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1.
An Acad Bras Cienc ; 91(3): e20190220, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531535

RESUMO

Liver fibrosis is the final common pathway of chronic liver diseases, having cirrhosis as a possible progression, which has liver transplantation as the only effective treatment. Human amniotic membrane represents a potential strategy as a therapy for liver fibrosis, due to its anti-inflammatory, anti-fibrotic and immunomodulatory properties. The aim of this study was to evaluate amniotic membrane effects as a treatment for hepatic fibrosis induced in rats by bile duct ligation (BDL), verifying alterations between two different forms of amniotic membrane application, around all the lobes of the liver and around only one lobe of the liver. Two weeks after inducing fibrosis, an amniotic membrane fragment was applied to the surface of the liver, covering it either totally or partially. Four weeks later, the animals were euthanized and liver samples were collected. Histopathological and quantitative analyses demonstrated fibrosis severity decrease and an extremely significant reduction in the deposition of collagen in the groups treated with amniotic membrane, particularly when the amniotic membrane was applied in only one liver lobe. It is concluded that the amniotic membrane acted on the repair of liver fibrosis in both modes of application, with the application of the amniotic membrane around only one hepatic lobe being more effective in reducing the severity / extent of fibrosis.


Assuntos
Âmnio/transplante , Cirrose Hepática/cirurgia , Animais , Ductos Biliares/cirurgia , Colágeno/metabolismo , Modelos Animais de Doenças , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Wistar
2.
Yonsei Med J ; 60(9): 854-863, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31433583

RESUMO

PURPOSE: Relaxin (RLX) is a transforming growth factor-ß1 (TGF-ß1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. MATERIALS AND METHODS: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. RESULTS: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-ß1 and upregulated TGF-ß3 mRNAs in pig scar tissues. CONCLUSION: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.


Assuntos
Adenoviridae/genética , Adenoviridae/metabolismo , Alginatos , Cicatriz/terapia , Colágeno/metabolismo , Relaxina/genética , Relaxina/metabolismo , Animais , Cicatriz/metabolismo , Matriz Extracelular/metabolismo , Metaloproteinase 1 da Matriz , Relaxina/farmacologia , Suínos , Inibidor Tecidual de Metaloproteinase-1 , Fator de Crescimento Transformador beta1
3.
Int J Nanomedicine ; 14: 5491-5502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410000

RESUMO

Purpose: Meniscus is a fibrocartilagenous tissue that cannot effectively heal due to its complex structure and presence of avascular zone. Thus, tissue engineering and regenerative medicine offer an alternative for the regeneration of meniscus tissues using bioscaffolds as a replacement for the damaged one. The aim of this study was to prepare an ideal meniscus bioscaffold with minimal adverse effect on extracellular matrix components (ECMs) using a sonication treatment system. Methods: The decellularization was achieved using a developed closed sonication treatment system for 10 hrs, and continued with a washing process for 5 days. For the control, a simple immersion treatment was set as a benchmark to compare the decellularization efficiency. Histological and biochemical assays were conducted to investigate the cell removal and retention of the vital extracellular matrix. Surface ultrastructure of the prepared scaffolds was evaluated using scanning electron microscope at 5,000× magnification viewed from cross and longitudinal sections. In addition, the biomechanical properties were investigated through ball indentation testing to study the stiffness, residual forces and compression characteristics. Statistical significance between the samples was determined with p-value =0.05. Results: Histological and biochemical assays confirmed the elimination of antigenic cellular components with the retention of the vital extracellular matrix within the sonicated scaffolds. However, there was a significant removal of sulfated glycosaminoglycans. The surface histoarchitecture portrayed the preserved collagen fibril orientation and arrangement. However, there were minor disruptions on the structure, with few empty micropores formed which represented cell lacunae. The biomechanical properties of bioscaffolds showed the retention of viscoelastic behavior of the scaffolds which mimic native tissues. After immersion treatment, those scaffolds had poor results compared to the sonicated scaffolds due to the inefficiency of the treatment. Conclusion: In conclusion, this study reported that the closed sonication treatment system had high capabilities to prepare ideal bioscaffolds with excellent removal of cellular components, and retained extracellular matrix and biomechanical properties.


Assuntos
Menisco/citologia , Ortopedia , Sonicação/métodos , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Fenômenos Biomecânicos , Bovinos , Colágeno/metabolismo , Força Compressiva , Glicosaminoglicanos/metabolismo
4.
J Agric Food Chem ; 67(35): 9782-9788, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31390859

RESUMO

Sulforaphane, a potent antioxidant compound, is unstable at ambient temperature, whereas its precursor glucoraphanin is stable and metabolized to sulforaphane. Thus, we hypothesized that glucoraphanin-rich diet could effectively induce antioxidant enzyme activities and investigated the protective effects of long-term intake of a glucoraphanin-enriched kale (GEK) diet on skin aging in senescence-accelerated mouse prone 1 (SAMP1) mice. The senescence grading score was significantly lower after treatment with GEK for 39 weeks than that of the control mice. GEK also suppressed the thinning of the dorsal skin layer. Moreover, the GEK treatment enhanced the collagen production and increased the nuclear translocation of Nrf2 and HO-1 expression level in the skin tissue. TßRII and Smad3 expressions were clearly higher in the GEK-treated group than in the control group. Thus, GEK suppressed senescence in SAMP1 mice by enhancing the antioxidant activity and collagen production via the TßRII/Smad3 pathway, suggesting its practical applications for protection against skin aging.


Assuntos
Brassica/metabolismo , Glucosinolatos/metabolismo , Imidoésteres/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Envelhecimento da Pele/fisiologia , Proteína Smad3/metabolismo , Animais , Antioxidantes/metabolismo , Brassica/química , Colágeno/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Transdução de Sinais , Envelhecimento da Pele/genética , Proteína Smad3/genética , Fatores de Tempo
5.
Life Sci ; 232: 116637, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288014

RESUMO

Keloid is characterized by overactive fibroblasts. Forkhead box M1 (FOXM1) is transcription factor that plays important roles in the progression of fibrosis. However, the role of FOXM1 in keloid has not been elucidated. In the present study, we examined the expression levels of FOXM1 in clinical keloid tissue specimens and primary keloid fibroblasts (KFs). The results showed that FOXM1 levels were significantly increased in both keloid tissues and KFs. To further investigate the biological functions of FOXM1, FOXM1 was knocked down in KFs by transfection with small interfering RNA targeting FOXM1 (si-FOXM1). Knockdown of FOXM1 inhibited transforming growth factor-ß1 (TGF-ß1)-induced cell proliferation and migration of KFs. Besides, the increased expressions of collagen (coll I), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in TGF-ß1-induced KFs were suppressed by si-FOXM1 transfection. Furthermore, TGF-ß1-induced increase in p-Smad2 and p-Smad3 expressions was attenuated by FOXM1 knockdown. These data indicated that knockdown of FOXM1 inhibited TGF-ß1-induced KFs activation and extracellular matrix (ECM) accumulation, which was attributed to the inhibition of TGF-ß1/Smad pathway.


Assuntos
Proteína Forkhead Box M1/deficiência , Queloide/metabolismo , Actinas/metabolismo , Adolescente , Adulto , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/metabolismo , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Técnicas de Silenciamento de Genes/métodos , Humanos , Queloide/genética , Masculino , Fosforilação , RNA Interferente Pequeno/genética , Transdução de Sinais , Proteína Smad2/antagonistas & inibidores , Proteína Smad2/metabolismo , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/metabolismo
6.
Chem Biol Interact ; 310: 108747, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301289

RESUMO

Pathological scarring is an intractable problem for both patients and clinicians. A major obstacle for the development of scar remediation therapies is the paucity of suitable in vivo and in vitro models. The "Scar-in-a-jar" model was previously established by our colleagues based on the principle of "Macromolecular crowding". This has been demonstrated to be an extracellular matrix-rich in vitro model offering a novel tool for studies related to the extracellular matrix. In the study reported herein, we have optimised this approach to model human dermal fibroblasts derived from hypertrophic tissues. This optimised in vitro model has been found to hold similar properties, such as increased collagen I, interleukins and transforming growth factor beta-1 expression, compared to that observed in hypertrophic scar tissue in vivo. In addition, Shikonin has been previously demonstrated to hold potential as a novel hypertrophic scar treatment due to its apoptosis-inducing property on hypertrophic scar fibroblasts. Other Shikonin analogues have also been reported to hold apoptosis-inducing properties in various cancer cell lines, however, the effects of these analogues on hypertrophic scar-related cells are unknown. We therefore evaluated the effects of Shikonin and its analogues on hypertrophic scar-derived human fibroblasts using the optimised "Macromolecular crowding" model. Our data indicates that Shikonin and Naphthazarin are the most effective molecules compared to related naphthoquinones. The data generated from the study offers a novel in vitro collagen-rich model of hypertrophic scar tissue. It also provides further evidences supporting the use of Shikonin and Naphthazarin as potential treatments for hypertrophic scars.


Assuntos
Cicatriz/tratamento farmacológico , Naftoquinonas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Cicatriz/patologia , Cicatriz Hipertrófica/tratamento farmacológico , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Humanos , Modelos Biológicos , Pele/patologia
7.
Curr Opin Ophthalmol ; 30(4): 220-228, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31170100

RESUMO

PURPOSE OF REVIEW: To review the efficacy of intrastromal corneal ring segments (ICRS) for keratoconus and with other interventions such as contacts lens, keratoplasty, and corneal collagen cross-linking. RECENT FINDINGS: Changes in ICRS thickness and size, combination of procedures, and the adaptation of a more sophisticated classification system have broadened our application of ICRS. Recent studies have shown the long-term efficacy of ICRS in visual acuity, keratometry, and astigmatism. SUMMARY: Studies have demonstrated the short-term and long-term efficacy of ICRS implantation in patients with keratoconus.


Assuntos
Substância Própria/cirurgia , Ceratocone/cirurgia , Próteses e Implantes , Implantação de Prótese/métodos , Colágeno/metabolismo , Lentes de Contato , Substância Própria/metabolismo , Reagentes para Ligações Cruzadas/uso terapêutico , Humanos , Ceratocone/metabolismo , Fotoquimioterapia/métodos , Resultado do Tratamento , Acuidade Visual/fisiologia
8.
DNA Cell Biol ; 38(7): 670-677, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31188027

RESUMO

Cutis laxa represents a heterogeneous group of rare, inherited, or acquired connective tissue disorders with the common feature of loose and redundant skin with decreased elasticity. The skin of affected deer showed abnormal collagen fiber morphology. To identify the differentially expressed genes of the unusual localized skin laxity in sika deer, we performed transcriptome analysis in the affected and control sika deer. The transcriptome analysis showed 700 genes with significant differential expression in the affected skin as compared with normal skin. Pathway analysis revealed an enrichment of genes involved in tumor necrosis factor signaling, the extracellular matrix-receptor interaction, platelet activation, and Huntington's disease. A gene network was constructed, and the hub nodes such as PTGS2, THBS1, COL1A1, FOS, and NOS3 were found through PPI network analysis, which may contributed to the unusual localized skin laxity in sika deer. Abnormal expression patterns of genes during the development of the affected sika deer were successfully uncovered in the present study, which provides a reference for revealing the related mechanism underlying cutis laxa in sika deer and human beings.


Assuntos
Cútis Laxa/veterinária , Cervos/genética , Transcriptoma , Animais , Colágeno/genética , Colágeno/metabolismo , Cútis Laxa/genética , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Redes Reguladoras de Genes , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Trombospondina 1/genética , Trombospondina 1/metabolismo
9.
Toxicol Lett ; 313: 30-41, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31181250

RESUMO

The hedgehog (HH) signaling pathway plays an important role in lung development, but its significance in silicosis is unclear. We showed that in human coal pneumoconiosis autopsy specimens, Sonic Hedgehog (SHH) and the Glioma-associated oncogene homolog transcription factors family (GLI) 1 proteins were up-regulated, whereas Patch-1 (PTC) was down-regulated. The protein levels of SHH, smoothened (SMO), GLI1, GLI2, α-smooth muscle actin (α-SMA) and collagen type Ⅰ (Col Ⅰ) were also elevated gradually in the bronchoalveolar lavage fluid (BALF) of different stages of coal pneumoconiosis patients, dynamic silica-inhalation rat lung tissue and MRC-5 cells induced by Ang II at different time points, whereas the PTC and GLI3 levels were diminished gradually. Ac-SDKP, an active peptide of renin-angiotensin system (RAS), is an anti-fibrotic tetrapeptide. Targeting RAS axis also has anti-silicotic fibrosis effects. However, their roles on the HH pathway are still unknown. Here, we reported that Ac-SDKP + Captopril, Ac-SDKP, Captopril, or Ang (1-7) could alleviate silicotic fibrosis and collagen deposition, as well as improve the lung functions of silicotic rat. These treatments decreased the expression of SHH, SMO, GLI1, GLI2, α-SMA, and Col Ⅰ and increased the expression of PTC and GLI3 on both the silicotic rat lung tissue and MRC-5 cells induced by Ang II. We also reported that Ang II may promote myofibroblast differentiation via the GLI1 transcription factor and independently of the SMO receptor.


Assuntos
Angiotensina II/farmacologia , Angiotensina I/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Diferenciação Celular/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Fibrose Pulmonar/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Silicose/prevenção & controle , Adulto , Idoso , Animais , Antracose/metabolismo , Antracose/patologia , Linhagem Celular , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Proteínas Hedgehog/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Silicose/metabolismo , Silicose/patologia
10.
Cornea ; 38(8): 1049-1057, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31169612

RESUMO

PURPOSE: To evaluate the safety, efficacy, and stability of topography-guided partial PRK combined with corneal cross-linking (CXL) (the Athens Protocol [AP]) in pediatric patients with keratoconus over a 4-year follow-up period. METHODS: This prospective study included 39 keratoconic eyes of 21 patients younger than 18 years with clinical and imaging evidence of keratoconus progression. Partial topography-guided excimer laser ablation in conjunction with high-fluence CXL was performed in all patients according to the AP. Uncorrected distance visual acuity, corrected distance visual acuity, refraction, keratometry, endothelial cell density, topography, and tomography using both Scheimpflug and optical coherence tomography (OCT) were evaluated for 4 years postoperatively. RESULTS: At 4 years postoperative, there was significant improvement in mean uncorrected distance visual acuity from 0.51 ± 0.31 (decimal) to 0.65 ± 0.26 (decimal; P < 0.05). Mean corrected distance visual acuity improved from 0.71 ± 0.22 (decimal) preoperatively to 0.81 ± 0.19 (decimal; P < 0.05), respectively. Mean flat keratometry (K1) and mean steep keratometry (K2) readings reduced from 44.95 ± 3.71 D and 49.32 ± 5.05 D, respectively, preoperatively to 43.14 ± 2.95 D and 46.28 ± 4.87 D, respectively, (P < 0.05) at 4 years. The mean anterior maximum keratometry (Kmax) reading reduced from 56.81 ± 2.94 D preoperatively to 48.11 ± 3.17 D at 48 months. The mean index of height decentration was 0.105 ± 0.054 µm preoperatively and 0.049 ± 0.024 (P < 0.05) at 4 years postoperative. Mean preoperative corneal thickness at the thinnest point was 436.7 ± 42.6 µm preoperatively, 392.50 ± 45.68 µm at 12 months postoperative, and 418.42 ± 17.01 µm at 4-year follow-up. Late-onset deep corneal haze, a potential intrinsic complication of this technique in pediatric patients, was encountered in 2 cases at least 1 year after the procedure. CONCLUSIONS: Long-term results of the AP seem to be safe and effective in pediatric patients, with marked improvement in visual function and keratometric symmetry indices.


Assuntos
Reagentes para Ligações Cruzadas , Ceratocone/terapia , Fotoquimioterapia/métodos , Ceratectomia Fotorrefrativa/métodos , Cirurgia Assistida por Computador/métodos , Adolescente , Criança , Protocolos Clínicos , Colágeno/metabolismo , Terapia Combinada , Substância Própria/metabolismo , Topografia da Córnea/métodos , Feminino , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/metabolismo , Ceratocone/cirurgia , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos , Refração Ocular/fisiologia , Riboflavina/uso terapêutico , Tomografia de Coerência Óptica , Raios Ultravioleta , Acuidade Visual/fisiologia
11.
Cornea ; 38(8): 986-991, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31180339

RESUMO

PURPOSE: To evaluate the changes in anterior corneal topography induced by short-time wear of scleral contact lenses (SLs) in keratoconic subjects with and without a history of corneal cross-linking (CXL). METHODS: Nine keratoconic patients (14 eyes) were fitted with 18.5 mm SLs for optical rehabilitation. Subjects were divided into 2 groups: 7 eyes without a history of CXL (Non-CXL group) and 7 with a history of CXL (CXL group). Corneal topography was performed at baseline and after 2 and 5 hours of lens wear. The differences for simulated flat (Kflat), steep (Ksteep) and maximal (Kmax) corneal curvatures, central corneal astigmatism (CCA), and central cornea thickness were evaluated. RESULTS: No statistically significant difference was detected between Non-CXL and CXL groups in any of these measures. Statistically significant flattening was detected in Ksteep Repeated measures analysis of variance ([RM-ANOVA), F (2,24) = 11.32, P < 0.0001], CCA [RM-ANOVA, F (2,24) = 15.34, P < 0.0001], and Kmax [RM-ANOVA, F (2,24) = 19.10, P < 0.0001). From baseline to 5 hours of SL wear, Ksteep decreased on average from 53.1 to 52.4 D, Kmax decreased from 56.7 to 55.8 D, and CCA decreased from 7.2 to 6.3 D. Kmax showed a trend toward more flattening in the Non-CXL group. Central cornea thickness showed significant thickening over time from baseline (451 µm) to 5 hours (458 µm) of SL wear [RM-ANOVA, F (1,12) = 319.3, P < 0.0001]. CONCLUSIONS: Short-term scleral lens wear in keratoconic patients may cause flattening of the anterior cornea. A history of CXL treatment does not guarantee corneal shape stability after scleral lens wear. Practitioners should be aware of these changes because scleral lens wear may mask the signs of keratoconus progression.


Assuntos
Lentes de Contato , Córnea/fisiopatologia , Topografia da Córnea , Reagentes para Ligações Cruzadas , Ceratocone/fisiopatologia , Ceratocone/terapia , Fotoquimioterapia/métodos , Adulto , Colágeno/metabolismo , Substância Própria/metabolismo , Feminino , Humanos , Ceratocone/tratamento farmacológico , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Esclera , Acuidade Visual/fisiologia , Adulto Jovem
12.
J Sci Food Agric ; 99(13): 5752-5759, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31162681

RESUMO

BACKGROUND: Sea cucumber (Stichopus japonicus) is easy to autolysis in response to a variety of environmental and mechanical factors. In the current study, collagen fibres were extracted from fresh sea cucumber body wall and then incubated with endogenous matrix metalloprotease (MMP) of sea cucumber. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), chemical analysis and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis were utilized to demonstrate the changes in collagen fibres, collagen fibrils and collagen proteins. Moreover, a verification experiment was also carried out to confirm the contribution of MMP to the autolysis of sea cucumber. RESULTS: Endogenous MMP caused complete depolymerization of collagen fibres into smaller collagen fibril bundles and collagen fibrils due to the fracture of proteoglycan interfibrillar bridges. Meanwhile, endogenous MMP also caused partial degradation of collagen fibrils by releasing soluble hydroxyproline and pyridinium cross-links. Furthermore, the treatment with MMP inhibitor (1,10-phenanthroline) prevented the autolysis of tissue blocks from S. japonicus dermis. CONCLUSION: Endogenous MMP was the key enzyme in the autolysis of sea cucumber, while its action still focused on high-level structures of collagens especially collagen fibres. © 2019 Society of Chemical Industry.


Assuntos
Autólise , Metaloproteases/metabolismo , Stichopus/enzimologia , Stichopus/fisiologia , Animais , Colágeno/metabolismo , Colágeno/ultraestrutura , Hidroxiprolina/metabolismo , Metaloproteases/genética , Microscopia Eletrônica de Varredura , Stichopus/ultraestrutura
13.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(3): 248-252, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31218856

RESUMO

OBJECTIVE: To verify the effect of the mutant gene vps4b on the expression of tooth development-related proteins, dentin sialophosphoprotein (DSPP) and collagenⅠ (COL-Ⅰ). METHODS: Paraffin tissue sections of the first molar tooth germ were obtained from the heads of fetal mice at the embryonic stages of 13.5, 14.5, and 16.5 days and from the mandibles of larvae aged 2.5 and 7 days after birth. The immunohistochemical method was used to detect the expression and location of DSPP and COL-Ⅰ in wild-type mouse and vps4b knockout mouse. RESULTS: DSPP and COL-Ⅰ were not found in the bud and cap stages of wild-type mouse molar germ. In the bell stage, DSPP was positively expressed in the inner enamel epithelium and dental papilla, whereas COL-Ⅰ was strongly expressed in the dental papilla and dental follicle. During the secretory and mineralized periods, DSPP and COL-Ⅰ were intensely observed in ameloblasts, odontoblasts, and dental follicles, but COL-Ⅰ was also expressed in the dental papilla. After vps4b gene knockout, DSPP was not expressed in the dental papilla of the bell stage and in the dental papilla and dental follicle of the secretory phase. The expression position of COL-Ⅰ in the bell and mineralization phase was consistent with that in the wild-type mice. Moreover, the expression of COL-Ⅰ in the dental papilla changed in the secretory stage. CONCLUSIONS: Gene vps4b plays a significant role in the development of tooth germ. The expression of DSPP and COL-Ⅰ may be controlled by gene vps4b and regulates the development of tooth dentin and cementum together with vps4b.


Assuntos
ATPases Associadas a Diversas Atividades Celulares , Complexos Endossomais de Distribuição Requeridos para Transporte , Proteínas da Matriz Extracelular , Fosfoproteínas , Sialoglicoproteínas , ATPases Associadas a Diversas Atividades Celulares/genética , Animais , Colágeno/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Proteínas da Matriz Extracelular/metabolismo , Camundongos , Camundongos Knockout , Dente Molar , Odontoblastos , Fosfoproteínas/metabolismo , Sialoglicoproteínas/metabolismo , Germe de Dente
14.
Cornea ; 38(7): 864-867, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31170104

RESUMO

PURPOSE: To assess corneal thickness changes with isotonic riboflavin (RF) solution with hydroxylpropyl methylcellulose in patients undergoing accelerated corneal collagen crosslinking (CXL) with and without an eyelid speculum. METHODS: Fifty-two eyes of 48 patients with progressive keratoconus were enrolled in this study. The patients in this study were divided into 2 groups: in group 1 an eyelid speculum was removed during 20-minute RF (0.1%) + hydroxylpropyl methylcellulose (Mediocross M; Avedro Inc, Waltham, MA) instillation, and in group 2 the eyelid speculum was retained in place during the entire CXL procedure. All patients underwent accelerated CXL using continuous ultraviolet-A (UVA) light exposure at 9 mW/cm for 10 minutes; total energy dose was 5.4 J/cm. Intraoperative ultrasound pachymetry measurements were obtained before and after epithelial removal, after RF loading, and after UVA light exposure at 5 and 10 minutes. RESULTS: The preoperative pachymetric measurements decreased in both groups after the removal of epithelium [group 1 (n = 26): -25 µm, group 2 (n = 26): -31 µm, P = 0.234]. Although the thinnest pachymetry significantly increased after soaking in both group 1 (52.26 µm) and group 2 (27.88 µm, P < 0.001), closure of the eyelids during RF instillation further increased the pachymetry readings (P < 0.0001). The corneal thickness remained stable in both groups during UVA irradiation at 5 and 10 minutes (P > 0.05). CONCLUSIONS: Closure of the eyelids further induces corneal swelling that may offer an advantage to improve safety of the procedure particularly in thin corneas.


Assuntos
Colágeno/metabolismo , Córnea/efeitos dos fármacos , Derivados da Hipromelose/uso terapêutico , Ceratocone/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Adolescente , Adulto , Criança , Reagentes para Ligações Cruzadas/uso terapêutico , Feminino , Humanos , Derivados da Hipromelose/farmacologia , Masculino , Fotoquimioterapia/instrumentação , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Instrumentos Cirúrgicos , Raios Ultravioleta , Adulto Jovem
15.
Mar Drugs ; 17(6)2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151236

RESUMO

Although collagens from vertebrates are mainly used in regenerative medicine, the most elusive issue in the collagen-based biomedical scaffolds is its insufficient mechanical strength. To solve this problem, electrospun collagen composites with chitins were prepared and molecular interactions which are the cause of the mechanical improvement in the composites were investigated by two-dimensional correlation spectroscopy (2DCOS). The electrospun collagen is composed of two kinds of polymorphs, α- and ß-chitin, showing different mechanical enhancement and molecular interactions due to different inherent configurations in the crystal structure, resulting in solvent and polymer susceptibility. The collagen/α-chitin has two distinctive phases in the composite, but ß-chitin composite has a relatively homogeneous phase. The ß-chitin composite showed better tensile strength with ~41% and ~14% higher strength compared to collagen and α-chitin composites, respectively, due to a favorable secondary interaction, i.e., inter- rather than intra-molecular hydrogen bonds. The revealed molecular interaction indicates that ß-chitin prefers to form inter-molecular hydrogen bonds with collagen by rearranging their uncrumpled crystalline regions, unlike α-chitin.


Assuntos
Quitina/metabolismo , Colágeno/metabolismo , Animais , Quitina/química , Quitina/ultraestrutura , Colágeno/química , Colágeno/ultraestrutura , Cristalização , Técnicas Eletroquímicas , Humanos , Ligações de Hidrogênio , Microscopia Eletrônica de Varredura , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier , Resistência à Tração
16.
Nat Commun ; 10(1): 2602, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197136

RESUMO

Temperature is a key factor for determining the lifespan of both poikilotherms and homeotherms. It is believed that animals live longer at lower body temperatures. However, the precise mechanism remains largely unknown. Here, we report that autophagy serves as a boost mechanism for longevity at low temperature in the nematode Caenorhabditis elegans. The adiponectin receptor AdipoR2 homolog PAQR-2 signaling detects temperature drop and augments the biosynthesis of two ω-6 polyunsaturated fatty acids, γ-linolenic acid and arachidonic acid. These two polyunsaturated fatty acids in turn initiate autophagy in the epidermis, delaying an age-dependent decline in collagen contents, and extending the lifespan. Our findings reveal that the adiponectin receptor PAQR-2 signaling acts as a regulator linking low temperature with autophagy to extend lifespan, and suggest that such a mechanism may be evolutionally conserved among diverse organisms.


Assuntos
Autofagia/fisiologia , Proteínas de Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/fisiologia , Longevidade/fisiologia , Proteínas de Membrana/fisiologia , Animais , Animais Geneticamente Modificados , Ácido Araquidônico/biossíntese , Temperatura Baixa , Colágeno/metabolismo , Epiderme/metabolismo , Ácidos Graxos Ômega-6/biossíntese , Interferência de RNA , Transdução de Sinais/fisiologia
17.
Cancer Sci ; 110(7): 2110-2118, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31120174

RESUMO

The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor-associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2ß1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2ß1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.


Assuntos
Cromonas/administração & dosagem , Colágeno/metabolismo , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Macrófagos/patologia , Morfolinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células , Cromonas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Integrina alfa2beta1/genética , Integrina alfa2beta1/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Microambiente Tumoral , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Life Sci ; 231: 116422, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31059689

RESUMO

This study was performed to evaluate the antidiabetic and wound healing activity of plumbagin in diabetic rats by macroscopical, biochemical, histological, immunohistochemical and molecular methods. Percentage of wound closure and contraction was delayed in diabetic rats when compared to non-diabetic group. There was significant reduction in period of epithelialization, collagen and protein content. Serum insulin level was significantly lowered together with increase in glucose level in diabetic rats. Lipid levels were increased significantly with concomitant decrease in HDL level. The mRNA levels of Nrf2, collagen-1, TGF-ß and α-SMA were significantly lowered whereas Keap-1 levels were increased in diabetic rats. The level of lipid peroxides was increased while the levels of antioxidants were lowered significantly. ELISA results reveal upregulated levels of inflammatory markers. Western blot result shows upregulated levels of CD68 and CD163 proteins in wound area of diabetic rats. Histopathological observation revealed increased inflammatory cells infiltration in diabetic control. Immunofluorescent staining and immunohistochemical analysis also displayed delayed wound healing in diabetic groups. Diabetic rats treated with 10% and 20% plumbagin showed increased epithelialization, collagen deposition, increased serum insulin level and increased antioxidant status. Lipid peroxides and lipid levels were lowered significantly with increase in HDL level. Inflammatory markers were lowered, and growth factors expressions were increased markedly. Thus, the results of the study indicated that plumbagin administration could improve wound healing activity and could serve as a potent antidiabetic and anti-inflammatory agent.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Naftoquinonas/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Insulina/sangue , Masculino , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismo
19.
Cornea ; 38(8): 980-985, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31107284

RESUMO

PURPOSE: To evaluate visual, refractive, topographic, and aberrometric outcomes of transepithelial phototherapeutic keratectomy (PTK) + corneal collagen crosslinking in the treatment of pellucid marginal degeneration. METHODS: This retrospective study includes 20 eyes of 15 patients with pellucid marginal degeneration treated with transepithelial PTK + accelerated corneal collagen crosslinking. Visual acuity, refraction, topographic keratometry, pachymetry, and aberrations were recorded pretreatment and 6, 12, 24, and 36 months after treatment. RESULTS: Stabilization in visual acuity was observed throughout the 36 months of follow-up (P > 0.05). The cylindrical value was significantly lower (P < 0.05) during the follow-up compared with the baseline (4.97 ± 2.00, 3.86 ± 2.01, 3.92 ± 2.27, 2.87 ± 1.70, and 3.28 ± 3.12 D at the baseline and postoperative 6th, 12th, 24th, and 36th month, respectively). Spherical equivalent was significantly lower at the 24th (P = 0.02) and 36th month (P = 0.01) follow-up intervals. A significant decrease (P < 0.05) in average keratometry readings was observed in all follow-up points (47.12 ± 4.66, 46.65 ± 4.38, 46.57 ± 4.57, 46.46 ± 4.81, and 46.27 ± 4.46 D, respectively). The maximum keratometry value remained stable (P > 0.05) in all visits (64.30 ± 10.70, 63.49 ± 10.05, 62.97 ± 9.50, 63.33 ± 10.06, and 62.27 ± 10.36 D, respectively). The Baiocchi Calossi Versaci index was significantly lower (P < 0.05) at all follow-up points compared with the baseline (3.21 ± 1.93, 2.99 ± 1.96, 2.96 ± 1.93, 2.82 ± 1.95, and 2.86 ± 1.99 µm, respectively). Central and minimum corneal thicknesses were significantly lower (P ≤ 0.01) compared with the baseline throughout the follow-up. Higher order aberration, trefoil, coma, and spherical aberration values remained stable during the follow-up compared with the baseline (P > 0.05). CONCLUSIONS: The combination of transepithelial PTK with accelerated corneal collagen crosslinking seems to be an effective treatment in patients with pellucid marginal degeneration in the long-term.


Assuntos
Colágeno/metabolismo , Distrofias Hereditárias da Córnea/terapia , Substância Própria/metabolismo , Reagentes para Ligações Cruzadas , Fotoquimioterapia/métodos , Ceratectomia Fotorrefrativa/métodos , Adulto , Terapia Combinada , Distrofias Hereditárias da Córnea/tratamento farmacológico , Distrofias Hereditárias da Córnea/metabolismo , Distrofias Hereditárias da Córnea/cirurgia , Topografia da Córnea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico , Refração Ocular/fisiologia , Estudos Retrospectivos , Riboflavina/uso terapêutico , Raios Ultravioleta , Acuidade Visual/fisiologia
20.
Cornea ; 38(8): 1033-1039, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31107761

RESUMO

PURPOSE: To report a case of bilateral and repetitive corneal perforations after corneal cross-linking (CXL) for keratoconus in a woman harboring potentially pathogenic variants in the ZNF469 gene and to characterize the keratoconus phenotype in this woman and her daughter who shared the same ZNF469 mutations. METHODS: Clinical characterization of the proband and her daughter followed by sequencing of the genes associated with brittle cornea syndrome, ZNF469 and PRDM5, in both individuals. RESULTS: An Ashkenazi Jewish woman in her sixth decade presented with diffuse corneal thinning and progressive steepening consistent with keratoconus. After CXL, epithelium-off in the first eye and epithelium-on in the second, she developed spontaneous corneal perforations in each eye. Her daughter in her fourth decade demonstrated a similar pattern of diffuse corneal thinning and progressive corneal steepening but did not undergo CXL and did not develop corneal perforation. Screening of the ZNF469 and PRDM5 genes revealed 3 missense ZNF469 variants (c.2035G>A, c.10244G>C, and c.11119A>G) in cis arrangement on 1 allele of ZNF469 in both proband and her daughter. Although the 3 variants share low (<0.01) global minor allele frequencies, each has significantly higher minor allele frequencies (0.01-0.03) in the Ashkenazi Jewish population, leading to uncertainty regarding a pathogenic role for the identified variants. CONCLUSIONS: CXL may be associated with the development of corneal perforation in particular at-risk individuals with keratoconus. Identifying clinical and genetic risk factors, including screening of ZNF469 and PRDM5, may be useful in the prevention of significant complications after CXL.


Assuntos
Perfuração da Córnea/etiologia , Reagentes para Ligações Cruzadas/efeitos adversos , Ceratocone/genética , Mutação de Sentido Incorreto , Fotoquimioterapia/efeitos adversos , Fatores de Transcrição/genética , Adulto , Colágeno/metabolismo , Perfuração da Córnea/diagnóstico , Substância Própria/metabolismo , Topografia da Córnea , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Judeus/genética , Ceratocone/tratamento farmacológico , Ceratocone/metabolismo , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/efeitos adversos , Reação em Cadeia da Polimerase , Raios Ultravioleta
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