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Quiescent hair follicle stem cells (HFSCs) reside in specialized bulge niche where they undergo activation and differentiation upon sensing niche-dependent signals during hair follicle (HF) homeostasis and wound repair. The underlying mechanism of HFSCs and bulge niche maintenance is poorly understood. Our previous study has reported that a transcription factor, forkhead box P1 (Foxp1), functions to maintain the quiescence of HFSCs. Here, we further discovered that forkhead box P4 (Foxp4), a close family member of Foxp1, had similar expression profiles in various components of HFs and formed a complex with Foxp1 in vitro and in vivo. The HF-specific deficiency of Foxp4 resulted in the precocious activation of HFSCs during hair cycles. In contrast to single Foxp1 or Foxp4 conditional knockout (cKO) mice, Foxp1/4 double cKO exerted an additive effect in the spectrum and severity of phenotypes in HFSC activation, hair cycling acceleration and hair loss, coupled with remarkable downregulation of fibroblast growth factor 18 (Fgf18) and bone morphogenetic protein 6 (Bmp6) expression in bulge cells. In addition, the double KO of Foxp1/4 induced the apoptosis of K6-positive (K6+) inner bulge cells, a well-established stem cell (SC) niche, thus resulting in the destruction of the bulge SC niche and recurrent hair loss. Our investigation reveals the synergistic role of Foxp1/4 in sustaining K6+ niche cells for the quiescence of HFSCs.
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Proteína Morfogenética Ósea 6 , Nicho de Células Madre , Alopecia/metabolismo , Animales , Apoptosis/genética , Proteína Morfogenética Ósea 6/metabolismo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Folículo Piloso , Ratones , Proteínas Represoras/metabolismoRESUMEN
BACKGROUND: The formation of hypertrophic scar is due to the abnormal accumulation and remodeling of the extracellular matrix, especially collagen tissue. Our research was designed to investigate the treatment effect of different administrations of human umbilical cord-derived stem cells and to hypertrophic scars on rabbit ears. METHODS: Thirty New Zealand female white rabbits were treated as hypertrophic scar models. PBS was injected into the scars on the right ear of each group as control, while human umbilical cord-derived stem cells or condition medium of human umbilical cord-derived stem cells were administrated into the left ear through subcutaneous injection or fractional laser-assisted administration. Gross examination, scar elevation index (SEI) calculation and sampling were executed 5 weeks after administration. Then H&E and Masson staining analysis and the expression levels detections of α-SMA, Collagen I, TGF-ß1, IL-1ß, and IL-6 were performed. RESULTS: Our results demonstrated that the severity of hyperplasia was lower than the model group after stem cells and conditioned medium treatment. H&E and Masson staining results showed that the inflammation in scars was greatly alleviated and the degree of fibrosis was reduced after treatment. There was no significant difference in the therapeutic effect between subcutaneous injection or fractional laser-assisted administration. Both stem cells and conditioned medium can down-regulate SEI and factors expression levels in all groups. However, compared with the stem cells, the therapeutic effects of the conditioned medium were lower. CONCLUSIONS: The results confirmed that stem cells had an available treatment effect on hypertrophic scars of rabbit ears. In addition to the paracrine pathway, stem cells may have other ways to treat hypertrophic scars. Fractional laser-assisted administration may become a potential administration of stem cell clinical application in the future.
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Cicatriz Hipertrófica , Células Madre Mesenquimatosas , Animales , Cicatriz Hipertrófica/patología , Cicatriz Hipertrófica/terapia , Colágeno , Medios de Cultivo Condicionados , Femenino , Humanos , Rayos Láser , Conejos , Cordón Umbilical/metabolismo , Cordón Umbilical/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Ablative fractional carbon dioxide laser (CO2 -AFL) for small-area burn scar management shows encouraging outcomes. Few studies, however, focused on comprehensive outcomes following CO2 -AFL treatment for extensive burn scars. This study evaluated whether CO2 -AFL surgery improved the quality of life (QoL) for burn survivors with extensive hypertrophic scars. METHODS: A retrospective nested case-control study was initiated to analyze the efficacy of CO2 -AFL treatment for patients with large-area burn scars. Patients with extensive burn scars (≥30% total body surface area [TBSA]) were registered in our hospital from March 2016 to October 2018. Patients undergoing CO2 -AFL surgery were divided into CO2 -AFL group, and patients undergoing conventional surgery were matched in a 1:1 ratio as the conventional surgery group according to the burned area. The questionnaires were collected and followed up. The 36-Item Short Form Health Survey (SF-36) and Burns Specific Health Scale-Brief (BSHS-B) were the primary parameters. Secondary parameters included the Pittsburgh Sleep Quality Index (PSQI), University of North Carolina "4P" Scars Scale (UNC4P), Patient Scars Assessment Scale for Patient (POSAS-P), and Douleur Neuropathique 4 questions (DN4). RESULTS: 23 patients (55.96 ± 21.59% TBSA) were included in CO2 -AFL group and 23 patients (57.87 ± 18.21% TBSA) in conventional surgery group. Both the BSHS-B total score (CO2 -AFL vs. conventional surgery: 115.35 ± 29.24 vs. 85.43 ± 33.19, p = 0.002) and the SF-36 total score (CO2 -AFL vs. conventional surgery: 427.79 ± 118.27 vs. 265.65 ± 81.66, p < 0.001) for the CO2 -AFL group were higher than those for the conventional surgery group. Parameters for the CO2 -AFL group were lower than those for the conventional surgery group in all of the following comparisons: PSQI total score (CO2 -AFL vs. conventional surgery: 7.70 ± 3.74 vs. 12.26 ± 4.61, p = 0.001), POSAS-P total score (CO2 -AFL vs. conventional surgery: 26.48 ± 6.60 vs. 33.04 ± 4.56, p < 0.001), UNC4P total score (CO2 -AFL vs. conventional surgery: 5.57 ± 1.97 vs. 7.26 ± 1.81, p = 0.004), and DN4 score (CO2 -AFL vs. conventional surgery: 3 [2-5] vs. 5 [4-8], p = 0.004). CONCLUSIONS: Compared to conventional surgery, whole scar CO2 -AFL surgery dramatically improved physical and mental health as well as QoL for people with extensive burn scars. Additionally, CO2 -AFL enhanced the evaluation of scars including their appearance, pain, itching, and a host of other symptoms.
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Quemaduras , Cicatriz Hipertrófica , Láseres de Gas , Quemaduras/complicaciones , Quemaduras/cirugía , Dióxido de Carbono , Estudios de Casos y Controles , Cicatriz/etiología , Cicatriz/cirugía , Cicatriz Hipertrófica/etiología , Cicatriz Hipertrófica/cirugía , Humanos , Láseres de Gas/uso terapéutico , Calidad de Vida , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Láseres de Gas , Enfermedades Vaginales , Femenino , Humanos , Láseres de Gas/uso terapéutico , Posmenopausia , VaginaRESUMEN
BACKGROUND: Microskin autografts with conventional wrap and compression are used extensively in the treatment of skin and tissue defects. This comparative study aimed at investigation of the clinical application of negative pressure wound therapy (NPWT) in combination with microskin autografts for repair of acute and chronic wounds. METHODS: A prospective case-control study was performed from December 1, 2010-December 31, 2013 in Changhai Hospital, Shanghai. We compared a study group of patients received microskin autografting covered by NPWT with that of a control group of patients received microskin autografting covered by a conventional gauze. RESULTS: A total of 81 patients were in this study, 27 patients were allocated to the study group and 54 patients to the control group. The study group exhibited significant low infection rate and pain score during removal of inner layer at first dressing change after skin grafting compared with those of the control group (P < 0.05). The time interval between skin grafting and first postoperative change was longer in the study group than that in the control group (P < 0.01), the study group showed a significant shorter 95% wound healing time (P < 0.05), and survival rate of microskin autografts in the study group was higher than that in the control group (P < 0.05). CONCLUSIONS: NPWT is beneficial for wound closure after microskin autografts, which prolongs the interval between skin transplantation and first postoperative dressing change, reduces pain during removal of inner layer dressing, increases skin graft survival rate, and shortens wound healing time. Therefore, NPWT can be recommended for repair of acute and chronic wounds with microskin autografts.
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Terapia de Presión Negativa para Heridas , Trasplante de Piel , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplante Autólogo/métodosRESUMEN
BACKGROUND: Circulating microRNA (miRNA) are promising biomarkers for diagnosing and prognosticating numerous diseases. Reports have demonstrated controversial or even contradictory conclusions in studies on circulating microRNA. This study aimed to evaluate the potential bias of using different reference genes for analyzing circulating microRNAs in the same malignant digestive diseases. MATERIAL AND METHODS: We measured plasma concentrations of U6-snRNA, let-7a, miRNA-21, miRNA-106a, miRNA-155, miRNA-219, miRNA-221, and miRNA-16 in patients with hepatocellular carcinoma (HCC), gastric carcinoma (GC), hepatic cirrhosis, hepatitis B, and healthy volunteers using quantitative real-time polymerase chain reaction (qPCR). The GeNorm, Normfinder, BestKeeper, and Comparative ΔCq algorithms integrated in RefFinder were used to screen the most suitable reference genes from the candidates. The 4 commonly used statistical evaluation software packages provided different results regarding the stability of the candidate reference genes. RESULTS: RefFinder revealed miRNA-106a and miRNA-21 as the most stably expressed reference genes, with comprehensive stability values of 1.189 and 1.861, respectively. U6-snRNA was the most unstable nucleic acid in our data. When 5 normalization strategies were compared using U6-snRNA, serum volume, miRNA-106a, miRNA-21, or the mean value of miRNA-106a and miRNA-21, obvious expression bias was detected in almost all target microRNAs. Intriguingly, all these normalization strategies indicated that circulating miRNA-155 is greatly upregulated in patients with HCC and GC, but downregulated in benign hepatic disease. CONCLUSIONS: Single reference genes used without justification in plasma microRNAs produce significant analysis bias or even erroneous results. Circulating miRNA-155 may be a promising non-invasive biomarker for discriminating malignant digestive tumors from the corresponding benign diseases.
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Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , MicroARNs/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Estudios de Casos y Controles , Regulación Neoplásica de la Expresión Génica , Genes Relacionados con las Neoplasias , Humanos , MicroARNs/genética , Estándares de ReferenciaRESUMEN
BACKGROUND: Smad3 is a principal intracellular mediator of signaling for transforming growth factor ß, a cytokine involved in pleiotropic pathophysiological processes including inflammation and immunity. The function of Smad3 in regulating inducible nitric oxide synthase (iNOS) expression and septic shock has not been characterized. METHODS: Smad3(-/-) (referred hereafter as KO) and wild-type (WT) mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce the septic hypotension. Mortality, blood pressure, and plasma levels of nitrite were measured. The iNOS messenger RNA and protein levels in lung, kidney, and spleen were also analyzed. RESULTS: Mice lacking functional Smad3 respond to LPS with greater mortality than their WT littermates. The high mortality of KO mice is accompanied by enhanced hypotension after intraperitoneal injection of LPS. Both KO and WT mice displayed an increase in plasma nitrite during the experimental period; however, LPS administration caused more dramatic changes in KO mice than WT mice. Likewise, the iNOS messenger RNA and protein levels in lung, kidney, and spleen were more strongly increased in KO mice than in WT mice after LPS administration. CONCLUSIONS: Defects in the Smad3 gene may increase susceptibility to the development of septic hypotension because of enhanced iNOS production.
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Endotoxemia/metabolismo , Hipotensión/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Sepsis/metabolismo , Proteína smad3/genética , Animales , Presión Sanguínea/fisiología , Modelos Animales de Enfermedad , Endotoxemia/inducido químicamente , Endotoxemia/mortalidad , Femenino , Hipotensión/inducido químicamente , Hipotensión/mortalidad , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Noqueados , Óxido Nítrico/sangre , Óxido Nítrico Sintasa de Tipo II/genética , ARN Mensajero/metabolismo , Sepsis/inducido químicamente , Sepsis/mortalidad , Proteína smad3/deficienciaRESUMEN
Purpose: This study assessed sleep quality in patients with burn scars and investigated risk factors of sleep disorders to guide clinical therapy. From the strategy of predictive, preventive, and personalized medicine (PPPM/3PM), we proposed that risk assessment based on clinical indicators could prompt primary prediction, targeted prevention, and personalized interventions to improve the management of sleep disorders present in patients with burn scars. Methods: This retrospective study recruited patients with burn scars and healthy volunteers from the Shanghai Burn Treatment Center between 2017 and 2022. Relevant information and data, including demographic characteristics, scar evaluation, and sleep quality, were obtained through the hospital information system, classical scar scale, and self-report questionnaires. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and monitored using a cardiopulmonary-coupled electrocardiograph. Pain and pruritus were assessed using the visual analog scale (VAS). Scar appearance was assessed using the modified Vancouver scar scale (mVSS). Results: The sample was comprised of 128 hypertrophic scar (HS) patients, with 61.7% males, a mean age of 41.1 ± 11.6 years, and burn area of 46.2 ± 27.9% total body surface area (TBSA). Patients with PSQI ≥ 7 accounted for 76.6%, and the global PSQI score was 9.4 ± 4.1. Objective sleep data showed that initial enter deep sleep time, light sleep time, awakening time, light sleep efficiency, and sleep apnea index were higher but deep sleep time, sleep efficiency, and deep sleep efficiency were lower in HS patients than that in healthy controls. Preliminary univariate analysis showed that age, hyperplasia time of scar, narrow airway, microstomia, VAS for pain and pruritus, and mVSS total (comprised of pigmentation, vascularity, height and pliability) were associated with the PSQI score (p < 0.1). Multivariable linear regression showed narrow airway, VAS for pain and pruritus, and mVSS specifically height, were the risk factors for PSQI score (p < 0.1). Conclusions: This study model identified that narrow airway, pain, pruritus and scar appearance specifically height may provide excellent predictors for sleep disorders in HS patients. Our results provided a basis for the predictive diagnostics, targeted prevention, and individualized therapy of somnipathy predisposition and progression of HS patients in the setting of PPPM/3PM health care system, which contributed to a paradigm shift from reactive cure to advanced therapy.
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BACKGROUND: Splanchnic ischemia is common in critically ill patients, and it can result in injury not only of the intestine but also in distant organs, particularly in the lung. Local inflammatory changes play a pivotal role in the development of acute lung injury after intestinal ischemia, but the underlying molecular mechanisms are not fully understood. We sought to examine the role of Toll-like receptor 4 (TLR4) in the mouse model of intestinal ischemia-reperfusion (I/R)-induced lung injury and inflammation. MATERIALS AND METHODS: Adult male TLR4 mutant (C3H/HeJ) mice and TLR4 wild-type (WT) (C3H/HeOuJ) mice were subjected to 40 min of intestinal ischemia by clamping the superior mesenteric artery followed by 6 h of reperfusion. Lung histology was assessed and parameters of pulmonary microvascular permeability, inflammatory cytokine expression, and neutrophil infiltration were measured. Activation of mitogen-activated protein kinases (MAPKs) and the transcription factors nuclear factor κB (NF-κB) and activator protein-1 (AP-1) in the lungs were also detected. RESULTS: After intestinal I/R, lungs from TLR4 mutant mice demonstrated a significantly lower histological injury, a marked reduction of epithelial apoptosis associated with the decreased level of cleaved caspase-3 and the increased ratio of Bcl-xL to Bax proteins, and a large reduction in pulmonary vascular permeability and myeloperoxidase (MPO) activity in comparison with WT mice. TLR4 mutant mice also displayed marked decreases in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) expression. Following intestinal I/R, phosporylation of p38 MAPK and activation of NF-κB and AP-1 were significantly inhibited in lung tissue from TLR4 mutant mice compared with WT controls. CONCLUSIONS: These data suggest that TLR4 plays an important role in the pathogenesis of intestinal I/R-induced acute lung injury and inflammation and that p38 kinase and NF-κB may be involved in TLR4 signaling-mediated lung inflammatory processes during intestinal I/R.
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Lesión Pulmonar Aguda/metabolismo , Intestinos/irrigación sanguínea , Daño por Reperfusión/complicaciones , Receptor Toll-Like 4/metabolismo , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Animales , Apoptosis , Permeabilidad Capilar , Citocinas/metabolismo , Activación Enzimática , Células Epiteliales/patología , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C3H , Subunidad p50 de NF-kappa B/metabolismo , Infiltración Neutrófila , Daño por Reperfusión/patología , Factor de Transcripción AP-1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: The liver is one of the organs most frequently affected by trauma and hemorrhagic shock; the exact role of p38 mitogen-activated protein kinase (MAPK) activation in response to hepatic hemorrhagic shock/resuscitation (HS/R) remains unclear. MATERIALS AND METHODS: C57Bl/6 mice were divided into four groups: sham-operated group, SB-only group, control group, and SB + HS/R group. Hepatocellular injury (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and tumor necrosis factor (TNF-α) and interleukin (IL-1ß) messenger ribonucleic acid (mRNA) expression in the liver were assessed 6 h after resuscitation, p38 MAPK activation in the liver was assessed at 30 min after resuscitation. RESULTS: p38 MAPK activation was higher in the control group than other groups 30 min after resuscitation. p38 MAPK activation level in the SB + HS/R group did not change significantly compared with that of sham and SB-only groups, but was significantly lower than that in the control group. The TNF-α mRNA expression in the control group was significantly higher than that in the sham group. The TNF-α mRNA levels after HS/R in the SB + HS/R group were significantly lower than those in the control group and were roughly the same as those in the sham and SB-only groups. IL-1ß mRNA expression showed similar changes in the four groups. Serum ALT and AST levels in the control group were significantly higher than those in the sham group. The increase in serum ALT and AST levels after HS/R in the SB + HS/R group was significantly less pronounced than that in the control group and markedly higher than that in the sham group. CONCLUSIONS: p38 MAPK was phosphorylated during the HS/R process. Inhibiting the activation of p38 MAPK may attenuate HS/R injury to the liver.
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Imidazoles/farmacología , Hígado/fisiopatología , Pirimidinas/farmacología , Resucitación , Choque Hemorrágico/fisiopatología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Interleucina-1beta/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/genética , Proteínas Quinasas p38 Activadas por Mitógenos/fisiologíaRESUMEN
Objective: To introduce our single-center experience of infant vascular tumor associated with Kasabach-Merritt phenomenon (KMP) which received combined medicine treatment with intralesional laser photocoagulation (ILP) and sclerotherapy. Methods: A retrospective study was conducted using medical records of all children with a diagnosis of kaposiform hemangioendothelioma (KHE) or tufted angioma (TA) associated with KMP treated with medicine, intralesional laser photocoagulation (ILP), and sclerotherapy between February 2017 and November 2020. Clinical features, response to comprehensive therapy, and outcomes were recorded. Results: A total of 23 patients including nine females (39%) and 14 males (61%) were identified. The mean age was 6.9 months (age range, 11 days-2 years) at the time of treatment. Nine children (39%) demonstrated sensitivity to single corticosteroid therapy; 14 children (61%) received combined therapy with intravenous Vincristine (VCR) and corticosteroid therapy. All children had at least two ILP and sclerotherapy performed, with a mean of 3.5 procedures (range: 2-6). Of these 14 children, only one experienced a relapse of thrombocytopenia and the remaining 13 children had no clinical symptoms recurred. Conclusion: The combined therapy modalities could induce a more rapid tumor response and resolution of KMP and decrease the rebound rates. This research presents a novel and safe multi-modality treatment for infant vascular tumors associated with KMP.
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BACKGROUND: Propranolol is used clinically to treat infantile hemangioma (IH), although the exact mechanism that underlies its effectiveness is not fully understood. The Jagged1/Notch signaling pathway is downstream of the ß2-adrenergic receptor (ß2-AR). Propranolol is a non-selective ß2-AR blocker that was shown to inhibit demethylation adrenaline-induced Jagged1 expression. A previous study has shown that propranolol dose-dependently inhibits the growth of IH. However, the effects of propranolol on stemness of IH are not known and are thus addressed in the current study. METHODS: We analyzed the expression of Jagged1 and Notch3 in IH specimens, using genetic tools to alter Notch signaling. The transduced IH cells were treated with different doses of propranolol, and the effects on IH cell proliferation, migration, and potential for tumor sphere formation were investigated. The effects of altered Notch signaling on tumor formation in vivo were also assessed. RESULTS: Notch3 and Jagged1 were significantly upregulated in IH. Augmented Notch signaling in IH cells increased cell proliferation, migration, the potential for tumor sphere formation and in vivo tumor formation. On the other hand, reduced Notch signaling in IH cells decreased cell proliferation, migration, the potential for tumor sphere formation and in vivo tumor formation. CONCLUSIONS: Jagged1/Notch signaling regulated the stemness of IH, and propranolol inhibited it through suppression of Notch signaling.
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BACKGROUND: Poor sleep quality is associated with a decrease in quality of life in patients with major burn scars, combined with pruritus and pain. Few interventions have been reported to improve the sleep quality of patients with scars. In the current prospective cohort study, we investigated the efficacy of CO2-ablative fractional laser (AFL) surgery vs conventional surgery in post-burn patients with hypertrophic scars with sleep quality as the primary study outcome. METHODS: In total 68 consecutive patients undergoing scar surgical treatment were recruited, including a CO2-AFL surgery cohort (n = 35) and a conventional surgery cohort (n = 33). A subgroup from the AFL cohort was selected. Sleep quality, pain and pruritus were evaluated. Multiple linear regression analyses were performed to reveal the effect of CO2-AFL surgery. RESULTS: The CO2-AFL surgery cohort had significantly lower Pittsburgh sleep quality index (PSQI) global scores than the conventional surgery cohort after the last surgical treatment. In the subgroup of patients receiving hardware sleep monitoring, CO2-AFL markedly increased deep sleep time, deep sleep efficiency and reduced initial sleep latency. Compared to the conventional surgery cohort, the CO2-AFL cohort presented significantly lower pain and pruritus scores. Correlation analysis showed pain and pruritus were significantly associated with PSQI scores, and there were also significant correlations between pain and pruritus scores. Multiple linear regression analysis showed that surgery method was negatively linearly correlated with visual analog scale (VAS) pain score, brief pain inventory (BPI) total, VAS pruritus score, 5-D itch scale total, four-item itch questionnaire (FIIQ) total and PSQI total. CONCLUSIONS: CO2-AFL surgery significantly improved sleep quality and reduced pain and pruritus of hypertrophic scar patients. The alleviation of sleep disorder was associated with improvement of deep sleep quality including deep sleep time and deep sleep deficiency. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR200035268) approved retrospectively registration on 5 May 2020.
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The generation of animals lacking Smad proteins has made it possible to explore the contribution of the TGF-beta-Smad signaling to immune activity in vivo. And there have been related issues actively pursued by many laboratories. Here we report that, in contrast to the markedly enhanced inflammatory response, Smad3 gene knockout (Smad3(ex8/ex8)) mice paradoxically show suppressed hepatic acute phase response to the injury induced by lipopolysaccharide (LPS) compared with wild-type mice, characterized by significantly weaker reaction of several typical acute phase proteins in mRNA level. The increase of positive acute phase proteins, e.g. alpha1-acid glycoprotein (alpha1-AGP), haptoglobin (HP) and C-reaction protein (CRP), and the decrease of negative acute phase proteins, including albumin (ALB) and transferrin (TRF), were both repressed according to the expression in liver estimated by optimized RT-PCR. Smad3(ex8/ex8) mice also exhibited lower survival rate as stimulated by LPS, which was probably on account of the suppressed acute phase response. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of acute phase response in the liver.
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Reacción de Fase Aguda/complicaciones , Reacción de Fase Aguda/inmunología , Hepatopatías/complicaciones , Hepatopatías/inmunología , Proteína smad3/deficiencia , Enfermedad Aguda , Proteínas de Fase Aguda/genética , Proteínas de Fase Aguda/metabolismo , Animales , Regulación de la Expresión Génica , Lipopolisacáridos , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Noqueados , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteína smad3/metabolismo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Infantile hemangioma (IH) is characterized by proliferation and regression. METHODS: Based on the GSE127487 dataset, the differentially expressed genes (DEGs) between 6, 12, or 24 months and normal samples were screened, respectively. STEM software was used to screen the continued up-regulated or down-regulated in common genes. The modules were assessed by weighted gene co-expression network analysis (WGCNA). The enrichment analysis was performed to identified the biological function of important module genes. The area under curve (AUC) value and protein-protein interaction (PPI) network were used to identify hub genes. The differential expression of hub genes in IH and normal tissues was detected by qPCR. RESULTS: There were 5,785, 4,712, and 2,149 DEGs between 6, 12, and 24 months and normal tissues. We found 1,218 DEGs were up-regulated or down-regulated expression simultaneously in common genes. They were identified as 10 co-expression modules. Module 3 and module 4 were positively or negatively correlated with the development of IH, respectively. These two module genes were significantly involved in immunity, cell cycle arrest and mTOR signaling pathway. The two module genes with AUC greater than 0.8 at different stages of IH were put into PPI network, and five genes with the highest degree were identified as hub genes. The differential expression of these genes was also verified by qRTPCR. CONCLUSION: Five hub genes may distinguish for proliferative and regressive IH lesions. The WGCNA and PPI network analyses may help to clarify the molecular mechanism of IH at different stages.
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Angiotensin II is critically involved in skin wound healing, but the underlying mechanism remains unclear. This study investigated the effect of angiotensin II on type I collagen gene activation in human dermal fibroblasts and the possible mechanism involved. Angiotensin II stimulated the mRNA and protein expression of type I collagen and TGF-beta1. Effects were abolished by the angiotensin AT1 receptor antagonist ZD7155 but not by the AT2 blocker PD123319. Blockade of TGF-beta1 markedly inhibited angiotensin II-induced type I collagen gene expression. Activator protein-1 (AP-1) decoy ODNs transfection suppressed angiotensin II-induced TGF-beta1 expression, and also, diminished type I collagen expression. These data indicated that angiotensin II induces collagen gene activation in human dermal fibroblasts through an AT1-mediated AP-1/TGF-beta1 signaling pathway.
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Angiotensina II/fisiología , Colágeno Tipo I/genética , Regulación de la Expresión Génica , Piel/metabolismo , Factor de Transcripción AP-1/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Angiotensina II/farmacología , Células Cultivadas , Cadena alfa 1 del Colágeno Tipo I , Fibroblastos/metabolismo , Expresión Génica , Humanos , Piel/citología , Piel/efectos de los fármacos , Factor de Transcripción AP-1/genética , Factor de Crecimiento Transformador beta1/genética , Cicatrización de Heridas/genéticaRESUMEN
QUESTIONS UNDER STUDY: Composite skin containing autologous keratinocytes is a new approach to solving the problem of extensive skin defects. We propose a new strategy to construct the composite skin by mixing autologous and non-autologous keratinocytes, so that the time and the cost for constructing the composite skin could be reduced. METHODS: Human keratinocytes were mixed with Balb/c mouse keratinocytes at appropriate proportions, seeded onto the surface of porcine acellular dermal matrix (ADM) and cultured in vitro to reconstruct composite skin, which was then transplanted to a Balb/c mouse skin defect. Quality of the wound healing as well as the homing of the non-autologous keratinocytes were observed. RESULTS: Wounds healed well with the transplanted composite skin containing two different keratinocytes. The take rate of the grafts ranged from 78.3% to 81.5%. Histological observation showed that both epidermal and dermal structures of the regenerated skin were perfect and that the basal membrane was obvious with the laminin and collagen IV positively stained. In the early grafting phase, there are many non-autologous keratinocytes in the new epidermis. With the lapse of time, non-autologous keratinocytes decreased gradually and were eventually replaced by the autologous keratinocytes. CONCLUSION: A composite skin was reconstructed by mixing two different keratinocytes at a certain proportion and then co-culturing them with dermal scaffold, which can be used for repairing full thickness skin defect wounds. This new strategy could save the source of autologous skin effectively and shorten in vitro culture time of composite skin.
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Queratinocitos , Piel Artificial , Cicatrización de Heridas , Animales , Técnicas de Cocultivo , Estudios de Factibilidad , Supervivencia de Injerto , Humanos , Ratones , Ratones Endogámicos BALB C , Andamios del Tejido , Cicatrización de Heridas/fisiologíaRESUMEN
Following injury, Asian skin has a tendency toward hyperpigmentation and scar formation than Caucasians. A standardized algorithm tailored to Asian patients, especially Chinese patients, is in great demand. Twelve independent, self-selected academic and military physicians from the department of burn/trauma, plastic surgery and dermatology with extensive experience in treating scars were assembled on January 17, 2015, establishing the consensus panel. This consensus was then appraised, drafted, reviewed, and finalized during the following 3 years, aiming to standardize and improve scar prevention and treatment in China. Hopefully, it may also provide some advices and references for the management of scarring in Asian patients.
Asunto(s)
Barotrauma/diagnóstico por imagen , Barotrauma/etiología , Radiografía Torácica , Lesión por Inhalación de Humo/complicaciones , Lesión por Inhalación de Humo/diagnóstico por imagen , Barotrauma/terapia , Broncoscopía , Femenino , Humanos , Lesión por Inhalación de Humo/terapia , Adulto JovenRESUMEN
The purpose of this article is to improve the treatment of severe extensive burns (SEB) patients by summarizing treatment experience in recent 12 years in China and analyzing the follow-up quality of life (QOL) in these patients. Clinical data and rescue measures of 103 SEB patients (≥70% TBSA) admitted in a burn center in Shanghai between 1997 and 2009 were reviewed, and QOL and hand function of those who survived more than 2 years were assessed by Brief Version of Burn Specific Health scale-B and Michigan Hand Outcome Questionnaire. Of these, 76.7% were caused by flames and 15.5% caused by scald. The median burn area was 87.5% (interquartile range, 77.0-95.0%) TBSA, of which third-degree burns accounted for 56.5% (interquartile range, 25.8-80.0%) TBSA; 71.8% were complicated by inhalation injury. The occurrence of in-hospital complications was 75.7%, with the respiratory system complications predominating (49.5%). The fatality rate was 28.2%, mainly due to sepsis and multiple organ dysfunction syndrome. Work, body image, and heat sensitivity got the lowest Brief Version of Burn Specific Health scale-B scores in all nine domains, and Michigan Hand Outcome Questionnaire scores were also relatively poor. Flame burns remain to be the main cause of SEB in China in recent 12 years. Treatment is still challenged because of the depth and extensive burn area and high occurrence of multiple system complications. How to ameliorate QOL of SEB patients, intensify the functional rehabilitation, and improve their physical appearance in particular remain to be a crux.