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1.
Dermatol Ther ; 34(1): e14690, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33342012

RESUMO

Axillary bromhidrosis is a widespread social problem in our society. Various modalities have been developed for the destruction or removal of the apocrine sweat glands to eliminate underarm odor. However, conventional surgical treatments often result in a high complication rate and frequent recurrence. In this study, we aimed to evaluate the effect of refined tumescent liposuction-curettage with pruning in small incisions as treatment for axillary bromhidrosis. Between July 2013 and April 2019, 110 patients (75 women and 35 men) with axillary bromhidrosis underwent refined tumescent liposuction-curettage with pruning. The results of eliminating underarm odor were evaluated by both the patients and doctors and rated as very satisfied (excellent), satisfied (good), slightly satisfied (fair), and not satisfied (poor). Postoperative complications, such as dehiscence, infection, wound contracture, cyst, subcutaneous hydrops, hematoma, or seroma, were also evaluated. Preoperative and postoperative histological examinations of axillary tissues were performed in two patients. In the subjective evaluation of 110 patients, 33 (30.0%) were very satisfied with the results, 70 (63.6%) were satisfied, and seven (6.4%) were slightly satisfied. The objective evaluation showed that 43 (39.1%) patients graded the results as excellent, whereas others graded the results as good. No serious complications occurred, except three patients with slight local subcutaneous hydrops and hematoma. Histologic examinations showed that the apocrine glands were significantly decreased or destroyed after the surgery. Refined tumescent liposuction-curettage with pruning in small incisions is an effective method for the treatment of axillary bromhidrosis.


Assuntos
Hiperidrose , Lipectomia , Axila/cirurgia , Curetagem , Feminino , Humanos , Hiperidrose/cirurgia , Lipectomia/efeitos adversos , Masculino , Recidiva Local de Neoplasia , Resultado do Tratamento
2.
Biodegradation ; 29(3): 233-243, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29502248

RESUMO

The increasing usage of partially hydrolyzed polyacrylamide (HPAM) in oilfields as a flooding agent to enhance oil recovery at so large quantities is an ecological hazard to the subsurface ecosystem due to persistence and inertness. Biodegradation of HPAM is a potentially promising strategy for dealing with this problem among many other methods available. To understand the responsible microorganisms and mechanism of HPAM biodegradation under anaerobic conditions, an enrichment culture from production waters of oil reservoirs were established with HPAM as the sole source of carbon and nitrogen incubated for over 328 days, and analyzed using both molecular microbiology and chemical characterization methods. Gel permeation chromatography, High-pressure liquid chromatography and Fourier-transformed infrared spectroscopy results indicated that, after 328 days of anaerobic incubation, some of the amide groups on HPAM were removed and released as ammonia/ammonium and carboxylic groups, while the carbon backbone of HPAM was converted to smaller polymeric fragments, including oligomers and various fatty acids. Based on these results, the biochemical process of anaerobic biodegradation of HPAM was proposed. The phylogenetic analysis of 16S rRNA gene sequences retrieved from the enrichments showed that Proteobacteria and Planctomycetes were the dominant bacteria in the culture with HPAM as the source of carbon and nitrogen, respectively. For archaea, Methanofollis was more abundant in the anaerobic enrichment. These results are helpful for understanding the process of HPAM biodegradation and provide significant insights to the fate of HPAM in subsurface environment and for possible bioremediation.


Assuntos
Resinas Acrílicas/metabolismo , Metano/metabolismo , Campos de Petróleo e Gás/microbiologia , Águas Residuárias/microbiologia , Resinas Acrílicas/química , Anaerobiose/efeitos dos fármacos , Archaea/efeitos dos fármacos , Archaea/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Biodegradação Ambiental/efeitos dos fármacos , Carbono/farmacologia , Ácidos Graxos Voláteis/análise , Hidrólise , Nitrogênio/farmacologia , Filogenia , RNA Ribossômico 16S/genética
3.
Int J Mol Sci ; 16(4): 7445-61, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25849654

RESUMO

Viscosity loss of high-molecular-weight partially hydrolyzed polyacrylamide (HPAM) solution was observed in a water injection pipeline before being injected into subterranean oil wells. In order to investigate the possible involvement of microorganisms in HPAM viscosity loss, both bacterial and archaeal community compositions of four samples collected from different points of the transportation pipeline were analyzed using PCR-amplification of the 16S rRNA gene and clone library construction method together with the analysis of physicochemical properties of HPAM solution and environmental factors. Further, the relationship between environmental factors and HPAM properties with microorganisms were delineated by canonical correspondence analysis (CCA). Diverse bacterial and archaeal groups were detected in the four samples. The microbial community of initial solution S1 gathered from the make-up tank is similar to solution S2 gathered from the first filter, and that of solution S3 obtained between the first and the second filter is similar to that of solution S4 obtained between the second filter and the injection well. Members of the genus Acinetobacter sp. were detected with high abundance in S3 and S4 in which HPAM viscosity was considerably reduced, suggesting that they likely played a considerable role in HPAM viscosity loss. This study presents information on microbial community diversity in the HPAM transportation pipeline and the possible involvement of microorganisms in HPAM viscosity loss and biodegradation. The results will help to understand the microbial community contribution made to viscosity change and are beneficial for providing information for microbial control in oil fields.


Assuntos
Resinas Acrílicas/química , Archaea/genética , Bactérias/genética , Campos de Petróleo e Gás/microbiologia , Biodegradação Ambiental , Biodiversidade , Peso Molecular , Filogenia , RNA Ribossômico 16S/genética , Soluções/química , Meios de Transporte/métodos , Viscosidade , Microbiologia da Água
4.
Aesthetic Plast Surg ; 37(1): 22-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23296762

RESUMO

BACKGROUND: In recent years, many mini-incisional techniques for double-eyelid plasty have been developed. However, the removal of pretarsal tissue has not been satisfactory because only small pockets of soft tissue just inferior to the skin have been removed to place the suture. The formed double eyelid may therefore not be durable. This report introduces a modified mini-incisional method that involves removing a long uncut strip of orbicularis through three mini-incisions. METHODS: A strip of orbicularis uncut from the inner canthus to the outer canthus was removed through three mini-incisions made on the upper eyelid, quite similar to that of a full incisional procedure. The left orbicularis then was pruned in three directions: left, right, and down (toward the palpebral margin). Finally, the incisions were sutured, and a vivid fold was created. RESULTS: From 2008 to 2012, the authors applied this technique to 90 patients (174 eyes). Although the trauma may have been more severe due to a large amount of orbicularis removed, including an uncut strip of orbicularis, bleeding during the operation was easy to control and usually very limited. The edema period for most patients ended within 3 weeks, mainly because of the skin bridge between each incision. The scars became unnoticeable after 3-6 months. Disappearance of the fold was not found in any case at either the 3- or 12-month (average, 9-month) follow-up evaluation or during the 4-year follow-up period. CONCLUSION: The described technique combines the advantages of both full incisional and the usual mini-incisional techniques in developing a long-lasting suprapalpebral fold with inconspicuous scars and a short recovery period. LEVEL OF EVIDENCE V: Opinions of respected authorities, based on clinical experience,descriptive studies, or reports of expert committees.


Assuntos
Blefaroplastia/métodos , Pálpebras/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Músculos Oculomotores , Técnicas de Sutura , Adulto Jovem
5.
Aesthetic Plast Surg ; 36(5): 1039-46, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22890861

RESUMO

BACKGROUND: The surgical procedure aimed at constructing the upper eyelid crease is the cosmetic operation most commonly requested by Asian patients. The incisional approach leaves a permanent crease, but the swelling period can last longer than 3 months, and a distinct scar usually is unavoidable. Many mini-incisional techniques with incisions of varying sizes and locations have been developed, but the removal of pretarsal tissue has not been sufficient because these procedures wipe out only small pockets of soft tissue immediately inferior to skin for placement of the suture. Thus, the formed double eyelid may not be durable. The technique the authors introduce is a modified mini-incisional technique that combines the benefits of both the incisional and the usual mini-incisional methods. METHODS: Three 3- to 4-mm mini-incisions were made on each upper eyelid. The orbicularis muscle was isolated carefully from the skin and then cut off as much as possible in three directions: down (toward the palpebral margin), left, and right. Finally, the three incisions were sutured, and a vivid fold was created. This technique was applied for 110 patients. The follow-up period ranged from 3 to 12 months. The patients were welcomed for further treatment if any problems occurred at any time. An extra 3 years of follow-up evaluation was applied for 24 patients (46 cases) to assess the long-term maintenance of the fold. RESULTS: This study enrolled 110 patients (212 cases). A natural-looking skin fold appeared after the edema period. The scar was not obvious. Disappearance of the fold was not found in any case during 3-12 months (mean, 9 months) of follow-up evaluation. Obvious shifting of the fold was found in four cases during the additional 3 years of follow-up evaluation, but disappearance of the fold was not found in any case. CONCLUSION: This modified technique was found to be successful in developing a natural-appearing, long-lasting suprapalpebral fold with an inconspicuous scar. It combines the best of both the open and usual mini-incisional techniques. Because a large amount of pretarsal soft tissue is removed, the double fold is less likely to fade away. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article.


Assuntos
Blefaroplastia/métodos , Pálpebras/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
6.
Front Microbiol ; 13: 855988, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401464

RESUMO

Microbial infections cause significant morbidity and mortality in neonates. Metagenomic next-generation sequencing is a hypothesis-free and culture-free test that enables broad identification of pathogens and antimicrobial resistance genes directly from clinical samples within 24 h. In this study, we used mNGS for etiological diagnosis and monitoring the efficacy of antibiotic treatment in a cohort of neonatal patients with severe infections. The median age was 19.5 (3-52) days, median gestational age was 37.96 (31-40+3) weeks, and the median birth weight was 3,261 (1,300-4,300) g. The types of infectious diseases included pneumonia, sepsis, and meningitis. mNGS reported microbial findings in all cases, which led to changes in antibiotic treatment. These included cases of Mycobacterium tuberculosis, Legionella pneumophila, and Bacillus cereus. Eight of ten infants recovered after antibiotic adjustment and showed normal development during follow-up. On the other hand, neurological retardation was seen in two infants with meningitis. mNGS enabled etiological diagnosis and guided antibiotic therapy when all conventional methods failed to discover the culprit. It has the potential to cut down the overall cost and burden of disease management in neonatal infections.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 188-192, 2021 Feb.
Artigo em Zh | MEDLINE | ID: mdl-33554817

RESUMO

OBJECTIVE: To understand the carrying rate, gene mutation frequency and composition ratio of thalassemia in pregnant women in Suxian and Beihu districts of Chenzhou, Hunan Province. METHODS: Thalassemia gene in 11 212 samples was analyzed by using Next-Generation Sequencing. RESULTS: Among the 11 212 samples, 938 were diagnosed as thalassemia, in which 618 (5.51%) were diagnosed as α-thalassemia, 268 (2.39%) as ß-thalassemia, 29(0.26%)as abnormal hemoglobin and 23 (0.21%) as αß-thalassemia. The gene mutations of --SEA /αα(40.29%) and -α3.7/αα(37.7%) in α-thalassemia were the most common, while for ß- thalassemia, the most commonly gene mutation were ß41-42M/ßN(24.26%) and ß654M/ßN(23.88%). The detection rate of rare type α,ß-thalassemia gene was 0.19%(21/11 212), 0.53%(59/11 212), respectively. CONCLUSION: The carrying rate of thalassemia in pregnant women is 8.37% in Suxian and Beihu districts of Chenzhou city, and the genotypes are complex. Next-Generation Sequencing can detect rare thalassemia genes and new gene mutations effectively.


Assuntos
Hemoglobinas Anormais , Talassemia alfa , Talassemia beta , China , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Gravidez , Gestantes , Talassemia alfa/genética , Talassemia beta/genética
8.
Aesthetic Plast Surg ; 34(4): 534-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20333522

RESUMO

Progressive facial hemiatrophy (PFH) was first described by Parry in 1825 and later by Romberg in 1846 and was also known as Parry-Romberg syndrome. Progressive facial hemiatrophy, as the name suggests, usually has unilateral presentation. However, bilateral manifestation has been reported in 5-10% of the cases. It is a rare disorder with few cases reported. Treatment involves augmentation of the atrophic region and restoration of symmetry of the face. Because many tissues are needed, it is very difficult to treat. In this article we report the use of a superficial temporal fascial flap plus lipofilling to treat bilateral progressive facial hemiatrophy. We obtained good facial volume, smooth contour, and soft palpation. It is safer, simple to perform, and more cost effective than free tissue transfer. It is a suitable technique of choice in the treatment of bilateral progressive facial hemiatrophy.


Assuntos
Tecido Adiposo/transplante , Hemiatrofia Facial/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Hemiatrofia Facial/patologia , Feminino , Humanos , Adulto Jovem
9.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 5): m502, 2009 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-21583750

RESUMO

The title compound, [Cd(C(5)H(3)N(2)O(2))(N(3))](n), has been pre-pared by the reaction of pyrazine-2-carboxylic acid, cadmium(II) nitrate and sodium azide. In the structure, the Cd(II) atom is six-coordinated by two azide anions and three pyrazine-2-carboxyl-ate ligands. Each pyrazine-2-carboxyl-ate ligand bridges three Cd(II) atoms, whereas the azide ligand bridges two Cd(II) atoms, resulting in the formation of a two-dimensional metal-organic polymer developing parallel to the (100) plane.

10.
Acta Crystallogr Sect E Struct Rep Online ; 64(Pt 7): m856, 2008 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-21202733

RESUMO

The title compound, [CoBr(2)(C(18)H(12)N(6)S)], is a mononuclear complex in which a twofold rotation axis passes through the Co and S atoms. The Co(II) center is six-coordinated by four N atoms from one bis-[4-(2-pyrid-yl)pyrimidin-2-yl] sulfide (L) ligand and two bromide anions, forming an octa-hedral coordination geometry, where the four donor N atoms are located in the equatorial plane and the Br atoms occupy the axial positions. The sum of the bond angles around the Co atom in the equatorial plane is 360.5°, with the four N atoms and the central Co atom almost coplanar. In the crystal structure, the mononuclear units are linked by π-π stacking inter-actions (the inter-planar distances are 3.469 and 3.533 Å, and the corresponding centroid-centroid distances are 3.791 and 3.896 Å) into a three-dimensional supra-molecular network.

11.
Front Pharmacol ; 9: 92, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29487530

RESUMO

Cisplatin, as the first-line anti-tumor agent, is widely used for treatment of a variety of malignancies including non-small cell lung cancer (NSCLC). However, the acquired resistance has been a major obstacle for the clinical application. Scutellarin is a active flavone extracted from Erigeron breviscapus Hand-Mazz that has been shown to exhibit anticancer activities on various types of tumors. Here, we reported that scutellarin was capable of sensitizing A549/DDP cells to cisplatin by enhancing apoptosis and autophagy. Mechanistic analyses indicated that cisplatin-induced caspase-3-dependent apoptosis was elevated in the presence of scutellarin through activating extracellular signal-regulated kinases (ERK)-mediated p53 pathway. Furthermore, scutellarin also promoted cisplatin-induced cytotoxic autophagy, downregulated expression of p-AKT and c-met. Deficiency of c-met reduced p-AKT level, and inhibition of p-AKT or c-met improved autophagy in A549/DDP cells. Interestingly, loss of autophagy attenuated the synergism of this combination. In vivo, the co-treatment of cisplatin and scutellarin notably reduced the tumor size when compared with cisplatin treatment alone. Notably, scutellarin significantly reduced the toxicity generated by cisplatin in tumor-bearing mice. This study identifies the unique role of scutellarin in reversing cisplatin resistance through apoptosis and autophagy, and suggests that combined cisplatin and scutellarin might be a novel therapeutic strategy for patients with NSCLC.

12.
Sci Rep ; 8(1): 3332, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463869

RESUMO

Angiotensin-converting enzyme inhibitors (ACEIs) can improve the fibrotic processes in many internal organs. Recent studies have shown a relationship between ACEI with cutaneous scar formation, although it has not been confirmed, and the underlying mechanism is unclear. In this study, we cultured mouse NIH 3T3 fibroblasts with different concentrations of ACEI. We measured cell proliferation with a Cell Counting Kit-8 and collagen expression with a Sirius Red Collagen Detection Kit. Flow cytometry and western blotting were used to detect transforming growth factor ß1 (TGF-ß1) signaling. We also confirmed the potential antifibrotic activity of ACEI in a rat scar model. ACEI reduced fibroblast proliferation, suppressed collagen and TGF-ß1 expression, and downregulated the phosphorylation of SMAD2/3 and TAK1, both in vitro and in vivo. A microscopic examination showed that rat scars treated with ramipril or losartan were not only narrower than in the controls, but also displayed enhanced re-epithelialization and neovascularization, and the formation of organized granulation tissue. These data indicate that ACEI inhibits scar formation by suppressing both TGF-ß1/SMAD2/3 and TGF-ß1/TAK1 pathways, and may have clinical utility in the future.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Cicatriz/prevenção & controle , Transdução de Sinais , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Animais , Células Cultivadas , Cicatriz/metabolismo , Cicatriz/patologia , Colágeno/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/metabolismo , Masculino , Camundongos , Fosforilação , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/antagonistas & inibidores , Proteína Smad2/metabolismo , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
13.
Oncotarget ; 8(70): 114945-114955, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29383132

RESUMO

There is an urgent need for effective molecular therapies for hepatocellular carcinoma (HCC), the third-leading cause of cancer-related deaths worldwide. Norcantharidin (NCTD), a demethylated derivative of cantharidin, reportedly exhibits anticancer activity against various types of tumors, including HCC, though the mechanisms involved remain largely unknown. Here, we report that NCTD reduces viability of human MHCC-97H (97H) and HepG2 HCC cells, and induces cell death by triggering high levels of autophagy. Moreover, a significant attenuation of tumor growth was observed after NCTD treatment of HepG2 tumors in vivo, and this effect was enhanced by co-treatment with the c-Met inhibitor crizotinib. Interestingly, western blot analyses showed that the cytotoxic autophagy induced by NCTD correlates with a reduction in the phosphorylation status of both c-Met and m-TOR. These results suggest that cytotoxic autophagy resulting from inhibition of c-Met/mTOR signaling may be achieved in HCC by combined NCTD and crizotinib administration. Further studies to validate the therapeutic potential of this approach are warranted.

14.
Menopause ; 23(4): 417-24, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26506499

RESUMO

OBJECTIVE: Our objective was to perform a meta-analysis examining the risk of ovarian cancer with different types and regimens (continuous or sequential) of hormone therapy (HT). METHODS: PubMed, Cochrane, and Embase databases were searched until December 2014 using the terms: HT, estrogen therapy (ET), ovarian cancer, postmenopausal, and menopausal. HT was considered unopposed ET, estrogen-progestin therapy (EPT), or ET+EPT (ET followed by EPT). RESULTS: Of 180 studies identified, 12 were included in the meta-analysis. Of the 12 studies, 9 were cohort studies including 2,350,546 women and 7,549 cases of ovarian cancer, and 3 were case-control studies including a total of 1,347 cases and 2,052 controls. ET, EPT, and ET+EPT were associated with an increased risk of ovarian cancer: pooled hazard ratio (HR)/relative risk (RR) =1.37, 95% CI: 1.19 to 1.58, P<0.001; pooled HR/RR=1.27, 95% CI: 1.18 to 1.36, P<0.001; pooled HR/RR=1.55, 95% CI: 1.05 to 2.30, P=0.027, respectively. Continuous and sequential regimens were associated with an increased risk: pooled HR/RR=1.27, 95% CI: 1.04 to 1.54, P=0.018; pooled HR/RR=1.31, 95% CI: 1.08 to 1.58, P=0.006, respectively. HT was associated with an increased risk of serous ovarian cancer (pooled HR/RR=1.46, 95% CI=1.28-1.67, P<0.001), but not clear cell, endometrioid, or mucinous ovarian cancer. CONCLUSIONS: Hormone therapy, regardless of type or regimen, is associated with an increased ovarian cancer risk.


Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Neoplasias Ovarianas/epidemiologia , Pós-Menopausa , Estudos de Casos e Controles , Estudos de Coortes , Estrogênios/efeitos adversos , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Progestinas/efeitos adversos , Modelos de Riscos Proporcionais , Risco
15.
J Hazard Mater ; 304: 388-99, 2016 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-26595898

RESUMO

Biofilms increase dragging force for liquid transportation, cause power consumption, and result in equipment corrosion in polymer-flooding oilfields. To reveal the responsible microorganisms for biofilm formation and stability of high-molecular-weight polyacrylamide (PAM), a biofilm, developed on the sieve of a piston plunger pump in a water transport and injection pipeline with partial hydrolyzed polyacrylamide (HPAM) in Daqing Oilfield, was collected and analyzed by molecular microbiology, chemical and physical methods. Diverse bacterial groups (11 families) were detected in the biofilm, including Pseudomonadaceae, Rhodocyclaceae, Desulfobulbaceae, Alcaligenaceae, Comamonadaceae, Oxalobacteraceae, Bacteriovoracaceae, Campylobacteraceae, Flavobacteriaceae, Clostridiales Incertae Sedis XIII and Moraxellaceae. Three archaeal orders of methanogens including Methanomicrobiales, Methanosarcinales and Thermoplasmatales were also detected separately. HPAM was degraded into lower molecular weight polymers and organic fragments with its amide groups hydrolyzed into carboxylic groups by the microorganisms. The microenvironment of the biofilm contained diverse bacterial and archaeal communities, correlating with the extracellular polymeric substance (EPS) and HPAM biodegradation. The results are helpful to provide information for biofilm control in oil fields.


Assuntos
Resinas Acrílicas/metabolismo , Biofilmes , Campos de Petróleo e Gás , Resinas Acrílicas/química , Archaea/genética , Archaea/isolamento & purificação , Archaea/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biodegradação Ambiental , Biopolímeros/metabolismo , Peso Molecular , RNA Arqueal/genética , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Água
16.
J Gynecol Oncol ; 26(4): 327-35, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26197772

RESUMO

OBJECTIVE: Vascular endothelial growth factor (VEGF) interaction with its receptor, VEGFR-3/Flt-4, regulates lymphangiogenesis. VEGFR-3/Flt-4 expression in cancer cells has been correlated with clinical stage, lymph node metastasis, and lymphatic invasion. The objective of this study is to identify a VEGFR-3/Flt-4-interacting peptide that could be used to inhibit VEGFR-3 for ovarian cancer therapy. METHODS: The extracellular fragment of recombinant human VEGFR-3/Flt-4 (rhVEGFR-3/Flt-4) fused with coat protein pIII was screened against a phage-displayed random peptide library. Using affinity enrichment and enzyme-linked immunosorbent assay (ELISA) screening, positive clones of phages were amplified. Three phage clones were selected after four rounds of biopanning, and the specific binding of the peptides to rhVEGFR-3 was detected by ELISA and compared with that of VEGF-D. Immunohistochemistry and immunofluorescence analyses of ovarian cancer tissue sections was undertaken to demonstrate the specificity of the peptides. RESULTS: After four rounds of biopanning, ELISA confirmed the specificity of the enriched bound phage clones for rhVEGFR-3. Sequencing and translation identified three different peptides. Non-competitive ELISA revealed that peptides I, II, and III had binding affinities for VEGFR-3 with K(aff) (affinity constant) of 16.4±8.6 µg/mL (n=3), 9.2±2.1 µg/mL (n=3), and 174.8±31.1 µg/mL (n=3), respectively. In ovarian carcinoma tissue sections, peptide III (WHWLPNLRHYAS), which had the greatest binding affinity, also co-localized with VEGFR-3 in endothelial cells lining lymphatic vessels; its labeling of ovarian tumors in vivo was also confirmed. CONCLUSION: These finding showed that peptide III has high specificity and activity and, therefore, may represent a potential therapeutic approach to target VEGF-VEGFR-3 signaling for the treatment or diagnosis of ovarian cancer.


Assuntos
Neoplasias Ovarianas/terapia , Biblioteca de Peptídeos , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Análise de Sequência de DNA , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
17.
J Zhejiang Univ Sci B ; 14(11): 961-72, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24190442

RESUMO

Orthotopic liver transplantation (OLT) is the only proven effective treatment for both end-stage and metabolic liver diseases. Hepatocyte transplantation is a promising alternative for OLT, but the lack of available donor livers has hampered its clinical application. Hepatocyte-like cells (HLCs) differentiated from many multi-potential stem cells can help repair damaged liver tissue. Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures. Recently, a novel mesenchymal stem cell derived from human menstrual blood (MenSC) has been discovered and obtained easily and repeatedly. In this study, we examined whether the MenSCs are able to differentiate into functional HLCs in vitro. After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor (HGF), fibroblast growth factor-4 (FGF-4), and oncostain M (OSM), cuboidal HLCs were observed, and cells also expressed hepatocyte-specific marker genes including albumin (ALB), α-fetoprotein (AFP), cytokeratin 18/19 (CK18/19), and cytochrome P450 1A1/3A4 (CYP1A1/3A4). Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis, glycogen storage, and indocyanine green (ICG) uptake. After intrasplenic transplantation into mice with 2/3 partial hepatectomy, the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein. We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals. In conclusion, MenSCs may serve as an ideal, easily accessible source of material for tissue engineering and cell therapy of liver tissues.


Assuntos
Diferenciação Celular , Doença Hepática Terminal/terapia , Hepatócitos/citologia , Menstruação/sangue , Células-Tronco Mesenquimais/citologia , Animais , Separação Celular , Hepatócitos/transplante , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
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