LncRNA-PCAT1 maintains characteristics of dermal papilla cells and promotes hair follicle regeneration by regulating miR-329/Wnt10b axis.

BACKGROUND: The failure of hair follicle regeneration is the major cause of alopecia, which is a highly prevalent disease worldwide. Dermal papilla (DP) cells play important role in the regulation of hair follicle regeneration. However, the molecular mechanism of how dermal papilla cells direct follicle regeneration is still to be elucidated. METHODS: In vitro DP 3D culturing and in vivo nude mice DP sphere implanted models were used to examine the molecular regulation of DP cells and follicle regeneration. qRT-PCR and Western blotting were used to detect gene and protein expression, respectively. Immunofluorescence was used to detect the expression level of Wnt10b, Ki-67 and ß-catenin. Luciferase assay was used to examine the relationship among PCAT1, miR-329 and Wnt10b. ALP activity was measured by ELISA. H&E staining was used to measure follicle growth in skin tissues. RESULTS: Up-regulation of PCAT1 and Wnt10b, however, down-regulation of miR-329 were found in the in vitro 3D dermal papilla. Bioinformatics analysis and luciferase assays demonstrated that PCAT1 promoted Wnt10b expression by sponging miR-329. Knockdown of PCAT1 suppressed the proliferation and activity, as well as ALP and other DP markers of DP cells by targeting miR-329. Knockdown of PCAT1 regulated miR-329/Wnt10b axis to attenuate ß-catenin expression and nucleus translocation to inhibit Wnt/ß-catenin signaling. Furthermore, knockdown of PCAT1 suppressed DP sphere induced follicle regeneration and hair growth in nude mice. CONCLUSION: PCAT1 maintains characteristics of DP cells by targeting miR-329 to activating Wnt/ß-catenin signaling pathway, thereby promoting hair follicle regeneration.

LncRNA-XIST promotes dermal papilla induced hair follicle regeneration by targeting miR-424 to activate hedgehog signaling.

BACKGROUND: Alopecia is a highly prevalent disease characterizing by the loss of hair. Dermal papilla (DP) cells are the inducer of hair follicle regeneration, and in vitro three-dimensional (3D) culturing DP cells have been proven to induce hair follicle regeneration. However, the molecular mechanisms behind the regulation of 3D culturing DP cells remain unclear. METHODS: 3D-cultivated DP cells were used as in vitro cell model. DP sphere xenograft to nude mice was performed for in vivo study of hair follicle regeneration. qRT-PCR, Western blotting, and immunofluorescence were used for detecting the level of XIST, miR-424 and Hedgehog pathway-related proteins, respectively. H&E staining was used to examine hair neogenesis. Cell viability, proliferation and ALP activity were measured by MTT, CCK-8 and ELISA assays, respectively. Luciferase assays were used for studying molecular regulation between XIST, miR-424 and Shh 3'UTR. RESULTS: XIST and Shh were up-regulated, and miR-424 was down-regulated in 3D DP cells. Molecular regulation studies suggested that XIST sponged miR-424 to promote Shh expression. Knockdown of XIST suppressed DP cell activity, cell proliferation, ALP activity and the expression of other DP markers by sponging miR-424. Knockdown of XIST suppressed Shh mediated hedgehog signaling by targeting miR-424. Moreover, the knockdown of XIST inhibited DP sphere induced in vivo hair follicle regeneration and hair development. CONCLUSION: XIST sponges miR-424 to promote Shh expression, thereby activating hedgehog signaling and facilitating DP mediated hair follicle regeneration.

Isolated Bilateral Macrostomia.

Macrostomia (Tessier's 7 cleft) is a rare congenital lip deformity. Macrostomia can occur unilateral or bilateral, isolated or associated with other syndromes. Isolated bilateral macrostomia is exceedingly rare with only a few cases reported to date. The authors report 6 cases of isolated bilateral macrostomia surgically repaired in 4-layered approaches. The traditional method was improved and the result obtained was satisfactory after longest follow-up of 3 years. The technique is easy to imitate, simple in design, aesthetically and functionally corrects the deformity.

Hirudin promotes angiogenesis by modulating the cross-talk between p38 MAPK and ERK in rat ischemic skin flap tissue.

Hirudin's ability to increase angiogenesis in ischemic flap tissue and improve the flaps survival has been demonstrated in our previous studies. However, the knowledge about hirudin functional role in angiogenesis is still limited. In the present study, we investigate the effects of locally injected hirudin on the expression of VEGF, endostatin and thrombospondin-1 (TSP-1) using rat model. Caudally based dorsal skin flaps were created and were treated with hirudin or normal saline. Result showed that the flap survival was improved by hirudin treatment relative to the control. Treatment of flaps with hirudin exerted significant angiogenic effect as evidenced by increased VEGF expression and reduced endostatin and TSP-1 production (p<0.01), and promoted neovascularization (microvascular density, p<0.01). Moreover, hirudin treatment increased the ERK1/2 phosphorylation, while attenuated the phosphorylation of p38 MAPK, and the addition of thrombin could reverse these effects of hirudin on ERK1/2 and p38 MAPK activity. The MEK inhibitor blocked the hirudin-induced VEGF expression, and the p38 MAPK inhibitor attenuated the thrombin-induced TSP-1 expression. Furthermore, a specific inhibitor of p38 MAPK activates ERK1/2 in ischemic flaps, suggesting that cross-talk between p38 MAPK and ERK might exist in rat ischemic flap tissue. Moreover, either the hirudin or SCH79797 (PAR1 antagonist) could attenuate the p38 MAPK phosphorylation and increases the ERK1/2 phosphorylation, indicating that the cross-talk between p38 MAPK and ERK1/2 modulated by thrombin/PAR1 signaling may participate in the process of hirudin-stimulated ERK1/2 signaling. In conclusion, these observations suggest that hirudin exerts its angiogenesis effect by regulating the expression of angiogenic and antiangiogenic factors via a cross-talk of p38 MAPK-ERK pathway.

Inverted Supernumerary Nostril Together with Tessier 3 Incomplete Cleft: A Rare Congenital Deformity Case Report.

Supernumerary nostril and oblique facial cleft are both rare congenital anomalies. Here, we present a 2-year-old patient with a supernumerary nostril and a Tessier 3 incomplete facial cleft, which have not been reported previously. It should also be mentioned that the nostril and ala of this supernumerary nostril were inverted, which differs from the previous cases. Surgery was undertaken to excise the supernumerary nostril and correct the facial cleft anomaly, and the outcomes were both functionally and aesthetically satisfactory.

The effect of local application of natural hirudin on random pattern skin flap microcirculation in a porcine model.

The aim of this study was to investigate the effect of local administration of hirudin in improving random pattern skin flap microcirculation in a porcine model. Five Chinese minipigs were used and six dorsal random pattern skin flaps were elevated in each animal (4 × 14 cm). All flaps (n = 30) were assigned to experimental (n = 10), control (n = 10), and sham (n = 10) groups. Flap edema measurement showed that edema in experimental flaps was more severe (P < 0.05) than either control or sham flaps. Local blood flow detection showed an increased image signal of blood flow in experimental flaps instead of an obvious avascular area in control and sham flaps. The survival area was significantly greater in experimental group (67.6 ± 2.1 %) as compared to control (45.2 ± 1.4 %) or sham (48.3 ± 1.1 %) group (P < 0.05). Our data showed that local administration of hirudin can significantly improve random pattern skin flap microcirculation in over dimensioned random pattern skin flaps in a porcine model.

Possibilities and potential roles of estrogen in the pathogenesis of proliferation hemangiomas formation.

Hemangiomas, often categorized as angiogenic diseases, are the most common tumors of infancy, the life span of which is generally divided into proliferating phase, involuting phase, and involuted phase. Despite their high prevalence, the mechanism leading to proliferation hemangiomas formation is poorly understood and the best approach to their management remains controversial. None of the current therapeutic modalities is ideal, partly because the pathogenesis of hemangioma and the mechanism of its proliferation are far from clear. Many clues reveal that estrogen has an important role in developing the vascular system, experimental and clinical evidences accumulated in recent years also suggest the potential for estrogen to influence neovascularization. Based on those, we hypothesize that estrogen play a potential role in the development of hemangiomas, mainly by regulating some key angiogenic factors, including MMP-9, EPCs, VEGF, NO, etc. Accepting the hypothesis to be correct, a therapy that identify estrogen as a potential target for the design of new, more specific treatments can be used to prevent the proliferation hemangiomas formation. The hypothesis may lead a new direction in the study of mechanisms for proliferation hemangiomas formation, and further study of the precise mechanisms for estrogen-induced hemangiomas will produce effective antiestrogens and estrogen receptor antagonists as new medication for the very difficult problem.

Infantile hemangioma is originated from placental trophoblast, fact or fiction?

Infantile hemangiomas are common, benign tumors, distinctive for their perinatal presentation, rapid growth and subsequent involution. Hemangiomas can pose serious concerns to the cosmetic and psychosocial development of the afflicted child, but none of the current therapeutic modalities is ideal to date, partly because the origin of the pathogenic ECs in infantile hemangioma is unknown. Many clues and evidences suggest a link between infantile hemangiomas and the maternal placental trophoblasts. Shared expression of distinct endothelial markers in hemangioma and placental tissues raises a possibility that infantile hemangioma is originated from placental trophoblast. Moreover, the findings of a very high similarity between the transcriptomes of placenta and hemangioma provide strong support for this theory. Furthermore, epidemiologic and clinical evidences accumulated in recent years also suggest the placental trophoblast as the cell of origin for infantile hemangioma. These findings imply a unique relationship between hemangioma and the placental trophoblast and suggest a hypothesis that infantile hemangioma is originated from placental trophoblast. The hypothesis could provide new understanding of these vascular tumors of childhood and may become the most promising research fields for the etiology of infantile hemangiomas. Further study of the precise mechanisms for the placental trophoblast originated hemangiomas will produce new preventive strategies and therapeutic avenues, possibly immunologic treatment, to the very difficult problem.

[Expression and significance of TRAIL protein and mRNA in hemangioma].

OBJECTIVE: To detect the expression of TRAIL protein and mRNA in hemangiomas and vascular malformations. METHODS: Sections of 33 proliferative hemangiomas,28 involuting hemangiomas and 29 vascular malformations were immunostained for TRAIL protein, TRAIL mRNA was examined by in situ hybridization in these tissue. RESULTS: The TRAIL protein positive rates in proliferative hemangiomas, involuting hemangiomas, vascular malformations and normal skins were respectively 45.45% (15/33), 78.57% (22/28), 0% and 0%. There were significant differences among the four pathologies (P < 0.01). The difference between proliferative hemangiomas and involuting hemangiomas was also significant (P < 0.01). The TRAIL mRNA positive rates were 66.67% (11/33), 89.29 (25/28), 0% and 0% respectively. There were also significant differences among the four pathologies (P < 0.01). The difference between proliferative hemangiomas and involuting hemangiomas was also significant (P < 0.01). CONCLUSIONS: TRAIL could induce endothelial apoptosis and cause regression of hemangiomas.

[Clinical treatment of venous malformations with retained copper needles].

UNLABELLED: OBJECTIVE; To evaluate a technique with retained copper needles for the treatment of venous malformations. METHODS: With 78 venous malformation cases, there were three methods were applied for the treatment respectively, including copper needles in the lesion only, vascular ligation with the copper needles in the lesion, and electrical puncture with the copper needles in the lesion. RESULTS: There were totally 96% effective rate achieved in this clinical data. CONCLUSIONS: The retained copper needles technique may be a simple and effective method for the treatment of venous, malformations resulting in vessel denaturation, fibrosis and disappearance of structure.