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1.
J Craniofac Surg ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38710036

RESUMO

Eyelid malignancies are often resected in the entire layer, typically requiring anterior and posterior lamellae reconstruction. Posterior lamella reconstruction has been reported using grafts from the nasal septum, palatal mucosa, and auricular cartilage, which have advantages and disadvantages. The authors performed anterior and posterior lamellar reconstruction using a local skin flap and stripe-shaped anti-helical cartilage with the perichondrium in 3 total defect cases after basal cell carcinoma resection of the lower eyelid. The auricular cartilage was excised in strips with the surrounding perichondrium attached and simultaneously reconstructed, with the auricular cartilage as the tarsal and the perichondrium as the conjunctival substitute. In all 3 cases, good results were obtained without eyelid ectropion or corneal irritation 1 year postoperatively. No auricular deformities were observed. However, partial lower eyelid ptosis was observed in 2 cases. In future cases, correctively over-fixating the lower eyelid morphology is necessary.

2.
Int J Mol Sci ; 23(13)2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35806092

RESUMO

Adult mammalian wounds leave visible scars, whereas skin wounds in developing mouse fetuses are scarless until a certain point in development when complete regeneration occurs, including the structure of the dermis and skin appendages. Analysis of the molecular mechanisms at this transition will provide clues for achieving scarless wound healing. The fibroblast growth factor (FGF) family is a key regulator of inflammation and fibrosis during wound healing. We aimed to determine the expression and role of FGF family members in fetal wound healing. ICR mouse fetuses were surgically wounded at embryonic day 13 (E13), E15, and E17. Expression of FGF family members and FGF receptor (FGFR) in tissue samples from these fetuses was evaluated using in situ hybridization and reverse transcription-quantitative polymerase chain reaction. Fgfr1 was downregulated in E15 and E17 wounds, and its ligand Fgf7 was upregulated in E13 and downregulated in E15 and E17. Recombinant FGF7 administration in E15 wounds suppressed fibrosis and promoted epithelialization at the wound site. Therefore, the expression level of Fgf7 may correlate with scar formation in late mouse embryos, and external administration of FGF7 may represent a therapeutic option to suppress fibrosis and reduce scarring.


Assuntos
Fator 7 de Crescimento de Fibroblastos/metabolismo , Cicatrização , Animais , Cicatriz/patologia , Feto/metabolismo , Fibrose , Mamíferos , Camundongos , Camundongos Endogâmicos ICR , Pele/metabolismo
3.
J Clin Biochem Nutr ; 64(1): 66-72, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30705514

RESUMO

Astaxanthin is a xanthophyll carotenoid, which possesses strong scavenging effect on reactive oxygen species. In this study, we examined the effect of astaxanthin on dextran sulfate sodium (DSS)-induced colitis in mice. Experimental colitis was induced by the oral administration of 4% w/v DSS in tap water in C57BL/6J mice. Astaxanthin was mixed with a normal rodent diet (0.02 or 0.04%). Astaxanthin significantly ameliorated DSS-induced body weight loss and reduced the disease activity index. The ameliorating effects was observed in a dose-dependent manner. Immunochemical analyses showed that astaxanthin markedly suppressed DSS-induced histological inflammatory changes (inflammatory cell infiltration, edematous changes and goblet cell depletion). Plasma levels of malondialdehyde and 8-hydroxy-2-deoxyguanosine were significantly reduced by the administration of 0.04% astaxanthin. Astaxanthin significantly suppressed the mucosal mRNA expression of IL-1ß, IL-6, TNF-α, IL-36α and IL-36γ. Astaxanthin blocked the DSS-induced translocation of NF-κB p65 and AP-1 (c-Jun) into the nucleus of mucosal epithelial cells, and also suppressed DSS-induced mucosal activation of MAPKs (ERK1/2, p38 and JNK). In conclusion, astaxanthin prevented the development of DSS-induced colitis via the direct suppression of NF-κB, AP-1 and MAPK activation. These findings suggest that astaxanthin is a novel candidate as a therapeutic option for the treatment of inflammatory bowel disease.

4.
J Clin Biochem Nutr ; 63(3): 217-223, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30487672

RESUMO

We examined the effect of bortezomib, a proteasome inhibitor, on the development of dextran sulfate sodium (DSS)-induced colitis in mice. DSS-colitis was induced by the administration of 3% DSS in water in C57BL/6J mice. Bortezomib was intraperitoneally administered daily for 9 days from the start of DSS. Ubiquitination of IκBα was evaluated by immunoblot. Bortezomib significantly ameliorated DSS-induced body weight loss and reduced the disease activity. The translocation of NF-κBp65 into the nucleus was markedly suppressed in the DSS + bortezomib group compared to the DSS group, but this difference was not detected in submucosal tissue. Ubiquitinated IκBα in the cytoplasm of colon epithelial cells was increased in the DSS + bortezomib group compared to the DSS group. In HT-29 cells, bortezomib blocked tumor necrosis factor-α (TNF-α)-induced nuclear translocation of NF-κB and this was accompanied by an increase in ubiquitinated IκBα in the cytoplasm. The mRNA expression of inflammatory mediators in colonic epithelial cells was significantly reduced by the treatment of bortezomib. Bortezomib inhibited the nuclear translocation of NF-κB in colonic epithelial cells by suppressing the degradation of IκBα and contributed to an improvement in DSS colitis. Our study suggests that bortezomib may be a new treatment option for IBD.

5.
Wound Repair Regen ; 24(1): 57-64, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26710090

RESUMO

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily known for its anti-inflammatory and macrophage differentiation effects, as well as its ability to promote fat cell differentiation and reduce insulin resistance. Pioglitazone (Pio) is a PPARγ agonist used clinically as an anti-diabetic agent for improving insulin sensitivity in patients with diabetes. The objective of this study was to develop a drug delivery system (DDS) for the local release of Pio to promote wound healing. Pio of low aqueous solubility was water-solubilized by micelles formed from gelatin grafted with L-lactic acid oligomers, and incorporated into a biodegradable gelatin hydrogel. An 8-mm punch biopsy tool was used to prepare two skin wounds on either side of the midline of 8-week-old mice. Wounds were treated by the hydrogels with (Pio-hydrogel group) or without (control group) Pio, and the wound area were observed 1, 4, 7, and 14 days after treatment. In addition, a protein assay and immunohistological stain were performed to determine the effects of the Pio-hydrogel on inflammation and macrophage differentiation. The Pio-hydrogels promote wound healing. Moreover, Western blotting analysis demonstrated that treatment with Pio-hydrogels resulted in decreased levels of the cytokines MIP-2 and TGF-ß, and increased levels of glucose-regulating adiponectin. It is concluded that Pio-incorporated hydrogels promote the proliferation and remodeling phases of wound healing, and may prove to be effective as wound dressings.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Macrófagos/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Cicatrização/efeitos dos fármacos , Adiponectina/metabolismo , Animais , Curativos Hidrocoloides , Western Blotting , Quimiocina CXCL2/efeitos dos fármacos , Quimiocina CXCL2/imunologia , Sistemas de Liberação de Medicamentos , Hipoglicemiantes/administração & dosagem , Imuno-Histoquímica , Resistência à Insulina , Macrófagos/imunologia , Masculino , Camundongos , Micelas , Pioglitazona , Tiazolidinedionas/administração & dosagem , Fator de Crescimento Transformador beta/efeitos dos fármacos , Fator de Crescimento Transformador beta/imunologia , Cicatrização/imunologia
6.
Materials (Basel) ; 17(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38473549

RESUMO

A physics-based model on polarization switching in ferroelectric polycrystalline films is proposed. The calculation results by the model agree well with experimental results regarding dynamic operations of ferroelectric-gate field-effect transistors (FeFETs). In the model, an angle θ for each grain in the ferroelectric polycrystal is defined, where θ is the angle between the spontaneous polarization and the film normal direction. Under a constant electric field for a single-crystal film with θ = 0, phenomena regarding polarization domain nucleation and wall propagation are well described by the Kolmogorov-Avrami-Ishibashi theory. Since the electric fields are time-dependent in FeFET operations and the θ values are distributed in the polycrystalline film, the model in this paper forms an extended Kolmogorov-Avrami-Ishibashi (EKAI) model. Under a low electric field, the nucleation and domain propagation proceed according to thermally activated processes, meaning that switching the time scale of a grain with the angle θ is proportional to an exponential form as exp(const./Ezcosθ) [Ez: the film-normal electric field]. Wide θ distribution makes the time response quite broad even on the logarithmic scale, which relates well with the broad switching time experimentally shown by FeFETs. The EKAI model is physics based and need not assume non-physical distribution functions in it.

7.
Plast Reconstr Surg Glob Open ; 12(3): e5675, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38515557

RESUMO

This case series aimed to describe a new technique for correcting contractures and deformities that reliably addresses lacrimal punctum deviation and severe cicatricial lower eyelid ectropion. This was a technical description and a retrospective interventional case series. Eyelid ectropion and lacrimal punctum deviation were treated surgically by grafting the fascia lata and suturing the tarsus-Horner muscle. In total, three patients underwent this surgery: one for burns, one for lower eyelid tumor resection, and the other for an orbital floor fracture following a motorcycle accident, all resulting in ectropion. All patients previously had failed ectropion correction procedures, including scar revision, skin grafting, auricular cartilage grafting, and lateral tarsal strips. The mean follow-up was 15.8 (12.5-18.5) months. Furthermore, all patients showed resolution of lower eyelid ectropion and significant improvement in lower eyelid contracture, with a mean increase of 4.0 (2.5-5) mm. No severe complications were observed, and they reported a significant improvement in ocular surface symptoms. Our study shows that tacking of the tarsus and Horner muscles in combination with fascia lata grafting is effective in correcting refractory cicatricial lower eyelid ectropion with deviation of the tear punctum.

8.
Plast Surg (Oakv) ; 32(2): 299-304, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38681251

RESUMO

Background: Various flap monitoring techniques have been used in the early detection of anastomotic thrombus; however, the use of automatic and continuous monitoring methods is presently uncommon. The purpose of this study was to investigate trends in interstitial fluid glucose concentration (IFG) in flap monitoring by measuring IFG automatically and continuously. Methods: Nine patients underwent unilateral breast reconstruction using a transverse rectus abdominis myocutaneous flap with vascular anastomosis. Two IFG measuring devices were attached to each patient. One device was attached to the flap (flap IFG) and the other to the healthy breast (control IFG). In each case, flap IFG, control IFG, and IFG ratio (flap IFG/control IFG) were recorded in the initial 72 h post-surgery (first half) and also in the subsequent 72 h (second half). In all of the cases, the mean values recorded in the first half and those in the second half were compared. Results: All flaps survived. The flap IFG didn't fall below 40 mg/dL in the first half. The minimum flap IFG and IFG ratio were 42 mg/dL and 0.55 in the first half. The flap IFG was significantly higher in the first half than in the second half in all cases, and the IFG ratio was similar in 8 cases. Furthermore, mean flap IFG and mean IFG ratio in all cases in the first half were significantly higher than in the second half. Conclusions: IFG measurements may complement conventional flap monitoring, particularly in the early postoperative period.


Historique: Diverses techniques de surveillance du lambeau sont utilisées pour favoriser le dépistage précoce du thrombus anastomotique, mais peu de méthodes de surveillance automatique et continue sont utilisées en ce moment. La présente étude visait à examiner les tendances du glucose interstitiel (GI) lors de la surveillance du lambeau par une mesure automatique et continue. Méthodologie: Neuf patientes ont subi une reconstruction mammaire unilatérale au moyen d'un lambeau myocutané du grand droit transverse avec anastomose vasculaire. Chaque patiente était dotée de deux dispositifs de mesure du GI. L'un d'eux était fixé au lambeau (GI du lambeau) et l'autre au sein en bonne santé (GI témoin). Dans chaque cas, les chercheurs ont enregistré le GI du lambeau, le GI témoin et le ratio du GI (GI du lambeau/GI témoin) pendant les 72 premières heures suivant l'opération (première moitié), puis pendant les 72 heures suivantes (deuxième moitié). Dans tous les cas, les chercheurs ont comparé les valeurs moyennes enregistrées pendant la première moitié à celles enregistrées pendant la deuxième moitié. Résultats: Tous les lambeaux ont survécu. Le GI du lambeau n'a pas chuté sous 40 mg/dl pendant la première moitié. Le ratio minimal du GI était de 42 mg/dl et 0,55 pendant la première moitié. Dans tous les cas, le GI du lambeau était beaucoup plus élevé pendant la première moitié que pendant la deuxième moitié, et le ratio du GI était semblable dans huit cas. De plus, dans tous les cas, le GI moyen du lambeau et le ratio moyen du GI était beaucoup plus élevé pendant la première moitié que la deuxième. Conclusions: Les mesures de GI peuvent compléter la surveillance habituelle du lambeau, notamment au début de la période postopératoire.

9.
Sci Rep ; 14(1): 16442, 2024 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013997

RESUMO

Wounds that occur in adults form scars due to fibrosis, whereas those in embryos regenerate. If wound healing in embryos is mimicked in adults, scarring can be reduced. We found that mouse fetuses could regenerate tissues up to embryonic day (E) 13, but visible scars remained thereafter. This regeneration pattern requires actin cable formation at the epithelial wound margin via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). Here, we investigated whether the AMPK-activating effect of salicylate, an anti-inflammatory drug, promotes regenerative wound healing. Salicylate administration resulted in actin cable formation and complete wound regeneration in E14 fetuses, in which scarring should have normally occurred, and promoted contraction of the panniculus carnosus muscle, resulting in complete wound regeneration. In vitro, salicylate further induced actin remodeling in mouse epidermal keratinocytes in a manner dependent on cell and substrate target-specific AMPK activation and subsequent regulation of Rac1 signaling. Furthermore, salicylate promoted epithelialization, enhanced panniculus carnosus muscle contraction, and inhibited scar formation in adult mice. Administration of salicylates to wounds immediately after injury may be a novel method for preventing scarring by promoting a wound healing pattern similar to that of embryonic wounds.


Assuntos
Proteínas Quinases Ativadas por AMP , Actinas , Cicatrização , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Cicatrização/efeitos dos fármacos , Camundongos , Actinas/metabolismo , Salicilatos/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Contração Muscular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Cicatriz/metabolismo , Cicatriz/patologia , Ativação Enzimática/efeitos dos fármacos
10.
Sci Rep ; 14(1): 10854, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740788

RESUMO

Unlike adult mammalian wounds, early embryonic mouse skin wounds completely regenerate and heal without scars. Analysis of the underlying molecular mechanism will provide insights into scarless wound healing. Twist2 is an important regulator of hair follicle formation and biological patterning; however, it is unclear whether it plays a role in skin or skin appendage regeneration. Here, we aimed to elucidate Twist2 expression and its role in fetal wound healing. ICR mouse fetuses were surgically wounded on embryonic day 13 (E13), E15, and E17, and Twist2 expression in tissue samples from these fetuses was evaluated via in situ hybridization, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction. Twist2 expression was upregulated in the dermis of E13 wound margins but downregulated in E15 and E17 wounds. Twist2 knockdown on E13 left visible marks at the wound site, inhibited regeneration, and resulted in defective follicle formation. Twist2-knockdown dermal fibroblasts lacked the ability to undifferentiate. Furthermore, Twist2 hetero knockout mice (Twist + /-) formed visible scars, even on E13, when all skin structures should regenerate. Thus, Twist2 expression correlated with skin texture formation and hair follicle defects in late mouse embryos. These findings may help develop a therapeutic strategy to reduce scarring and promote hair follicle regeneration.


Assuntos
Folículo Piloso , Regeneração , Pele , Proteína 2 Relacionada a Twist , Cicatrização , Animais , Camundongos , Feto/metabolismo , Fibroblastos/metabolismo , Folículo Piloso/metabolismo , Camundongos Endogâmicos ICR , Camundongos Knockout , Regeneração/genética , Proteínas Repressoras , Pele/metabolismo , Proteína 1 Relacionada a Twist , Proteína 2 Relacionada a Twist/metabolismo , Proteína 2 Relacionada a Twist/genética , Cicatrização/genética , Cicatrização/fisiologia
11.
Sci Rep ; 14(1): 17215, 2024 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060558

RESUMO

This study investigated the three-dimensional (3D) cellular interactions and tunneling nanotubes (TNTs) during fetal mouse skin regeneration on embryonic days 13 (E13) and 15 (E15). We aimed to understand spatial relationships among cell types involved in skin regeneration and assess the potential role of TNTs. Full-thickness skin incisions were performed in E13 and E15 embryos. Wound sites were collected, embedded in epoxy resin, processed for 3D reconstruction (1 µm thickness sections), and subjected to whole-mount immunostaining. We conducted in vitro co-culture experiments with fetal macrophages and fibroblasts to observe TNT formation. To assess the effect of TNTs on skin regeneration, an inhibiting agent (cytochalasin B) was administered to amniotic fluid. Results revealed that E13 epidermal keratinocytes interacted with dermal fibroblasts and macrophages, facilitating skin regrowth. TNT structures were observed at the E13-cell wound sites, among macrophages, and between macrophages and fibroblasts, confirmed through in vitro co-culture experiments. In vitro and utero cytochalasin B administration hindered those formation and inefficient skin texture regeneration at E13 wound sites. This emphasizes the necessity of 3D cellular interactions between epidermal and dermal cells during skin regeneration in mouse embryos at E13. The prevalence of TNT structures indicated their involvement in achieving complete skin texture restoration.


Assuntos
Técnicas de Cocultura , Fibroblastos , Nanotubos , Regeneração , Pele , Animais , Camundongos , Regeneração/fisiologia , Pele/metabolismo , Nanotubos/química , Queratinócitos/citologia , Queratinócitos/fisiologia , Macrófagos/metabolismo , Feto , Feminino , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia , Comunicação Celular , Citocalasina B/farmacologia
12.
Nihon Shokakibyo Gakkai Zasshi ; 110(2): 243-7, 2013 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-23381212

RESUMO

A 33-year-old woman with Crohn disease complained of diarrhea and hematochezia from the fifth week of her third pregnancy and was hospitalized. Because her CDAI indicated 307.1 points and colonoscopy showed multiple longitudinal ulcers in the distal colon, adalimumab therapy was initiated. The CDAI had decreased to 160.0 points and the colonic ulcers improved by 22 days after beginning the administration of adalimumab. Although adalimumab therapy was continued every 2 weeks during the third trimester, fetus growth was not affected and the woman delivered a healthy child. Adalimumab should be considered as one treatment for Crohn disease during pregnancy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adalimumab , Adulto , Estudos de Viabilidade , Feminino , Humanos , Gravidez
13.
Biomedicines ; 11(2)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36830884

RESUMO

Scar treatments include fractional laser treatment, cell transplantation, surgery, skin needling, and dermal fillers. Fractional laser treatments are used to reduce scarring and blurring. Cell transplantation is promising, with mature fibroblasts and adipose-derived stem cells being used clinically, while embryonic fibroblasts are used experimentally. Herein, we developed a combination of ablative CO2 (carbon dioxide) fractional laser and cell transplantation for the treatment of scars. Eight-week-old male C57Bl/6 mice were used to create a full-layer skin defect in the back skin and create scars. The scar was then irradiated using a CO2 fractional laser. The cells were then transplanted onto the scar surface and sealed with a film agent. The transplanted cells were GFP-positive murine fetal fibroblasts (FB), fetal fibroblasts with a long-term sphere-forming culture (LS), and fetal skin with a short-term sphere-forming culture (SS). After transplantation, green fluorescent protein (GFP)-positive cells were scattered in the dermal papillary layer and subcutis in all the groups. LS significantly reduced the degree of scarring, which was closest to normal skin. In conclusion, the combination of ablative fractional laser irradiation and fetal fibroblast transplantation allowed us to develop new methods for scar treatment.

14.
Biomedicines ; 11(4)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37189631

RESUMO

Unlike adults, early developing fetuses can completely regenerate tissue, and replicating this could lead to the development of treatments to reduce scarring. Mice epidermal structures, including wound healing patterns, are regenerated until embryonic day (E) 13, leaving visible scars thereafter. These patterns require actin cable formation at the epithelial wound margin through AMP-activated protein kinase (AMPK) activation. We aimed to investigate whether the administration of compound 13 (C13), a recently discovered AMPK activator, to the wound could reproduce this actin remodeling and skin regeneration pattern through its AMPK activating effect. The C13 administration resulted in partial formations of actin cables, which would normally result in scarring, and scar reduction during the healing of full-layer skin defects that occurred in E14 and E15 fetuses. Furthermore, C13 was found to cause AMPK activation in these embryonic mouse epidermal cells. Along with AMPK activation, Rac1 signaling, which is involved in leaflet pseudopodia formation and cell migration, was suppressed in C13-treated wounds, indicating that C13 inhibits epidermal cell migration. This suggests that actin may be mobilized by C13 for cable formation. Administration of C13 to wounds may achieve wound healing similar to regenerative wound healing patterns and may be a potential candidate for new treatments to heal scars.

16.
Plast Reconstr Surg Glob Open ; 11(4): e4960, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37101613

RESUMO

Deep inferior epigastric perforator flaps are commonly used for breast reconstruction using autologous tissue. For such free flaps, the internal mammary artery provides stable blood flow as the recipient for anastomosis. We report a novel dissection method of the internal mammary artery. First, the perichondrium and costal cartilage of the sternocostal joint are dissected with electrocautery. Then, the incision on the perichondrium is extended along the cephalic and caudal ends. Next, this C-shaped superficial layer of perichondrium is elevated from the cartilage. The cartilage is incompletely fractured with electrocautery, with the deep layer of perichondrium intact. Then, the cartilage is completely fractured by leverage and removed. The remaining deep layer of perichondrium is incised at the costochondral junction and shifted aside, revealing the internal mammary artery. The preserved perichondrium creates a rabbet joint to protect the anastomosed artery. This method not only enables a more reliable, safer dissection of the internal mammary artery, but also allows reusage of the perichondrium as underlayment in the setting of anastomosis, and coverage for the incised rib edge, protecting the anastomosed vessels.

17.
Biomedicines ; 11(12)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38137571

RESUMO

Mammalian skin, including human and mouse skin, does not regenerate completely after injury; it is repaired, leaving a scar. However, it is known that skin wounds up to a certain stage of embryonic development can regenerate. The mechanism behind the transition from regeneration to scar formation is not fully understood. Panniculus carnosus muscle (PCM) is present beneath the dermal fat layer and is a very important tissue for wound contraction. In rodents, PCM is present throughout the body. In humans, on the other hand, it disappears and becomes a shallow fascia on the trunk. Fetal cutaneous wounds, including PCM made until embryonic day 13 (E13), regenerate completely, but not beyond E14. We visualized the previously uncharacterized development of PCM in the fetus and investigated the temporal and spatial changes in PCM at different developmental stages, ranging from full regeneration to non-regeneration. Furthermore, we report that E13 epidermal closure occurs through actin cables, which are bundles of actomyosin formed at wound margins. The wound healing process of PCM suggests that actin cables may also be associated with PCM. Our findings reveal that PCM regenerates through a similar mechanism.

18.
Biomedicines ; 10(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36551853

RESUMO

Wounds on embryonic mouse fetuses regenerate up to embryonic day (E) 13, but after E14, the pattern is lost and a visible scar remains. We hypothesized that the sonic hedgehog (Shh), which is involved in patterning during development, is involved in the regeneration of texture. Embryos of ICR mice were surgically injured at E13, E14, and E15 and analyzed for the expression of Shh. For external Shh administration, recombinant Shh-containing slow-release beads were implanted in the wounds of mice. In contrast, cyclopamine was administered to wounds of adult mice to inhibit Shh. The expression of Shh was unaltered at E13, whereas it was upregulated in the epidermis of the wound from E14 onward. Implantation of recombinant Shh-containing beads into E13 wounds inhibited skin texture regeneration. Cyclopamine treatment inhibited epithelialization and thickening of the epidermis in the wounds of adult mice. In vitro, Shh promoted proliferation and inhibited the migration of epidermal keratinocytes through the activation of cyclin D proteins. Thus, our results suggested that the expression of Shh is involved in the regeneration of texture during wound healing, especially in epidermal keratinocyte migration and division, and could inhibit skin texture regeneration after E14.

19.
Front Immunol ; 13: 875407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664010

RESUMO

Background: Fibrotic scars are common in both human and mouse skin wounds. However, wound-induced hair neogenesis in the murine wounding models often results in regenerative repair response. Herein, we aimed to uncover cellular functional heterogeneity in dermis between fibrotic and regenerative wound healing fates. Methods: The expression matrix of single-cell RNA sequencing (scRNA-seq) data of fibrotic and regenerative wound dermal cells was filtered, normalized, and scaled; underwent principal components analysis; and further analyzed by Uniform Manifold Approximation and Projection (UMAP) for dimension reduction with the Seurat package. Cell types were annotated, and cell-cell communications were analyzed. The core cell population myofibroblast was identified and the biological functions of ligand and receptor genes between myofibroblast and macrophage were evaluated. Specific genes between fibrotic and regenerative myofibroblast and macrophage were identified. Temporal dynamics of myofibroblast and macrophage were reconstructed with the Monocle tool. Results: Across dermal cells, there were six cell types, namely, EN1-negative myofibroblasts, EN1-positive myofibroblasts, hematopoietic cells, macrophages, pericytes, and endothelial cells. Ligand and receptor genes between myofibroblasts and macrophages mainly modulated cell proliferation and migration, tube development, and the TGF-ß pathway. Specific genes that were differentially expressed in fibrotic compared to regenerative myofibroblasts or macrophages were separately identified. Specific genes between fibrotic and regenerative myofibroblasts were involved in the mRNA metabolic process and organelle organization. Specific genes between fibrotic and regenerative macrophages participated in regulating immunity and phagocytosis. We then observed the underlying evolution of myofibroblasts or macrophages. Conclusion: Collectively, our findings reveal that myofibroblasts and macrophages may alter the skin wound healing fate through modulating critical signaling pathways.


Assuntos
Células Endoteliais , Cicatrização , Animais , Derme/patologia , Fibrose , Ligantes , Camundongos , Análise de Sequência de RNA , Cicatrização/genética
20.
Plast Reconstr Surg Glob Open ; 10(4): e4245, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35425688

RESUMO

Background: Variations in skin healing capacities are observed during different murine embryonic developmental stages. Through embryonic day 16 (E16), embryos are able to regenerate dermal architecture following flank skin wounding; however, after E17, wounds heal incompletely, inducing scar formation. The regenerative ability of the E16 fetal dermis depends on the migration of dermal mesenchymal cells. Decorin is a small molecule known to affect tissue tensile strength, cell phenotype, and tissue repair, including skin wound healing. In the current study, we evaluated the expression and roles of decorin in wound healing. Methods: Surgical injury was induced at E16 and E17 in ICR mouse embryos. Decorin expression was evaluated in tissue samples from these embryos using immunohistochemistry and reverse transcription quantitative polymerase chain reaction. Cell migration assays were used to evaluate wound healing capability of separated dermal and fascial tissues. Results: Our results showed that decorin exhibited distinct expression patterns during wound healing at E16 versus E17. Additionally, decorin expression altered cell migration in vitro. Dermal and fascial mesenchymal cells were found to exhibit distinct migration patterns concomitant with altered decorin expression. Specifically, decorin inhibited migration and favored scar formation. Conclusion: Decorin expression may contribute to scar formation in the late stage of mouse embryos by inhibiting the migration of dermal mesenchymal cells.

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