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1.
Sci Rep ; 13(1): 15174, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704744

RESUMO

Clastic successions found in the carbonate platform of continental margin during the Ordovician-Silurian Transition (OST) period are archives for interpreting paleo-depositional systems. Here, we report in-situ δ18Oquartz and 87Sr/86Srcarbonate isotope chemo-stratigraphy for an unconformable clastic unit from the Cathaysia terrane that rifted off the Gondwana Supercontinent in the Early Paleozoic Era. Our results suggest a depositional proxy and model for geological events attributed to rapid changes in the sedimentary environment during the OST period. Importantly, these results present crucial clues that infer the influence of Paleo-Tethys Sea opening, global eustatic regression, and rapid sedimentary provenance change. Our study provides insight into paleo-tracer that could be a key method for interpreting depositional system of carbonate platform based on in-situ mineral isotope chemo-stratigraphy that preserves the original value of provenance and geochemical condition.

2.
J Pers Med ; 13(5)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37240903

RESUMO

BACKGROUND: The mainstay of treatment for early-stage cervical cancer is surgery; we present a 5-year experience of robotic single-site radical hysterectomy (RSRH) focused on surgical and oncologic outcomes. METHODS: This retrospective study included 44 cases of RSRH performed in patients with early-stage cervical cancer. RESULTS: The median follow-up period for the 44 patients was 34 months. The mean total operation time was 156.07 ± 31.77 min, while mean console time was 95.81 ± 24.95 min. Two cases had complications, which required surgical management, while four cases (9.1%) exhibited recurrence. The disease-free survival rate at 5 years was 90.9%. The sub-division analysis showed that Stage Ia2 and stage Ib1 patient sub-group showed better DFS than that of the stage Ib2 patient sub-group. The learning curve analysis showed that the CUSUM-T initially peaks at the sixth case then gradually decreases before rising and peaking at the 24th case. After 24th case, the CUSUM-T gradually decreases and reaches zero. CONCLUSION: The surgical outcomes of RSRH for early-stage cervical cancer treatment were safe and acceptable. However, RSRH could be considered carefully only in well-selected patient groups. Large-scale prospective studies are necessary in the future to validate the results.

3.
Sci Rep ; 11(1): 21146, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34707151

RESUMO

Fluid flux through Earth's surface and its interior causes geochemical cycling of elements in the Earth. Quantification of such process needs accurate knowledge about the composition and properties of the fluids. Knowledge about the fluids in Earth's interior is scarce due to limitations in both experimental methods and thermodynamic modeling in high/ultrahigh pressure-temperature conditions. In this study, we present halogen (Cl, F) measurements in apatite grains from the mafic (metagabbro), and felsic (two-pyroxene granulite, charnockite, hornblende-biotite gneiss) rocks preserved in the Nilgiri Block, southern India. Previous experiments show that it is difficult to incorporate Cl in apatite compared to F at high pressure and temperature conditions. Based on regional trends in Cl and F content in apatite (with highest Cl content 2.95 wt%), we suggest the presence of acidic C-O-H fluids in the lower crust (~20-40 km deep) during the high-grade metamorphism of these rocks. These fluids are capable of causing extreme chemical alterations of minerals, especially refractory ones. They also have significant potential for mass transfer, causing extensive geochemical variations on a regional scale and altering the chemical and isotope records of rocks formed in the early Earth. Our findings have important relevance in understanding speciation triggered by acidic fluids in the lower crust, as well as the role of fluids in deep Earth processes.

4.
J Gynecol Oncol ; 32(6): e94, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34708596

RESUMO

Since the human papillomavirus (HPV) vaccine guidelines were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2011, 2016, and 2019, several recent studies on the efficacy and safety of HPV vaccines in middle-aged women and men have been reported. Furthermore, there has been an ongoing debate regarding the efficacy of the HPV vaccine in women with prior HPV infection or who have undergone conization for cervical intraepithelial neoplasia (CIN). We searched and reviewed studies on the efficacy and safety of the HPV vaccine in middle-aged women and men and the efficacy of the HPV vaccine in patients infected with HPV and those who underwent conization for CIN. The KSGO updated their guidelines based on the results of the studies included in this review.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , República da Coreia , Neoplasias do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/prevenção & controle
5.
Artigo em Inglês | MEDLINE | ID: mdl-34201984

RESUMO

This study investigates changes in fine particulate matter (PM2.5) concentration and air-quality index (AQI) in Asia using nine different Coupled Model Inter-Comparison Project 6 (CMIP6) climate model ensembles from historical and future scenarios under shared socioeconomic pathways (SSPs). The results indicated that the estimated present-day PM2.5 concentrations were comparable to satellite-derived data. Overall, the PM2.5 concentrations of the analyzed regions exceeded the WHO air-quality guidelines, particularly in East Asia and South Asia. In future SSP scenarios that consider the implementation of significant air-quality controls (SSP1-2.6, SSP5-8.5) and medium air-quality controls (SSP2-4.5), the annual PM2.5 levels were predicted to substantially reduce (by 46% to around 66% of the present-day levels) in East Asia, resulting in a significant improvement in the AQI values in the mid-future. Conversely, weak air pollution controls considered in the SSP3-7.0 scenario resulted in poor AQI values in China and India. Moreover, a predicted increase in the percentage of aged populations (>65 years) in these regions, coupled with high AQI values, may increase the risk of premature deaths in the future. This study also examined the regional impact of PM2.5 mitigations on downward shortwave energy and surface air temperature. Our results revealed that, although significant air pollution controls can reduce long-term exposure to PM2.5, it may also contribute to the warming of near- and mid-future climates.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Ásia , China , Exposição Ambiental , Ásia Oriental , Índia , Material Particulado/análise
6.
Int J Med Robot ; 17(4): e2255, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33817949

RESUMO

BACKGROUND: This study aimed to compare the surgical outcomes and cost of robotic single-site radical hysterectomy (RSSRH) versus robotic multiport radical hysterectomy (RMPRH) with pelvic lymph node dissection in early stage cervical cancer. METHODS: Sixty-two patients with early stage cervical cancer were recruited between November 2011 and July 2017 and underwent RSSRH (20 patients) and RMPRH (42 patients) for early stage cervical cancer using the da Vinci Si Surgical System (Intuitive Surgical). RESULTS: There were no significant difference between the two groups in most of parameters. However, postoperative hospital discharge and total hospital costs for RSSRH were significantly shorter than RMPRH (both p < 0.001). However, lymph node retrieval of RMPRH was significantly higher than RSSRH in (18.0 vs. 9.5, respectively; p < 0.001). CONCLUSIONS: RSSRH has comparable surgical outcomes to the RMPRH method. RSSRH could be considered a surgical option in a well-selected patient group.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/cirurgia
7.
J Clin Med ; 10(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578930

RESUMO

This study aimed evaluate the feasibility of modified laparoscopic transabdominal cervicoisthmic cerclage (LTCC) and its impact on recurrent pregnancy loss (RPL) and is a retrospective observational cohort study of patients who underwent modified LTCC from 2003 to 2018 (n = 299). The surgery was performed at a mean gestational age of 12.5 weeks (range 10.5-17.5 weeks). Of the 299 patients, 190 were reported as having undergone abortion (one abortion: 91 (47.9%), two: 59 (31.1%), three or more: 40 (21.1%)) before the present pregnancy and prior to the surgery. The mean operation time was 47.4 min (range 15-100 min). We followed up with 205 of 299 patients and recorded their obstetric outcomes. There were 176 successful deliveries via cesarean section, and the fetal survival rate was 85.9% (176/205). The results of this study suggest that modified LTCC is a safe and feasible surgical option during pregnancy for patients with a history of RPL due to cervical factors.

8.
Sci Rep ; 10(1): 19869, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199786

RESUMO

Equilibrium omphacite-garnet-bearing mafic rocks have been classified as eclogites, either pristine or retrogressed, that were formed at great depths in the lithosphere. Here we report a unique natural example of eclogite resembling assemblage in disequilibrium formed through fluid-induced metasomatic reactions under the amphibolite to granulite facies. Primarily, the amphibolized protolith experienced a garnet-amphibolite facies metamorphism at ~ 500-700 °C and ~ 0.8-1 GPa. Subsequently, CO2 fluid induced fracturing and dissolution-reprecipitation reactions occurred at peak metamorphic conditions of ~ 700 °C and ~ 1 GPa. Occasional omphacite-albite assemblage, which gradually replace diopside-oligoclase symplectite adjacent to albite veins along fractures, indicates fluid-induced coupled dissolution-reprecipitation disequilibrium reactions. Here the albite-omphacite assemblage is in local equilibrium at least on 1 mm length scale, during cooling, below ~ 600 ºC and ~ 1 GPa, within the amphibolite facies conditions. The results from this study clearly suggest that disequilibrium garnet-omphacite assemblage in mafic rocks could be formed by crustal reworking processes below granulite facies conditions, and their textural equilibrium is an important criterion while defining eclogite facies.

9.
Gynecol Oncol Rep ; 34: 100663, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33204794

RESUMO

BACKGROUND: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare tumor belonging to a group of smooth muscle tumors that possess both benign and malignant features, complicating the diagnosis.Case report.We present the case of a 41-year-old primiparous woman who complained of heavy menstrual bleeding and severe pressure symptoms in the lower abdomen for 3 months. Magnetic resonance imaging revealed a large intramural myoma measuring 35 × 25 cm in the lower uterine corpus. A laparotomy including total hysterectomy was performed. Grossly, the uterine mass measured 38.5 × 35.4 × 20.4 cm in the largest diameter and weighed 18.3 kg. Pathological analysis revealed a uterine mass diagnosed as a smooth muscle tumor of uncertain malignant potential. The patient was normally discharged 7 days after surgery and decided to follow up without further treatment. At the time of this report, the patient had been followed up as an outpatient for 18 months without recurrence. CONCLUSION: Giant uterine STUMP is extremely rare and difficult to diagnose on physical examination and imaging findings alone. It is important to consider the possibility of an underlying malignancy when performing a preoperative examination and to perform frozen biopsy if malignancy is suspected. During follow-up, patients should undergo consultation with a gynecologic oncologist and should be surveilled closely because of the possibility of recurrence or metastasis.

10.
PLoS Genet ; 16(6): e1008808, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32497036

RESUMO

Metastasis is responsible for 90% of human cancer mortality, yet it remains a challenge to model human cancer metastasis in vivo. Here we describe mouse models of high-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), the most common and deadliest human ovarian cancer type. Mice genetically engineered to harbor Dicer1 and Pten inactivation and mutant p53 robustly replicate the peritoneal metastases of human HGSC with complete penetrance. Arising from the fallopian tube, tumors spread to the ovary and metastasize throughout the pelvic and peritoneal cavities, invariably inducing hemorrhagic ascites. Widespread and abundant peritoneal metastases ultimately cause mouse deaths (100%). Besides the phenotypic and histopathological similarities, mouse HGSCs also display marked chromosomal instability, impaired DNA repair, and chemosensitivity. Faithfully recapitulating the clinical metastases as well as molecular and genomic features of human HGSC, this murine model will be valuable for elucidating the mechanisms underlying the development and progression of metastatic ovarian cancer and also for evaluating potential therapies.


Assuntos
Antineoplásicos/farmacologia , Cistadenocarcinoma Seroso/genética , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/genética , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Instabilidade Cromossômica , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/secundário , RNA Helicases DEAD-box/genética , Reparo do DNA , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Estudos de Viabilidade , Feminino , Humanos , Camundongos , Camundongos Knockout , Mutação , Gradação de Tumores , Metástase Neoplásica/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Cultura Primária de Células , Ribonuclease III/genética , Proteína Supressora de Tumor p53/genética
11.
BMC Cancer ; 20(1): 385, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375688

RESUMO

BACKGROUND: Primary debulking surgery (PDS) and adjuvant chemotherapy is the standard treatment for advanced ovarian, fallopian or primary peritoneal cancer. However, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced as an alternative, showing similar efficacy and decreased postoperative complications compared with PDS. Although there is still no evidence for whether three or four cycles of NAC used clinically could be adequate, reducing one cycle of NAC is expected to remove more visible tumours and thereby improve prognosis. Thus, we proposed with this study to evaluate the efficacy and safety of reducing one cycle of NAC for advanced ovarian, fallopian or primary peritoneal cancer. METHODS: This study is a prospective, multi-centre, open-label, randomized phase III trial. A total of 298 patients with advanced ovarian, fallopian or primary peritoneal cancer will be recruited and randomly assigned to either three (control group) or two cycles of NAC (experimental group). After the NAC, we will conduct IDS with maximal cytoreduction and then administer the remaining three or four cycles for a total of six cycles of adjuvant chemotherapy. The primary end point is progression-free survival, and the secondary end points are time to tumour progression, overall survival, tumour response after NAC, IDS and adjuvant chemotherapy, radiologic investigation after IDS, tumour response by positron emission tomography-computed tomography after NAC, quality of life, adverse events, success rate of optimal cytoreduction, surgical complexity, postoperative complications and safety of IDS. We will assess these factors at screening, at every cycle of chemotherapy, at IDS, after the completion of chemotherapy, every 3 months for the first 2 years after the planned treatment and every 6 months thereafter for 3 years. DISCUSSION: We hypothesize that reducing one cycle of NAC will contribute to more resection of visible tumours despite 10% reduction of optimal cytoreduction, which could improve survival. Moreover, two cycles of NAC may increase postoperative complications by 5% compared with three cycles, which may be acceptable. TRIAL REGISTRATION: This study has been prospectively registered at ClinicalTrials.gov on Oct. 2nd, 2018 (NCT03693248, URL: https://clinicaltrials.gov/ct2/show/NCT03693248).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Quimioterapia Adjuvante/mortalidade , Neoplasias das Tubas Uterinas/tratamento farmacológico , Terapia Neoadjuvante/mortalidade , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/patologia , Estudos de Casos e Controles , Neoplasias das Tubas Uterinas/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto Jovem
12.
Entropy (Basel) ; 23(1)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396224

RESUMO

The discrete geodesic flow on Nagao lattice quotient of the space of bi-infinite geodesics in regular trees can be viewed as the right diagonal action on the double quotient of PGL2Fq((t-1)) by PGL2Fq[t] and PGL2(Fq[[t-1]]). We investigate the measure-theoretic entropy of the discrete geodesic flow with respect to invariant probability measures.

13.
Obstet Gynecol Sci ; 62(3): 149-156, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31139590

RESUMO

OBJECTIVE: The aims of this study were to introduce surgical guidelines, and to evaluate the feasibility and safety of a robotic single-site staging (RSSS) operation for early-stage endometrial cancer. METHODS: Patients with a preoperative diagnosis of endometrial cancer (International Federation of Gynecology and Obstetrics stages IA to IB) from endometrial curettage and preoperative imaging studies were selected at Dongsan Medical Center from March 2014 to November 2015. All surgical procedures, including hysterectomy, salpingo-oophorectomy, bilateral pelvic node dissection, and cytology aspiration, were performed by robotic single-site instruments (da Vinci Si® surgical system; Intuitive Surgical, Sunnyvale, CA, USA). RESULTS: A total of 15 women with early-stage endometrial cancer underwent the RSSS operation. The median patient age and body mass index were 53 years (range, 37-70 years) and 25.4 kg/m2 (range, 18.3-46.4 kg/m2). The median docking time, console time, and total operative time were 8 minutes (range, 4-15 minutes), 75 minutes (range, 55-115 minutes), and 155 minutes (range, 125-190 minutes), respectively. The median retrieval of both pelvic lymph nodes was 9 (range, 6-15). There were no conversions to laparoscopy or laparotomy. CONCLUSION: The RSSS operation is feasible and safe in patients with early-stage endometrial cancer. In this study, operative times were reasonable, and the surgical procedure was well-tolerated by the patients. Further evaluation of patients with early-stage endometrial cancer should be performed in large-scale comparative studies using the laparoendoscopic, single-site staging operation to confirm the safety and benefits of the RSSS operation for early-stage endometrial cancer.

14.
J Cancer ; 9(1): 64-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29290770

RESUMO

Objective: To measure hematologic parameters derived from the white blood cell (WBC) count and differential count (DC) as prognostic factors for survival in patients with stage IB and IIA cervical cancer. Methods: We retrospectively examined demographic, clinicopathologic, and laboratory parameters in a cohort of 233 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer who underwent surgical resection. We further assessed the effects of the WBC count and DC-derived hematologic parameters on progression-free survival (PFS) and overall survival (OS) after controlling for other parameters. Results: Patients were followed up for a median of 46.6 months (range, 9-142 months). The Kaplan-Meier estimates of PFS and OS at 5 years were 88.5% and 92.3%, respectively. In a multivariate analysis, we identified the absolute monocyte count (AMC) (hazard ratio [HR], 11.78; P <0.001) and tumor size (HR, 5.41; P = 0.003) as the strongest prognostic factors affecting PFS. We also identified AMC (HR, 23.29; P <0.001), tumor size, (HR, 5.27; P = 0.033), and lymph node involvement (HR, 3.90; P = 0.027) as the strongest prognostic factors affecting OS. AMC remained prognostic with respect to PFS or OS in a Cox model that controlled for the neutrophil-lymphocyte ratio or lymphocyte-monocyte ratio, although neither ratio was a significant prognostic factor for survival. Conclusions: Monocytosis and an increased tumor size were found to be independent prognostic factors affecting both PFS and OS in patients with stage IB and IIA cervical cancer.

15.
Obstet Gynecol Sci ; 60(6): 549-557, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29184863

RESUMO

OBJECTIVE: The aim of our study is to compare the overall survival (OS), progression-free survival (PFS), and treatment-related morbidities between primary concurrent chemoradiation therapy (CCRT) vs. radical hysterectomy (RH) with or without tailored adjuvant therapy in patients with stages IB2 and IIA cervical cancer. METHODS: This was a retrospective study of 113 patients with IB2 or IIA cervical cancer treated with either primary CCRT (n=49) or RH (n=64) with or without tailored adjuvant therapy between 2002 and 2011 at Keimyung University Dongsan Medical Center. Patients in RH group was divided into those undergoing surgery alone (n=26) and those undergoing surgery with adjuvant therapy (n=38). RESULTS: The median follow up period was 66 months. The 5-year OS by treatment modality was 88.7% for the 64 patients in the RH group and 72.8% for 49 patients in the CCRT group (P=0.044). The 5-year PFS was 82.3% and 65.6% after RH group and CCRT group (P=0.048), respectively. Grade 3-4 complication was less frequent after RH alone (7.7%) than RH with adjuvant therapy (34.2%) or CCRT group (28.6%) (P=0.047). CONCLUSION: The RH group seems to be superior to the CCRT group in oncologic outcomes. However, considering the selection bias including tumor size, lymph node meta, and parametrial invasion in pretreatment magnetic resonance imaging, both treatment modalities are reasonable and feasible in cervical cancer IB2 and IIA. It is important to choose the appropriate treatment modality considering the age and general condition of the patient. Randomized controlled study is needed to confirm the result of our study and determine the optimal treatment.

16.
Nat Commun ; 8(1): 864, 2017 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-29021522

RESUMO

Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Here, we show that cholesterol mediates the metastatic effects of a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant animal models of cancer. The robust effects of 27-hydroxycholesterol on metastasis requires myeloid immune cell function, and it was found that this oxysterol increases the number of polymorphonuclear-neutrophils and γδ-T cells at distal metastatic sites. The pro-metastatic actions of 27-hydroxycholesterol requires both polymorphonuclear-neutrophils and γδ-T cells, and 27-hydroxycholesterol treatment results in a decreased number of cytotoxic CD8+T lymphocytes. Therefore, through its actions on γδ-T cells and polymorphonuclear-neutrophils, 27-hydroxycholesterol functions as a biochemical mediator of the metastatic effects of hypercholesterolemia.High cholesterol is a risk factor for breast cancer recurrence. Here the authors show that cholesterol promotes breast cancer metastasis via its metabolite 27-hydroxycholesterol (27HC) that acts on immune myeloid cells residing at the distal metastatic sites, thus promoting an immune suppressive environment.


Assuntos
Neoplasias da Mama/imunologia , Carcinoma/imunologia , Colesterol na Dieta/efeitos adversos , Hidroxicolesteróis/efeitos adversos , Células Mieloides/efeitos dos fármacos , Metástase Neoplásica , Animais , Linhagem Celular Tumoral , Colesterol na Dieta/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
17.
J Biol Chem ; 292(42): 17312-17323, 2017 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-28808064

RESUMO

Sirtuin 3 (SIRT3) deacetylates and regulates many mitochondrial proteins to maintain health, but its functions are depressed in aging and obesity. The best-studied sirtuin, SIRT1, counteracts aging- and obesity-related diseases by deacetylating many proteins, but whether SIRT1 has a role in deacetylating and altering the function of SIRT3 is unknown. Here we show that SIRT3 is reversibly acetylated in the mitochondria and unexpectedly is a target of SIRT1 deacetylation. SIRT3 is hyperacetylated in aged and obese mice, in which SIRT1 activity is low, and SIRT3 acetylation at Lys57 inhibits its deacetylase activity and promotes protein degradation. Adenovirus-mediated expression of SIRT3 or an acetylation-defective SIRT3-K57R mutant in diet-induced obese mice decreased acetylation of mitochondrial long-chain acyl-CoA dehydrogenase, a known SIRT3 deacetylation target; improved fatty acid ß-oxidation; and ameliorated liver steatosis and glucose intolerance. These SIRT3-mediated beneficial effects were not observed with an acetylation-mimic SIRT3-K57Q mutant. Our findings reveal an unexpected mechanism for SIRT3 regulation via SIRT1-mediated deacetylation. Improving mitochondrial SIRT3 functions by inhibiting SIRT3 acetylation may offer a new therapeutic approach for obesity- and aging-related diseases associated with mitochondrial dysfunction.


Assuntos
Envelhecimento/metabolismo , Mitocôndrias/enzimologia , Obesidade/enzimologia , Proteólise , Sirtuína 1/metabolismo , Sirtuína 3/metabolismo , Acetilação , Acil-CoA Desidrogenase de Cadeia Longa/genética , Acil-CoA Desidrogenase de Cadeia Longa/metabolismo , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Substituição de Aminoácidos , Animais , Dieta/efeitos adversos , Estabilidade Enzimática , Masculino , Camundongos , Mutação de Sentido Incorreto , Obesidade/induzido quimicamente , Obesidade/genética , Sirtuína 1/genética , Sirtuína 3/genética
18.
Mol Cell Biol ; 37(15)2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28533219

RESUMO

Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including nonalcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase 2 (CK2), the levels of which were dramatically elevated in obesity. Mechanistically, phosphorylation of SIRT1 at Ser-164 substantially inhibited its nuclear localization and modestly affected its deacetylase activity. Adenovirus-mediated liver-specific expression of SIRT1 or a phosphor-defective S164A-SIRT1 mutant promoted fatty acid oxidation and ameliorated liver steatosis and glucose intolerance in diet-induced obese mice, but these beneficial effects were not observed in mice expressing a phosphor-mimic S164D-SIRT1 mutant. Remarkably, phosphorylated S164-SIRT1 and CK2 levels were also highly elevated in liver samples of NAFLD patients and correlated with disease severity. Thus, inhibition of phosphorylation of SIRT1 by CK2 may serve as a new therapeutic approach for treatment of NAFLD and other obesity-related diseases.


Assuntos
Caseína Quinase II/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Sirtuína 1/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Caseína Quinase II/análise , Nucléolo Celular/metabolismo , Nucléolo Celular/patologia , Ácidos Graxos/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Moleculares , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Oxirredução , Fosforilação , Sirtuína 1/análise
19.
J Robot Surg ; 11(2): 139-143, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27550318

RESUMO

To describe a simple and efficient technique for suturing the vaginal cuff in robotic-assisted single-site hysterectomy using barbed suture and a straight needle. Consecutive patients undergoing robotic-assisted single-site hysterectomy from February 2014 to August 2015 at Dong San Hospital, Keimyung University were included. Surgeons used two barbed sutures in a running fashion to close the vaginal cuff. A barbed suture was exclusively used with a straightened needle in upward direction from posterior vaginal cuff to anterior vaginal cuff which played a pivotal role for closure. A total of 100 patients underwent robotic-assisted single-site hysterectomy. The total operation time was 132.5 min and vaginal cuff closure time was 12.0 min. There were no postoperative complications; vaginal cuff dehiscence, vaginal cuff infection, and vaginal bleeding that require surgical intervention or admission. The use of barbed suture with straightened needle to close the vaginal cuff in robotic-assisted single-site hysterectomy is easy to perform and demonstrates safety and efficacy. This technique offers secure, fast, and effective incision closure.


Assuntos
Histerectomia Vaginal/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Técnicas de Sutura , Vagina/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Duração da Cirurgia
20.
Obstet Gynecol Sci ; 59(4): 261-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27462592

RESUMO

OBJECTIVE: The identification of cancer stem-like cells is a recent development in ovarian cancer. Compared to other cancer cells, cancer stem-like cells present more chemo-resistance and more aggressive characteristics. They play an important role in the recurrence and drug resistance of cancer. Therefore, the target therapy of cancer stem-like cell may become a promising and effective approach for ovarian cancer treatment. It may also help to provide novel diagnostic and therapeutic strategies. METHODS: The OVCAR3 cell line was cultured under serum-free conditions to produce floating spheres. The CD44(+)CD117(+) cell line was isolated from the human ovarian cancer cell line OVCAR3 by using immune magnetic-activated cell sorting system. The expression of stemness genes such as OCT3/4, NANOG and SOX2 mRNA were determined by reverse transcription polymerase chain reaction. OVCAR3 parental and OVCAR3 CD44(+)CD117(+) cells were grown in different doses of paclitaxel and salinomycin to evaluate the effect of salinomycin. And growth inhibition of OVCAR3 CD44(+)CD117(+) cells by paclitaxel combined with salinomycin was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. RESULTS: Tumor spheroids generated from the OVCAR3 cell line are shown to have highly enriched CD44 and CD117 expression. Treatment with a combination of paclitaxel and salinomycin demonstrated growth inhibition of OVCAR3 CD44(+)CD117(+) cells. CONCLUSION: The present study is a detailed investigation on the expression of CD44 and CD117 in cancer stem cells and evaluates their specific tumorigenic characteristics in ovarian cancer. This study also demonstrates significant growth inhibition of cancer stem-like cells by paclitaxel combined with salinomycin. Identification of these cancer stem-like cell markers and growth inhibition effect of salinomycin may be the next step to the development of novel target therapy in ovarian cancer.

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