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1.
Plast Reconstr Surg Glob Open ; 12(3): e5634, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435463

RESUMO

Background: The demand for genital plastic surgery has increased dramatically among female patients globally. Although various labia minora reduction procedures have been applied with different indications, advantages, and disadvantages, none has been universally accepted as the best method. So, we presented an innovative strategy for this increasingly demanded reconstructive procedure. Methods: In this retrospective study, we included 29 patients seen between November 2020 and May 2023 with hypertrophic labia minora. The patients with hypertrophic labia minora after serrated-shaped resection were included for analysis. Patient satisfaction and complications were evaluated through the follow-up after the operation. Results: Patients with a mean age of 27.1 years (range 19-47 y) performed labia minora reduction via serrated-shaped resection. One patient experienced incision dehiscence, requiring additional surgical revision. One patient experienced postoperative cosmetic asymmetry and also performed secondary repair surgery. One patient experienced urinary retention, which was relieved after urinary catheterization. High overall patient satisfaction has been achieved after a median follow-up of 6.7 months (range 1-24 months). No flap necrosis, sexual dysfunction, or hypertrophic scarring has been reported. Conclusions: Results suggested that serrated-shaped resection is a novel technique for repairing hypertrophic labia minora with high efficiency and satisfaction. The procedure could effectively improve the appearance of the labia minora and reduce complications.

2.
Lasers Med Sci ; 39(1): 89, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38453744

RESUMO

Various treatment modalities have been applied to atrophic scars. Fractional CO2 laser treatment has attracted increasingly more attention because of its quicker recovery time and fewer side effects. However, its limitation of sculpting the edge is an urgent shortcoming. In order to achieve a more effective result with fewer complications, we have integrated ultrapulse CO2 and fractional CO2 lasers to for the treatment of facial atrophic scars. The study included 25 patients (10 males and 15 females) diagnosed with moderate to severe atrophic scars between August 2020 and July 2022. All subjects underwent the same surgical treatment. The effects were assessed at baseline, 1 week, 1 month, and 3 months using photographic evidence. Objective evaluation of the results was conducted using a quartile grading scale, while the subjects' satisfaction and any adverse events were also recorded. The patients in the study underwent more than two laser sessions (2-5), resulting in substantial improvement in their appearance. The time interval between each session was 3-6 months. The majority of the patients (19/25, 76%) had a significant or even excellent improvement. Any adverse events observed, such as erythema, superficial crusting, and PIH, were of a mild nature and temporary in duration. This treatment combined two CO2 lasers is an effective and safe choice for atrophic scars in Asians.


Assuntos
Acne Vulgar , Lasers de Gás , Masculino , Feminino , Humanos , Cicatriz/patologia , Dióxido de Carbono , Resultado do Tratamento , Acne Vulgar/complicações , Eritema/etiologia , Lasers de Gás/uso terapêutico , Atrofia/complicações
3.
Am J Transl Res ; 15(2): 1204-1214, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36915740

RESUMO

OBJECTIVES: Scarring is a common but intricate problem, and topical anti-scarring drugs are the most widely used treatment. However, the wide range of drugs available makes it difficult for doctors and patients to choose from because of the lack of clinical comparisons. Therefore, we conducted an observational study to compare the clinical efficacy of different topical anti-scarring drugs. METHODS: Patients with post-suturing facial scars were enrolled in this study. The questionnaire was designed to record the basic characteristics of the patients. The Vancouver Scar Scale, SCAR scale, and measurements of scar width and thickness were used to evaluate scar quality. Patients who met the inclusion criteria were divided into four groups for comparison: the silicone preparation (SP), onion extract (OE), asiaticoside (AC) groups, and the untreated blank control (BC) group. The overall data were analyzed before they were confined to the zygomatic region. RESULTS: A total of 127 eligible patients were enrolled in this study. The results of the total and zygomatic scars demonstrated that SP, OE, and AC groups resulted in narrower scars and lower scar scale scores. The SP group depicted higher melanin efficacy than the other two groups. The OE group had the best pliability, whereas the AC group had the thinnest scar. CONCLUSIONS: In this study, we acquired expertise with different topical anti-scar agents: SP significantly reduced melanin levels, OE mainly benefited scar pliability, and AC was better at reducing scar thickness. These differences may be more instructive for clinical applications.

4.
J Appl Biomater Funct Mater ; 19: 2280800021989698, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33560909

RESUMO

The present study was designed to fabricate a new chitosan-collagen sponge (CCS) for potential wound dressing applications. CCS was fabricated by a 3.0% chitosan mixture with a 1.0% type I collagen (7:3(w/w)) through freeze-drying. Then the dressing was prepared to evaluate its properties through a series of tests. The new-made dressing demonstrated its safety toward NIH3T3 cells. Furthermore, the CCS showed the significant surround inhibition zone than empty controls inoculated by E. coli and S. aureus. Moreover, the moisture rates of CCS were increased more rapidly than the collagen and blank sponge groups. The results revealed that the CCS had the characteristics of nontoxicity, biocompatibility, good antibacterial activity, and water retention. We used a full-thickness excisional wound healing model to evaluate the in vivo efficacy of the new dressing. The results showed remarkable healing at 14th day post-operation compared with injuries treated with collagen only as a negative control in addition to chitosan only. Our results suggest that the chitosan-collagen wound dressing were identified as a new promising candidate for further wound application.


Assuntos
Quitosana , Animais , Bandagens , Quitosana/farmacologia , Colágeno , Escherichia coli , Camundongos , Células NIH 3T3 , Staphylococcus aureus , Cicatrização
5.
Am J Trop Med Hyg ; 102(2): 468-475, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31802727

RESUMO

Wound dressings are always needed after skin injury; however, most of the dressings still leave room for improvement. Here, we would like to develop an effective dressing with the ability to improve wound healing. A chitosan-Vaseline gauze (CVG) dressing was developed by coating the chitosan mixture and Vaseline on sterile gauze with subsequent drying. Infrared spectroscopy and electron microscopy were used to investigate the miscibility and structure of the dressing. The cytotoxicity and antibacterial nature were evaluated in vitro. The studies of water retention rate, wound healing, and tissue compatibility were carried out over a period of 14 days on full-thickness skin wounds of male Sprague-Dawley rats. It was observed that the CVG dressing demonstrated functional structure by miscibility, non-cytotoxicity, and good antibacterial effects against both Gram-positive and Gram-negative bacteria. The water retention rate incresased up to 25% after applying CVG for 3 hours. Besides, CVG treatment increased angiogenesis and improved microvascular density in wounds. The wounds treated with CVG showed size deduction with new collagen aggregations similar to those in the normal dermis. All the aforementioned results suggest that CVG dressing could be a promising candidate for wound treatment.


Assuntos
Bandagens , Quitosana/farmacologia , Vaselina/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos , Sobrevivência Celular , Quitosana/administração & dosagem , Escherichia coli , Masculino , Camundongos , Células NIH 3T3 , Vaselina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Staphylococcus aureus
6.
Biomed Pharmacother ; 118: 109394, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545259

RESUMO

The renin-angiotensin system (RAS) plays an important role in scar formation. We have previously shown that oral administration of ramipril and losartan could inhibit scarring. For easier application, here we developed a series of topical ramipril and losartan creams in different concentrations and formulations to explore the effect on scar formation in a C57BL/6 mouse scar model. The harvested scar tissues were analyzed with H&E staining, Masson staining and immunohistochemical staining. We found the group treated with 0.2% losartan urea cream (Prep. 1) or 0.1% ramipril cream (Prep. 2) had significantly smaller scars compared to the negative control, while the proliferation of fibroblasts was less active and the collagen fibers were more regular; both groups showed similar efficacy with the positive control (triamcinolone acetonide urea). We also found that drug transdermalness couldn't directly determine the efficacy. Our findings indicate that local application of angiotensin converting enzyme inhibitor drugs (ACEIs) and angiotensin receptor blocker drugs (ARBs) can reduce scarring by reducing the expression of collagen I, collagen III, phosphorylated small mothers against decapentaplegic 3 (p-Smad3) and transforming growth factor-ß 1 (TGF-ß1). This may provide new insight on scar treatment in clinic.


Assuntos
Cicatriz/tratamento farmacológico , Losartan/administração & dosagem , Losartan/uso terapêutico , Ramipril/administração & dosagem , Ramipril/uso terapêutico , Creme para a Pele/uso terapêutico , Administração Tópica , Animais , Cicatriz/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Losartan/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Proteína Smad3/metabolismo , Suínos , Fator de Crescimento Transformador beta1/metabolismo
7.
Cleft Palate Craniofac J ; 56(1): 39-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29652536

RESUMO

OBJECTIVES: To evaluate the feasibility, effectiveness, and safety of computed tomography-assisted auricular cartilage grafting for treating alar base depression secondary to unilateral cleft lip. DESIGN AND SETTING: For patients with obvious depression of the alar base, the difference in heights of the alar base and the piriform margin between the cleft side and the noncleft side were measured with computed tomography. If both were >3.0 mm, the cartilage was harvested postauricularly and subdivided into 2 to 4 pieces. A multiple layer graft was inserted under the depressed alar base. The procedure was performed from 2006 to 2013, and the follow-up period was 3 to 15 months. PARTICIPANTS: Chinese patients with alar base depression secondary to unilateral cleft lip were selected. INTERVENTION: Suture and cartilage graft techniques. MAIN OUTCOMES MEASURES: Differences in bilateral alar base heights and piriform apertures. RESULTS: There was no wound dehiscence, exposure of bone, or donor site morbidity. The difference in heights in the bilateral alar bases and piriform apertures decreased. There were no obvious scars in any of the cases. CONCLUSIONS: This technique has several advantages including ease of operation, minimal trauma, satisfactory outcomes, and useful references for operation provided by computed tomography. It is a superior alternative for reconstruction of secondary alar depression.


Assuntos
Fenda Labial , Cartilagem da Orelha , Rinoplastia , Fenda Labial/cirurgia , Cartilagem da Orelha/transplante , Humanos , Nariz/cirurgia , Tomografia Computadorizada por Raios X
8.
Complement Med Res ; 25(6): 406-412, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30372690

RESUMO

BACKGROUND: The aim of this systematic review was to evaluate the available evidence from randomized controlled trials (RCTs) of auricular acupressure (AA) therapy for preventing constipation in leukemia patients undergoing chemotherapy. METHODS: We searched 5 English databases and 4 Chinese databases, from their inception until August 2017. Quantitative syntheses of RCTs were conducted using RevMan 5.3 software. Study selection, data extraction, and validation were performed independently by 2 reviewers. Cochrane criteria for risk-of-bias were used to assess the methodological quality of the trials. RESULTS: Five RCTs met the inclusion criteria, and most were of low methodological quality. All RCTs compared AA + routine care with routine care alone. Our analysis found that complementary effects of AA can improve the scores of the Bristol Stool Form (BSF), the Constipation Assessment Scale (CAS), and the Patient Assessment of Constipation-Quality of Life (PAC-QOL). However, the same positive results were not found in terms of the Fatigue Severity Scale (FSS), the EuroQoL 5-domain (EQ-5D), and the Hospital Anxiety Depression Scale (HADS). CONCLUSIONS: Overall, as a potential safety therapy, AA may be recommended in addition to routine care including use of laxatives to prevent constipation in leukemia patients undergoing chemotherapy. In the future, more rigorous RCTs must be conducted to overcome the limitations of our existing data and to confirm the effect and safety of AA for managing constipation in leukemia patients undergoing chemotherapy.


Assuntos
Acupuntura Auricular/normas , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Leucemia/complicações , Leucemia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos
9.
Biomed Res Int ; 2018: 9470198, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050948

RESUMO

BACKGROUND: Skin grafts and pedicled flaps are the traditional methods of reconstructing injuries; both have some disadvantages. Here, we introduce a new clinical application of split-thickness skin with pedicle for repairing finger wounds. METHODS: We present the new method of split-thickness skin with pedicle used on 12 patients (18 fingers) between 2012 and 2016. The graft was sketched on the abdomen at random according to the shape of the wounds on a skin area of 1.0 × 1.0 cm-8.0 × 1.5 cm. The pedicle was divided at 7-22 days. RESULTS: During the follow-up time of 13-20 months, there were no reported cases of skin necrosis; 17 fingers obtained primary healing except 1, which required a dressing change. CONCLUSION: The split-thickness skin with pedicle proved to be valuable in the treatment of finger wounds and has the advantages of both pedicled flaps and free skin grafting.


Assuntos
Traumatismos dos Dedos/cirurgia , Transplante de Pele , Retalhos Cirúrgicos , Humanos , Procedimentos de Cirurgia Plástica , Pele , Lesões dos Tecidos Moles , Resultado do Tratamento
10.
Ann Plast Surg ; 81(3): 316-321, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29851729

RESUMO

BACKGROUND: Although there are numerous skin closure methods, there is no special method for suturing triangular skin wounds. The authors have summarized and modified their experience with a 3-dimensional (3D) continuous suturing technique for triangular wounds. METHODS: From December 2015 to September 2017, the 3D continuous suturing technique for triangular wounds has been used in 32 cleft lip repairs (48 surgical triangular incisions) and 11 cases of facial trauma (15 traumatic triangular wounds). The patients, 3 months to 39 years of age, had triangular flaps designed for esthetic purposes or triangular defects secondary to accidents. To evaluate the effectiveness of this technique, the mean follow-up was 7 months (range, 1-15 months). RESULTS: The 3D continuous suturing technique for triangular wounds can shorten the suturing time, decrease the number of thread knots, and shorten the time of surgery. All patients healed well and the stitches were removed 7 days postoperatively. The wound on both sides of the triangle was well arranged, with a good appearance and no scar hyperplasia. CONCLUSIONS: Our experience showed that the 3D continuous suturing technique for triangular wounds is a time-saving and convenient method and can make the wounds closed tighter, more stable, and reliable. The technique can be applied to any type of triangular wounds or incisions and is not limited to the clinical scenarios described in this article.


Assuntos
Fenda Labial/cirurgia , Procedimentos Cirúrgicos Dermatológicos/métodos , Traumatismos Faciais/cirurgia , Pele/lesões , Técnicas de Sutura , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Adulto Jovem
11.
FASEB J ; 32(9): 5199-5208, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29750573

RESUMO

Angiotensin-converting enzyme (ACE) has been found in the pathogenesis of various fibrosis diseases, and ACE inhibitor (ACEI) may affect wound healing and cutaneous fibrosis. However, there is no scientific evidence as to where the ACE is produced during scar formation. Whether it is from the cutaneous tissue or the bone marrow, or both remains unknown. In this study, we investigated the source of ACE using bone marrow transplantation in genetically modified mice, analyzed the inflammatory milieu and some growth factors in the middle of the wound healing period (4 d after the wound was induced). After having deleted the ACE from bone marrow or skin tissue, the wound/scar width in the low-ACE groups were narrower than those in wild-type (WT) controls. Loosely arranged collagen deposition and reduced vessel density were also detected in ACE-deficient mice. Lower ACE levels during scar formation were also accompanied by lower levels of TGF-ß1. In the middle of the wound healing period, ACE levels affected the inflammatory cells significantly. In the mice with a deficiency in ACE, the expression of TGF-ß1 and TNF-α decreased, but not that of IL-4. Our findings indicate that both bone marrow and skin tissue release ACE during scar formation. Deleting either of them can affect the inflammatory cells and growth factors and reduce the expression of TGF-ß1, resulting in a decreased level of scarring.-Fang, Q.-Q., Wang, X.-F., Zhao, W.-Y., Chen, C.-Y., Zhang, M.-X., Shi, B.-H., Zhang, L.-Y., Tan, W.-Q. The source of ACE during scar formation is from both bone marrow and skin tissue.


Assuntos
Medula Óssea/metabolismo , Peptidil Dipeptidase A/metabolismo , Dermatopatias/metabolismo , Pele/metabolismo , Cicatrização/fisiologia , Animais , Colágeno/metabolismo , Fibrose/metabolismo , Interleucina-4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
12.
Biomed Res Int ; 2018: 3975974, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29682541

RESUMO

BACKGROUND: Madelung's disease is a rare lipid metabolic disorder characterized by diffuse, uncapsulated lipomas in the neck, shoulder, and other areas. It mainly affects middle-aged men and is related to alcohol abuse, and the cause is not clear. Surgical treatments include lipectomy and liposuction. METHODS: This systematic review analyzed the treatment of Madelung's disease described in 52 articles including complete patient details, published between 2000 and 2015, and retrieved from the Web of Science, PubMed, Medline, and Embase. RESULTS: Lipectomy was performed in most cases and achieved more complete removal and better control of iatrogenic lesions of nearby structures than liposuction. Liposuction achieved good cosmetic results and is simpler and less invasive than lipectomy, but clinical experience is limited. CONCLUSIONS: Both lipectomy and liposuction have advantages and drawbacks. Surgeons should base the choice of optimal treatment on patient characteristics. Novel surgical techniques and etiologically targeted treatments hold promise as future therapies.


Assuntos
Lipomatose Simétrica Múltipla/cirurgia , Animais , Comportamento de Escolha/fisiologia , Humanos , Lipectomia/métodos , Cirurgiões
13.
Breast ; 39: 89-96, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29631098

RESUMO

BACKGROUND: AlloDerm-RTU is a new member of human acellular dermal matrix (HADM) which was launched in 2012. The present meta-analysis aimed to investigate whether AlloDerm-RTU was superior compared with previous HADMs. METHODS: All available databases were searched for retrospective or prospective studies regarding breast reconstruction with AlloDerm-RTU compared with other HADMs. The primary outcome was the incidence of complications among different HADMs. RESULTS: Two prospective and seven retrospective studies with a total of 1406 patients were enrolled. There was no significant difference in any of the complications, including the incidence of hematoma (RR 0.78, 95%CI 0.19 to 3.19; P = 0.73), seroma (RR 0.98, 95%CI 0.43 to 2.26; P = 0.97), cellulitis (RR 0.82, 95%CI 0.32 to 2.11; P = 0.68), necrosis (RR 0.69, 95%CI 0.44 to 1.10; P = 0.12), infection (RR 0.68, 95%CI 0.37 to 1.25; P = 0.22), explantation (RR 0.61, 95%CI 0.35 to 1.06; P = 0.08), and total complications (RR 0.91, 95%CI 0.55 to 1.52; P = 0.73). Subgroup analysis showed that AlloDerm-RTU demonstrated no superiority compared with FD AlloDerm, AlloMax, or DermACELL. Sensitivity analysis indicated that the outcomes were stabilized. No publication bias existed in the present meta-analysis. CONCLUSION: Four HADM products, AlloDerm-RTU, FD AlloDerm, AlloMax, and DermACELL, showed similar risks of complications. However since most of the included studies had a low level of evidence, further random trials with large numbers of patients are needed.


Assuntos
Implantes de Mama , Neoplasias da Mama/cirurgia , Colágeno/uso terapêutico , Mamoplastia/instrumentação , Dispositivos para Expansão de Tecidos , Colágeno/efeitos adversos , Feminino , Hematoma/epidemiologia , Hematoma/etiologia , Humanos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Seroma/epidemiologia , Seroma/etiologia , Resultado do Tratamento
14.
Curr Pharm Des ; 23(15): 2268-2275, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27784253

RESUMO

Cutaneous scars (particularly hypertrophic and keloid scars), not only can cause adverse cosmetic problems, but also can be associated with emotional distress such as anxiety and depression. Comparing with other surgical treatments, patients who do not opt for or cannot opt for invasion therapies are more eligible for using the topical anti-scarring agents. In this mini-review, we have researched for and collected the data between October 2005 and October 2015, in PubMed and Web of Science, and identified those agents including silicone-based products, imiquimod, corticosteroids, 5-fluorouracil, bleomycin, mitomycin, and plant extracts such as onion extract, asiaticoside, aloe vera, vitamin E, and so on. Besides, we have listed these popular products in commercial market with their useful information. We have also described the combined process according to our clinical experience. However, to establish the more effective treatment among different types of topical agents or their combined process, large, well-designed head-to-head comparisons between individual and combined preparations in relevant patient populations are urgently needed.


Assuntos
Cicatriz/tratamento farmacológico , Cicatriz/prevenção & controle , Pele/efeitos dos fármacos , Administração Tópica , Alantoína/uso terapêutico , Cicatriz/patologia , Combinação de Medicamentos , Heparina/uso terapêutico , Pomadas/uso terapêutico , Extratos Vegetais/uso terapêutico , Pele/patologia , Triterpenos/uso terapêutico
15.
PLoS One ; 11(12): e0167746, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27936188

RESUMO

BACKGROUND: Reduction mammoplasty (RM) is a proven method of treating macromastia, but the risk factors for postoperative complications have not been clearly identified. Through this meta-analysis, the authors aimed to identify the risk factors of RM complications. METHODS: An extensive search of the literature describing complications after RM was performed using the PubMed Central, Embase, and Cochrane databases. The following risk factors were extracted: age, body mass index (BMI), tissue resection weight per breast (TRW), smoking and radiation therapy. Odds ratios (OR) were pooled with 95% confidence intervals (CI) to evaluate the relationship between these risk factors and complications after RM. RESULTS: A total of 16 unique studies including 10 593 patients were included in the final analysis. It showed that there was a significant difference in complications in BMI ≥30 kg/m2 (OR 0.73; 95% CI: 0.61-0.89, p = 0.001) and smoking (OR 1.56; 95% CI: 0.98-2.49, p = 0.06). Infection in those with BMI ≥30 kg/m2 showed a significant difference (OR 0.68; 95% CI: 0.52-0.89, p = 0.004), as well as wound dehiscence in smokers (OR 2.73; 95% CI: 1.60-4.67, p = 0.0002) and infection in irradiated breasts (OR 20.38; 95% CI: 3.42-121.35, p = 0.0009). However, there was no significant difference in age ≥50 years (OR 0.96; 95% CI: 0.71-1.29, p = 0.78), combined TRW ≥1000 g (OR 1.04; 95% CI: 0.43-2.50, p = 0.93). CONCLUSIONS: BMI ≥30 kg/m2 and smoking increase the risk of complications. Persons who are obese or irradiated are more likely to develop infections, and smokers experienced a higher incidence of wound dehiscence than did nonsmokers. However, patients aged ≥50 years and TRW ≥1000 g are not associated with complications from RM.


Assuntos
Mama/anormalidades , Mama/cirurgia , Hipertrofia/cirurgia , Mamoplastia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Fatores Etários , Índice de Massa Corporal , Feminino , Humanos , Hipertrofia/terapia , Fatores de Risco , Fumar/efeitos adversos , Infecção da Ferida Cirúrgica/etiologia
17.
Bioorg Med Chem Lett ; 26(1): 72-5, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26597536

RESUMO

Targeting LDHA represents a promising strategy for the development of new anti-cancer agents. We report herein the identification of a potent compound as a direct LDHA inhibitor. The in vitro enzymatic assay revealed that the VS-2 had good inhibitory potency (IC50=0.25µM) to LDHA. Cytotoxic assay suggested that the VS-2 could inhibit MCF-7 cancer cell growth, with the IC50 value low to 1.54µM. The seahorse XF24 experiment validated that the VS-2 served as a modulator to reprogram MCF-7 cancer cell metabolism from glycolysis to mitochondrial respiration.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , L-Lactato Desidrogenase/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Células MCF-7 , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
19.
PLoS One ; 8(7): e68617, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23874689

RESUMO

Delphinidin-3-glucoside (Dp) is a member of a family of bioactive compounds known as anthocyanins that occur naturally in pigmented plants and are known to ameliorate oxidative stress. Previous studies have showed that Dp decreased oxidative stress in vascular endothelial cells, however, the underlying mechanisms remain largely unknown. In the present study, we showed that pretreatment with Dp significantly suppressed oxidized low-density lipoprotein (oxLDL)-induced cell proliferation inhibition and apoptosis in primary human umbilical vein endothelial cells (HUVECs). Also, Dp pretreatment attenuated oxLDL-induced mitochondrial dysfunction via decreased reactive oxygen species (ROS) and superoxide anion generation, thereby repressing mitochondrial membrane potential and closing mitochondrial permeability transition pore. Furthermore, in vitro and in vivo data showed that Dp was transported into endothelial cells in a temperature, concentration, and time-dependent manner via the sodium-dependent glucose transporter (SGLT1). Suppression of SGLT1 by its substrate glucose, its inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1 significantly inhibited Dp function of ameliorating mitochondrial dysfunction induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c, Caspase-3 and Bax/Bcl-2 ratio). Taken together, our data indicate that Dp protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to elucidate the molecular mechanisms underlying the vascular protection afforded by Dp, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.


Assuntos
Antocianinas/farmacologia , Células Endoteliais/metabolismo , Glucosídeos/farmacologia , Lipoproteínas LDL/toxicidade , Doenças Mitocondriais/induzido quimicamente , Doenças Mitocondriais/tratamento farmacológico , Transportador 1 de Glucose-Sódio/metabolismo , Análise de Variância , Animais , Antocianinas/química , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Feminino , Citometria de Fluxo , Formazans , Glucosídeos/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Fluorescência , Sais de Tetrazólio
20.
Biochimie ; 94(9): 2035-44, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22683914

RESUMO

Increased intracellular reactive oxygen species (ROS) is crucial for vascular endothelial dysfunction, a key step in the initiating of atherosclerosis (AS). The antioxidant activity of flavonoids has been suggested to contribute to AS prevention. However, The association of the structure characteristics to antioxidant capacities in relation to the inhibitory effects on endothelial dysfunction has not been well established. In this study, four subclasses of flavonoids with similar structures, including two anthocyanins (delphinidin and cyanidin), two flavonols (myricetin and quercetin), two flavones (luteolin and apigenin) and two isoflavones (genistein and daidzein) were examined for their inhibitory effects on intracellular ROS-mediated signaling pathway in the human umbilical vein endothelial cell EA.hy926. Cells were pretreated with different flavonoids for 2 h and then exposed to oxLDL of 100 µg/ml for another 24 h. It was found that treatment with different flavonoids alone had no notable effects on cell viability. However, the oxLDL-induced decrease of cell viability, generation of O(2)(·-) and ROS, p38MAPK activation, NF-κB nuclear translocation, NF-κB-modulated transcriptional activity as well as the mRNA expression of genes including ICAM-1, VCAM-1, E-selectin, MMP-1, MMP-2 and MMP-9 were notably inhibited by the pretreatment of different flavonoids through blunting ROS-triggered signaling pathway, in spite of apparent differences. And the number of hydroxyl groups in total, 3',4'-ortho-dihydroxyl in B-ring and 3-hydroxyl group in C-ring of flavonoids were important structure characteristics for the inhibitory effects. Thus, anthocyanins and flavonols such as delphinidin and myricetin exert higher ROS scavenging activities and more significant endothelium-protective effects compared to the other compounds. Our results provide evidence for AS prevention and a basis for designing the potent anti-atherosclerotic agents.


Assuntos
Células Endoteliais/citologia , Flavonoides/farmacologia , Sequestradores de Radicais Livres/farmacologia , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Aterosclerose/genética , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citoproteção/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipoproteínas LDL/toxicidade , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxidos/metabolismo , Fator de Transcrição RelA/metabolismo , Transcrição Gênica/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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