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1.
Plast Reconstr Surg ; 151(5): 748e-757e, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729398

RESUMO

BACKGROUND: Gluteal augmentation is used to improve the size and shape of the buttocks. Unlike other anatomical areas, such as the breasts, where there are classification systems for size and projection, no standardized methods for classifying gluteal size and shape exist. Patients seeking augmentation rely on photographs to communicate their desired result to surgeons. The authors' study objectively reviews this topic and proposes a novel classification system for the buttocks that can provide an organized framework for patients and providers. METHODS: A systematic of the literature was conducted on March 17, 2021, using various combinations of the following terms: "gluteal augmentation," "classification," "size," "gluteoplasty," and "Brazilian butt lift." All eligible articles were included for analysis. RESULTS: The PubMed/MEDLINE searches yielded 49 articles and abstracts. After review, eight publications were chosen for analysis. All publications were found in plastic surgery journals, with the most common journals as follows: Aesthetic Surgery Journal ( n = 4), Clinics in Plastic Surgery ( n = 2), Annals of Plastic Surgery ( n = 1), and Plastic and Reconstructive Surgery ( n = 1). There are no articles in the plastic surgery literature that provide a standardized classification system for gluteal size determination. CONCLUSIONS: The authors' study revealed the need for a standardized classification system for gluteal size and shape. Although the publications analyzed discussed various techniques for related procedures and provided ways to improve aesthetic outcomes, none presented a system for reproducibly classifying size and shape. By introducing a classification system, we hope to enable plastic surgeons to more accurately and efficiently discuss their patient's goals.


Assuntos
Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Humanos , Retalhos Cirúrgicos/cirurgia , Estética , Nádegas/cirurgia
4.
Plast Reconstr Surg ; 143(3): 734-742, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30817644

RESUMO

BACKGROUND: Online reviews increasingly influence patients' decision-making. This is the first systematic, quantitative analysis of online reviews for abdominoplasty. METHODS: Reviews for abdominoplasty were sampled from RealSelf, Yelp, and Google for six major metropolitan areas. A standard social sciences framework known as grounded theory was used to evaluate factors affecting satisfaction. The relative importance of factors was quantified using odds ratios. RESULTS: Seven hundred ninety-four reviews met inclusion criteria. There was significant geographic variation with respect to number of reviews (p < 0.01) and average rating (p = 0.014). The authors identified 10 statistically significant themes affecting satisfaction. Of these, aesthetic outcome was the most mentioned theme [n = 368 (46.3 percent)] and the most dominant driver of satisfaction. Interactions with staff had the second highest odds ratio, driven by the fact that all negative staff interactions led to negative reviews. Postoperative care had the next highest odds ratio, and was demonstrated to counteract the negative effects of poor surgical outcomes on satisfaction. The occurrence of a surgical complication and the cost of surgery were least associated with satisfaction. CONCLUSIONS: This analysis is the first to use quantitative methods to identify dominant and nondominant factors affecting patient satisfaction in cosmetic surgery. The authors found that aesthetic outcome, staff interactions, and postoperative diligence were the most critical factors affecting satisfaction in abdominoplasty, whereas postoperative complications and cost were least important. Understanding the relative importance of factors may help to improve and protect one's online reputation.


Assuntos
Abdominoplastia/estatística & dados numéricos , Tomada de Decisões , Estética , Satisfação do Paciente/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Abdominoplastia/efeitos adversos , Abdominoplastia/economia , Estudos de Casos e Controles , Competência Clínica/estatística & dados numéricos , Teoria Fundamentada , Humanos , Internet/estatística & dados numéricos , Satisfação do Paciente/economia , Relações Médico-Paciente , Cuidados Pós-Operatórios/psicologia , Cuidados Pós-Operatórios/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cirurgiões/psicologia
5.
Aesthet Surg J ; 39(4): 447-451, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30346492

RESUMO

BACKGROUND: Patients increasingly rely on online resources to make healthcare decisions. Google dominates the search engine market; first-page results receive most of the web traffic and therefore serve as an important indicator of consumer reach. OBJECTIVES: Our objective was to analyze the respective importance of physician academic pedigree, experience, and social media presence on plastic surgeon Google first-page search result placement. METHODS: A Google.com search was conducted in the top 25 United States metropolitan areas to identify the top 20 websites of board-certified plastic surgeons. Social media presence was quantified by tracking the number of followers on Facebook, Twitter, and Instagram for every surgeon as well as medical school and year of graduation. The primary outcome was website ranking in the first page of Google search results. To identify the independent predictors of presence on the front page, we performed a multivariate logistic regression. RESULTS: Total number of social medial followers was associated with Google front-page placement (P < 0.001), whereas medical school ranking and years in practice were not (P = 0.17 and 0.39, respectively). A total 19.6% of plastic surgeon practices in our study cohort still had no social media accounts whatsoever. CONCLUSIONS: For the past few decades, plastic surgery practices relied on referrals, word of mouth, and the surgeon's reputation and academic pedigree to attract new patients. It is now clear that this practice-building model is being rapidly supplanted by a new paradigm based on social media presence to reach potential patients.


Assuntos
Internet/estatística & dados numéricos , Mídias Sociais/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Cirurgia Plástica/estatística & dados numéricos , Humanos , Ferramenta de Busca , Cirurgiões/normas , Cirurgia Plástica/normas , Estados Unidos
6.
Neoplasia ; 20(7): 745-756, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29925042

RESUMO

Metastasis is the most important feature of gastric cancer (GC) and the most widely recognized reason for GC-related deaths. Unfortunately, the underlying mechanism behind this metastasis remains unknown. Mounting evidence suggests the dynamic regulatory role of sirtuin2 (SIRT2), a histone deacetylase (HDAC), in cell migration and invasion. The present study aims to evaluate the biological function of SIRT2 in GC and identify the target of SIRT2 as well as evaluate its therapeutic efficacy. We found that SIRT2 was upregulated in GC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. Although CCK8 and colony-formation assays showed that SIRT2 overexpression marginally promoted proliferation in GC cell lines, SIRT2 knockdown or treatment with SirReal2 decreased the migration and invasion of GC cells. We demonstrated both in vitro and in vivo that SirReal2 could inhibit the deacetylation activity of SIRT2 and its downstream target PEPCK1, which is related to mitochondrial metabolism and RAS/ERK/JNK/MMP-9 pathway. Taken together, these results demonstrate for the first time that SirReal2 selectively targets SIRT2 and decreases migration as well as invasion in human GC cells. SirReal2 therefore shows promise as a new drug candidate for GC therapy.


Assuntos
Sistema de Sinalização das MAP Quinases , Metaloproteinase 9 da Matriz/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Sirtuína 2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Proteínas ras/metabolismo , Animais , Biomarcadores , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Metabolismo Energético , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Prognóstico , Sirtuína 2/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Plast Reconstr Surg ; 141(5): 663e-673e, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29697608

RESUMO

BACKGROUND: Online reviews have become modern versions of the word-of-mouth recommendation, and prospective patients are increasingly consulting them before making decisions about their surgical care. The authors' objectives were to (1) identify trends in the use of online reviews, and (2) important reasons for patient satisfaction and dissatisfaction with aesthetic surgery. The authors selected breast augmentation as the primary procedure of interest. METHODS: Reviews of the top 10 to 20 most reviewed plastic surgeons in each of six large metropolitan areas were obtained from Google, Yelp, and RealSelf. Reviews were assessed for predefined dimensions of satisfaction and dissatisfaction. RESULTS: A total of 1077 breast augmentation reviews were obtained. Ratings were distributed bimodally, with peaks at five stars and one star. The majority of reviews were positive (87.5 percent). Relative popularity of Google versus Yelp varied across geographic regions, and average rating varied by platform. Between 2011 and 2016, the number of online reviews for breast augmentation grew at an average rate of 42.6 percent per year. Aesthetic outcome was the most commonly cited dimension (69.8 percent of reviews), whereas cost was mentioned in only 7.8 percent of reviews. A substantial minority of negative Yelp (37 percent) and Google (9.4 percent) reviews were written by patients who did not actually undergo surgery. Free-text analysis of heterogeneous reviews (containing positive and negative attributes) classified dimensions as critical, redeemable, or protective. CONCLUSION: As the influence of online review platforms continues to grow, understanding drivers of positive and negative reviews may help surgeons improve patient satisfaction.


Assuntos
Competência Clínica , Mamoplastia/efeitos adversos , Satisfação do Paciente/estatística & dados numéricos , Relações Médico-Paciente , Cirurgiões/organização & administração , Adulto , Tomada de Decisões , Estética , Feminino , Humanos , Internet , Mamoplastia/métodos , Influência dos Pares , Estudos Prospectivos , Cirurgiões/psicologia
8.
Aesthet Surg J ; 38(6): 605-613, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29267860

RESUMO

BACKGROUND: While recent studies have reported modest to no difference in breast aesthetics for shaped and round implant types in breast augmentations, the anatomy and biomechanics in the setting of breast reconstruction is different. OBJECTIVES: Accordingly, we endeavored to evaluate whether two implant types impacted nipple position and aesthetic features in prosthetic breast reconstruction. METHODS: A retrospective chart review was carried out on patients who underwent nipple-sparing mastectomy (NSM) with immediate tissue expander breast reconstruction. Patients were divided into two cohorts: smooth round implants and textured shaped implants. Postoperative photographs were evaluated to assess nipple displacement vis-à-vis a vector of maximal projection and aesthetic outcome for features of breast shape. RESULTS: Of 102 breasts meeting the inclusion criteria, 41 had tissue expander-implant reconstruction with anatomical shaped implants, and 61 had reconstruction with smooth round implants. The shaped implant cohort had less nipple deviation from the point of maximal projection (3.69 ± 6.24 vs 7.52 ± 10.50; P < 0.0001). Graded semi-quantitative aesthetic scores were also higher (4.04 ± 0.67 vs 3.72 ± 0.93; P = 0.0044) in the shaped implants than in the round cohort. CONCLUSIONS: Unlike breast augmentation, there is a paucity of overlying breast tissue and larger dissected spaces in prosthetic breast reconstruction. Our analysis suggests that in this setting, textured anatomic implants result in less nipple deviation from the point of maximum projection and improved aesthetic outcomes compared to round implants. When considering implant choice in NSM reconstruction, the manifold risks of shaped textured implants must thus be informed by potential aesthetic benefits with respect to shape and enhanced nipple sensation.


Assuntos
Implante Mamário/instrumentação , Implantes de Mama , Neoplasias da Mama/cirurgia , Mastectomia Subcutânea/efeitos adversos , Dispositivos para Expansão de Tecidos , Adulto , Idoso , Implante Mamário/métodos , Estética , Feminino , Humanos , Pessoa de Meia-Idade , Mamilos/anatomia & histologia , Satisfação do Paciente , Estudos Retrospectivos , Propriedades de Superfície , Resultado do Tratamento
9.
Plast Reconstr Surg ; 141(4): 892-901, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29256998

RESUMO

BACKGROUND: Combining liposuction and abdominoplasty is controversial because of concerns for increased complications and potential for vascular compromise of the abdominoplasty flap. Also, the lipoaspirate volume in abdominoplasty is regulated in some areas to as little as 500 ml when performed with abdominoplasty. This study measures abdominoplasty complication rates when performed with and without trunk liposuction, and evaluates the effect of lipoaspirate volume on complications. METHODS: Abdominoplasty and liposuction of the trunk procedures were identified in the Tracking Operations and Outcomes for Plastic Surgeons database. Multivariate regression models determined the effect of liposuction with abdominoplasty on complications compared with abdominoplasty alone and determined the effect of liposuction volume on complications. RESULTS: Eleven thousand one hundred ninety-one patients were identified: 9638 (86.1 percent) having abdominoplasty with truncal liposuction and 1553 (13.9 percent) having abdominoplasty alone. Overall complication rates were 10.5 percent and 13.0 percent, respectively. Combined liposuction and abdominoplasty was independently associated with a reduced risk of both overall complications (p = 0.046) and seroma (p = 0.030). Given existing laws limiting liposuction volume to 500 or 1000 ml in combination with abdominoplasty, each of these thresholds was evaluated, with no effect on complications. Surprisingly, increasing liposuction volume was not independently associated with an increased risk of any complication. CONCLUSIONS: When done by board-certified plastic surgeons, abdominoplasty with truncal liposuction is safe, with fewer complications than abdominoplasty alone. Regulations governing liposuction volumes in abdominoplasty are arbitrary and do not reflect valid thresholds for increased complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Abdominoplastia/métodos , Lipectomia/métodos , Complicações Pós-Operatórias/etiologia , Abdominoplastia/efeitos adversos , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Lipectomia/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
10.
Aesthet Surg J ; 38(3): 332-338, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29040378

RESUMO

BACKGROUND: Recent data suggest patients are seeking aesthetic surgery to improve their appearance on Instagram and other social media. Despite the rising influence of Instagram in plastic surgery, few academic publications address Instagram, let alone evaluate its utilization in plastic surgery. OBJECTIVES: We set out to answer the following three questions: 1) what plastic surgery-related content is being posted to Instagram; 2) who is posting this content; and 3) what specific hashtags are they using? METHODS: Our study queried 21 Instagram plastic surgery-related hashtags. Content analysis was used to qualitatively evaluate each of the nine "top" posts associated with each hashtag (189 posts). Duplicate posts and those not relevant to plastic surgery were excluded. RESULTS: A total of 1,789,270 posts utilized the 21 hashtags sampled in this study. Of the top 189 posts for these 21 queried hashtags, 163 posts met inclusion criteria. Plastic surgeons eligible for membership in American Society for Aesthetic Plastic Surgery (ASAPS) accounted for only 17.8% of top posts, whereas noneligible physicians accounted for 26.4%. All nonplastic surgery trained physicians marketed themselves as "cosmetic surgeons." Nine top posts (5.5%) were by nonphysicians, including dentists, spas with no associated physician, and a hair salon. The majority of these posts were self-promotional (67.1%) as opposed to educational (32.9%). Board-certified plastic surgeons were significantly more likely to post educational content to Instagram as compared to nonplastic surgeons (62.1% vs 38.1%, P = 0.02). CONCLUSIONS: ASAPS eligible board-certified plastic surgeons are underrepresented amongst physicians posting top plastic surgery-related content to Instagram.


Assuntos
Marketing de Serviços de Saúde/métodos , Mídias Sociais , Cirurgia Plástica/educação , Humanos , Sociedades Médicas/economia , Cirurgia Plástica/economia , Cirurgia Plástica/métodos
11.
Can Bull Med Hist ; 35(1): 160-192, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28938080

RESUMO

The National Foundation for Infantile Paralysis (NFIP), the March of Dimes, and the Georgia Warm Springs Resort were reflections of Franklin D. Roosevelt's (FDR) complicated and personal relationship with polio. Between 1934 and 1957, significant advances were made in the care of polio survivors, and new and innovative medical fields gained both public attention and funding. The plight of disabled Americans and questions of accessibility also received widespread national attention. The NFIP helped establish a new prototype for grassroots philanthropy and personified FDR's vision for national health insurance. Drawing upon a variety of archival and primary sources, this article aims to revisit Roosevelt's contribution to the medical field. Rather than condone or defend FDR's public persona as a survivor of polio, this article argues that Roosevelt and his affiliated organizations played an important medical role during this period.

12.
J Reconstr Microsurg ; 34(1): 47-58, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28992647

RESUMO

BACKGROUND: Increased surgical duration can impact patient outcomes and operative efficiency metrics. In particular, there are studies suggesting that increased surgical duration can increase the risk of venous thromboembolism (VTE). One of the longer duration plastic surgery procedures commonly performed is microsurgical breast reconstruction. With the widening indications for multiple and "stacked" free flaps to reconstruct breasts, we endeavored to assess (1) the relationship between duration of microsurgical breast reconstruction and VTE; and (2) determine if a threshold operative time exists that connotes VTE higher risk. METHODS: Patients from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) between 2005 and 2014 who underwent microsurgical breast reconstruction were identified by Current Procedural Terminology code. Three models of multivariate logistic regression were used to characterize the adjusted risk for VTE by operative duration, bilaterality, the length of stay, and patient demographics. RESULTS: A total of 4,782 patients who underwent microsurgical breast reconstruction were identified. Overall VTE incidence was 1.13%. The mean operative duration was 8:31 hours:minutes (standard deviation: 2:59). Operative duration was statistically associated with VTE in continuous, quintile, and dichotomized risk models. Beyond an operative duration of 11 hours, adjusted VTE risk increases fourfold corresponding to a number needed to harm of 45.8. CONCLUSIONS: Increasing surgical duration heightens the risk of VTE in microsurgical breast reconstruction. Increasing body mass index and age enhances this VTE risk. Moreover, limiting surgical duration to 11 hours or less can decrease VTE risk by fourfold vis-à-vis baseline. LEVEL OF EVIDENCE: Risk, II.


Assuntos
Mamoplastia , Microcirurgia , Duração da Cirurgia , Tromboembolia Venosa/prevenção & controle , Adulto , Índice de Massa Corporal , Comorbidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Mamoplastia/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco , Tromboembolia Venosa/etiologia
13.
Oncotarget ; 8(59): 99402-99413, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29245911

RESUMO

Class I histone deacetylases (HDACs) inhibit expression of tumor suppressor genes by removing acetyl groups from histone lysine residues, thereby increasing cancer cell survival and proliferation. We evaluated the expression of class I HDACs in cholangiocarcinoma (CCA). HDAC3 expression was specifically increased in CCA tissues and correlated with reduced patient survival. HDAC3 overexpression inhibited apoptosis and promoted CCA cell proliferation. Conversely, HDAC3 knockdown or pharmacological inhibition decreased CCA cell growth and increased caspase-dependent apoptosis. Inhibition of class I HDACs blocked HDAC3-catalyzed deacetylation and increased expression of downstream pro-apoptotic targets in vitro and in vivo. These results demonstrate for the first time that down-regulation of HDAC3 induces apoptosis in human CCA cells, indicating that inhibiting HDAC3 may be an effective therapeutic strategy for treating CCA .

14.
Plast Reconstr Surg ; 140(4): 825-836, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28953737

RESUMO

Recent videos shared by plastic surgeons on social media applications such as Snapchat, Instagram, and YouTube, among others, have blurred the line between entertainment and patient care. This has left many in the plastic surgery community calling for the development of more structured oversight and guidance regarding video sharing on social media. To date, no official guidelines exist for plastic surgeons to follow. Little is known about the ethical implications of social media use by plastic surgeons, especially with regard to video sharing. A systematic review of the literature on social media use in plastic surgery was performed on October 31, 2016, with an emphasis on ethics and professionalism. An ethical analysis was conducted using the four principles of medical ethics. The initial search yielded 87 articles. Thirty-four articles were included for analyses that were found to be relevant to the use of social media in plastic surgery. No peer-reviewed articles were found that mentioned Snapchat or addressed the ethical implications of sharing live videos of plastic surgery on social media. Using the four principles of medical ethics, it was determined that significant ethical concerns exist with broadcasting these videos. This analysis fills an important gap in the plastic surgery literature by addressing the ethical issues concerning live surgery broadcasts on social media. Plastic surgeons may use the guidelines proposed here to avoid potential pitfalls.


Assuntos
Análise Ética/métodos , Procedimentos de Cirurgia Plástica/ética , Guias de Prática Clínica como Assunto , Mídias Sociais/ética , Gravação em Vídeo , Humanos
15.
J Plast Reconstr Aesthet Surg ; 70(7): 876-883, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28539245

RESUMO

INTRODUCTION: The Breast reconstruction Risk Assessment (BRA) Score estimates patient-specific risk for postsurgical complications using an individual's unique combination of preoperative variables. In this report, we externally validate the BRA Score models for surgical site infection, seroma, and explantation in a large sample of intra-institutional patients who underwent prosthetic breast reconstruction. METHODS: We reviewed all initiated tissue expander/implant reconstructions by the senior authors from January 2004 to December 2015. BRA Score risk estimates were computed for each patient and compared against observed rates of complications. Hosmer-Lemeshow goodness-of-fit test, concordance statistic, and Brier score were used to assess the calibration, discrimination, and accuracy of the models, respectively. RESULTS: Of the 1152 patients (1743 breasts) reviewed, 855 patients (1333 breasts) had complete data for BRA-score calculations and were included for analysis. Hosmer-Lemeshow tests for calibration demonstrated a good agreement between observed and predicted outcomes for surgical site infection (SSI) and seroma models (P-values of 0.33 and 0.16, respectively). In contrast, predicted rates of explantation deviated from observed rates (Hosmer-Lemeshow P-value of 0.04). C statistics demonstrated good discrimination for SSI, seroma, and explantation (0.73, 0.69, and 0.78, respectively). CONCLUSIONS: In this external validation study, the BRA Score tissue expander/implant reconstruction models performed with generally good calibration, discrimination, and accuracy. Some weaknesses in certain models were identified as targets for future improvement. Taken together, these analyses validate the clinical utility of the BRA score risk models in predicting 30-day outcomes.


Assuntos
Remoção de Dispositivo , Mamoplastia/efeitos adversos , Modelos Estatísticos , Seroma/etiologia , Infecção da Ferida Cirúrgica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Previsões , Humanos , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de Risco , Adulto Jovem
16.
Sci Rep ; 7(1): 7, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28127057

RESUMO

Phosphoenolpyruvate carboxykinase 1 (PEPCK1) is the critical enzyme for gluconeogenesis and is linked with type II diabetes. Previous studies have found that SIRT2, a deacetylase, plays an important role in deacetylating PEPCK1 and little is known about the anti-diabetic activity of SIRT2 inhibitors. In this study, we investigated the anti-diabetic effects of sirtinol, a SIRT2 inhibitor, on cell gluconeogenesis in vivo and in vitro. Immunoblotting analysis revealed that sirtinol significantly decreased the protein level of PEPCK1, and was accompanied by the hyperacetylation of PEPCK1 as well as decreased glucose output in a dose-dependent manner. Furthermore, sirtinol exerted little impact on endogenous PEPCK1 levels in SIRT2-knockdown cells. The in vitro experiments further confirmed the in vivo data; sirtinol decreased liver PEPCK1 protein level and prevented pyruvate-induced blood glucose from increasing. Based on our results, the rate-limiting enzyme PEPCK1 is the primary target of sirtinol, and the inhibition of SIRT2 activity may play an important role in cell gluconeogenesis. Thus, SIRT2 may be a novel molecular target for diabetes therapy and may thus shed light on the underlying diabetes treatment mechanisms of sirtinol.


Assuntos
Benzamidas/farmacologia , Gluconeogênese/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Naftóis/farmacologia , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Sirtuína 2/antagonistas & inibidores , Acetilação , Animais , Glicemia , Células HEK293 , Humanos , Fígado/metabolismo , Camundongos , Sirtuína 2/metabolismo
17.
Exp Ther Med ; 12(4): 2554-2562, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27698758

RESUMO

Gut microbiota composition of patients with ulcerative colitis (UC) is markedly altered compared with healthy individuals. There is mounting evidence that probiotic therapy alleviates disease severity in animal models and patients with inflammatory bowel disease (IBD). Bacillus subtilisis, as a probiotic, has also demonstrated a protective effect in IBD. However, the therapeutic mechanism of its action has yet to be elucidated. In the present study, a dextrose sulfate sodium (DSS)-induced UC mouse model was used to investigate the role of B. subtilis in the restoration of gut flora and determine its effective dose. Mucosal damage was assessed by performing alcian blue staining, cytokine levels were analyzed by ELISA and microbiota composition was investigated using 454 pyrosequencing to target hypervariable regions V3-V4 of the bacterial 16S ribosomal RNA gene. The results demonstrated that a higher dose B. subtilisis administration ameliorated DSS-induced dysbiosis and gut inflammation by balancing beneficial and harmful bacteria and associated anti- and pro-inflammatory agents, thereby aiding intestinal mucosa recovery from DSS-induced injuries. These findings indicate that choosing the correct dose of B. subtilis is important for effective UC therapy. The present study also helped to elucidate the mechanisms of B. subtilis action and provided preclinical data for B. subtilis use in UC therapy.

18.
BMC Gastroenterol ; 16(1): 84, 2016 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-27473867

RESUMO

BACKGROUND: Butyrate is an energy source for colonocytes that is formed by bacterial fermentation of dietary fiber in the colon and that exerts broad anti-inflammatory activities. Although the administration of butyrate improves homeostasis in patients and ameliorates IBD (Inflammatory Bowel Disease)-related lesions and symptoms, the anti-inflammatory mechanisms of butyrate still remain unclear. To explore the impact of butyrate on Treg (Regulatory T cell)/Th17 (T helper 17 cell) differentiation and colitis in rats. METHODS: The effect of butyrate on the expression of markers related to both Tregs and Th17 cells were determined in human monocytes as well as a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid. Rats were treated with butyrate in vivo, whereas the rat splenocytes and human monocytes were treated in vitro. RESULTS: We found that butyrate administration increased peripheral blood Treg cell levels as well as plasma levels of anti-Th17 cytokines (IL-10 and IL-12). Butyrate administration further suppressed IL-17 levels in both plasma and colonic mucosa, and ameliorated colonic colitis lesions in rats. This promotion of Treg activity and inhibition of IL-17 release was also observed in human venous monocytes and rat splenocytes in vitro. CONCLUSIONS: Our results suggest that butyrate plays a key role in regulating the Treg/Th17 balance and ultimately protects the colon mucosa against the development of IBD.


Assuntos
Anti-Inflamatórios/farmacologia , Butiratos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Colite Ulcerativa/tratamento farmacológico , Interleucina-17/antagonistas & inibidores , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Animais , Peso Corporal , Butiratos/metabolismo , Células Cultivadas , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colo/patologia , Citocinas/sangue , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Linfócitos T Reguladores/citologia
19.
Oncotarget ; 7(16): 22285-94, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-26993777

RESUMO

Histone deacetylases (HDACs) play critical roles in apoptosis and contribute to the proliferation of cancer cells. AR-42 is a novel Class I and II HDAC inhibitor that shows cytotoxicity against various human cancer cell lines. The present study aims to identify the target of AR-42 in hepatocellular carcinoma (HCC) as well as evaluate its therapeutic efficacy. We found that HDAC5 was upregulated in HCC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. CCK8 and colony-formation assays showed that HDAC5 overexpression promotes proliferation in HCC cell lines. Treatment with AR-42 decreased HCC cell growth and increased caspase-dependent apoptosis, and this was rescued by HDAC5 overexpression. We demonstrated that AR-42 can inhibit the deacetylation activity of HDAC5 and its downstream targets in vitro and in vivo. Taken together, these results demonstrate for the first time that AR-42 targets HDAC5 and induces apoptosis in human hepatocellular carcinoma cells. AR-42 therefore shows potential as a new drug candidate for HCC therapy.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Hepáticas/patologia , Fenilbutiratos/farmacologia , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Histona Desacetilases/efeitos dos fármacos , Histona Desacetilases/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
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