RESUMEN
Hypertrophic scar (HS) is characterized by excessive collagen deposition and myofibroblasts activation. Endothelial-to-mesenchymal transition (EndoMT) and oxidative stress were pivotal in skin fibrosis process. Exosomes derived from adipose tissue-derived stem cells (ADSC-Exo) have the potential to attenuate EndoMT and inhibit fibrosis. The study revealed reactive oxygen species (ROS) levels were increased during EndoMT occurrence of dermal vasculature of HS. The morphology of endothelial cells exposure to H2O2, serving as an in vitro model of oxidative stress damage, transitioned from a cobblestone-like appearance to a spindle-like shape. Additionally, the levels of endothelial markers decreased in H2O2-treated endothelial cell, while the expression of fibrotic markers increased. Furthermore, H2O2 facilitated the accumulation of ROS, inhibited cell proliferation, retarded its migration and suppressed tube formation in endothelial cell. However, ADSC-Exo counteracted the biological effects induced by H2O2. Subsequently, miRNAs sequencing analysis revealed the significance of mir-486-3p in endothelial cell exposed to H2O2 and ADSC-Exo. Mir-486-3p overexpression enhanced the acceleration of EndoMT, its inhibitors represented the attenuation of EndoMT. Meanwhile, the target regulatory relationship was observed between mir-486-3p and Sirt6, whereby Sirt6 exerted its anti-EndoMT effect through Smad2/3 signaling pathway. Besides, our research had successfully demonstrated the impact of ADSC-Exo and mir-486-3p on animal models. These findings of our study collectively elucidated that ADSC-Exo effectively alleviated H2O2-induced ROS and EndoMT by inhibiting the mir-486-3p/Sirt6/Smad axis.
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Tejido Adiposo , Exosomas , Células Endoteliales de la Vena Umbilical Humana , Peróxido de Hidrógeno , MicroARNs , Estrés Oxidativo , Transducción de Señal , Sirtuinas , Animales , Humanos , Tejido Adiposo/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Exosomas/metabolismo , Exosomas/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/toxicidad , MicroARNs/metabolismo , MicroARNs/genética , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Sirtuinas/metabolismo , Sirtuinas/genética , Proteínas Smad/metabolismo , Células Madre/metabolismo , Células Madre/efectos de los fármacosRESUMEN
End-stage organ failure often requires solid organ transplantation. Nevertheless, transplant rejection remains an unresolved issue. The induction of donor-specific tolerance is the ultimate goal in transplantation research. In this study, an allograft vascularized skin rejection model using BALB/c-C57/BL6 mice was established to evaluate the regulation of the poliovirus receptor signaling pathway using CD226 knockout or T cell immunoglobulin and ITIM domain (TIGIT)-crystallizable fragment (Fc) recombinant protein treatment. In the TIGIT-Fc-treated and CD226 knockout groups, graft survival time prolonged significantly, with a regulatory T cell proportion increase and M2-type macrophage polarization. Donor-reactive recipient T cells became hyporesponsive while responding normally after a third-party antigen challenge. In both groups, serum interleukin (IL)-1ß, IL-6, IL-12p70, IL-17A, tumor necrosis factor-α, interferon gamma, and monocyte chemoattractant protein-1 levels decreased, and the IL-10 level increased. In vitro, M2 markers, such as Arg1 and IL-10, were markedly increased by TIGIT-Fc, whereas iNOS, IL-1ß, IL-6, IL-12p70, tumor necrosis factor-α, and interferon gamma levels decreased. CD226-Fc exerted the opposite effect. TIGIT suppressed TH1 and TH17 differentiation by inhibiting macrophage SHP-1 phosphorylation and enhanced ERK1/2-MSK1 phosphorylation and nuclear translocation of CREB. In conclusion, CD226 and TIGIT competitively bind to poliovirus receptor with activating and inhibitory functions, respectively. Mechanistically, TIGIT promotes IL-10 transcription from macrophages by activating the ERK1/2-MSK1-CREB pathway and enhancing M2-type polarization. CD226/TIGIT-poliovirus receptor are crucial regulatory molecules of allograft rejection.
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Antígenos de Diferenciación de Linfocitos T , Rechazo de Injerto , Macrófagos , Receptores Inmunológicos , Trasplante de Piel , Animales , Ratones , Antígenos de Diferenciación de Linfocitos T/metabolismo , Unión Competitiva , Rechazo de Injerto/etiología , Interferón gamma , Interleucina-10 , Interleucina-6 , Macrófagos/metabolismo , Factor de Necrosis Tumoral alfaRESUMEN
Severe coloboma of ocular malignant neoplasms post-resection poses a reconstructive challenge to surgeons. To compare the practicability, manipulability and outcomes of temporal (myocutaneous) flaps (TFs), forehead (supratrochlear artery/supraorbital artery) flaps (FFs) and buccal (facial artery) flaps (BFs) for periorbital defects reconstruction, a retrospective case series was conducted and evaluated between March 2014 and March 2021. Patient demographics and clinical parameters including age, gender, pathological diagnosis, operative methods, flap selection, operation time, aesthetic satisfaction and follow-up period were collected. The differences in complications were compared and assessed of the three flaps, including flap survival, venous congestion and donor site healing. Totally, 68 patients who underwent periorbital reconstructive operations because of common ocular malignant tumours were reviewed in this study. As for aesthetic satisfaction, a score more than "moderately dissatisfied" was obtained in 21 patients with TFs (95.5%), and of which the scores in FFs group were 12 cases (60%) and 16 cases with BFs reconstruction (61.5%) (P < .05). Severe microvascular complications underwent re-exploration operation occurred in one patient with FFs (1.5%) (P > .05). Notable flap necrosis was observed in two patients with BFs repair (2.9%) and in one case with FFs repair (1.5%), with no statistical difference between the three flap selections (P > .05). Moderate venous congestion occurred in one patient with TFs (1.5%), which was fully meliorated non-surgically. The three familiar facial island flaps are considered as minor trauma and time-saving process for reconstructing the extensive periorbital defects with comparable ranks of complications.
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Hiperemia , Neoplasias , Procedimientos de Cirugía Plástica , Humanos , Estudios Retrospectivos , Estudios de Factibilidad , Colgajos Quirúrgicos/irrigación sanguínea , Resultado del Tratamiento , Trasplante de Piel/métodosRESUMEN
Hypertrophic scar (HS) is a severe fibrotic skin disease. It has always been a major problem in clinical treatment, mainly because its pathogenesis has not been well understood. The roles of bacterial contamination and prolonged wound inflammation were considered significant. IL-10 is a potent anti-inflammatory cytokine and plays a pivotal role in wound healing and scar formation. Here, we investigate whether IL-10 alleviates lipopolysaccharide (LPS)-induced inflammatory response and skin scarring and explore the possible mechanism of scar formation. Our results showed that the expression of TLR4 and pp65 was higher in HS and HS-derived fibroblasts (HSFs) than their counterpart normal skin (NS) and NS-derived fibroblasts (NSFs). LPS could up-regulate the expression of TLR4, pp65, Col I, Col III and α-SMA in NSFs, but IL-10 could down-regulate their expression in both HSFs and LPS-induced NSFs. Blocking IL-10 receptor (IL-10R) or the phosphorylation of STAT3, their expression was up-regulated. In addition, in vitro and in vivo models results showed that IL-10 could alleviate LPS-induced fibroblast-populated collagen lattice (FPCL) contraction and scar formation. Therefore, IL-10 alleviates LPS-induced skin scarring via IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts by reducing ECM proteins deposition and the conversion of fibroblasts to myofibroblasts. Our results indicate that IL-10 can alleviate the LPS-induced harmful effect on wound healing, reduce scar contracture, scar formation and skin fibrosis. Therefore, the down-regulation of inflammation may lead to a suitable scar outcome and be a better option for improving scar quality.
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Fibroblastos/metabolismo , Interleucina-10/metabolismo , Lipopolisacáridos/administración & dosificación , FN-kappa B/metabolismo , Receptores de Interleucina-10/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Animales , Biopsia , Cicatriz Hipertrófica/etiología , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Citocinas/metabolismo , Susceptibilidad a Enfermedades , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Modelos Biológicos , Conejos , Piel/metabolismo , Piel/patologíaRESUMEN
For over several decades, 595-nm pulsed dye laser (PDL) has been used effectively, reducing erythema and improving the pliability and texture of burn scars. Children usually tolerate PDL treatment as it is non-invasive and causes only mild pain compared to other laser treatments. However, currently, there are limited data on scar management in children who underwent PDL treatment, especially for Fitzpatrick skin types III and IV. The objective of the study was to identify the optimal parameters for the PDL treatment that induce inhibitory effects on scar tissue in children with Fitzpatrick skin types III and IV. Besides, the study assessed the usefulness of high-frequency ultrasound (20 MHz) and laser Doppler flowmetry in assessing these lesions. A total of 165 (79 males and 86 females) children with hypertrophic scars treated by PDL were assessed by the Vancouver scar scale (VSS), high-frequency ultrasound (20 MHz), and laser Doppler flowmetry. The parameters used for the 595-nm PDL treatment were pulse duration of 0.45 ms, fluence between 5 and 9 J/cm2, a spot size of 7 mm, and treatment intervals from 3 to 8 weeks. There were no significant differences between pretreatment and post-treatment in terms of the distribution of sex, type of skin color, and low and high fluences. While the mean scores of all scar parameters based on VSS, except thickness and pliability between pre and post-treatment, showed significant differences in ≤3-year-old children vs. to >3-year-old children, except for the subscore, a significant improvement was observed when PDL was initiated within 4 to 6 months of the scar age. In Chinese children with Fitzpatrick skin types III and IV, early intervention, appropriate treatment intervals, and low fluence of PDL were optimal parameters in treating hypertrophic burn scars. The combined high-frequency ultrasound and laser Doppler flowmetry assessment of scars helped assess these lesions and compare the efficacy of different treatment modalities.
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Quemaduras , Cicatriz Hipertrófica , Láseres de Colorantes , Terapia por Luz de Baja Intensidad , Quemaduras/complicaciones , Preescolar , China , Cicatriz Hipertrófica/etiología , Cicatriz Hipertrófica/patología , Femenino , Humanos , Láseres de Colorantes/uso terapéutico , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Deformities in human soft tissue caused by trauma or burn present a difficult problem in plastic surgery. In this study, we encapsulated troglitazone and angiotensin 1-7 mimetic AVE0991 in gelation microspheres with the goal of inducing epithelial transformation for potential applications in tissue reconstruction. After troglitazone or AVE0991 were encapsulated to gelation microspheres, their release kinetics and bioactivity were examined. Surface morphology and diameter of the gelation microspheres were evaluated using light microscopy. The release of the drugs was assessed in the presence of human adipose-derived stem cells (ADSCs). Treatment with troglitazone microspheres increased cell viability and activated the ß-catenin in ADSCs. Moreover, the AVE0991 microspheres also increased cell viability and C-myc expression of ADSCs. These results showed that troglitazone and AVE0991 microspheres promoted the activity of ADSCs. Furthermore, ADSCs were co-treated with troglitazone and AVE0991 microspheres. Western blot and immunofluorescent staining showed that co-treatment with troglitazone and AVE0991 microspheres elevated the expression of epithelialization associated protein CK14 in ADSCs. In conclusion, our findings indicate that microspheres with troglitazone and AVE0991 can significantly improve the viability and epithelialization of ADSCs, which provides a new approach for the construction of tissue-engineered skin.
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Gelatina/química , Imidazoles/farmacocinética , Células Madre Mesenquimatosas/efectos de los fármacos , Ingeniería de Tejidos/métodos , Troglitazona/farmacocinética , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Liberación de Fármacos , Humanos , Hipoglucemiantes/farmacología , Imidazoles/farmacología , Células Madre Mesenquimatosas/metabolismo , Microesferas , Tamaño de la Partícula , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Repitelización , Reacción en Cadena en Tiempo Real de la Polimerasa , Troglitazona/farmacología , beta Catenina/metabolismoRESUMEN
Hypertrophic scars (HS) are characterized by the excessive production and deposition of extracellular matrix (ECM) proteins. Pentoxifylline (PTX), a xanthine derived antioxidant, inhibits the proliferation, inflammation and ECM accumulation of HS. In this study, we aimed to explore the effect of PTX on HS and further clarify the mechanism of PTX-induced anti-proliferation. We found that PTX could significantly attenuate proliferation of HS fibroblasts and fibrosis in an animal HS model. PTX inhibited the proliferation of HSFs in a dose- and time-dependent manner, and this growth inhibition was mainly mediated by cell cycle arrest. Transcriptome sequencing showed that PTX affects HS formation through the PI3K/Akt/FoxO1 signalling pathway to activate p27Kip1 . PTX down-regulated p-Akt and up-regulated p-FoxO1 in TGF-ß1 stimulated fibroblasts at the protein level, and simultaneously, the expression of p27Kip1 was activated. In a mouse model of HS, PTX treatment resulted in the ordering of collagen fibres. The results revealed that PTX regulates TGFß1-induced fibroblast activation and inhibits excessive scar formation. Therefore, PTX is a promising agent for the treatment of HS formation.
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Cicatriz Hipertrófica/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Proteína Forkhead Box O1/genética , Proteínas Proto-Oncogénicas c-akt/genética , Animales , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cicatriz Hipertrófica/patología , Modelos Animales de Enfermedad , Matriz Extracelular/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis/genética , Fibrosis/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Pentoxifilina/farmacología , Fosfatidilinositol 3-Quinasas/genética , Transducción de Señal/efectos de los fármacos , Transcriptoma/genética , Factor de Crecimiento Transformador beta/genéticaRESUMEN
Liver injury plays vital roles in the development of inflammation and organ dysfunction during sepsis. MCP-1-induced protein 1 (MCPIP1), as an endoribonuclease, is a critical regulator for the maintenance of immune homeostasis. However, whether MCPIP1 participates in the septic liver injury remains unknown. The aim of this study was to investigate the role of MCPIP1 in lipopolysaccharides-induced liver injury and the underlying modulatory mechanisms. Quantitative real-time polymerase chain reaction and immunoblotting were used to determine proinflammatory cytokines, MCPIP1, retinoid-related orphan receptor α (RORα), miR-155, and related protein from nuclear factor-κB (NF-κB) pathway expression. Dual luciferase reporter assay was used to analyze whether miR-155 regulates RORα transcription. Secretion of inflammatory cytokines into sera in mice were measured by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining, alanine aminotransferase, and aspartate transaminase, assay were used to evaluate liver function. We found that MCPIP1 expression was notably upregulated and significantly downregulated inflammatory cytokine secretion and NF-κB signaling activation in macrophages following exposure to lipopolysaccharide. Moreover, miR-155, lowered by MCPIP1, directly targeted on 3'-untranslated region of RORα to activate an inflammatory response. Importantly, MCPIP1 overexpression in mice alleviated septic liver injury symptoms following lipopolysaccharides stimulation. Collectively, these data highlight MCPIP1/miR-155/RORα axis as a novel modulation of inflammation in liver injury and potential therapeutic target for future research.
RESUMEN
BACKGROUND: This study introduces a technique for the reconstruction of deep toe defects in diabetic patients using a method that combines free vascularized fascia flap with skin grafting. METHODS: In this retrospective study, conducted between March 2010 and February 2016, 15 diabetic patients with deep toe ulcer received surgeries that combined free vascularized fascia flap with skin grafting, including nine anterolateral thigh fascia lata flaps and six superficial temporal fascia flaps. Their medical records were systematically reviewed from electronic databases. The donor artery was anastomosed to the dorsalis pedis artery in an end-to-side manner, and the vein was anastomosed to the accompanying vein in an end-to-end manner. RESULTS: Thirteen fascia flaps completely survived without any rejection. Partially necrosed grafted skins, which were found in two cases, were healed after routine dressing changes. Patients achieved an esthetic outcome and acceptable functions without further revisions. Two patients suffered from ischemic necrosis of the fascia flap and eventually underwent amputation. CONCLUSIONS: The present study demonstrated that vascularized fascia flap combined with skin grafting has great advantages for correcting deep toe ulcer in diabetic patients characterized by the esthetic outcome, abundant vascularity, surgical simplicity, and good deformability.
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Pie Diabético/cirugía , Fascia/trasplante , Colgajos Tisulares Libres , Colgajo Perforante , Trasplante de Piel , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Dedos del Pie/cirugíaRESUMEN
Intense pulsed light (IPL) has been used to treat postinflammatory hyperpigmentation and telangiectasia in Fitzpatrick type I -II skin. However, its therapeutic effects after superficial second-degree burns in Asian populations with Fitzpatrick type III-IV skin are uncertain. Thirty-five Han Chinese patients with facial or hand hyperpigmentation and telangiectasia due to second-degree fire burns received treatment with IPL. Each patient underwent 2-6 treatments over 3-5 weeks. The laser wavelength was 560-615 nm. Skin pigmentation was evaluated by two plastic surgeons as well as by the patients themselves (self-evaluation) before treatment at the end of the treatment cycle and 1 year after the first treatment. Blood flow in telangiectasia skin was measured by laser Doppler flow. The results showed that IPL significantly lessened hyperpigmentation so that close to normal skin color was achieved after the treatment cycles, and pigmentation did not reoccur 1 year after the first treatment. Approximately 82.9% of the patients were satisfied with their treatment outcomes. There were no post-treatment complications. Doppler showed a significant decreased blood flow in telangiectasia after treatment. In conclusion, IPL is an effective and safe modality for Chinese patients with hyperpigmentation and telangiectasia after fire burns.
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Quemaduras/complicaciones , Hiperpigmentación/etiología , Hiperpigmentación/terapia , Telangiectasia/etiología , Telangiectasia/terapia , Adolescente , Adulto , Pueblo Asiatico , China , Femenino , Humanos , Tratamiento de Luz Pulsada Intensa , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Flujo Sanguíneo Regional , Adulto JovenRESUMEN
The transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ) functions to regulate cell differentiation and lipid metabolism. Recently, its agonist has been documented to regulate extracellular matrix production in human dermal fibroblasts. This study explored the underlying molecular mechanisms and gene interactions in hypertrophic scar fibroblasts (HSFBs) in vitro. HSFBs were cultured and treated with or without PPAR-γ agonist or antagonist for gene expression. Bioinformatical analysis predicted that miR-145 could target Smad3 expression. Luciferase assay was used to confirm such an interaction. The data showed that PPAR-γ agonist troglitazone suppressed expression of Smad3 and Col1 in HSFBs. PPAR-γ agonist induced miR-145 at the gene transcriptional level, which in turn inhibited Smad3 expression and Col1 level in HSFBs. Furthermore, ELISA data showed that Col1 level in HSFBs was controlled by a feedback regulation mechanism involved in PPAR-γ agonist and antagonist-regulated expression of miR-145 and Smad3 in HSFBs. These findings indicate that PPAR-γ-miR-145-Smad3 axis plays a role in regulation of collagen synthesis in HSFBs.
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Cromanos/farmacología , Cicatriz Hipertrófica/patología , Colágeno/biosíntesis , PPAR gamma/agonistas , Proteína smad3/genética , Tiazolidinedionas/farmacología , Anilidas/farmacología , Células Cultivadas , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/metabolismo , Colágeno/genética , Colágeno Tipo I/biosíntesis , Colágeno Tipo I/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/genética , MicroARNs/metabolismo , PPAR gamma/antagonistas & inhibidores , PPAR gamma/metabolismo , Proteína smad3/metabolismo , TroglitazonaRESUMEN
The essential roles of Notch pathway in angiogenesis have been reported for years. However, how Notch pathway plays its role in regulating endothelial cells remains largely unknown. In this study we found that blockade of Notch signaling with a γ-secretase inhibitor increased reactive oxygen species (ROS) in primary human umbilical vein endothelial cells (HUVECs) under both normaxic and ischemia/reperfusion (I/R) conditions. Abruption of ROS generation with ROS scavengers or specific inhibitors of ROS production in HUVECs abolished Notch blockade-induced HUVEC proliferation, migration and adhesion, suggesting that the regulation of Notch pathway on endothelial cell behavior is at least partially dependent on its down-regulation of ROS level. We further showed that the enhanced generation of ROS after blocking Notch signal was accompanied by augmented expression of Nox4, which led to increased phosphorylation of VEGFR2 and ERK in HUVECs. In summary, our results have shown that Notch signaling regulates ROS generation by suppressing Nox4, and further modulates endothelial cell proliferation, migration and adhesion.
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Células Endoteliales de la Vena Umbilical Humana/metabolismo , NADPH Oxidasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores Notch/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Adhesión Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/enzimología , Humanos , NADPH Oxidasa 4 , NADPH Oxidasas/genética , Neovascularización Fisiológica , Oligopéptidos/farmacología , Estrés Oxidativo/efectos de los fármacos , Receptores Notch/genética , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación hacia ArribaRESUMEN
Mongolian is the eighth largest ethnic minority on Chinese population data according to the 2010 census. In the present study, we presented the first report about the allelic frequencies and forensic statistical parameters at the 21 new STRs and analyzed linkage disequilibrium of pairwise loci in the Mongolian ethnic minority, China. Hardy-Weinberg equilibrium tests demonstrated no significant deviations except for the D1S1627 locus. The cumulative power of discrimination and power of exclusion of all the loci are 0.9999999999999999992576 and 0.9999997528, respectively. The results of analysis of molecular variance showed that significant differences between the Mongolian and the other eight populations were found at 1-9 STR loci. In population genetics, the results of principal component analysis, structure analysis, and phylogenetic reconstruction analysis indicated shorter genetic distance between the Mongolian group and the Ningxia Han. All the results suggest that the 21 new STR loci will contribute to Chinese population genetics and forensic caseworks in the Mongolian group.
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Pueblo Asiatico/genética , Etnicidad/genética , Polimorfismo Genético , China , Análisis por Conglomerados , Frecuencia de los Genes , Humanos , Desequilibrio de Ligamiento , Repeticiones de Microsatélite , Filogenia , Análisis de Componente PrincipalRESUMEN
X-chromosomal STRs (X-STRs) have been used as complements of autosomal STR application in recent years. In this work, we present population genetic data of 12 X-STRs including DXS101, DXS10159, DXS10162, DXS10164, DXS6789, DXS7133, DXS7423, DXS7424, DXS8378, DXS981, GATA165B12, and GATA31E08 loci in a sample of 231 unrelated healthy individuals from the Hui ethnic group in Ningxia Hui Autonomous Region, China. Allelic frequencies of the 12 X-STR loci and haplotypic frequencies of the reported linkage groups (DXS7424-DXS101 and DXS10159-DXS10164-DXS10162) were investigated in the group, respectively. No STR loci showed significant deviations from the Hardy-Weinberg equilibriums and no linkage disequilibriums of pairwise loci were found after Bonferroni correction, respectively. A combined power of discrimination in female individuals was 0.999999999985 and that in male individuals was 0.99999967, respectively. The combined mean exclusion chance in deficiency cases, normal trios and duo cases were 0.999934, 0.995754, and 0.999796, respectively. Significant differences were observed from 0 to 8 loci, when making comparisons between the data of Hui ethnic group and previously reported data from other 16 populations. The results indicated the new panel of 12 X-STR loci might be useful for forensic science application.
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Pueblo Asiatico/genética , Cromosomas Humanos X , Etnicidad/genética , Genética de Población/métodos , Repeticiones de Microsatélite , Polimorfismo Genético , China , Femenino , Técnicas de Genotipaje , Haplotipos , Humanos , Desequilibrio de Ligamiento , MasculinoRESUMEN
Intensive insulin therapy during critical illness protects the endothelium and thereby prevents organ failure. This study tested the hypothesis that insulin directly affects the attenuation of burn injury-induced damage to pulmonary endothelial tight junction and investigated the underlying mechanisms. Sprague Dawley rats with severe burn injury were randomized to treatment with insulin dissolved in normal saline (maintenance of blood glucose at a level between 5.0 and 7.0 mmol/L) or normal saline alone (in vivo treatment). Pulmonary damage was evaluated. Rat pulmonary microvascular endothelial cells were treated with 20% burn serum or 20% burn serum + insulin (in vitro treatment). Selected cultures were pretreated with phosphatidylinositol 3-kinase/protein kinase B (AKT) inhibitor (LY294002). Permeability was assessed by migration of bovine serum albumin across cell monolayers. Cells were stained with rhodamine phalloidin and were examined. Cell extracts were obtained to assess zonula occludens-1, occludin, and phosphorylated AKT levels by immunoblotting. Treatment with insulin attenuated the pulmonary edema, hemorrhage, and inflammatory cell infiltration of rats with severe burn injury. Burn serum significantly enhanced monolayer permeability to albumin, whereas treatment with insulin (10(-7 ) mol/L) limited this effect. Meanwhile, insulin (10(-7 ) mol/L) reduced burn serum-induced F-actin stress fiber formation and decreased zonula occludens-1 expression. LY294002 decreased cytoplasmic AKT phosphorylation and inhibited the protection effects of insulin. Through the phosphatidylinositol 3-kinase/AKT pathway, insulin independent of glucose toxicity can attenuate increased pulmonary endothelial permeability induced by burn injury. The effect is attributed to the attenuation of the architectural disruption of protein components of the endothelial tight junction. This result is useful in inhibiting multiple organ failure after burn injury.
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Actinas/metabolismo , Quemaduras/tratamiento farmacológico , Cromonas/farmacología , Endotelio Vascular/patología , Inhibidores Enzimáticos/farmacología , Insulina/farmacología , Morfolinas/farmacología , Proteína Oncogénica v-akt/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Mucosa Respiratoria/patología , Uniones Estrechas/patología , Cicatrización de Heridas , Proteína de la Zonula Occludens-1/metabolismo , Actinas/biosíntesis , Animales , Glucemia/metabolismo , Quemaduras/metabolismo , Quemaduras/patología , Quemaduras/fisiopatología , Permeabilidad de la Membrana Celular , Células Cultivadas , Células Endoteliales/metabolismo , Endotelio Vascular/efectos de los fármacos , Activación Enzimática , Hemorragia/prevención & control , Insuficiencia Multiorgánica/prevención & control , Proteína Oncogénica v-akt/antagonistas & inhibidores , Fosforilación , Edema Pulmonar/prevención & control , Ratas , Ratas Sprague-Dawley , Mucosa Respiratoria/efectos de los fármacos , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/biosíntesisRESUMEN
Hypertrophic scars (HS) and keloids (KD) are lesions that develop as a result of excessive fibroblast proliferation and collagen deposition in response to dermal injury, leading to dysregulation of the inflammatory, proliferative, and remodeling phases during wound healing. HS and KD affect up to 90 % of the population and are associated with lower quality of life, physical health, and mental status in patients. Efficient targeted treatment represents a significant challenge, primarily due to our limited understanding of their underlying pathogenesis. Non-coding RNAs (ncRNAs), which constitute a significant portion of the human transcriptome with minimal or no protein-coding capacity, have been implicated in various cellular physiologies and pathologies and may serve as diagnostic indicators or therapeutic targets. NcRNAs have been found to be aberrantly expressed and regulated in HS and KD. This review provides a summary of the expression profiles and molecular mechanisms of three common ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in HS and KD. It also discusses their potential as biomarkers for the diagnosis and treatment of these diseases and provides novel insights into epigenetic-based diagnosis and treatment strategies for HS and KD.
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Cicatriz Hipertrófica , Queloide , MicroARNs , ARN Largo no Codificante , Humanos , Cicatriz Hipertrófica/genética , Queloide/genética , Calidad de Vida , Cicatrización de Heridas , MicroARNs/genéticaRESUMEN
OBJECTIVE: Treating scalp defects after revascularization surgery is difficult because the scalp microcirculation is severely compromised. We aimed to review the clinical effects of using rotational flaps in scalp defect reconstruction and explore risk factors for wound-related complications (WRC) after reconstruction surgery. METHODS: We retrospectively identified patients with scalp defects after combined revascularization surgery who were surgically treated with rotational flap reconstruction at our institution between January 2018 and December 2022. We analyzed treatment results in different surgical technique and revascularization strategy cohorts, including direct bypass superficial temporal artery branch selection, indirect bypass types, and skin incisions. RESULTS: Eleven patients were included. The superficial temporal artery parietal branch was selected for direct bypass surgery in 10 (90.9%) patients, 4 (40%) of whom had WRC after flap reconstruction. Five types of indirect bypass surgeries were performed; three patients treated by encephalo-duro-myo-arterio-perio-synangiosis and 1 patient treated by encephalo-duro-myo-perio-synangiosis had WRC after flap reconstruction. Question mark (n = 6, 54.5%), curved (n = 4, 36.65%), and Y-shaped (n = 1, 9.1%) incisions were used; in the first three incision cohorts, 2 patients in each cohort had WRC after flap reconstruction. CONCLUSIONS: Patients had the following commonalities that may be risk factors for WRC after flap reconstruction: 1) wounds with nonviable bone exposure after revascularization surgery; 2) three or more tissues used as donor tissues and donor tissues containing the periosteum; and 3) thin scalp around the defect.
Asunto(s)
Revascularización Cerebral , Enfermedad de Moyamoya , Herida Quirúrgica , Humanos , Enfermedad de Moyamoya/cirugía , Enfermedad de Moyamoya/etiología , Cuero Cabelludo/cirugía , Estudios Retrospectivos , Revascularización Cerebral/métodos , Arteria Cerebral Media/cirugíaRESUMEN
Hypertrophic scarring (HS) is a pathological condition characterized by excessive fibrosis and inflammation, resulting in excessive extracellular matrix formation in the skin. MIR155HG, a long non-coding RNA, is abnormally upregulated in fibrotic tissues; however, its underlying mechanism is poorly understood. Using single-cell sequencing data, we analyzed connective tissue growth factor (CTGF) expression in various cell types in HS and normal skin tissues and MIR155HG expression in clinical samples. To investigate the mechanism of fibrosis, an in vitro model using CTGF-treated hypertrophic scar fibroblasts (HSFBs) was established and qRT-PCR, western blotting and ELISA assays were performed to investigate the expression of interleukin (IL)-1ß, IL-6, and mesenchymal markers α-smooth muscle actin (α-SMA). CTGF stimulates MIR155HG level through phosphorylated STAT3 binding to the MIR155HG promoter. We analyzed the methylation of MIR155HG, assessed the levels of miR-155-5p/-3p in CTGF-treated HSFBs and identified differentially expressed genes among HS and NS samples using the Gene Expression Omnibus RNA sequencing data. The binding between miR-155-5p/-3p and AZGP1 was confirmed using a dual-luciferase assay and inflammatory cytokine production and α-SMA expression were investigated in rescue experiments. The findings revealed that CTGF elevated inflammatory cytokine production, α-SMA and MIR155HG expression in HSFBs. MIR155HG is upregulated in HS tissues due to low DNA methylation. Mechanistically, miR-155-5p/-3p was directly bound to MIR155HG 3'UTR. MIR155HG silencing inhibited cytokine production and α-SMA expression by repressing the generation of miR-155-5p/-3p in CTGF-treated HSFBs. Bioinformatics analysis and luciferase reporter assays revealed that miR-155-5p/-3p targets AZGP1. In addition, transfection with plasmids carrying AZGP1 cDNA significantly inhibited the signaling activity of miR-155-5p/-3 p-overexpressing HSFBs. Our findings highlight the importance of the MIR155HG/miR-155/AZGP1 axis in regulating cytokine production and α-SMA in HS.
Asunto(s)
Actinas , Cicatriz Hipertrófica , Factor de Crecimiento del Tejido Conjuntivo , Citocinas , Fibroblastos , MicroARNs , Regulación hacia Arriba , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/genética , Fibroblastos/metabolismo , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Cicatriz Hipertrófica/genética , Actinas/metabolismo , Citocinas/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Glicoproteínas/metabolismo , Glicoproteínas/genética , Masculino , Femenino , Transducción de SeñalRESUMEN
Based on deep learning, monocular visual 3D reconstruction methods have been applied in various conventional fields. In the aspect of medical endoscopic imaging, due to the difficulty in obtaining real information, self-supervised deep learning has always been a focus of research. However, current research on endoscopic 3D reconstruction is mainly conducted in laboratory environments, lacking experience in dealing with complex clinical surgical environments. In this work, we use an optical flow-based neural network to address the problem of inconsistent brightness between frames. Additionally, attention modules and inter-layer losses are introduced to tackle the complexity of endoscopic scenes in clinical surgeries. The attention mechanism allows the network to better focus on pixel texture details and depth differences, while the inter-layer losses supervise the network at different scales. We have established a complete monocular endoscopic 3D reconstruction framework and conducted quantitative experiments on a clinical dataset using the cross-correlation coefficient as a metric. Compared with other self-supervised methods, our framework can better simulate the mapping relationship between adjacent frames during endoscope motion. To validate the generalization performance of our framework, we tested the model trained on the clinical dataset on the SCARED dataset and achieved equally excellent results.
RESUMEN
Introduction: Postburn scarring often presents a specific reconstructive challenge from both functional and cosmetic perspectives. The purpose of this study was to investigate whether autologous nanofat harvested from the donor site of full skin or a skin flap can be reused for the treatment of early postburn scaring. Methods: From July 2018 to April 2022, patients with early postburn scarring underwent scar reconstruction surgery with full-thickness skin or a skin flap for a contour deformity and/or scar contracture, and autologous nanofat grafting was performed during the same operation. The Vancouver Scar Score (VSS) and the itch and pain scores were evaluated at the preoperation time point as well as at 2-3 weeks and 3-months postoperation. A comparison was made among the same patients at different time points. Results: A total of 17 patients, aged from 18 months to 62 years old were included in this analysis. The VSS was reduced from 10.00 ± 2.12 to 7.41 ± 1.277 at the 2-3-week postoperation time point, and to 5.53 ± 1.37 at the 3-month postoperation time point. The pain and itch score were reduced from 4.65 ± 1.37 and 6.35 ± 1.27, to 3.70 ± 1.10 and 4.94 ± 1.30 at the 2-3-week postoperation time point, and to 3.00 ± 1.28 and 3.94 ± 0.97 at the 3-month postoperation time point respectively. The VSS and pain and itch scores showed a statistically significant reduction (P < 0.05) at the 2-3-week and 3-month postoperative follow-ups compared with the preoperation time point. Conclusion: Autologous nanofat grafting from donor sites of full thickness skin or skin flap may be a promising treatment for an early postburn scaring as it promotes scar softening, improves itching and pain within the scar. However, this is a small case series with only 17 patients. Further conclusions need to be drawn through expanded samples for randomized controlled clinical trials. Lay Summary: Hypertrophic scarring is the most common complication after partial thickness burn injury, and the complex pathogenesis and prolonged dynamic process render treatments only marginally effective. In the past few decades, with the technological advances of liposuction and fat grafting, nanofat grafting has been used in a variety of surgical fields, including wound healing, scleroderma, facial rejuvenation, and neuralgia. However, the role of nanofat grafting is not well documented in the prevention and treatment of early postburn scarring. Full-thickness skin grafting or skin flap transplantation is the most common method for the reconstruction of a hypertrophic scaring until now. In the current study, we harvested subcutaneous fat during the preparation of the full-thickness skin or skin flap, prepared nanofat and injected it in the scar located at a nonsurgical site. Comparison of the pre- and postoperation scores for scar color, scar thickness, scar stiffness, and scar regularity showed that the postoperation scores were decreased significantly and that there was a significant improvement in scar pigmentation and thickness as well astheaesthetic outcome after treatment. Most importantly, reductions in the scores for pain and itching could be assessed objectively. It seems that the nanofat grafting is a potential method for prevention and treatment for early postburn scaring.