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1.
Ann Plast Surg ; 79(6): 546-551, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29053518

RESUMO

Epithelial-mesenchymal transition (EMT) plays a critical role in fibrotic keloid formation, which is characterized by excessive collagen and extracellular matrix synthesis and deposition. Growing evidence suggests that the serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) acts upstream of several major fibrosis signaling pathways; however, the role of HIPK2 in the keloid fibrogenesis remains unknown. In the current study, we investigated the roles of HIPK2 in the pathogenesis of keloids. Primary normal skin and keloid keratinocytes were cultured and pretreated with transforming growth factor (TGF)-ß1. Next, keratinocytes were transfected with scrambled small interfering RNA (siRNA) and anti-HIPK2 siRNA. The TGF-ß1-associated HIPK2 alterations were investigated by quantitative real-time polymerase chain reaction. Protein levels were analyzed by western blotting. The HIPK2 was markedly increased in the keloid-derived keratinocytes compared with normal skin keratinocytes. In addition, HIPK2 induced the expression of EMT markers in normal skin keratinocytes by TGF-ß1-SMAD family member 3 (SMAD3). The effect of TGF-ß1-related EMT markers and SMAD3 phosphorylation in response to added TGF-ß1 was significantly abrogated when the cells were transfected with HIPK2 siRNA. We conclude that HIPK2 is a crucial factor in the pathogenesis of keloids, suggesting that HIPK2 might be a novel potential drug target for antikeloid therapy.


Assuntos
Proteínas de Transporte/genética , Transição Epitelial-Mesenquimal/genética , Queloide/genética , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/farmacologia , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/farmacologia , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Queloide/fisiopatologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Valores de Referência , Transdução de Sinais , Regulação para Cima
2.
Ann Plast Surg ; 75(3): 290-4, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25003436

RESUMO

PURPOSE: This study aimed to develop a scoring system for evaluating the nail appearance after nail fusion plasty of the duplicated thumb, and to investigate the operation indication of the combination procedure and its effect on the postoperative nail appearance. METHODS: The nail fusion plasty technique was carried out in 20 patients with congenital thumb duplication. The patients were followed up to observe the appearance of nail, and the results were assessed by our nail appearance evaluation criteria. RESULTS: Twenty patients were followed up for 18 to 92 months (48 months on average). According to our criteria, we achieved excellent results in 12 cases, good in 6 cases, fair in 1 case, and poor in 1 case. CONCLUSIONS: The combination procedure is recommended when the size of the thumb is less than 80% of the size of the normal side or the width of the nail is less than 80% of that of the normal side. Satisfactory results can be obtained by careful operation. The newly devised scoring system assesses the nail appearance in a very comprehensive manner.


Assuntos
Unhas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Polidactilia/cirurgia , Polegar/anormalidades , Criança , Pré-Escolar , Estética , Feminino , Seguimentos , Humanos , Lactente , Masculino , Polegar/cirurgia , Resultado do Tratamento
3.
Exp Dermatol ; 23(9): 639-44, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24981855

RESUMO

The proliferation of human skin dermal fibroblasts (HDFs) is a critical step in skin fibrosis, and transforming growth factor-beta1 (TGF-ß1) exerts pro-oxidant and fibrogenic effects on HDFs. In addition, the oxidative stress system has been implicated in the pathogenesis of skin disease. However, the role of NADPH oxidase as a mediator of TGF-ß1-induced effects in HDFs remains unknown. Thus, our aim was to investigate the role of NADPH in human skin dermal fibroblasts. Primary fibroblasts were cultured and pretreated with various stimulants. Real-time Q-PCR and Western blotting analyses were used for mRNA and protein detection. In addition, siRNA technology was applied for gene knock-down analysis. Hydrogen peroxide production and 2',7'-dichlorofluorescein diacetate (DCFDA) measurement assay were performed. Here, our findings demonstrated that HDFs express key components of non-phagocytic NADPH oxidase mRNA. TGF-ß1 induced NOX2 and reactive oxygen species formation via NADPH oxidase activity. In contrast, NOX3 was barely detectable, and other NOXs did not display significant changes. In addition, TGF-ß1 phosphorylated MAPKs and increased activator protein-1 (AP-1) in a redox-sensitive manner, and NOX2 suppression inhibited baseline and TGF-ß1-mediated stimulation of Smad2 phosphorylation. Moreover, TGF-ß1 stimulated cell proliferation, migration, collagen I and fibronectin expression, and bFGF and PAI-1 secretion: these effects were attenuated by diphenylene iodonium (DPI), an NADPH oxidase inhibitor, and NOX2 siRNA. Importantly, NOX2 siRNA suppresses collagen production in primary keloid dermal fibroblasts. These findings provide the proof of concept for NADPH oxidase as a potential target for the treatment of skin fibrosis.


Assuntos
Fibroblastos/enzimologia , Glicoproteínas de Membrana/metabolismo , NADPH Oxidases/metabolismo , Pele/enzimologia , Células Cultivadas , Colágeno/biossíntese , Colágeno/genética , Inibidores Enzimáticos/farmacologia , Fibrose , Técnicas de Silenciamento de Genes , Humanos , Queloide/enzimologia , Queloide/genética , Queloide/terapia , Sistema de Sinalização das MAP Quinases , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , NADPH Oxidase 2 , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/genética , Oniocompostos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Proteínas Smad/metabolismo , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
4.
J Plast Reconstr Aesthet Surg ; 84: 505-513, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37418849

RESUMO

BACKGROUND: Multi-territory perforator flaps have become the preferred option for the repair and reconstruction of large soft tissue defects. Although methods (e.g., pharmacological agents, mechanical stimulation, and thermal stimulation) were developed to open choke vessels to improve flap survival, the flap necrosis rate is still as high as 28.8%. The authors hypothesized that high-pressure infusion might enhance flap viability by dilating choke arteries intraoperatively in a rat model of multi-territory perforator flap. METHODS: Two-month-old male Sprague-Dawley rats were randomized into two groups (n = 32 each). During the multi-territory perforator flap elevation based on the right superficial epigastric angiosome, one group received continuous high-pressure infusion (mean pressure, 250 mmHg; duration, 1 min) of an isotonic heparin sodium solution (12,500 U/L) via the artery in the pedicle, whereas the other group received no infusion. At 7 days postoperatively, arteriography was performed; endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expression and microvascular density were evaluated by western blot and histology, respectively; and flap survival was compared. Moreover, intraluminal diameters were examined at 1 day and 7 days postoperatively using hematoxylin and eosin staining, and coagulation function was assessed immediately postoperatively. RESULTS: High-pressure infusion significantly promoted the dilation of choke arteries at 1 day and 7 days postoperatively. It also increased eNOS and VEGF expression, flap survival, and microvascular density. The coagulation function remained unaffected. CONCLUSIONS: High-pressure infusion allowed intraoperative and postoperative dilation of the choke arteries that enhanced the viability of multi-territory perforator flaps in rats.


Assuntos
Retalho Perfurante , Ratos , Masculino , Animais , Retalho Perfurante/irrigação sanguínea , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismo , Dilatação , Artérias , Sobrevivência de Enxerto
5.
Artigo em Inglês | MEDLINE | ID: mdl-37060893

RESUMO

BACKGROUND: To explore the clinical efficacy of using tongue-shaped flaps and advancement flaps to reconstruct the fingertips in congenital syndactyly patients with osseous fusion of the distal phalanges. METHODS: From January 2016 to January 2019, 12 patients with congenital syndactyly, involving 30 digits in total, presented to our hospital and were surgically treated with tongue-shaped flaps, as well as with advancement flaps to reconstruct the fingertips. The flap infection rate, necrosis rate and any other early complications were recorded. Fingertip aesthetics were reported according to the modified Bulic scale. A questionnaire was used to assess the satisfaction of the patients' family members. RESULTS: All cases were thoroughly reviewed. The postoperative period for inclusion in this study ranged from 36 to 60 months, with an average follow-up time of 45 months. During this period, no complications such as infection and/or necrosis of any flap were observed. Significant improvements in finger aesthetics and functioning compared to preoperative values were observed in most cases. Based on the modified Bulic scale, of 30 fingertips, an excellent result was obtained for 3, a very good result for 13, a good result for 13 and a poor result for just 1. Family members were satisfied with the treatment outcome. CONCLUSIONS: This technique employing tongue-shaped flaps and advancement flaps to reconstruct fingertips is effective, which enables the attainment of favourable aesthetic and functional outcomes in congenital syndactyly patients with osseous fusion of the distal phalanges.


Assuntos
Traumatismos dos Dedos , Procedimentos de Cirurgia Plástica , Sindactilia , Humanos , Transplante de Pele/métodos , Retalhos Cirúrgicos/cirurgia , Sindactilia/cirurgia , Resultado do Tratamento , Língua/cirurgia , Traumatismos dos Dedos/cirurgia
6.
Biomed Pharmacother ; 169: 115887, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37984303

RESUMO

BACKGROUND: Introduced in clinical practice in 1989, perforator flaps are vital for tissue defect repair, but they are challenged by distal necrosis. Tetrahydropalmatine (THP) from celandine is renowned for its anti-inflammatory and analgesic effects. This study investigates THP's use in perforator flaps. METHODS: Thirty rats were divided into a control group and four THP concentration groups, while seventy-eight rats were categorized as control, THP, THP combined with rapamycin (RAP), and RAP alone. We created 11 cm by 2.5 cm multi-regional perforator flaps on rat backs, assessing survival blood flow and extracting skin flap tissue for autophagy, oxidative stress, apoptosis, and angiogenesis markers. RESULTS: The THP group exhibited significantly reduced distal necrosis, increased blood flow density, and survival area on the seventh day compared to controls. Immunohistochemistry and Western blot results demonstrated improved anti-oxidative stress and angiogenesis markers, along with decreased autophagy and apoptosis indicators. Combining THP with RAP diminished flap survival compared to THP alone. This was supported by protein expression changes in the PI3K-AKT-mTOR pathway. CONCLUSION: THP enhances flap survival by modulating autophagy, reducing tissue edema, promoting angiogenesis, and mitigating apoptosis and oxidative stress. THP offers a potential strategy for enhancing multi-regional perforator flap survival through the PI3K/AKT/mTOR pathway. These findings highlight THP's promise in combatting perforator flap necrosis, uncovering a novel mechanism for its impact on flap survival.


Assuntos
Retalho Perfurante , Ratos , Animais , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/fisiologia , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases , Ratos Sprague-Dawley , Apoptose , Necrose/metabolismo , Serina-Treonina Quinases TOR , Autofagia
7.
Int J Gen Med ; 15: 2163-2169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35241931

RESUMO

PURPOSE: We aimed to evaluate the use of magnetic resonance imaging (MRI) to visualize unossified bone sites that are often not visible with radiography in pediatric radial polydactyly patients with bifurcation at the metacarpophalangeal (MP) joint level. The MRI validation could help in planning for surgical procedures. PATIENTS AND METHODS: A total of 141 thumbs in 139 pediatric patients with bifurcation at the MP joint on radiography were included in this study. All the patients had undergone MRI with proton density-weighted fat-suppressed fast spin-echo (FS PDWI) sequence and fast fat-suppressed 3D spoiled gradient-recalled echo (FS 3D SPGR) sequence. The MR images of the cartilaginous structure and joint characteristics at the MP joint were evaluated and categorized by two experienced radiologists. RESULTS: Our analysis demonstrated that MR imaging, especially the FS 3D SPGR sequence, yields better visibility of the cartilaginous structure and shows clearer joint characteristics that could not be detected by radiography. The abnormalities included a cartilaginous connection on the base of duplicated proximal phalanx, cartilaginous joint connection and the shape of articular cartilage on the head of metacarpal and soft tissue band. Radiologically encountered duplications at the MP joint level were successfully classified into six types based on the MRI-detected structural changes. The distribution of the six types was 17.7% (25/141) in type 1, 53.9% (76/141) in type 2, 2.8% (4/141) in type 3, 9.9% (14/141) in type 4, and 13.5% (19/141) in type 5. CONCLUSION: This data showed that MR imaging provides practical information on the anatomic characteristics in radial polydactyly with bifurcation at the MP joint level that could aid surgical decision-making processes. Thus, the FS 3D SPGR sequence could be used as a MR imaging technique in radial polydactyly.

8.
J Plast Reconstr Aesthet Surg ; 75(2): 651-658, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34740566

RESUMO

BACKGROUND: The free 1st toe hemi-pulp transfer for finger pulp reconstruction was acknowledged as the optimal one. However, the treatment of the 1st toe donor defect, owning to the impossibility of primary closure, was frequently oversimplified. This study presented a "hitchhiking" approach to resurface finger pulp and the subsequent 1st toe donor site defect in a one-stage procedure. METHODS: From 2014 to 2019, finger pulp amputations (13 digits in 12 patients) were reconstructed with free 1st toe pulp flaps, and the donor site was resurfaced by the 2nd toe pedicled flap with the 2nd toe's primary closure. Therapeutic evaluation of repaired fingers and toes was based on cold intolerance, two-point discrimination (2PD), and gait disturbance. RESULTS: All finger and toe pulp flaps survived uneventfully. The average size of free 1st toe and pedicled 2nd toe flap was 3.1 cm × 2.0 cm (3.5 cm × 1.4 cm to 4.2 cm × 2.5 cm) and 3.0 cm × 1.1 cm (2.0 cm × 0.9 cm to 3.8 cm × 1.5 cm), respectively. The regained average static 2PD on the finger and 1st toe pulps was 6 mm (ranged 5-10 mm) and 4 mm (ranged 2-6 mm), respectively. All reconstructed 1st toe pulps were qualified for normal gait. One patient complained the mild cold intolerance, and hammer-toe deformities were involved in two cases. CONCLUSION: To fulfill donor site care and cost-effective rule, the toe-to-finger pulp reconstruction can't underestimate the morbidity on 1st toe donor site due to inappropriate intervention. Equally importantly, the hitchhiking pedicled 2nd toe flap should be recruited in the reconstructive scheme.


Assuntos
Traumatismos dos Dedos , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Traumatismos dos Dedos/cirurgia , Dedos/cirurgia , Retalhos de Tecido Biológico/cirurgia , Humanos , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Dedos do Pé/cirurgia , Resultado do Tratamento
9.
Cell Prolif ; 55(12): e13318, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35932176

RESUMO

OBJECTIVES: Diabetes mellitus is associated with refractory wound healing, yet current therapies are insufficient to accelerate the process of healing. Recent studies have indicated chemically modified mRNA (modRNA) as a promising therapeutic intervention. The present study aimed to explore the efficacy of small skin engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) facilitating wound healing in a full-thickness skin defect rat model. This study, devised therapeutic strategies for diabetic wounds by pre-treating small skin with SDF-1α modRNA. MATERIALS AND METHODS: The in vitro transfection efficiency was evaluated using fluorescence microscopy and the content of SDF-1α in the medium was determined using ELISA after the transfection of SDF-1α into the small skin. To evaluate the effect of SDF-1α modRNA and transplantation of the small skin cells on wound healing, an in vivo full-thickness skin defect rat model was assessed. RESULTS: The results revealed that a modRNA carrying SDF-1α provided potent wound healing in the small skin lesions reducing reduced scar thickness and greater angiogenesis (CD31) in the subcutaneous layer. The SDF-1α cytokines were significantly secreted by the small skin after transfection in vitro. CONCLUSIONS: This study demonstrated the benefits of employing small skin combined with SDF-1α modRNA in enhancing wound healing in diabetic rats having full-thickness skin defects.


Assuntos
Quimiocina CXCL12 , Diabetes Mellitus Experimental , Ratos , Animais , Quimiocina CXCL12/genética , Quimiocina CXCL12/farmacologia , RNA Mensageiro/genética , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/patologia , Neovascularização Fisiológica , Cicatrização , Pele/patologia
10.
Aesthetic Plast Surg ; 35(4): 530-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21359993

RESUMO

BACKGROUND: Many techniques for web space reconstruction have been described over the years. However, few techniques are completely satisfactory in terms of cosmetic requirement and functional recovery due to scar contracture, web creep, or conspicuous scarring resulting from skin grafting or additional incisions on the dorsal palm. Based on the anatomy of the dorsal metacarpal artery, the authors describe a local pentagonal advancement flap including perforators of the dorsal metacarpal artery to optimize web reconstruction and facilitate direct closure in the syndactyly treatment. METHODS: A local dorsal pentagonal advancement flap was used to reconstruct 17 web spaces in ten patients. The skin of the syndactylized fingers was brought to the web space from the dorsum of the two adjacent syndactylized fingers to cover the web area, facilitating a skin graft-free procedure for web reconstruction. RESULTS: All 17 web releases were successfully reconstructed. During the follow-up period of 23-35 months, the appearance of all the reconstructed webs was similar to that of the adjacent normal webs, and all the patients had full functional recovery. No case of web creep was reported during this period, and none of the patients required a secondary operation. CONCLUSION: The dorsal pentagonal advancement flap is a dependable flap based on known perforators from the dorsal metacarpal arteries. The reported technique is a simple and effective technique for the correction of simple syndactyly and is especially suitable for reconstruction of two webs in multiple syndactyly simultaneously, avoiding the need for skin grafts and leaving acceptable scars on the dorsum of the hand for web reconstruction.


Assuntos
Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Sindactilia/cirurgia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Transplante de Pele
11.
J Hand Surg Eur Vol ; 46(4): 360-366, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33459144

RESUMO

We present the MRI findings for 39 Wassel Type IV duplicated thumbs in 38 patients. We found that MRI revealed the morphology of the cartilaginous connection between the thumb anlages and the location of the deviation corresponding to the classification of Horii, which allowed precise preoperative planning of corrective osteotomies. All 39 thumbs were available for follow-up after surgical reconstruction at a mean of 29 months (range 25 to 39). Four out of nine Horii Type A cases and all 12 Type B, as well as the six Type C and the six Type D cases, achieved good results according to the Tada scoring system. Five Type A cases achieved fair results with residual stiffness of the interphalangeal joint. No secondary operations were needed. We conclude that MRI proved useful in subclassifying Wassel Type IV duplicated thumbs and may aid in planning the osteotomies needed for their reconstruction.Level of evidence: IV.


Assuntos
Deformidades da Mão , Procedimentos de Cirurgia Plástica , Polidactilia , Deformidades da Mão/cirurgia , Humanos , Imageamento por Ressonância Magnética , Osteotomia , Polidactilia/cirurgia , Polegar/diagnóstico por imagem , Polegar/cirurgia
12.
Front Cell Dev Biol ; 9: 623959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614652

RESUMO

Random skin flaps are frequently applied in plastic and reconstructive surgery for patients suffering from soft tissue defects caused by congenital deformities, trauma and tumor resection. However, ischemia and necrosis in distal parts of random skin flaps remains a common challenge that limits the clinical application of this procedure. Recently, chemically modified mRNA (modRNA) was found to have great therapeutic potential. Here, we explored the potential of fibroblasts engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) to improve vascularization and survival of therapeutic random skin flaps. Our study showed that fibroblasts pre-treated with SDF-1α modRNA have the potential to salvage ischemic skin flaps. Through a detailed analysis, we revealed that a fibroblast SDF-1α modRNA combinatorial treatment dramatically reduced tissue necrosis and significantly promoted neovascularization in random skin flaps compared to that in the control and vehicle groups. Moreover, SDF-1α modRNA transcription in fibroblasts promoted activation of the SDF-1α/CXCR4 pathway, with concomitant inactivation of the MEK/ERK, PI3K/AKT, and JAK2/STAT3 signaling pathways, indicating a possible correlation with cell proliferation and migration. Therefore, fibroblast-mediated SDF-1α modRNA expression represents a promising strategy for random skin flap regeneration.

13.
J Plast Reconstr Aesthet Surg ; 72(4): 636-641, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30661916

RESUMO

PURPOSE: To evaluate nail appearance after nail fusion plasty to treat thumb duplication. METHODS: A modified form of nail fusion plasty was performed on 17 reconstructed thumbs of 16 children with thumb duplications, commencing in January 2010. We assessed nail width and nail, lunular, and nail fold deformities using the Wang-Gao scoring system. All 17 thumbs were evaluated over an average of 32 months (range, 12-48 months) of follow-up. RESULTS: One patient with bilateral thumb deformities was excluded. The width ratios of 15 reconstructed nails (compared with those of the contralateral thumbs) were 82-118% (average, 97%). Nine thumbs exhibited nail ridges or gaps; the average ridge/gap score was 1.23 (maximum, 2). Six thumbs exhibited lunular deformities; the average score was 1.58 (maximum, 2). Another six thumbs evidenced nail fold deformities; the average score was 1.64 (maximum, 2). Only one thumb exhibited nail dehiscence. Two thumbs had no nail deformity. The final assessments were excellent in 14 cases, good in 2 cases, and fair in 1 case. CONCLUSIONS: We could not significantly reduce the deformity rate of the nail plate, nail fold, or lunula using our new technique, but the deformities were much less marked than previously. Nail fusion plasty usefully enlarges the nail and pulp in patients with hypoplastically duplicated thumbs.


Assuntos
Deformidades da Mão/cirurgia , Unhas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Polegar/anormalidades , Estética , Feminino , Humanos , Lactente , Masculino , Unhas/patologia , Polegar/cirurgia
14.
Chem Biol Interact ; 274: 116-123, 2017 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-28712788

RESUMO

The anti-malarial drug artesunate (ARS) has been shown to possess anti-inflammatory activity. Its effect on autoimmune hepatitis remains unclear. Concanavalin A (Con A)-induced hepatitis was used in this study to reveal the potential action of ARS and the related mechanism. Mice were pretreated with ARS followed by Con A challenge. Con A caused obvious hepatic injury with higher levels of liver enzymes, elevated pro-inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways. However, ARS pretreatment notably inhibited Con A-induced liver injury with remarkable reduction of liver enzymes, and dramatically suppressed the expression of inflammatory cytokines including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-17, and increased anti-inflammatory cytokines IL-10. In line with cytokines, the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), nuclear factor-κBα (IκBα) and NF-κB p65 was also significantly inhibited by ARS pretreatment. As a contrast, the specific inhibitor of NF-κB pyrrolidine dithiocarbamate (PDTC) achieved similar repressive effects as ARS on phosphorylation of p65 and IκBα, and serum levels of aminotransferases. Taken together, these data highlight that ARS has facilitating to make a better understanding of ARS against acute autoimmune hepatitis, and indicating a promising therapy candidate for autoimmune hepatitis.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Hepatite Autoimune/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Artesunato , Concanavalina A/toxicidade , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hepatite Autoimune/etiologia , Interleucina-17/análise , Interleucina-6/análise , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Pirrolidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tiocarbamatos/farmacologia , Fator de Necrose Tumoral alfa/análise , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Mol Med Rep ; 13(4): 3619-26, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26934832

RESUMO

Fibroblast growth factor (FGF)21 functions in the maintenance of glucose homeostasis and exerts protective effects on the liver, heat and kidneys. However, the roles of FGF21 in other tissue types are yet to be fully elucidated. The present study detected elevated expression levels of FGF21 in skin tissue. Furthermore, it was revealed that FGF21 expression in the skin was induced upon wounding. In addition, ß­klotho expression was detected in the skin tissue. To examine the role of FGF21 in the wound healing process, recombinant human (h)FGF21 was expressed in a the yeast strain Pichia (P.) pastoris, a well­known system for recombinant protein production. Based on the sequence of hFGF21 and the optimal codon of P. pastoris, codon­optimized FGF21 open reading frame sequences were obtained using seven pairs of 55­59­nt primers with seven rounds of PCR. The recombinant FGF21 was purified and its function was examined in human fibroblast cells using a wound healing cell migration assay. Treatment with FGF21 promoted cell migration, which is an important step in wound healing. Furthermore, FGF21 treatment enhanced the activity of c­Jun N­terminal kinase, a key regulator in fibroblast­cell migration. In conclusion, FGF21 is induced after wounding and FGF21 expressed and purified from yeast markedly accelerates wound healing. The present study was the first to elucidate the function of FGF21 in skin tissues and provided a theoretical basis for the use of FGF21 in the treatment of skin wounds.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Pichia/metabolismo , Animais , Western Blotting , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/farmacologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Pele/metabolismo , Pele/patologia , Cicatrização/efeitos dos fármacos
16.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 29(9): 1117-20, 2015 Sep.
Artigo em Zh | MEDLINE | ID: mdl-26750011

RESUMO

OBJECTIVE: To investigate the effectiveness of dorsal pentagonal flap for reconstruction of the web space in congenital toe syndactyly. METHODS: Between January 2009 and June 2014, 10 patients with congenital toe syndactyly were treated for web space reconstruction with dorsal pentagonal flap. There were 6 boys and 4 girls with the average age of 42 months (range, 8 months to 9 years). The congenital toe syndactyly located at the left foot in 5 cases, the right foot in 4 cases, and both feet in 1 case; 7 patients had polydactyly and 1 patient had brachydactylia. During follow-up, the toe function and web space appearance, web space depth, and web space gradient were observed to evaluate the effectiveness. RESULTS: All 13 flaps survived and incisions healed by first intention. Ten patients were followed up 6-50 months (mean, 26 months). The skin color and texture in 13 reconstructed web spaces were close to normal web space. in 9 patients undergoing web spaces reconstruction of single foot, the abduction angle of toes was (42.879±3.703) at the injured side, showing no significant difference when compared with the normal side [(45.922±2.657)°] (t= -2.004, P=0.062); the web space depth was (1.881±0.266) cm at the injured side and was (1.631±0.202) cm at the normal side, showing significant difference (t=2.248, P=0.039); and the web space gradient was (42.733±3.421)° at the injured side and was (41.189±5.593)° at the normal side, showing no significant difference (t=0.707, P=0.490). The web space appearance, web space depth, and web space gradient were close to those of the normal web space in 1 patient undergoing bilateral web spaces reconstruction. CONCLUSION: Web space reconstruction with dorsal pentagonal flap is easy to perform with reliable blood supply and low re-operated rate. The cosmetic and functional results are satisfactory.


Assuntos
Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Sindactilia/cirurgia , Dedos do Pé/cirurgia , Feminino , , Humanos , Masculino , Dedos do Pé/anormalidades , Resultado do Tratamento
17.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 27(1): 35-9, 2011 Jan.
Artigo em Zh | MEDLINE | ID: mdl-21548386

RESUMO

OBJECTIVE: To investigate the effect of Hirudin on random skin flap survival in rats. METHODS: 24 SD rats were randomly divided into control group and experimental group. The "McFarlane flap (3 cm x 9 cm)" rat models were established on the rat dorsum. 3 ml Hirudin (30 ATU) was injected into the flap in the experimental group, while 3 ml saline in the control group. The injection was performed for 7 days. The flap survival area in the two groups was measured. The tissue samples were taken from proximal (I), middle (II) and distal (III) portions of flaps for histologic study. The VEGF and bFGF expression was also detected with immunohistochemistry method. RESULTS: 7 days after operation, the flap survival rate was (69.52 +/- 3.23)% in the experimental group, while (50.36 +/- 2.37)% in control group, showing a significant difference between the two groups (P < 0. 01). In the middle portion, tissue edema and infiltration of neutrophils in experimental group was markedly slighter than that in control group. The VEGF and bFGF expression and neovascularization was enhanced markedly in experimental group. CONCLUSIONS: Hirudin can increase the survival of random pattern skin flaps. It may increase the VEGF, bFGF expression through a series of complex regulatory pathway. Then flap neovascularization is promoted and the flap blood supply is increased.


Assuntos
Sobrevivência de Enxerto/efeitos dos fármacos , Hirudinas/farmacologia , Retalhos Cirúrgicos , Animais , Fator 2 de Crescimento de Fibroblastos/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Transplante de Pele , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 26(5): 325-8, 2010 Sep.
Artigo em Zh | MEDLINE | ID: mdl-21174783

RESUMO

OBJECTIVE: To investigate the therapeutic effect of dorsal pentagonal flap for reconstruction of the web space in congenital syndactyly. METHODS: From October 2007 to August 2009, 10 patients with congenital syndactyly were treated with dorsal pentagonal flap for web space reconstruction. During the follow-up period, the patients underwent finger functional assessment and web space appearance examination. The satisfactory rate of patients was also investigated. RESULTS: 10 patients with 17 reconstructed web spaces were followed up for 4-25 months (median, 15 months). Normal passive flexion and extension of fingers were achieved with good cosmetic result at web space. The abduction angle of fingers ranged from 30 degrees to 45 degrees. No web creep occurred and no secondary procedures were required. All the parents of the patients were satisfied with the results. CONCLUSIONS: Web space reconstruction with dorsal pentagonal flap is easily performed with reliable blood supply and low re-operated rate. The cosmetic and functional result is satisfactory.


Assuntos
Retalhos Cirúrgicos , Sindactilia/cirurgia , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Resultado do Tratamento
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