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OBJECTIVE: Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM). BACKGROUND: DM and end-stage liver diseases are significant health concern worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount. METHODS: We utilized the islet transplantation combined ischemia-free liver transplantation (ITIFLT) technique to treat a patient with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM). The liver was procured and preserved using the ischemia-free liver transplantation (IFLT) technique, and during normothermic machine perfusion (NMP), isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply. RESULTS: The patient received both liver and islet graft from the same donor. The patient achieved insulin-independence by post-transplant day (PTD) 9, and both liver and islet function remained robust. The patient was discharged on PTD 18 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation. CONCLUSIONS: This landmark case marks the inaugural application of ITIFLT in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.
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Wound healing is a complex biological process involving multiple cell types with their critical functions. The diabetic wounds show delayed wound healing, while the anagen wounds display accelerated wound closure. However, the mechanisms underlying the effect of cellular heterogeneity on wound healing are still unclear. CD34+ cells exhibit high heterogeneity in wound skins and improve wound healing. Herein, we investigated the phenotypic and functional heterogeneity of CD34+ cells in normal, anagen, and diabetic wounds. We obtained CD34 lineage tracing mice, constructed distinct wound models, collected CD34+ cells from wound edges, and performed single-cell RNA sequencing. We identified 10 cell clusters and 6 cell types of CD34+ cells, including endothelial cells, fibroblasts, keratinocytes, neutrophils, macrophages, and T cells. 5 subclusters were defined as fibroblasts. The CD34+ fibroblasts C2 highly expressed papillary fibroblastic markers took up the largest proportion in anagen wounds and were associated with inflammation and extracellular matrix. Increased CD34+ endothelial cells, fibroblasts C4, and neutrophils as well as decreased fibroblasts C1 were discovered in diabetic wounds. We also filtered out differentially expressed genes (DEGs) of each cell cluster in anagen wounds and diabetic wounds. Functional enrichment analysis was performed on these DEGs to figure out the enriched pathways and items for each cell cluster. Pseudotime analysis of CD34+ fibroblasts was next carried out indicating fibroblast C4 mainly with low differentiation. Our results have important implications for understanding CD34+ cell type-specific roles in anagen and diabetic wounds, provide the possible mechanisms of wound healing from a new perspective, and uncover potential therapeutic approaches to treating wounds.
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Diabetes Mellitus , Células Endoteliais , Camundongos , Animais , Cicatrização , Queratinócitos , Análise de Célula Única , FibroblastosRESUMO
BACKGROUND: Diacylglycerol (DAG)-enriched oil has been attracting attention because of its nutritional benefits and biological functions, although the composition of its various free fatty acids (FFAs) and an unclear relationship between substrate and yield make it difficult to be identified and qualified with respect to its production. In the present study, linoleic acid-enriched diacylglycerol (LA-DAG) was synthesized and enriched from Camellia oil by the esterification process using the combi-lipase Lipozyme TL IM/RM IM system. RESULTS: The relationship between FFA composition and DAG species productivity was revealed. The results showed that heterogeneous FFA with a major constituent (more than 50%) exhibited higher DAG productivity and inhibited triacylglycerol productivity compared to homogeneous constituents. Joint characterization by high-performance liquid chromatography-evaporative light scattering detection, gas chromatography-mass spectrometry and ultra-performance liquid chromatography-heated electrospray ionization-tandem mass spectrometry identified that DAG components contained dilinoleic acid acyl glyceride, linoleyl-oleyl glyceride and dioleic acid acyl glyceride in esterification products. Under the optimum conditions, 60.4% 1,3-DAG and 61.3% LA-DAG in the crude product at 1 h reaction were obtained, and further purified to 81.7% LA-DAG and 94.7% DAG via silica column chromatography. CONCLUSION: The present study provides a guideline for the identification of DAG species, as well as a structure-guided preparation method of DAG-enriched oils via the cost-effective combi-lipase. © 2022 Society of Chemical Industry.
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Camellia , Diglicerídeos , Diglicerídeos/química , Ácido Linoleico , Lipase/química , Óleos de Plantas/química , Glicerídeos , Ácidos Graxos não EsterificadosRESUMO
BACKGROUND: It is no consensus on the best management for patients with large hepatic hemangiomas. This study was designed to evaluate the efficacy and safety of percutaneous sclerotherapy compared to surgical resection for large hepatic hemangiomas. METHODS: A total of 89 patients with large hepatic hemangiomas from single center underwent either percutaneous sclerotherapy (n = 14) or surgical resection (n = 75) as first-line treatment was retrospectively studied, followed up for 9-24 months using ultrasound. Terms of intraoperative and postoperative information, postoperative complications, and treatment effectiveness were compared between the two groups. RESULTS: Percutaneous sclerotherapy had shorter operative time (p < 0.001), less blood loss, lower rate of prophylactic abdominal drainage (97.3% vs. 0%, p < 0.001), fewer minor complications (48.0% vs. 7.1%, p < 0.01), shorter hospital stay (p < 0.001), lower hospital cost (p < 0.001), higher Alb level (p < 0.001) and lower postoperative clinical index including ALT, AST and WBC (p < 0.001 for both) than did surgical resection. The major complications were demonstrated no significant difference between the two groups. In addition, the mean maximum cross-sectional areas of hemangioma dropped from 5044.1 ± 2058.0 mm2 to 1924.6 ± 1989.5 mm2 (65.2% reduction) during 9-24 months follow-up (p < 0.001) in the percutaneous sclerotherapy group, while all patients in the surgical resection group achieved complete response. CONCLUSION: Percutaneous sclerotherapy is the preferred method for the treatment of large hepatic hemangioma over surgical resection when compared with the items of postoperative recovery, blood loss, complications, hospital stays, and lower hospital costs. The reduction of the maximum cross-sectional area of hepatic hemangioma in the percutaneous sclerotherapy group is satisfactory.
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Hemangioma , Neoplasias Hepáticas , Hemangioma/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Escleroterapia , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
Local transplantation of stem cells has therapeutic effects on skin damage but cannot provide satisfactory wound healing. Studies on the mechanisms underlying the therapeutic effects of stem cells on skin wound healing will be needed. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. We first isolated EpiSCs from mouse skin tissues and established stable EpiSCs with overexpression of Caveolin-1 using a lentiviral construct. We then evaluated the epidermal growth factor (EGF)-induced cell proliferation ability using cell counting Kit-8 (CCK-8) assay and assessed EpiSC pluripotency by examining Nanog mRNA levels in EpiSCs. Furthermore, we treated mice with skin burn injury using EpiSCs with overexpression of Caveolin-1. Histological examinations were conducted to evaluate re-epithelialization, wound scores, cell proliferation and capillary density in wounds. We found that overexpression of Caveolin-1 in EpiSCs promoted EGF-induced cell proliferation ability and increased wound closure in a mouse model of skin burn injury. Histological evaluation demonstrated that overexpression of Caveolin-1 in EpiSCs promoted re-epithelialization in wounds, enhanced cellularity, and increased vasculature, as well as increased wound scores. Taken together, our results suggested that Caveolin-1 expression in the EpiSCs play a critical role in the regulation of EpiSC proliferation ability and alteration of EpiSC proliferation ability may be an effective approach in promoting EpiSC-based therapy in skin wound healing.
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Caveolina 1/fisiologia , Cicatrização/fisiologia , Animais , Queimaduras/genética , Queimaduras/patologia , Queimaduras/fisiopatologia , Caveolina 1/antagonistas & inibidores , Caveolina 1/genética , Proliferação de Células/genética , Proliferação de Células/fisiologia , Células Epidérmicas/patologia , Células Epidérmicas/fisiologia , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica/genética , Ratos , Reepitelização/genética , Reepitelização/fisiologia , Células-Tronco/patologia , Células-Tronco/fisiologia , Regulação para Cima , Cicatrização/genéticaRESUMO
BACKGROUND AIMS: Cutaneous wound management is a major health problem and imposes a huge economic burden worldwide. Previous studies have demonstrated that wound healing is a highly coordinated process including epithelialization, angiogenesis, remodeling and scarring. This progression requires self-renewal, preservation and repair properties of stem cells. However, our understanding of the detailed internal regulatory mechanism following injury and the means to accelerate wound healing are limited. METHODS: Our previous research revealed that porcine acellular dermal matrix (ADM) effectively promotes wound healing and scar formation through epidermal stem cells (ESCs), and this process is relevant to the alteration of internal miRNA levels. In this study, we investigated the regulatory function of porcine ADM treatment on miRNAs in ESCs. RESULTS: We report that the treatment of porcine ADM reduced the levels of miR-124-3p.1 and miR-139-5p in wounds. MiR-124-3p.1 and miR-139-5p inhibited the expression of JAG1 and Notch1, respectively, by directly targeting miRNAs in ESCs. CONCLUSIONS: This work demonstrates that porcine ADM induced down-regulation of miR-124-3p.1/139-5p in wounds and up-regulation of JAG1/Notch1 in ESCs, thus enhancing cutaneous wound healing.
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Derme Acelular/metabolismo , MicroRNAs/metabolismo , Cicatrização/genética , Animais , Antagomirs/metabolismo , Sequência de Bases , Proliferação de Células/genética , Sobrevivência Celular/genética , Cicatriz/patologia , Colágeno/metabolismo , Modelos Animais de Doenças , Proteína Jagged-1 , Camundongos , MicroRNAs/genética , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Receptor Notch1/metabolismo , Suínos , Regulação para CimaRESUMO
We aimed to explore the effect of curcumin on epidermal stem cells (ESCs) in regulating wound healing and the underlying molecular mechanism. We treated mouse ESCs isolated from skin tissues with curcumin, and then assessed the proliferation ability of cells induced by epidermal growth factor using cell counting kit-8 assay. The pluripotency of ESCs was evaluated as well through examination of Nanog expression in ESCs. Further, mice with skin burns were treated with ESCs with or without curcumin pretreatments. Histological evaluations were then preformed to determine wound scores, cell proliferation, reepithelialization, and capillary density in wounds. Curcumin treatment promoted the proliferative ability of ESCs and conditioned medium from curcumin-treated ESCs enhanced human umbilical vein endothelial cell (HUVEC) tube formation. We also found curcumin treatment elevated caveolin-1 expression in ESCs, which was required for the beneficial effect of curcumin on ESC proliferation and HUVEC tube formation. Next, using a mouse model of burn wound healing, curcumin-treated ESCs exhibited enhanced wound closure, which also required caveolin-1 expression. Our current study demonstrates the beneficial effect of curcumin on burn wound healing in mice, which is mediated by upregulating caveolin-1 in ESCs, and supports the potential therapeutic role of curcumin in ESC-based treatment against skin wound healing.
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Queimaduras/tratamento farmacológico , Caveolina 1/genética , Curcumina/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Células Epidérmicas/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pele/patologia , Células-Tronco/efeitos dos fármacos , Regulação para CimaRESUMO
Epidermal growth factor (EGF)-like family members mediate a wide range of biological activities including cell proliferation and migration. Increasing evidence indicated that EGF plays an important role in the process of wound healing by stimulating fibroblast motility. The aim of this study was to see whether EGF-like domain 7 (EGFL7)-overexpressing epidermal stem cells (EGFL7-ESCs) would promote fibroblast proliferation and migration. We found that mRNA and protein levels of EGFL7 expression were significantly increased in EGFL7-ESCs. The protein expression of EGFL7 was significantly elevated in conditioned media (CM) of EGFL7-ESCs compared to ESCs CM or vector-ESCs CM. The cell count and cell viability of EGFL7-ESCs CM-treated fibroblasts were also significantly increased compared to control. In addition, EGFL7-ESCs CM-treated fibroblasts showed elevated migration compared with control. Moreover, the expressions of ß1-integrin, ß-tubulin, ß-actin, and Vimentin were increased, while that of E-cadherin was decreased in EGFL7-ESCs CM-treated fibroblasts. These results indicate that EGFL7-ESCs contribute towards promoting fibroblast migration through enhancing cell adhesion, strengthening cytoskeleton, and reducing intercellular aggregation. These findings suggest that the stimulating effect of EGFL7-ESCs on fibroblast proliferation and migration may provide a useful strategy for wound healing.
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Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Citoesqueleto/metabolismo , Fatores de Crescimento Endotelial/biossíntese , Epiderme/metabolismo , Fibroblastos/metabolismo , Células-Tronco/metabolismo , Caderinas/metabolismo , Proteínas de Ligação ao Cálcio , Adesão Celular/fisiologia , Linhagem Celular , Família de Proteínas EGF , Células Epidérmicas , Fibroblastos/citologia , Humanos , Células-Tronco/citologia , Cicatrização/fisiologiaRESUMO
Objective: To investigate the effectiveness of the reverse traction device in the preoperative treatment of high-energy tibial plateau fractures. Methods: A retrospective study was conducted to analyze the clinical data of 33 patients with high-energy tibial plateau fractures who met the selection criteria between December 2020 and December 2023. All patients were treated by open reduction and internal fixation. According to the preoperative traction method, they were divided into the observation group (16 cases, treated with a reverse traction device on the day of admission) and the control group (17 cases, treated with heel traction on the day of admission). There was no significant difference in baseline data such as gender, age, body mass index, affected side, cause of injury, fracture Schatzker classification between the two groups ( P>0.05). Preoperative waiting time, preoperative related complications (nail channel loosening, nail channel oozing, nail channel infection, soft tissue necrosis, soft tissue infection, deep vein thrombosis of the lower extremity, etc.), operation time, and total hospitalization time were recorded and compared between the two groups. On the 4th day after traction, visual analogue scale (VAS) score was used to evaluate the pain relief of the patients, the swelling value of the affected limb was measured, and the Immobilization Comfort Questionnaire (ICQ) score was used to evaluate the perioperative hospital comfort of the patients. Results: Both groups of patients completed the operation successfully, and the operation time, total hospitalization time, and preoperative waiting time of the observation group were significantly less than those of the control group ( P<0.05). There was no preoperative related complications in the observation group; in the control group, 3 patients had nail channel loosening and oozing, and 2 cases had the deep vein thrombosis of the lower extremity; the difference in the incidence of complication between the two groups was significant ( P<0.05). On the 4th day after traction, the ICQ score, VAS score, and limb swelling value of the observation group were significantly better than those of the control group ( P<0.05). X-ray films showed that the tibial plateau fracture separation and lower limb alignment recovered after calcaneal traction in the control group, but not as obvious as in the observation group. The fracture gap in the observation group significantly reduced, the tibial plateau alignment was good, and the lateral angulation deformity was corrected. Conclusion: The use of reverse traction treatment in patients with high-energy tibial plateau fractures on admission can accelerate the swelling around the soft tissues to subside, reduce patients' pain, shorten the preoperative waiting time, improve the patients' preoperative quality of life, and contribute to the shortening of the operation time, with a good effectiveness.
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Fixação Interna de Fraturas , Fraturas da Tíbia , Tração , Humanos , Tração/métodos , Fraturas da Tíbia/cirurgia , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Feminino , Masculino , Placas Ósseas , Resultado do Tratamento , Duração da Cirurgia , Complicações Pós-Operatórias , Fraturas do Planalto TibialRESUMO
RATIONALE AND OBJECTIVES: We aimed to analyze the safety, feasibility, and efficacy of human islet transplantation (IT) using ultrasound (US) throughout the entire procedure. MATERIALS AND METHODS: A total of 22 recipients (18 males; mean age 42.6 ± 17.5years) with 35 procedures were retrospective included. Under US guidance, percutaneous transhepatic portal catheterization was successfully performed through a right-sided transhepatic approach, and islets were infused into the main portal vein. Color Doppler and contrast-enhanced ultrasound were used to guide the procedure and monitor the complications. After infusion of the islet mass, the access track was embolized by embolic material. If hemorrhage persisted, US-guided radiofrequency ablation (RFA) was performed to stop bleeding. Factors that could affect the complication were analyzed. After transplantation, primary graft function was evaluated with a ß-score 1month after the last islet infusion. RESULTS: The technical success rates were 100% with a single puncture attempt. Six (17.1%) abdominal bleeding episodes were immediately stopped by US-guided RFA. No portal vein thrombosis were encountered. Dialysis (OR (Odd Ratio): 32.0; 95% CI: 1.561-656.054; and P = .025) was identified as a significant factor associated with bleeding. Primary graft function was optimal in eight patients (36.4%), suboptimal in 13 patients (59.1%), and poor in one patient (4.5%). CONCLUSION: In conclusion, whole-procedure US-guided IT is a safe, feasible, and effective method for diabetes. Complications are either self-limiting or manageable with noninvasive treatment.
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Transplante das Ilhotas Pancreáticas , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Transplante das Ilhotas Pancreáticas/métodos , Estudos Retrospectivos , Estudos de Viabilidade , Ultrassonografia de IntervençãoRESUMO
Skin wound healing involves Notch/Jagged1 signaling. However, little is known how Jag1 expression level in epidermal stem cells (ESCs) contributes to wound healing and scar formation. We applied multiple cellular and molecular techniques to examine how Jag1 expression in ESCs modulates ESCs differentiation to myofibroblasts (MFB) in vitro, interpret how Jag1 expression in ESCs is involved in wound healing and scar formation in mice, and evaluate the effects of porcine acellular dermal matrix (ADM) treatment on wound healing and scar formation. We found that Jag1, Notch1 and Hes1 expression was up-regulated in the wound tissue during the period of wound healing. Furthermore, Jag1 expression level in the ESCs was positively associated with the level of differentiation to MFB. ESC-specific knockout of Jag1 delayed wound healing and promoted scar formation in vivo. In addition, we reported that porcine ADM treatment after skin incision could accelerate wound closure and reduce scar formation in vivo. This effect was associated with decreased expression of MFB markers, including α-SMA Col-1 and Col-III in wound tissues. Finally, we confirmed that porcine ADM treatment could increase Jag1, Notch1 and Hesl expression in wound tissues. Taken together, our results suggested that ESC-specific Jag1 expression levels are critical for wound healing and scar formation, and porcine ADM treatment would be beneficial in promoting wound healing and preventing scar formation by enhancing Notch/Jagged1 signaling pathway in ESCs.
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Derme Acelular/metabolismo , Cicatriz/patologia , Células Epidérmicas/patologia , Proteína Jagged-1/metabolismo , Células-Tronco/metabolismo , Cicatrização , Animais , Diferenciação Celular , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Células-Tronco Embrionárias Murinas/metabolismo , Miofibroblastos/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , SuínosRESUMO
OBJECTIVE: To investigate the influence of xenogenic (porcine) acellular dermal matrix on the systematic inflammatory reaction syndrome (SIRS), and the reaction of burn patients to tissue damage upon application to second-degree burn wounds. METHOD: Seventy-two cases of patients with acute second-degree burns were enrolled in the study. According to the total burn surface area (TBSA) and the treatment methods, we randomly divided the patients into four groups. Group A (treatment group): patients with less than 30% TBSA covered with xenogenic acellular dermal matrix. Group B (control group): patients with less than 30% TBSA covered with betadine ointment gauzes. Group C (treatment group): patients with more than 30% TBSA covered with porcine acellular dermal matrix. Group D (control group): patients with more than 30% TBSA covered with betadine ointment gauzes. Serum level of C-reactive protein (CRP) was measured by single radial immunodiffusion method on 1, 4, 7 and 14 days postburn. RESULTS: The serum level of CRP in group A was significantly less than that of in group B (P<0.05) on days 4, 7 and 14. The serum level of CRP in group C increased slowly, descended quickly and was significantly less than that of in group D on days 4, 7 and 14. CONCLUSION: The application of xenogenic (porcine) acellular dermal matrix on second-degree burn wound can decrease serum level of CRP of the patients, which may play an important role in reducing SIRS and sepsis incidence.
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Curativos Biológicos , Queimaduras/terapia , Derme/transplante , Síndrome de Resposta Inflamatória Sistêmica/prevenção & controle , Adolescente , Adulto , Animais , Queimaduras/sangue , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade , Pele Artificial , Suínos , Síndrome de Resposta Inflamatória Sistêmica/sangue , Transplante HeterólogoRESUMO
OBJECTIVE: To explore the effect of one dressing of porcine acellular dermal matrix on deep partial thickness burns. METHODS: From January 1997 to January 2004, sixty-seven cases of deep partial thickness total burned surface area (TBSA) from 50% to 90% burn wound were treated by a single dressing of porcine acellular dermal matrix (the porcine acellular dermal matrix group). Ten cases of deep partial thickness burned patients with the same TBSA treated by exposure method served as the exposure method group. The healing time of the wound was observed. The patients were followed up for 3 months to 2 years, and the scar proliferation was observed. RESULTS: The deep partial-thickness wound would be healed without dressing change in the porcine acellular dermal matrix group, and the average healing time was (12.2 +/- 2.6) days. The average healing time of the exposure method group was (27.4 +/- 3.5) days. Follow up of the patients within 3 months to 2 years showed that scar proliferation in the porcine acellular dermal matrix group was much less than that in the exposure method group, even no scar proliferation was observed in some patients. CONCLUSION: Without tangential excision, autografting and dressing change, a single dressing of porcine acellular dermal matrix on deep partial thickness burn wound could shorten the healing time and inhibit scar proliferation.
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Curativos Biológicos , Queimaduras/terapia , Animais , Queimaduras/patologia , Cicatriz/prevenção & controle , Feminino , Seguimentos , Humanos , Masculino , Suínos , Resultado do Tratamento , CicatrizaçãoRESUMO
Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro Importantly, Jag1 overexpression improves diabetic wound healing in vivo These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound.
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Diabetes Mellitus Experimental/genética , Epiderme/metabolismo , Proteína Jagged-1/genética , Receptor Notch1/genética , Células-Tronco/metabolismo , Cicatrização/genética , Animais , Movimento Celular , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Epiderme/lesões , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Proteína Jagged-1/antagonistas & inibidores , Proteína Jagged-1/metabolismo , Lentivirus/genética , Lentivirus/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Estreptozocina , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismoRESUMO
The aim of this study was to explore the clinical value of the porcine acellular dermal xenograft (ADX) in combination with autologous split-thickness skin and pure autologous split-thickness skin grafting applied in deep full-thickness burns and scar wounds. A total of 30 patients with deep burns were randomly divided into experimental and control groups following escharectomy. The patients were separately treated with porcine acellular dermal xenograft (ADX) in combination with autologous split-thickness skin and pure autologous split-thickness skin graft. The wound healing was observed routinely and the scores were evaluated using Vancouver scar scale at different times following transplant surgery. The samples of cograft regions and the control group (pure transplant split-thickness skin autograft) were observed using light microscopy and electron microscopy, and the follow-up results were recorded. No conspicuous rejections on the cograft wound surface were observed. Compared with the control group, the cograft wounds were smooth, presented no scar contracture and exhibited good skin elasticity and recovery of the joint function. The cografted skin combined well and displayed a clear and continuous basal membrane, as well as gradually combined skin structure, a mature stratum corneum, downward extended rete pegs, a mainly uniform dermal collagen fiber structure, regular alignment, and fewer blood capillaries. Clear desmosome cograft regions were identified among heckle cells, as well as a clear and continuous basal membrane. The cografted skin of the combined split-thickness autograft and the acellular heterologous (porcine) dermal matrix showed an improved shape and functional recovery compared with the pure split-thickness skin autograft. The combination of the meshed ADX and the split-thickness skin autograft applied in deep full-thickness burns and scar wounds may induce tissue regeneration via dermis aiming. This method also has superior shape and functional recovery, and has an extensive clinical application value.
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To study the effect of porcine acellular dermal matrix (ADM) on the burn wound healing. Seventy healthy Wistar rats were inflicted with 2 cm second degree burn and divided into 2 groups; one group was treated with porcine ADM and the other with Povidone Iodine Cream. Biopsies were taken on day 1, 3, 5, 7, 10, 14, 21 for histopathological and biochemical analysis to test PCNA, K19, Integrin-ß1, PDGF, EGF and FGF. The results revealed relatively better and faster regeneration after treatment of porcine ADM, along with greatly increased synthesis in collagen in the experimental group. PCNA, K19, Integrin-ß1 had an increase and then tapered down, and were stronger in the experimental group than in the contrast group during 21 days after burns. PDGF, EGF and FGF levels increased on day 3, peaked on day 5 and then started to decrease, while significantly enhanced expression of relevant growth factors were observed in the experimental group. Porcine ADM stimulate collagen synthesis, stem cells proliferation and differentiation, and the expression of relevant growth factors and ultimately improve the burn wound healing.
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Derme Acelular , Queimaduras/cirurgia , Transplante de Pele/instrumentação , Pele/patologia , Cicatrização , Administração Cutânea , Animais , Biomarcadores/metabolismo , Queimaduras/tratamento farmacológico , Queimaduras/metabolismo , Queimaduras/patologia , Diferenciação Celular , Proliferação de Células , Colágeno/biossíntese , Modelos Animais de Doenças , Xenoenxertos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Povidona-Iodo/administração & dosagem , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismo , Creme para a Pele/administração & dosagem , Células-Tronco/metabolismo , Células-Tronco/patologia , Suínos , Fatores de Tempo , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVE: To evaluate the effect of rosuvastatin on the functions of the surviving myocardium and arteriosclerosis plaque in patients with ST-segment elevation after acute myocardial infarction (STEMI) and percutaneous coronary intervention (PCI). METHODS: Sixty-five STEMI patients were randomized to receive 40 mg simvastatin (n=32) or 10 mg rosuvastatin (n=33) before sleep in addition to conventional medications. Before PCI and after the 12-month medications, the plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were measured, and echocardiography and (99)Tc(m)-MIBI single-photon emission computed tomography (SPECT) were performed to assess the therapeutic effects. RESULTS: At the end of 12 months, the patients in simvastatin group showed significantly reduced total cholesterol, LDL-C, CRP, TNF-α, and (99)Tc(m)-MIBI uptake fraction. In rosuvastatin group, these reductions were even more obvious; the intima media thickness (IMT) of the common carotid artery was reduced significantly after a 12-month rosuvastatin therapy, but almost remained unchanged after simvastatin therapy. CONCLUSION: Rosuvastatin therapy in addition to conventional medications can significantly reduce IMT and improve the functions of the surviving myocardium in patients with STEMI after PCI.
Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana/patologia , Fluorbenzenos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/terapia , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Eletrocardiografia , Feminino , Coração/fisiopatologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Rosuvastatina CálcicaRESUMO
OBJECTIVE: To investigate the effect of metoprolol succinate sustained-release tablets on cardiac function, serum vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) in elderly hypertensive patients and its relation with pulse pressure (PP). METHODS: A total of 330 elderly hypertensive patients with chronic heart failure receiving basic therapy were included. Before initiation and 3 months after the maximal tolerated dose of metoprolol succinate sustained-release tablets, the parameters of blood pressure, clinical features, radionuclide ventriculographic and laboratory findings of the patients were analyzed. RESULTS: As the PP was elevated, the serum levels of VEGF, hs-CRP and BNP increased and the cardiac systolic and diastolic functions decreased. In patients with PP of 59-68 mmHg and > 68 mmHg, 3 months of treatment with the tablets caused significantly increased LVEF by (3.32 ± 2.35)% and (4.12 ± 3.05)% and LVPER by 0.37 ± 0.26 and 0.53 ± 0.37, respectively; PP were decreased by 8.2 ± 3.1 mmHg and 9.4 ± 4.3 mmHg and VEGF by 18.39 ± 8.43 pg/ml and 26.79 ± 14.32 pg/ml, respectively. The treatment also resulted in lowered hs-CRP and BNP in these patients by 0.26 ± 0.13 mg/L and 0.33 ± 0.16 mg/L and by 140.36 ± 68.62 ng/L and 155.39 ± 73.58 ng/L, respectively. CONCLUSION: Obvious elevation of PP is associated with a better response to metoprolol succinate sustained-release tablets in elderly hypertensive patients with chronic heart failure, and 3 months of treatment with the tablets can significantly improve the cardiac function and lower the levels of VEGF, hs-CRP and BNP in these patients.
Assuntos
Proteína C-Reativa/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/tratamento farmacológico , Metoprolol/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/sangue , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Doença Crônica , Preparações de Ação Retardada , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/sangue , Hipertensão/complicações , Masculino , Metoprolol/administração & dosagem , Metoprolol/uso terapêutico , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangueRESUMO
OBJECTIVE: To investigate the relationship between B-type natriuretic peptides (BNP) and subclinical target organ damage in essential hypertensive (EH) patients. METHODS: A total of 317 EH patients were divided into 3 groups according to BNP levels, namely normal (BNP<600 ng/L) group (n=102), moderate (600-883.5 ng/L) group (n=116), and elevated BNP (>883.5 ng/L) group (n=99). The blood pressure, left ventricular mass index (LVMI), the intima media thickness (IMT) of the common carotid artery, the plaque size in the coronary artery (CS) and microalbuminuria levels were analyzed in these patients. RESULTS: The EH patients with moderate and elevated BNP showed significantly higher LVMI, IMT, CS and microalbuminuria levels than those with normal BNP level (LVMI: 102.8∓23.12 and 123.9∓26.47 vs 91.09∓18.71 g/m2; IMT: 0.95∓0.32 and 1.16∓0.37 vs 0.84∓0.28 mm; microalbuminuria: 31.36∓20.55 and 36.73∓22.07 vs 23.21∓18.68, P<0.01). After adjustment, BNP was positively correlated to LVMI, IMT, CS and microalbuminuria level (r=0.45, 0.43, 0.39 and 0.41, respectively, P<0.01). Multivariate logistic regression analysis showed that age, systolic blood pressure, BNP, FPG, and microalbuminuria, LDL-C, and BMI were all related to the occurrence of subclinical target organ damages. CONCLUSION: BNP is positively correlated to subclinical target organs damages in EH patients.
Assuntos
Hipertensão/sangue , Hipertensão/patologia , Peptídeo Natriurético Encefálico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/patologia , Artéria Carótida Primitiva/patologia , Espessura Intima-Media Carotídea , Feminino , Humanos , Hipertrofia Ventricular Esquerda/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To observe the effect of rosuvastatin on left ventricular cardiac function, arteriosclerotic plaque and high sensitive C-reactive protein (hs-CRP) in hypertensive patients with mild elevation of LDL-C. METHODS: Seventy-nine patients with a SBP of 140-179 mmHg and/or a DBP of 90-109 mmHg and mild elevated LDL-C were treated with rosuvastatin for 12 months (n=40) or not (n=39). The changes of hs-CRP, arteriosclerosis plaque and cardiac function at the end of the 12-months treatment relative to the baseline levels were analyzed. RESULTS: After 12 months of treatment, LDL-C was decreased by 33.2% in rosuvastatin group but remained unchanged in patients without rosuvastatin treatment. The left ventricular peak filling rate (LVPFR) increased significantly from 1.85 to 2.59 (P<0.05) and the serum levels of hs-CRP reduced significantly (P<0.05) after rosuvastatin treatment. The size of the plaques reduced significantly after a 12-month rosuvastatin therapy. CONCLUSION: Rosuvastatin therapy on the basis of conventional anti-hypertensive drugs can obviously improve the left ventricular diastolic function and produce favorable effects on arteriosclerotic plaques.