 expression is significantly downregulated in lesional skin, but not in non-lesional skin in psoriasis patients, nor in a group of diseases known as psoriasiform dermatitis clinically and histologically similar to psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote development of psoriatic lesions, as evidenced by more severe skin inflammation in galectin-3 knockout (gal3-/-) mice, compared to wild-type mice, after imiquimod treatment, and in skin from gal3-/- mice grafted onto wildtype mice. The development of psoriatic-like lesions is attributable to 1) the spontaneously tuning up of psoriasis signatures in keratinocytes through JNK pathway; and 2) neutrophil accumulation caused by the enhanced leukocyte-recruiting capacity associated with overexpression of S100A7-9 and CXCL-1, 8 in keratinocytes with impaired galectin-3 expression. Psoriasis-like skin inflammation is significantly improved in gal-3-/- mice both by inhibition of neutrophils accumulation with a selective CXCR2 antagonist of SB225002, and by intracutaneous injection of recombinant galectin-3. Overall, these findings offer promising galectin-3-related diagnostic and therapeutic resolutions of psoriasis.

[Influence of Cibotium barametz and its processed samples on haemorheology index in mice with adjuvant arthritis].

OBJECTIVE: To discuss the influence of the rhizome of Cibotium barametz on the heamorheology index in mice with adjuvant arthritis and to compare the effect of raw medicinals with that of the processed ones. METHOD: Mice was injected with Freund's complete adjuvant on the rihgt behind foot to make model of adjuvant arthritis (AA). Hydroxyacrbamide tablets were orally administrated by mice with AA to make model of AA due to deficiency in the kidney (DK-AA). And then we determined the heamorheology index of the normal group, positive control group, AA group, DK-AA group and medicinals-treated groups. RESULT: In the groups of AA, and DK-AA, the heamorheology index, such as high shearing, middle shearing, low shearing, plasma viscosity, whole blood reduction viscosity, erythrocyte aggregation exponent, erythrocyte degeneration exponent, sedimentation, sedimentation equation K value, erythrocyte rigidity exponent, erythrocyte electrophoresis time, casson viscosity, casson yield stress, increased significantly. After treated with Cibotium barametz, the heamorheology index except red blood count, packed cell volume, fibrinogen decreased obviously to get normal. CONCLUSION: Rhizome of Cibotium barametz could promote heamorheology in mice with AA and DK-AA to exhibit effect of promoting blood circulation and remove blood stasis. The medicinal rhizomes processed with sand have the effect enhanced.