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1.
Front Surg ; 9: 1025557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338621

RESUMO

Background: Biochemical processes involved in complex skin diseases (skin cancers, psoriasis, and wound) can be identified by combining proteomics analysis and bioinformatics tools, which gain a next-level insight into their pathogenesis, diagnosis, and therapeutic targets. Methods: Articles were identified through a search of PubMed, Embase, and MEDLINE references dated to May 2022, to perform system data mining, and a search of the Web of Science (WoS) Core Collection was utilized to conduct a visual bibliometric analysis. Results: An increased trend line revealed that the number of publications related to proteomics utilized in skin diseases has sharply increased recent years, reaching a peak in 2021. The hottest fields focused on are skin cancer (melanoma), inflammation skin disorder (psoriasis), and skin wounds. After deduplication and title, abstract, and full-text screening, a total of 486 of the 7,822 outcomes met the inclusion/exclusion criteria for detailed data mining in the field of skin disease tooling with proteomics, with regard to skin cancer. According to the data, cell death, metabolism, skeleton, immune, and inflammation enrichment pathways are likely the major part and hotspots of proteomic analysis found in skin diseases. Also, the focuses of proteomics in skin disease are from superficial presumption to depth mechanism exploration within more comprehensive validation, from basic study to a combination or guideline for clinical applications. Furthermore, we chose skin cancer as a typical example, compared with other skin disorders. In addition to finding key pathogenic proteins and differences between diseases, proteomic analysis is also used for therapeutic evaluation or can further obtain in-depth mechanisms in the field of skin diseases. Conclusion: Proteomics has been regarded as an irreplaceable technology in the study of pathophysiological mechanism and/or therapeutic targets of skin diseases, which could provide candidate key proteins for the insight into the biological information after gene transcription. However, depth pathogenesis and potential clinical applications need further studies with stronger evidence within a wider range of skin diseases.

2.
Heliyon ; 8(10): e10874, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36276718

RESUMO

Background: Rosacea is a common and complex chronic inflammatory skin disorder, the pathophysiology and etiology of which remain unclear. Recently, significant new insights into rosacea pathogenesis have enriched and reshaped our understanding of the disorder. A systematic analysis based on current studies will facilitate further research on rosacea pathogenesis. Objective: To establish an international core outcome and knowledge system of rosacea pathogenesis and develop a challenge, trend and hot spot analysis set for research and clinical studies on rosacea using bibliometric analysis and data mining. Methods: A search of the WoS, and PubMed, MEDLINE, Embase and Cochrane collaboration databases was conducted to perform visual bibliometric and data analysis. Results: A total of 2,654 studies were used for the visualization and 302 of the 6,769 outcomes for data analysis. It reveals an increased trend line in the field of rosacea, in which its fast-growing pathogenesis attracted attention closely related to risk, comorbidity and therapeutic strategies. The rosacea pathogenesis has undergone the great development on immunology, microorganisms, genes, skin barriers and neurogenetics. The major of studies have focused on immune and microorganisms. And keyword visualization and data analyses demonstrated the cross-talk between cells or each aspect of pathogenesis, such as gene-gene or gene-environment interactions, and neurological mechanisms associated with the rosacea phenotype warrant further research. Limitations: Inherent limitations of bibliometrics; and reliance on research and retrospective studies. Conclusions: The understanding of rosacea's pathogenesis has been significantly enhanced with the improved technology and multidisciplinary integration, but high-quality, strong evidence in favor of genomic and neurogenic requires further research combined with a better understanding of risks and comorbidities to guide clinical practice.

3.
Front Endocrinol (Lausanne) ; 13: 859638, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370989

RESUMO

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that attacks pancreatic ß-cells, leading to the destruction of insulitis-related islet ß-cells. Islet ß-cell transplantation has been proven as a curative measure in T1DM. However, a logarithmic increase in the global population with diabetes, limited donor supply, and the need for lifelong immunosuppression restrict the widespread use of ß-cell transplantation. Numerous therapeutic approaches have been taken to search for substitutes of ß-cells, among which stem cell transplantation is one of the most promising alternatives. Stem cells have demonstrated the potential efficacy to treat T1DM by reconstitution of immunotolerance and preservation of islet ß-cell function in recent research. cGMP-grade stem cell products have been used in human clinical trials, showing that stem cell transplantation has beneficial effects on T1DM, with no obvious adverse reactions. To better achieve remission of T1DM by stem cell transplantation, in this work, we explain the progression of stem cell transplantation such as mesenchymal stem cells (MSCs), human embryonic stem cells (hESCs), and bone marrow hematopoietic stem cells (BM-HSCs) to restore the immunotolerance and preserve the islet ß-cell function of T1DM in recent years. This review article provides evidence of the clinical applications of stem cell therapy in the treatment of T1DM.


Assuntos
Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Ilhotas Pancreáticas , Diabetes Mellitus Tipo 1/cirurgia , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Transplante de Células-Tronco
4.
J Cell Mol Med ; 25(23): 10990-11001, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34755462

RESUMO

Skin cutaneous melanoma (SKCM) is one of the most destructive skin malignancies and has attracted worldwide attention. However, there is a lack of prognostic biomarkers, especially tumour microenvironment (TME)-based prognostic biomarkers. Therefore, there is an urgent need to investigate the TME in SKCM, as well as to identify efficient biomarkers for the diagnosis and treatment of SKCM patients. A comprehensive analysis was performed using SKCM samples from The Cancer Genome Atlas and normal samples from Genotype-Tissue Expression. TME scores were calculated using the ESTIMATE algorithm, and differential TME scores and differentially expressed prognostic genes were successively identified. We further identified more reliable prognostic genes via least absolute shrinkage and selection operator regression analysis and constructed a prognostic prediction model to predict overall survival. Receiver operating characteristic analysis was used to evaluate the diagnostic efficacy, and Cox regression analysis was applied to explore the relationship with clinicopathological characteristics. Finally, we identified a novel prognostic biomarker and conducted a functional enrichment analysis. After considering ESTIMATEScore and tumour purity as differential TME scores, we identified 34 differentially expressed prognostic genes. Using least absolute shrinkage and selection operator regression, we identified seven potential prognostic biomarkers (SLC13A5, RBM24, IGHV3OR16-15, PRSS35, SLC7A10, IGHV1-69D and IGHV2-26). Combined with receiver operating characteristic and regression analyses, we determined PRSS35 as a novel TME-based prognostic biomarker in SKCM, and functional analysis enriched immune-related cells, functions and signalling pathways. Our study indicated that PRSS35 could act as a potential prognostic biomarker in SKCM by investigating the TME, so as to provide new ideas and insights for the clinical diagnosis and treatment of SKCM.


Assuntos
Biomarcadores Tumorais/metabolismo , Melanoma/metabolismo , Neoplasias Cutâneas/metabolismo , Microambiente Tumoral/fisiologia , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Melanoma/patologia , Prognóstico , Curva ROC , Transdução de Sinais/fisiologia , Neoplasias Cutâneas/patologia
5.
Stem Cell Res Ther ; 12(1): 453, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380571

RESUMO

Hair follicle stem cells (HFSCs) are among the most widely available resources and most frequently approved model systems used for studying adult stem cells. HFSCs are particularly useful because of their self-renewal and differentiation properties. Additionally, the cyclic growth of hair follicles is driven by HFSCs. There are high expectations for the use of HFSCs as favourable systems for studying the molecular mechanisms that contribute to HFSC identification and can be applied to hair loss therapy, such as the activation or regeneration of hair follicles, and to the generation of hair using a tissue-engineering strategy. A variety of molecules are involved in the networks that critically regulate the fate of HFSCs, such as factors in hair follicle growth and development (in the Wnt pathway, Sonic hedgehog pathway, Notch pathway, and BMP pathway), and that suppress apoptotic cues (the apoptosis pathway). Here, we review the life cycle, biomarkers and functions of HFSCs, concluding with a summary of the signalling pathways involved in HFSC fate for promoting better understanding of the pathophysiological changes in the HFSC niche. Importantly, we highlight the potential mechanisms underlying the therapeutic targets involved in pathways associated with the treatment of hair loss and other disorders of skin and hair, including alopecia, skin cancer, skin inflammation, and skin wound healing.


Assuntos
Folículo Piloso , Células-Tronco , Cabelo , Proteínas Hedgehog , Via de Sinalização Wnt
6.
World J Stem Cells ; 13(5): 386-415, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34136072

RESUMO

Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery. However, transplanted stem cells show a high death percentage, creating challenges to successful transplantation and prognosis. Thus, it is necessary to investigate the mechanisms underlying stem cell death, such as apoptotic cascade activation, excessive autophagy, inflammatory response, reactive oxygen species, excitotoxicity, and ischemia/hypoxia. Targeting the molecular pathways involved may be an efficient strategy to enhance stem cell viability and maximize transplantation success. Notably, a more complex network of cell death receives more attention than one crucial pathway in determining stem cell fate, highlighting the challenges in exploring mechanisms and therapeutic targets. In this review, we focus on programmed cell death in transplanted stem cells. We also discuss some promising strategies and challenges in promoting survival for further study.

7.
Zhonghua Nan Ke Xue ; 26(12): 1096-1110, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34898084

RESUMO

OBJECTIVE: To investigate the causes of abnormally short frenulum induced by circumcision with disposable circumcision suture device and the improvement of the surgical method. METHODS: We retrospectively analyzed the clinical data on 320 cases of phimosis or redundant prepuce treated from January 2020 to September 2020, including 160 children (group A) and 160 adults (group B), each further divided into an observation group (n = 80, groups A1 and B1) and a control group (n = 80, groups A2 and B2). The patients in groups A1 and B1 underwent circumcision by suture positioning at the frenulum with the disposable circumcision suture device, and those in groups A2 and B2 received conventional circumcision with the disposable circumcision suture device. We compared the operation time, incidence rate of abnormally short frenulum and Visual Analogue Scale (VAS) score at 6 hours after surgery among the four groups of patients. RESULTS: Statistically significant differences were observed between groups A1 and A2 in the operation time (12.00 ï¼»11.00, 13.00ï¼½ vs 8.50 ï¼»8.50, 9.00ï¼½ min, P < 0.05) and the incidence rate of abnormally short frenulum (0 vs 10%, P < 0.05) but not in the VAS score (3.00 ï¼»3.00, 4.00ï¼½ vs 3.00 ï¼»3.00, 3.75ï¼½, P > 0.05). Statistically significant differences were also found between groups B1 and B2 in the operation time (12.00 ï¼»11.00, 12.00ï¼½ vs 6.25 ï¼»6.00, 7.00ï¼½ min, P < 0.05) and the incidence rate of abnormally short frenulum (0 vs 7.5%, P < 0.05) but not in the VAS score (2.00 ï¼»2.00, 3.00ï¼½ vs 2.00 ï¼»2.00, 3.00ï¼½, P > 0.05). CONCLUSIONS: Abnormally short frenulum induced by circumcision with the disposable circumcision suture device is mainly attributed to ligation and fixation of the prepuce with the fixation band. Circumcision with the disposable circumcision suture device by suture positioning at the frenulum is a safe and effective method worthy of clinical promotion.


Assuntos
Circuncisão Masculina , Fimose , Adulto , Criança , Equipamentos Descartáveis , Humanos , Masculino , Fimose/etiologia , Fimose/cirurgia , Estudos Retrospectivos , Suturas
8.
Thorac Cancer ; 10(6): 1388-1394, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31017733

RESUMO

BACKGROUND: This study was conducted to investigate the effect of P14 promoter aberrant methylation on the biological function of human lung adenocarcinoma cells. METHODS: We used nested methylation-specific PCR (NMSP) to detect the methylation status of the p14ARF promoter region in SPCA1 and BEAS2B cell lines. The experimental groups were treated with 5-aza-2'-deoxycytidine (5-Aza). Quantitative real-time PCR, Western blot, flow cytometry, and Cell Counting Kit 8 were used to detect the expression of p14ARF messenger RNA and protein in each group, apoptosis, and cell proliferation inhibition, respectively. RESULTS: NMSP detected that the p14 promoter region of SPCA1 cells has abnormal methylation status. After treatment with 5-Aza, the expression of p14ARF messenger RNA and protein in SPCA1 cells (P < 0.05) and the inhibition rate of cell proliferation (P < 0.05) were significantly increased, while the apoptosis rate was markedly increased (P < 0.05). However, no differences were observed in BEAS2B cells (P > 0.05). CONCLUSION: Abnormal methylation of the p14ARF promoter region plays an important role in the development of lung cancer cells. Our results suggest the use of P14 promoter aberrant methylation as a therapeutic target for drug research or to improve the sensitivity of other drugs.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Decitabina/farmacologia , Neoplasias Pulmonares/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Metilação de DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Regiões Promotoras Genéticas , Regulação para Cima
9.
Organogenesis ; 14(1): 25-35, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29420128

RESUMO

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.


Assuntos
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 , Suínos
10.
Methods Appl Fluoresc ; 6(2): 024001, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29350185

RESUMO

Cyanine has been widely utilized as a near infrared (NIR) fluorophore for detection of glutathione (GSH). However, the excitation of most of the reported cyanine-based probes was less than 800 nm, which inevitably induce biological background absorption and lower the sensitivity, limiting their use for detection of GSH in blood samples. To address this issue, here, a heptamethine cyanine probe (DNIR), with a NIR excitation wavelength at 804 nm and a NIR emission wavelength at 832 nm, is employed for the detection of GSH and its oxidized form (GSSG) in blood. The probe displays excellent selectivity for GSH over GSSG and other amino acids, and rapid response to GSH, in particular a good property for indirect detection of GSSG in the presence of enzyme glutathione reductase and the reducing agent nicotinamideadenine dinucleotide phosphate, without further separation prior to fluorescent measurement. To the best of our knowledge, this is the first attempt to explore NIR fluorescent approach for the simultaneous assay of GSH and GSSG in blood. As such, we expect that our fluorescence sensors with both NIR excitation and NIR emission make this strategy suitable for the application in complex physiological systems.


Assuntos
Carbocianinas/química , Glutationa/sangue , Espectroscopia de Luz Próxima ao Infravermelho , Corantes Fluorescentes/química , Glutationa/química , Humanos , NADP/química , Oxirredução
11.
Zhonghua Nan Ke Xue ; 24(11): 983-986, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-32212471

RESUMO

OBJECTIVE: To present our experience in the diagnosis and treatment of prostate sarcoma and the clinical and prognostic features of the malignancy. METHODS: We retrospectively analyzed the clinical data on 26 cases of prostate sarcoma treated in our hospital from June 1998 to March 2018. The patients ranged in age from 15 to 64 years (ï¼»41 ± 14ï¼½ yr) and in the PSA level from 0.345 to 5.213 µg/L (ï¼»1.762 ± 1.184ï¼½ µg/L), all diagnosed with prostate sarcoma by prostatic biopsy and pathological examination after transurethral resection of the prostate (TURP). RESULTS: Postoperative pathological examination showed 11 cases of leiomyosarcoma, 6 cases of rhabdomyosarcoma, 4 cases of spindle cell sarcoma, 4 cases of fibrosarcoma and 1 case of undifferentiated sarcoma among the total number of patients. Twenty-four of the patients were followed up for 3 to 18 (mean 13) months, of whom 21 died within 12 months and the other 3 within 13-18 months after diagnosis, all due to extensive metastases. CONCLUSIONS: Prostate sarcoma is a rare malignancy clinically, highly aggressive and with very poor prognosis. Surgery remains the main treatment option, but multiple disciplinary diagnosis and treatment could probably achieve a better prognosis for prostate sarcoma.


Assuntos
Neoplasias da Próstata , Sarcoma , Ressecção Transuretral da Próstata , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Sarcoma/diagnóstico , Sarcoma/cirurgia , Adulto Jovem
12.
Mol Cell Biochem ; 423(1-2): 1-8, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27766530

RESUMO

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.


Assuntos
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/fisiologia
13.
Biosci Rep ; 36(4)2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27129289

RESUMO

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.


Assuntos
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/metabolismo
14.
Int J Clin Exp Med ; 7(9): 2511-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25356104

RESUMO

Polyethylene terephthalate LARS ligament were the remnant of LARS ligament used for repairing posterior cruciate ligament obtained from operation. We want to study histological characteristics and ultrastructure of polyethylene terephthalate LARS ligament after the reconstruction of anterior cruciate ligament in rabbits. Therefore, we replaced the original ACL with polyethylene terephthalate LARS ligament which was covering with the remnant of ACL in 9 rabbits (L-LARS group), while just only polyethylene terephthalate LARS ligament were transplanted in 3 rabbits (LARS group) with the remnant of ACL. Compared with group LARS, inflammatory cell reaction and foreign body reaction were more significant in group L-LARS. Moreover, electron microscopy investigation showed the tissue near LARS fibers was highly cellular with a matrix of thin collagen fibrils (50-100 nm) in group L-LARS. These above findings suggest the polyethylene terephthalate LARS ligament possess the high biocompatibility, which contributes to the polyethylene terephthalate LARS covered with recipient connective tissues.

15.
Int J Clin Exp Pathol ; 7(6): 2998-3007, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25031718

RESUMO

Hypertrophic scars are fibroproliferative disorders of excessive wound healing after skin injury. Vascular endothelial growth factor (VEGF)-induced angiogenesis plays a major role in fibrogenesis and hypertrophic scar formation. Over recent years, there has been a major interest in homeobox gene regulation of VEGF-VEGFR mediated angiogenesis in dermal tissue. In the current study, we investigated the role of homeobox genes in the epidermis, for their role in angiogenesis, with a focus on epidermal-mesenchymal interactions. As epidermal stem cells (ESCs) have a central role in epidermal homeostasis, we tested the hypothesis that these cells play a key role in the pathogenesis of hypertrophic scars through the HOXA9-VEGF/VEGFR signaling pathways. We found significant differences in the expression of homeobox A9 in hyperplastic scar tissue during different phases of development. These differences coincided with similar regulations in VEGF expression and with the distribution of ESCs. HOXA9 is expressed in cultured human ESCs in vitro. Antisense suppression of HOXA9 expression was found to suppress VEGF levels in ESCs. Together these findings indicate that homeobox A9 regulates the expression of VEGF in ESCs.


Assuntos
Cicatriz Hipertrófica/metabolismo , Células Epiteliais/metabolismo , Proteínas de Homeodomínio/metabolismo , Neovascularização Patológica/metabolismo , Células-Tronco/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Western Blotting , Criança , Pré-Escolar , Cicatriz Hipertrófica/patologia , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/patologia , Feminino , Imunofluorescência , Humanos , Lactente , Masculino , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Transfecção , Adulto Jovem
16.
Amino Acids ; 46(6): 1481-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24633452

RESUMO

Bombesin (BBN) is a peptide exhibiting high affinity for the gastrin-releasing peptide receptor (GRPR), which is overexpressed on several types of cancers. Various GRPR antagonists and agonists have been labeled with radiometals for positron emission tomography (PET) imaging of GRPR-positive tumors. However, unfavorable hepatobiliary excretion such as high intestinal activity may prohibit their clinical utility for imaging abdominal cancer. In this study, the modified BBN peptide with a new hydrophilic linker was labeled with (68)Ga for PET imaging of GRPR-expressing PC-3 prostate cancer xenograft model. GRPR antagonists, MATBBN (Gly-Gly-Gly-Arg-Asp-Asn-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH2CH3) and ATBBN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHCH2CH3), were conjugated with 1,4,7-triazacyclononanetriacetic acid (NOTA) and labeled with (68)Ga. Partition coefficient and in vitro stability were also determined. GRPR binding affinity of both tracers was investigated by competitive radioligand binding assay. The in vivo receptor targeting potential and pharmacokinetic of (68)Ga-NOTA-MATBBN were also evaluated in PC-3 prostate tumor model and compared with those of (68)Ga-NOTA-ATBBN. NOTA-conjugated BBN analogs were labeled with (68)Ga within 20 min with a decay-corrected yield ranging from 90 to 95 % and a radiochemical purity of more than 98 %. The specific activity of (68)Ga-NOTA-MATBBN and (68)Ga-NOTA-ATBBN was at least 16.5 and 11.9 GBq/µmol, respectively. The radiotracers were stable in phosphate-buffered saline and human serum. (68)Ga-NOTA-MATBBN was more hydrophilic than (68)Ga-NOTA-ATBBN, as indicated by their log P values (-2.73 ± 0.02 vs. -1.20 ± 0.03). The IC50 values of NOTA-ATBBN and NOTA-MATBBN were similar (102.7 ± 1.18 and 124.6 ± 1.21 nM). The accumulation of (68)Ga-labeled GRPR antagonists in the subcutaneous PC-3 tumors could be visualized via small animal PET. The tumors were clearly visible, and the tumor uptakes of (68)Ga-NOTA-MATBBN and (68)Ga-NOTA-ATBBN were determined to be 4.19 ± 0.32, 4.00 ± 0.41, 2.93 ± 0.35 and 4.70 ± 0.40, 4.10 ± 0.30, 3.14 ± 0.30 %ID/g at 30, 60, and 120 min, respectively. There was considerable accumulation and retention of (68)Ga-NOTA-ATBBN in the liver and intestines. In contrast, the abdominal area does not have much retention of (68)Ga-NOTA-MATBBN. Biodistribution data were in accordance with the PET results, showing that (68)Ga-NOTA-MATBBN had more favorable pharmacokinetics and higher tumor to background ratios than those of (68)Ga-NOTA-ATBBN. At 1 h postinjection, the tumor to liver and intestine of (68)Ga-NOTA-MATBBN were 8.05 ± 0.56 and 21.72 ± 3.47 and the corresponding values of unmodified counterpart were 0.85 ± 0.23 and 3.45 ± 0.43, respectively. GRPR binding specificity was demonstrated by reduced tumor uptake of radiolabeled tracers after coinjection of an excess of unlabeled BBN peptides. (68)Ga-NOTA-MATBBN exhibited GRPR-targeting properties both in vitro and in vivo. The favorable characterizations of (68)Ga-NOTA-MATBBN such as convenient synthesis, specific GRPR targeting, high tumor uptake, and satisfactory pharmacokinetics warrant its further investigation for clinical cancer imaging.


Assuntos
Bombesina/metabolismo , Radioisótopos de Gálio , Marcação por Isótopo/métodos , Receptores da Bombesina/metabolismo , Animais , Bombesina/análogos & derivados , Linhagem Celular Tumoral , Compostos Heterocíclicos/química , Compostos Heterocíclicos com 1 Anel , Xenoenxertos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Distribuição Tecidual
17.
Int J Clin Exp Pathol ; 6(11): 2529-34, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24228116

RESUMO

The management of burns and injuries using novel treatment strategies involving epidermal stem cells (ESC) requires a better understanding of the biology of these cells, in particular, their isolation and the maintenance of their unique characteristics in culture. The purpose of this study was to describe an improved method for isolating putative ESC from fetal rat skin and to maintain them long term in culture. Single ESC suspensions were obtained from fetal rat skin by enzyme digestion containing 0.5% neutral protease. The target cells were harvested by rapid adherence on type IV collagen plates and were cultured in complex DMEM. After primary isolation, cells were continuously cultured in K-serum free medium. After reaching 70-80% confluence, the cells were digested with 0.25% trypsin at 37°C for 5-10 minutes, and passaged at a ratio of 1:2. The cultured ESC showed good growth, resulting in cell viability of over 98%. Four days later, clones containing 100-200 cells were detected, showing cobblestone-like characteristics. The rapidly adherent cells were positive for keratin 15, 19 and P63. Eighty three percent of cells expressed ß1 integrin. The growth-curve showed that the rapidly adherent cells were in the exponential growth phase. The protocol described in this paper provides a simplified and effective method to isolate and maintain long-term culture of epidermal stem cells from fetal rat skin. This method should be valuable for isolating and studying ESC from various transgenic rat lines that are currently available.


Assuntos
Separação Celular/métodos , Células Epidérmicas , Células-Tronco/fisiologia , Animais , Biomarcadores/metabolismo , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Epiderme/embriologia , Idade Gestacional , Integrina beta1/metabolismo , Queratina-15/metabolismo , Queratina-19/metabolismo , Ratos , Ratos Sprague-Dawley , Células-Tronco/metabolismo , Fatores de Tempo , Proteína Supressora de Tumor p53/metabolismo
18.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 29(3): 189-92, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-25069345

RESUMO

OBJECTIVE: To introduce different surgical treatment for gyncomastia at different grades. METHODS: 37 cases with gynecomastia were divided into three grades as: grade I with fat as main tissue, grade II with proliferated fibro-gland as main tissue, grade III with big and ptosis breasts and sagging skin. Different surgical methods were chosen according to the different grades of gyncomastia. These include liposuction, subareolar fibroglandular tissue removing, combined technique of the two methods, and breasts resection with free transplantation of nipple-areola complex. RESULTS: All patients were satisfied for the appearance of post-operative flat male chest. Complications, such as scar, numbness of nipple and areola were acceptable for them. CONCLUSIONS: Different surgical methods should be chosen for the gynecomastia at different grades. It can improve both the physical and psychological problems for patients.


Assuntos
Ginecomastia/cirurgia , Mamoplastia/métodos , Adolescente , Ginecomastia/classificação , Humanos , Lipectomia , Masculino , Mamilos/transplante , Estudos Retrospectivos
19.
Bioorg Med Chem Lett ; 21(21): 6376-80, 2011 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-21937227

RESUMO

Iron is a critical element for the survival of bacteria. We have designed and synthesized two novel 3-hydroxypyridin-4-one hexadentate ligands with high affinity for iron(III), which disrupt bacterial iron absorption. Biological studies demonstrate that these two chelators have significant inhibitory effect against both Gram-positive and Gram-negative bacteria, and therefore have potential as antimicrobial agents.


Assuntos
Antibacterianos/metabolismo , Ferro/metabolismo , Piridinas/metabolismo , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Técnicas In Vitro , Ligantes , Testes de Sensibilidade Microbiana , Modelos Moleculares , Simulação de Dinâmica Molecular , Piridinas/farmacologia , Espectrofotometria Ultravioleta
20.
Zhonghua Shao Shang Za Zhi ; 25(3): 207-10, 2009 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19842558

RESUMO

OBJECTIVE: To study the effect of blister fluid obtained from burn patient on human MSCs in vitro and its phenotypic modulation in culture. METHODS: Blister fluid from burn patients was collected at 12, 24, 48 post burn hour (PBH). The human MSCs were isolated, cultured, amplified and identified in vitro, then were divided into A (culture with 20% blister fluid collected at 12 PBH) , B (culture with 20% blister fluid collected at 24 PBH), C (culture with 20% blister fluid collected at 48 PBH), N (with ordinary culture medium) groups. The growth of MSCs and micro-organisms in blister fluid were observed. Positive expression rates of CD44 and CK7 were detected by flow cytometry after culture for 8 days. RESULTS: Bacterial and fungal growths were absent in 15 blister fluid samples. There was no obvious change in MSC morphology in each group. Compared with that of N group, the number of MSCs in A, B, C groups was decreased, especially in C group. CD44 positive expression rate in A, B, C groups was (83.0 +/- 3.1)%, (77.2 +/- 2.9)% and (65.1 +/- 2.3)%, respectively,which was obviously lower than that in N group [(89.5 +/- 3.2)%, P < 0.01]. CK7 positive expression rate in A, B, C groups was (24.06 +/- 0.11)%, (16.41 +/- 0.09)% and (4.48 +/- 0.07)%, respectively, which was obviously higher than that in N group [(3.87 +/- 0.04)%, P < 0.01]. CONCLUSIONS: Burn blister fluid can obviously inhibit the growth of human MSC cultured in vitro, and may promote modulation of its phenotype to certain extent.


Assuntos
Vesícula , Células da Medula Óssea/citologia , Queimaduras , Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Vesícula/metabolismo , Separação Celular , Células Cultivadas , Citometria de Fluxo , Humanos
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