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BACKGROUND: The effects of thoracic endovascular aneurysm repair (TEVAR) with additional distal bare metal stents (BMSs) in patients with subacute complicated type B aortic dissection (cTBAD) are unclear and are investigated in this retrospective study. METHODS: The medical records of 67 patients who received TEVAR due to subacute cTBAD were reviewed. Areas of true lumen (TL) and false lumen at 5 levels-- pulmonary artery (PA), diaphragm, renal artery (RA), middle of the infrarenal aorta, and aortic bifurcation-were measured using computed tomography before and 3, 6, and 12 months after surgery. The TL ratio (TL area/total aortic area) and total aortic area at each time point were compared between the TEVAR+BMS (n=37) and TEVAR-only (n=30) groups. The effects of BMS use and time were evaluated using generalized estimating equations and generalized linear regression models. RESULTS: Baseline characteristics, remodeling types, and clinical outcomes did not differ significantly between the 2 groups. Postoperative TL ratios at the diaphragm and RA were significantly higher in the TEVAR+BMS group than in the TEVAR-only group (p < 0.05). BMS use and time had significant interaction effects at the PA, diaphragm, and RA (all p < 0.05), but effects on total aortic area were not significant at any of the 5 parts. TL ratios at the diaphragm and RA exhibtied greater improvement in the TEVAR+BMS group than in the TEVAR-only group at postoperative months 6 and 12 (all p < 0.001). Aortic diameters at all 5 parts were significantly smaller in the TEVAR+BMS group than in the TEVAR-only group (all p < 0.05). CONCLUSION: In patients with subacute cTBAD, TEVAR with BMS implantation effectively expands the TL from the thoracic aorta to the RA but neither enhances aortic remodeling nor elicits any change in total aortic area in whole dissected aorta relative to TEVAR only.
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Background: No recommendations have been made regarding the puncture position during tunnelled dialysis catheter (TDC) insertion from right internal jugular vein (RIJV). We investigated the effect of puncture positioning along with other characteristics and clinical factors associated with TDCs to determine their correlation with catheter patency rate. Methods: We retrospectively reviewed TDC insertion procedures performed between January 2018 and December 2020 at a single institution. Patients were monitored for at least 1 year or until TDC removal or replacement. The distance on the post-operative chest radiography were measured to determine the height of puncture position. End points were freedom from catheter dysfunction. Results: Total 949 catheters met the eligibility criteria. Catheter dysfunction occurred in 233 patients and catheter infection in 127 patients. By multivariate analysis, female sex [hazard ratio (HR) =1.497, 95% confidence interval (CI): 1.119-2.002; P=0.007] and split-tip catheter (HR =1.453, 95% CI: 1.087-1.944; P=0.012) were associated with an increased rate of catheter dysfunction. Every 10-year increment in age (HR =1.243, 95% CI: 1.123-1.376; P<0.001) and every 1-cm increase in the height of the catheter insertion site (HR =1.270, 95% CI: 1.096-1.473; P=0.001) were also associated with an increased rate of catheter dysfunction. After classifying the height of puncture position into 3 groups, significant worse patency was observed in the catheter with puncture height more than 4 cm (P=0.025). No immediate complications were observed. Conclusions: TDC insertion at a high puncture site correlates with an increased risk of catheter dysfunction. Puncturing the RIJV close to the clavicle is safe and enhances catheter patency.
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BACKGROUND: This study investigated whether initial SGLT2 (sodium-glucose cotransporter 2) inhibitor-based treatment is superior to metformin-based regimens as a primary prevention strategy among low-risk patients with diabetes. METHODS AND RESULTS: In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors-based and metformin-based regimens were 1:2 matched by propensity score. Study outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end-stage renal disease. Compared with 1928 patients receiving metformin-based regimens, 964 patients receiving SGLT2 inhibitor-based regimens had similar all-cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51-1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25-1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59-1.92]), stroke (HR, 0.78 [95% CI, 0.48-1.27]), and progression to end-stage renal disease (HR, 0.88 [95% CI, 0.32-2.39]). However, SGLT2 inhibitors were associated with a lower risk of all-cause mortality (HR, 0.47 [95% CI, 0.23-0.99]; P for interaction=0.008) and progression to end-stage renal disease (HR, 0.22 [95% CI, 0.06-0.82]; P for interaction=0.04) in patients under the age of 65. CONCLUSIONS: In comparison to metformin-based regimens, SGLT2 inhibitor-based regimens showed a similar risk of all-cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first-line therapy in select low-risk patients, for example, younger patients with diabetes.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Falência Renal Crônica , Metformina , Inibidores do Transportador 2 de Sódio-Glicose , Acidente Vascular Cerebral , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos de Coortes , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , Fatores de Risco , Resultado do Tratamento , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/induzido quimicamente , Fatores de Risco de Doenças Cardíacas , Acidente Vascular Cerebral/induzido quimicamente , Glucose , Hipoglicemiantes/uso terapêuticoRESUMO
Uterine fibroids, the most common benign tumors of the myometrium in women, are characterized by abnormal extracellular matrix deposition and uterine smooth muscle cell neoplasia, with high recurrence rates. Here, we investigated the potential of the marine natural product manzamine A (Manz A), which has potent anti-cancer effects, as a treatment for uterine fibroids. Manz A inhibited leiomyoma cell proliferation in vitro and in vivo by arresting cell cycle progression and inducing caspase-mediated apoptosis. We performed target prediction analysis and identified sterol o-acyltransferases (SOATs) as potential targets of Manz A. Cholesterol esterification and lipid droplet formation were reduced by Manz A, in line with reduced SOAT expression. As a downstream target of SOAT, Manz A also prevented extracellular matrix deposition by inhibiting the ß-catenin/fibronectin/metalloproteinases axis and enhanced autophagy turnover. Excessive free fatty acid accumulation by SOAT inhibition led to reactive oxygen species to impair mitochondrial oxidative phosphorylation and trigger endoplasmic reticulum stress via PERK/eIF2α/CHOP signaling. The inhibitory effect of ManzA on cell proliferation was partially restored by PERK knockdown and eliminated by tauroursodeoxycholic acid, suggesting oxidative stress plays a critical role in the mechanism of action of Manz A. These findings suggest that targeting SOATs by Manz A may be a promising therapeutic approach for uterine fibroids.
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Leiomioma , Estresse Oxidativo , Feminino , Humanos , Carbazóis , Leiomioma/tratamento farmacológico , Leiomioma/genética , Proliferação de CélulasRESUMO
BACKGROUND: Pump exchange surgery of left ventricular assist device (LVAD) has been demonstrated in several studies; however, information for Asian patients was limited. CASE PRESENTATION: A 63-year-old man underwent a pump upgrade from HeartMate II to HeartMate 3 for driveline damage through limited left anterior thoracotomy and lower partial sternotomy. He did not experience any hemodynamic adverse events or device malfunction during postoperative follow-ups of 12 months. We also reviewed all published cases with HeartMate II exchange to HeartMate 3. CONCLUSIONS: The case demonstrated that it was safe and feasible to perform HMII LVAD exchange to HM3 through a limited approach for Asian patients.
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Coração Auxiliar , Masculino , Humanos , Pessoa de Meia-Idade , Coração Auxiliar/efeitos adversos , Período Pós-Operatório , EsternotomiaRESUMO
Melissa officinalis (MO), known as lemon balm, is a popular ingredient blended in herbal tea. In recent decades, the bioactivities of MO have been studied in sub-health and pathological status, highlighting MO possesses multiple pharmacological effects. We previously showed that hot water MO extract exhibited anticancer activity in colorectal cancer (CRC). However, the detailed mechanisms underlying MO-induced cell death remain elusive. To elucidate the anticancer regulation of MO extract in colon cancer, a data-driven analysis by proteomics approaches and bioinformatics analysis was applied. An isobaric tandem mass tags-based quantitative proteome analysis using liquid chromatography-coupled tandem mass spectrometry was performed to acquire proteome-wide expression data. The over-representation analysis and functional class scoring method were implemented to interpret the MO-induced biological regulations. In total, 3465 quantifiable proteoforms were identified from 24,348 peptides, with 67 upregulated and 54 downregulated proteins in the MO-treated group. Mechanistically, MO impeded mitochondrial respiratory electron transport by triggering a reactive oxygen species (ROS)-mediated oxidative stress response. MO hindered the mitochondrial membrane potential by reducing the protein expression in the electron transport chain, specifically the complex I and II, which could be restored by ROS scavenger. The findings comprehensively elucidate how MO hot water extract activates antitumor effects in colorectal cancer (CRC) cells.
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Neoplasias do Colo , Melissa , Mitocôndrias , Extratos Vegetais , Neoplasias do Colo/tratamento farmacológico , Humanos , Melissa/química , Mitocôndrias/fisiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteoma , Espécies Reativas de Oxigênio/metabolismo , ÁguaAssuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Humanos , Hipoglicemiantes/farmacologia , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disease of the heart muscle. Clinical challenges remain, however, in identifying patients with ARVC in the early or concealed stages with subtle clinical manifestations. Therefore, we wanted to identify potential targets by immunohistochemical (IHC) analysis in comparison with controls. Pathogenic mutations were identified in 11 of 37 autopsied patients with ARVC. As observed from IHC analysis of the RV, expression of αT-catenin and plakophilin-2 is significantly decreased in autopsied patients with ARVC as compared to controls, and the decreased expression is consistent in patients with and without pathogenic mutations. Furthermore, ARVC specimens demonstrated a reduced localization of αT-catenin, desmocollin-2, desmoglein-2, desmoplakin, and plakophilin-2 on intercalated discs. These findings have been validated by comparing RV specimens obtained via endomyocardial biopsy between patients with ARVC and those without. The pathogenic mutation was present in 3 of 5 clinical patients with ARVC. In HL-1 myocytes, siRNA was used to knockdown CTNNA3, and western blotting analysis demonstrated that the decline in αT-catenin expression was accompanied by a significant decline in the expression of plakophilin-2. The aforementioned effect was directed towards protein degradation rather than mRNA stability. Plakophilin-2 expression decreases concurrently with the decline in CTNNA3 expression. Therefore, the expression of αT-catenin and plakophilin-2 could be potential surrogates for the diagnosis of ARVC.
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Displasia Arritmogênica Ventricular Direita , Cateninas , Placofilinas , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/metabolismo , Displasia Arritmogênica Ventricular Direita/patologia , Cateninas/metabolismo , Moléculas de Adesão Celular/metabolismo , Humanos , Imuno-Histoquímica , Mutação , Miocárdio/metabolismo , Miocárdio/patologia , Placofilinas/biossíntese , Placofilinas/genética , Placofilinas/metabolismoRESUMO
Background: The clinical significance and outcomes of ventricular tachyarrhythmias (VTa) in patients undergoing valve replacement have rarely been reported. Objective: This study aimed to investigate the incidence and outcome of VTa after surgical valve replacement. Methods: We conducted a population-based retrospective cohort study using data obtained from the Taiwan National Health Insurance Research Database. In total, 10,212 patients were selected after 1:1 propensity-score matching based on the type of prosthetic valve used (mechanical vs. bioprosthetic). Various outcomes during long-term follow-up were analyzed. Results: After a median follow-up period of 59.6 months, the crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased after surgery. Furthermore, the occurrences of VTa after valve replacement significantly increased the risk of cardiovascular (CV) death (P < 0.001, HR 1.67, 95% CI 1.41-1.96), stroke- (P < 0.001, HR 1.66, 95% CI 1.37-2.01), atrial fibrillation- (P < 0.001, HR 2.80, 95% CI 2.42-3.24), and congestive heart failure-related hospitalization (P < 0.001, HR 2.61, 95% CI 2.30-2.95). Among patients with VTa, all-cause mortality (P = 0.001, HR 0.49, 95% CI 0.32-0.75) and CV death (P = 0.047, HR 0.58, 95% CI 0.34-0.99) in those with implantable cardioverter-defibrillator (ICD) implantation were lower than those without. Conclusion: The crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased during follow-up. The presence of VTa after surgical valve replacement increases hospitalization and CV death, while ICD implantation reduced the mortality rate in these patients.
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5-Fluorouracil (5-FU) is one of several chemotherapeutic agents in clinical use as a standard of care to treat colorectal cancers (CRCs). As an antimetabolite, 5-FU inhibits thymidylate synthase to disrupt the synthesis and repair of DNA and RNA. However, only a small proportion of patients benefit from 5-FU treatment due to the development of drug resistance. This study applied pharmacogenomic analysis using two public resources, the Genomics of Drug Sensitivity in Cancer (GDSC) and the Connectivity Map, to predict agents overcoming 5-FU resistance in CRC cells based on their genetic background or gene expression profile. Based on the genetic status of adenomatous polyposis coli (APC), the most frequent mutated gene found in CRC, we found that combining a MEK inhibitor with 5-FU exhibited synergism effects on CRC cells with APC truncations. While considering the gene expression in 5-FU resistant cells, we demonstrated that targeting ROCK is a potential avenue to restore 5-FU response to resistant cells with wild-type APC background. Our results reveal MEK signaling plays a pivotal role in loss-of-function, APC-mediated 5-FU resistance, and ROCK activation serves as a signature in APC-independent 5-FU resistance. Through the use of these available database resources, we highlight possible approaches to predict potential drugs for combinatorial therapy for patients developing resistance to 5-FU treatment.
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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of <8%. Therefore, finding new treatment strategies against PDAC cells is an imperative issue. Betulinic acid (BA), a plant-derived natural compound, has shown great potential to combat cancer owing to its versatile physiological functions. In this study, we observed the impacts of BA on the cell viability and migratory ability of PDAC cell lines, and screened differentially expressed proteins (DEPs) by an LC-MS/MS-based proteomics analysis. Our results showed that BA significantly inhibited the viability and migratory ability of PDAC cells under a relatively low dosage without affecting normal pancreatic cells. Moreover, a functional analysis revealed that BA-induced downregulation of protein clusters that participate in mitochondrial complex 1 activity and oxidative phosphorylation, which was related to decreased expressions of RNA polymerase mitochondrial (POLRMT) and translational activator of cytochrome c oxidase (TACO1), suggesting that the influence on mitochondrial function explains the effect of BA on PDAC cell growth and migration. In addition, BA also dramatically increased Apolipoprotein A1 (APOA1) expression and decreased NLR family CARD domain-containing protein 4 (NLRC4) expression, which may be involved in the dampening of PDAC migration. Notably, altered expression patterns of APOA1 and NLRC4 indicated a favorable clinical prognosis of PDAC. Based on these findings, we identified potential proteins and pathways regulated by BA from a proteomics perspective, which provides a therapeutic window for PDAC.
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Adenocarcinoma/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Proteoma/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fosforilação Oxidativa/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Proteômica/métodos , Espectrometria de Massas em Tandem , Ácido BetulínicoRESUMO
[This corrects the article DOI: 10.1021/acsomega.0c04489.].
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OBJECTIVES: To compare the outcomes of using iliac branch devices (IBD) and the crossover chimney (COCh) technique for preserving the internal iliac artery (IIA) during endovascular aortic repair in patients with common iliac aneurysm (CIA). METHODS: From February 2010 to July 2016, we recruited 61 consecutive and elective patients. Thirty of them received the IBD, and the remaining 31 received the COCh. Their medical chart was reviewed retrospectively, and computed tomographic angiography was performed at 3, 6, and 12 months postoperatively and then yearly as a follow-up. RESULTS: The median follow-up time was 19.72 ± 5.45 months. The technical success rate reached 100% in both groups. The 12-month and 24-month primary IIA patency rates between IBD and COCh group were 90.00% versus 93.54% (p = 0.67) and 83.33% versus 93.54% (p = 0.25). The numbers of stents were 1.00 ± 0.00 and 1.93 ± 0.24 in the IBD and COCh group (p < 0.001). No significant difference was observed for the incidence of type 1a (IBD/COCh = 3.33%/6.45%, p > 0.99) and type 2 endoleak (IBD/COCh = 13.33%/12.90%, p > 0.99) between two groups. Neither type 1b or type 3 endoleak nor delayed aortic rupture appeared in our series. The postoperative complication rates did not exhibit significant differences either. Free from reintervention was also similar in both groups (IBD/COCh = 22.50 ± 4.62/23.00 ± 3.87 months, p = 0.64). CONCLUSIONS: The IBD and COCh techniques exhibited similar success rates and IIA patency rates at the 24-month follow-up. Both these techniques are feasible for the preservation of IIA in patients with CIA.
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Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Aneurisma Ilíaco/cirurgia , Artéria Ilíaca/cirurgia , Idoso , Angiografia por Tomografia Computadorizada , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Seguimentos , Humanos , Aneurisma Ilíaco/diagnóstico , Artéria Ilíaca/diagnóstico por imagem , Masculino , Desenho de Prótese , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background: Abdominal aortic stent graft infection (AAGI) is a severe complication. The optimal management of AAGI remains unclear. This study provides updated results of bilateral axillofemoral bypasses (AFBs) for patients with AAGI. Patients and Methods: In total, 31 patients (25 men; mean age, 67.1 years) with AAGI treated using AFB between January 2006 and April 2020 were included. Overall, the mean follow-up duration was 24 months (range, 1-72). In the 23 patients who survived the post-operative period, the mean follow-up duration was 32 months (range, 12-72). Results: Thirty-day and in-hospital mortality rates was 16% and 26%, respectively. The 12-month primary and secondary patency rates for the AFB graft were both 91%. In total, seven (30%) patients received re-interventions such as thrombectomy and balloon angioplasty. No amputation was required during follow-up. Culture results were positive in 87% of pre-operative cultures and 84% of intra-operative cultures. Staphylococcus aureus was the most prevalent pathogen, with four cases of methicillin-resistant Staphylococcus aureus and one each of vancomycin-resistant enterococci, carbapenem-resistant Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae. In-hospital mortality rate was 57% in patients with drug-resistant pathogens. Conclusions: Reconstruction with bilateral AFB and stent graft removal in patients with AAGI is a feasible treatment modality and provided an acceptable patency rate and low amputation rate. Additional studies investigating long-term results and the optimal treatment of AAGI are required.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Staphylococcus aureus Resistente à Meticilina , Idoso , Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Remoção de Dispositivo , Humanos , Masculino , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: Although commercial iliac branch devices offer a new and valid endovascular approach to treating iliac aneurysm and effectively preserve antegrade flow of the internal iliac artery, their use may not be suited for all types of challenging anatomy, especially isolated common iliac artery aneurysm. Our custom-made iliac bifurcation device has a unique design and excludes both combined and isolated iliac branch aneurysm. This study validated the efficacy and safety of the custom device by comparing clinical outcomes between groups receiving commercial and custom devices. METHODS: Data of consecutive patients receiving iliac bifurcation device implantation for iliac aneurysm with or without concomitant endovascular repair for abdominal aortic aneurysm from January 2010 to May 2019 were reviewed. RESULTS: Iliac bifurcation device implantation with or without concomitant abdominal aortic aneurysm stent grafting was completed in 46 patients (commercial, n = 35; custom, n = 11). No significant differences were observed regarding postoperative complications, occlusion or endoleak. Comparisons of primary (80.8% vs 85.7%, P = 0.88) and secondary (86.5% vs 85.7%, P = 0.85) patency and freedom from reintervention (88.2% vs 100%, P = 0.33), all-cause mortality (78.6% vs 100%, P = 0.25) and aneurysm-related mortality (100% vs 100%, P = 1.00) also indicated no differences at a 5-year surveillance point. Furthermore, the iliac aneurysms of the groups displayed similar shrinkage 1 year after procedures. CONCLUSIONS: For iliac aneurysm, the novel custom-made iliac bifurcation device is an adaptable design not inferior to commercial devices with regard to postoperative complications, bridge occlusion, endoleak and short-term aneurysm remodelling. It provides an alternative for treatment, particularly when certain anatomic challenges are present. CLINICAL TRIAL REGISTRATION: 2018-07-050BC, 2017-01-023ACF.
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Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/instrumentação , Aneurisma Ilíaco/complicações , Aneurisma Ilíaco/cirurgia , Idoso , Idoso de 80 Anos ou mais , Implante de Prótese Vascular/efeitos adversos , Feminino , Seguimentos , Humanos , Aneurisma Ilíaco/mortalidade , Artéria Ilíaca/cirurgia , Estimativa de Kaplan-Meier , Masculino , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Lifestyle-related factors, such as diet, are associated with the development of CRC. Cumulating evidence indicates noticeable chemopreventive effects of phytochemicals on CRC, suggesting that drinking herbal tea potentially reduces the risk of distal colon cancer via its antiproliferative and anti-angiogenic activities. We examine the antitumor effects of nine components frequently found in herbal tea and uncover the underlying molecular mechanism. Among them, the hot water extract of Melissa officinalis (MO) exhibited the highest anticancer activity on CRC cells. We revealed that MO reduced cell proliferation, induced cell cycle arrest at the G2/M phase, triggered caspase-dependent apoptotic cell death, and inhibited cell migration ability by modulating the epithelial-mesenchymal transition in HCT116 CRC cells. To examine the metabolite composition in the MO hot water extract, we applied mass spectrometry-based analysis and identified 67 compounds. Among them, the phenolic compounds, including lignans, phenylpropanoids, and polyketides, are widely found in natural products and possess various bioactivities such as anti-inflammatory, antioxidation, and anticancer effects. The results indicate that herbal tea consumption benefits CRC prevention and management.
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OBJECTIVE. The purpose of this study was to compare the volume alteration and effective renal plasma flow of kidneys supplied by false lumens (FLs) with those of kidneys supplied by true lumens (TLs), to show the discrepancy in perfusion between the two lumens. We sought to corroborate malperfusion of FL-supplied kidneys with imaging characteristics observed on CT angiography. MATERIALS AND METHODS. A retrospective analysis was conducted using prospectively collected data for 87 patients with a diagnosis of residual chronic aortic dissection between 2005 and 2013 who had one kidney perfused by a TL and the other kidney perfused by a FL. RESULTS. Overall, at follow-up, FL-supplied kidneys had a mean (± SD) effective renal plasma flow (117.5 ± 42.6 vs 146.6 ± 41.0 mL/min; p = 0.004) and volume (131.1 ± 37.1 vs 146.5 ± 33.3 cm3; p = 0.004) that were lower than those of TL-supplied kidneys. Multivariate analysis revealed the presence of a proximal major inlet (odds ratio, 0.306; 95% CI, 0.103-0.910; p = 0.033) and large FL area (odds ratio, 0.104; CI, 0.012-0.880; p = 0.038) as factors protecting against malperfusion of FL-supplied kidneys. In patients with dissected renal arteries, the FL-supplied kidney had low effective renal plasma flow (mean, 88.5 ± 26.8 vs 149.6 ± 43.5 mL/min; p = 0.004) and diminished volume (mean, 120.4 ± 30.4 vs 152.3 ± 24.6 cm3; p = 0.001). CONCLUSION. In the present study, kidneys perfused by FLs showed decreased volume and reduced effective renal plasma flow during follow-up, particularly those kidneys with dissected renal arteries, a small FL area at the renal level, and lack of a proximal major inlet. Further studies are warranted to identify the clinical relevance of malperfusion in FL-supplied kidneys.
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Dissecção Aórtica/complicações , Angiografia por Tomografia Computadorizada/métodos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Doença Crônica , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
MYCN-amplified (MNA) neuroblastoma is an aggressive neural crest-derived pediatric cancer. However, MYCN is indispensable for development and transcriptionally regulates extensive network of genes. Integrating anti-MYCN ChIP-seq and gene expression profiles of neuroblastoma patients revealed the metabolic enzymes, MTHFD2 and PAICS, required for one-carbon metabolism and purine biosynthesis were concomitantly upregulated, which were more susceptible to metastatic neuroblastoma. Moreover, we found that MYCN mediated the folate cycle via MTHFD2, which contributed one-carbon unit to enhance purine synthesis, and further regulated nucleotide production by PAICS in response to cancer progression. Dual knockdown of the MYCN-targeted gene pair, MTHFD2 and PAICS, in MNA neuroblastoma cells synergically reduced cell proliferation, colony formation, migration ability, and DNA synthesis. By systematically screening the compound perturbagens, the gene expression levels of MTHFD2 and PAICS were specifically suppressed by anisomycin and apicidin across cell lines, and our co-treatment results also displayed synergistic inhibition of MNA neuroblastoma cell proliferation. Collectively, targeting a combination of MYCN-targeted genes that interrupts the interconnection of metabolic pathways may overcome drug toxicity and improve the efficacy of current therapeutic agents in MNA neuroblastoma.
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Aminoidrolases/metabolismo , Carboxiliases/metabolismo , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Enzimas Multifuncionais/metabolismo , Purinas/biossíntese , Aminoidrolases/genética , Carboxiliases/genética , Ciclo Celular/fisiologia , Processos de Crescimento Celular , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Metabolômica , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Terapia de Alvo Molecular , Enzimas Multifuncionais/genética , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Neuroblastoma/terapia , Transcriptoma , Transfecção , Regulação para CimaRESUMO
BACKGROUND: Endovascular repair with stent-graft is a treatment option for patient with common iliac artery aneurysm (CIAA). However, the preservation of the internal iliac artery (IIA) is a concern. The commercially available iliac branched device (IBD) requires a common iliac length of at least 5 cm, which is usually too long for Asian people. Here, we report our medium-term results of using tailor-made IBD for patients with short common iliac artery (CIA) with and without abdominal aortic aneurysm (AAA). METHODS: A selected iliac limb of the AAA stent-graft was unloaded from the delivery system. A 6-mm fenestration hole was made at the length of the CIA from the proximal end. The edge of the hole was reinforced with the soft and radiopaque tip of a 0.014´´ wire. Then, the iliac limb was reloaded into the introduced sheath as the tailor-made IBD. It was inserted from the selected side of the femoral artery and deployed. The ipsilateral IIA was cannulated through the fenestration hole. Then, a balloon-expandable or self-expandable covered stent with an appropriate size was deployed as the bridging stent-graft. RESULTS: Between March 2013 and March 2017, a total of 10 patients received the tailor-made IBDs. One patient died of systemic thromboembolism 2 days after the operation. The bridging stent-grafts remained patent in all patients, except one occluded at 1 year after operation. CONCLUSION: A tailor-made IBD is an easy-to-apply, alternative option for preserving the IIA perfusion in short CIAA patients with and without AAA.
Assuntos
Implante de Prótese Vascular/instrumentação , Procedimentos Endovasculares/instrumentação , Aneurisma Ilíaco/cirurgia , Stents , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the effect of renal stent-graft placement on kidney function and size alternation in chronic aortic dissection. MATERIALS AND METHODS: Twenty-five consecutive patients with chronic aortic dissection after thoracic endovascular aortic repair who underwent renal stent-graft placement between January 2015 and December 2016 were retrospectively reviewed. Forty-three patients with chronic aortic dissection who received thoracic endovascular aortic repair in the same period were reviewed as a control group for kidney volume comparison. RESULTS: Twenty-five stent-grafts were deployed over 25 renal arteries. Overall renal function was assessed by the slope of the regression line constructed from the plots of creatinine clearance versus time within 2 years after the procedure (-0.2810 vs -0.3146 mL/min-1/mo-1, P = .868), kidney volume at 12 months (129.4 ± 40.9 vs 137.0 ± 44.2 cm2, P = .193) and effective renal plasma flow at 6 months (106.3 ± 46.9 vs 124.4 ± 55.5 mL/min, P = .050) and was not significantly deteriorated. Seven treated patients (87.5%) with a renal artery supplied by a false lumen had a decrease in kidney volume, as did 14 patients (56%) in the control group (P = .206). Three patients with a dissected renal artery (75%) in the stent-graft group had an increase in kidney volume compared with 1 patient (11.1%) in the control group (P = .052). CONCLUSIONS: Occlusion of the re-entry tear by a stent-graft in the renal artery remains a safe strategy to promote false lumen thrombosis. The stent-graft poses a potential risk of reducing the kidney volume in kidneys supplied by the false lumen but may provide a positive effect in kidney volume with a concomitant dissected renal artery in chronic aortic dissection.