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Under challenging common femoral artery access scenarios, the "wall PIERCE" technique, which utilizes a larger puncture needle to pierce the vessel wall along the guidewire, facilitates sheath insertion. This method proved successful in two cases without any complications, presenting a valuable addition to strategies for addressing challenging sheath insertion scenarios.
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The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines and detected frequent genetic mutations in the NOTCH pathway in addition to previously reported alterations in GATA-1 and the JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient-derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis. and NOTCH activation holds the potential for therapeutic application in AMKL.
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Proliferação de Células , Leucemia Megacarioblástica Aguda , Receptores Notch , Transdução de Sinais , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/patologia , Leucemia Megacarioblástica Aguda/metabolismo , Humanos , Animais , Receptores Notch/metabolismo , Receptores Notch/genética , Camundongos , Sobrevivência Celular , Linhagem Celular Tumoral , Mutação , Feminino , MasculinoRESUMO
BACKGROUND: Despite the effectiveness of the retrograde approach for chronic total occlusion (CTO) lesions, there are no standardized tools to predict the success of retrograde percutaneous coronary intervention (PCI). OBJECTIVES: The aim of this study was to develop a prediction tool to identify CTO lesions that will achieve successful retrograde PCI. METHODS: This study evaluated data from 2,374 patients who underwent primary retrograde CTO-PCI and were enrolled in the Japanese CTO-PCI Expert Registry between January 2016 and December 2022 (NCT01889459). All observations were randomly assigned to the derivation and validation cohorts at a 2:1 ratio. The prediction score for guidewire failure in retrograde CTO-PCI was determined by assigning 1 point for each factor and summing all accrued points. RESULTS: The JR-CTO score (moderate-severe calcification, tortuosity, Werner collateral connection grade ≤1, and nonseptal collateral channel) demonstrated a C-statistic for guidewire failure of 0.72 (95% CI: 0.67-0.76) and 0.71 (95% CI: 0.64-0.77) in the derivation and validation cohorts, respectively. Patients with lower scores had higher guidewire and technical success rates and decreased guidewire crossing time and procedural time (P < 0.01). CONCLUSIONS: The JR-CTO (Japanese Retrograde Chronic Total Occlusion) score, a simple 4-item score that predicts successful guidewire crossing in patients undergoing retrograde CTO-PCI, has the potential to support clinical decision-making for the retrograde approach.
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Oclusão Coronária , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Sistema de Registros , Humanos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Oclusão Coronária/fisiopatologia , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Japão , Feminino , Idoso , Doença Crônica , Pessoa de Meia-Idade , Resultado do Tratamento , Fatores de Risco , Reprodutibilidade dos Testes , Técnicas de Apoio para a Decisão , Medição de Risco , Circulação Coronária , Circulação Colateral , Tomada de Decisão Clínica , Fatores de Tempo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/terapia , População do Leste AsiáticoRESUMO
The synthesis of zeolites from two-dimensional layered precursors through interlayer crosslinking of the layers is a promising avenue for realizing meticulously designed synthesis routes. However, the presence of defective silanol species in the precursors hinders the achievement of desirable synthesis outcomes. This study focuses on PREFER-a layered precursor for FER-type zeolites-which was synthesized and subjected to a liquid-mediated defect-healing treatment that we recently developed. The defect-healing process involves the use of fluoride compounds for reconstruction and organic pore fillers to stabilize the framework. The effects of the treatment on the structure, composition, and iron insertion behavior of PREFER were examined. Characterization results revealed a reduction in the number of intralayer silanol defects, whereas interlayer silanols were unaffected by the defect-healing treatment. Furthermore, the subsequent alterations observed in the crosslinking behavior with iron atoms indicated that the defect-healing treatment may enhance the insertion of iron species between the layers in more homogeneous environments compared with the untreated precursor. These findings provide valuable insights into the prospects of controlled interlayer linkage in two-dimensional zeolite materials.
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Although the coronary chronic total occlusion (CTO) crossing algorithm has been published, the characteristics associated with the first strategy selection for short-length lesions <20 mm is still debatable. This study aimed to determine the characteristics associated with primary retrograde approach (PRA) for native CTO with short occlusion length in percutaneous coronary intervention (PCI). Between January 2014 and December 2021, we examined data on 4,088 lesions in the Japanese CTO-PCI Expert Registry with occlusion lengths <20 mm. Then, the characteristics for short-length CTO, which was performed by way of the PRA, were assessed. PRA was performed in 785 patients (19.2%). The guidewire success rate was 93.6%, and the technical success rate was 91.3%. Previous coronary artery bypass grafting, chronic kidney disease, and 6 lesion/anatomic characteristics (i.e., blunt stump, distal runoff <1 mm, CTO lesion tortuosity, reattempt procedures, ostial location, and the presence of collateral channel grade 2) were associated with PRA (p <0.05). Moreover, hemodialysis was an independent factor of unsuccessful anterograde guidewire crossing, along with distal runoff <1 mm, the existence of calcification, and CTO lesion tortuosity (all p <0.05). In clinical settings, these independent factors for PRA in short-length CTO can help in selecting the CTO-PCI strategy.
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Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Oclusão Coronária/cirurgia , Intervenção Coronária Percutânea/métodos , Japão , Fatores de Risco , Angiografia Coronária , Doença Crônica , Fatores de Tempo , Sistema de Registros , Resultado do TratamentoRESUMO
Gastric cancer metastasis is a major cause of mortality worldwide. Inhibition of RUNX3 in gastric cancer cell lines reduced migration, invasion, and anchorage-independent growth in vitro. Following splenic inoculation, CRISPR-mediated RUNX3-knockout HGC-27 cells show suppression of xenograft growth and liver metastasis. We interrogated the potential of RUNX3 as a metastasis driver in gastric cancer by profiling its target genes. Transcriptomic analysis revealed strong involvement of RUNX3 in the regulation of multiple developmental pathways, consistent with the notion that Runt domain transcription factor (RUNX) family genes are master regulators of development. RUNX3 promoted "cell migration" and "extracellular matrix" programs, which are necessary for metastasis. Of note, we found pro-metastatic genes WNT5A, CD44, and VIM among the top differentially expressed genes in RUNX3 knockout versus control cells. Chromatin immunoprecipitation sequencing and HiChIP analyses revealed that RUNX3 bound to the enhancers and promoters of these genes, suggesting that they are under direct transcriptional control by RUNX3. We show that RUNX3 promoted metastasis in part through its upregulation of WNT5A to promote migration, invasion, and anchorage-independent growth in various malignancies. Our study therefore reveals the RUNX3-WNT5A axis as a key targetable mechanism for gastric cancer metastasis. SIGNIFICANCE: Subversion of RUNX3 developmental gene targets to metastasis program indicates the oncogenic nature of inappropriate RUNX3 regulation in gastric cancer.
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Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Genes Controladores do Desenvolvimento , Neoplasias Gástricas/genética , Regulação para Cima/genéticaRESUMO
The Agent device consists of a semi-compliant balloon catheter, which is coated with a therapeutic low-dose formulation of paclitaxel (2 µg/mm2) blended with an inactive excipient acetyl-tri-n-butyl citrate (ATBC). AGENT Japan SV is a randomized controlled study that enrolled 150 patients from 14 Japanese sites treated with Agent or SeQuent Please paclitaxel-coated balloon. This study also includes a single-arm substudy evaluating the safety and effectiveness of Agent in patients with in-stent restenosis (ISR). Patients with a single de novo native lesion (lesion length ≤ 28 mm and reference diameter ≥ 2.00 to < 3.00 mm) were randomized 2:1 to receive either Agent (n = 101) or SeQuent Please (n = 49). The ISR substudy enrolled 30 patients with lesion length ≤ 28 mm and reference diameter ≥ 2.00 to ≤ 4.00 mm. In the SV RCT, target lesion failure (TLF) at 1 year occurred in four patients treated with Agent (4.0%) versus one patient with SeQuent Please (2.0%; P = 1.00). None of the patients in either treatment arm died. There were no significant differences in the rates of myocardial infarction, target lesion revascularization and target lesion thrombosis through 1 year. In the ISR substudy, the 1-year rates of TLF and target lesion thrombosis were 6.7% and 0.0%, respectively. These data support the safety and effectiveness of the Agent paclitaxel-coated balloon in patients with small vessels and ISR.
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Angioplastia Coronária com Balão , Reestenose Coronária , Trombose , Humanos , Paclitaxel/farmacologia , Reestenose Coronária/etiologia , Reestenose Coronária/terapia , Resultado do Tratamento , Fatores de Risco , Trombose/etiologia , Materiais Revestidos BiocompatíveisRESUMO
BACKGROUND: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is still challenging due to complex lesion morphology. Success rates may vary among the 3 major coronary arteries, influenced by clinical and angiographic characteristics. OBJECTIVES: This study sought to evaluate the differences in the predictors of unsuccessful PCI in first-attempt CTO lesions of the 3 major coronary arteries compared with the J-CTO (Japanese CTO) score. METHODS: This study assessed 6,408 first-attempt CTO patients from the Japanese CTO-PCI expert registry between January 2014 and December 2021, randomly assigned to derivation and validation sets. Difficulty scores for each artery were determined by assigning points to predictive unsuccessful factors. RESULTS: The CTO lesions were distributed as follows: left anterior descending coronary artery: 2,245 (35%), left circumflex coronary artery: 1,131 (18%), and right coronary artery (RCA): 3,032 (47%). Regarding success rates, left circumflex coronary artery CTO had the lowest procedural success rate (90%) followed by RCA CTO (92%) and left anterior descending coronary artery CTO (94%). RCA CTO was significantly longer and more severely angulated, requiring more often the retrograde approach. A multivariate logistic analysis revealed that predictors of failed PCI were different in CTO lesions among the 3 major coronary arteries, respectively. Moreover, our difficulty score for RCA CTO was superior to the J-CTO score in predicting unsuccessful PCI. CONCLUSIONS: Clinical and angiographic differences might explain the discrepancies of success rates in CTO lesions among the 3 major coronary arteries. Our novel difficulty score was comparable to the J-CTO score in predicting unsuccessful CTO-PCI with a superior discriminatory capacity.
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Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Resultado do Tratamento , Intervenção Coronária Percutânea/efeitos adversos , Angiografia Coronária , Doença Crônica , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Sistema de Registros , Fatores de RiscoRESUMO
OBJECTIVES: We analyzed the 2-year clinical outcomes of patients with de novo femoropopliteal (FP) lesions who underwent drug-coated balloon (DCB) angioplasty and the angiographic predictors of restenosis. METHODS: This single-center, retrospective, and observational study evaluated 129 de novo FP lesions treated with DCB angioplasty without bailout stenting. Clinical outcomes and risk factors for loss of primary patency were analyzed using univariate and multivariate Cox proportional hazards regression models. RESULTS: The participants were aged 48-93 (mean: 73.6 ± 9.8) years, and 31% were women. Approximately 33% of the patients were receiving regular dialysis, and 35% of the affected limbs had critical ischemia. The mean lesion length was 132 ± 96 mm, and the mean reference vessel diameter (RVD) was 4.7 ± 0.8 mm. Forty-three (33%) limbs had chronic total occlusion of the target artery segment. Fifty-seven (44%) and 72 (56%) lesions were treated with DCB angioplasty using IN.PACT Admiral and Lutonix, respectively. The primary patency and amputation-free survival at 2 years were 59.3% and 89.5%, respectively. RVD was found to be an independent predictor of loss of primary patency. Based on the receiver operating characteristic analysis, an RVD of 4.2 mm was the best predictor of loss of primary patency at 2 years. CONCLUSIONS: The short-term clinical outcome of DCB angioplasty for de novo FP lesions was acceptable. Moreover, an RVD of <4.2 mm was an independent predictor of restenosis after DCB angioplasty.
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Angioplastia com Balão , Doença Arterial Periférica , Feminino , Humanos , Masculino , Materiais Revestidos Biocompatíveis , Constrição Patológica/etiologia , Artéria Femoral/cirurgia , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/cirurgia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: New-generation drug-eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first-generation DES in clinical trials with 3-5 years follow-up. However, detailed clinical outcome data in very long-term follow-up is still scarce. OBJECTIVES: To evaluate 10-year clinical outcomes after first- and new-generation DES implantation. METHODS: In this extende follow-up study of the RESET, which is a largest randomized trial comparing everolimus-eluting stent (EES) with Sirolimus-eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10-year follow-up was achieved in 87.9% of patients. RESULTS: Cumulative 10-year incidences of TLR and non-TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log-rank p = 0.20, and 33.4% vs. 31.3%, Log-rank p = 0.30). The cumulative 10-year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log-rank p = 0.18). Cumulative 10-year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log-rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log-rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log-rank p = 0.006). CONCLUSION: During 10-year of follow-up, the risks for primary efficacy and safety endpoints were not significantly different between new-generation EES and first-generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.
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MYC is one of the most commonly dysregulated proto-oncogenes in cancer. MYC promotes cancer initiation and maintenance by regulating multiple biological processes, such as proliferation and stem cell function. Here, we show that developmental regulator RUNX3 targets MYC protein for rapid degradation through the glycogen synthase kinase-3 beta-F-box/WD repeat-containing protein 7 (GSK3ß-FBXW7) proteolytic pathway. The evolutionarily conserved Runt domain of RUNX3 interacts directly with the basic helix-loop-helix leucine zipper of MYC, resulting in the disruption of MYC/MAX and MYC/MIZ-1 interactions, enhanced GSK3ß-mediated phosphorylation of MYC protein at threonine-58 and its subsequent degradation via the ubiquitin-proteasomal pathway. We therefore uncover a previously unknown mode of MYC destabilization by RUNX3 and provide an explanation as to why RUNX3 inhibits early-stage cancer development in gastrointestinal and lung mouse cancer models.
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Núcleo Celular , Subunidade alfa 3 de Fator de Ligação ao Core , Neoplasias Pulmonares , Animais , Camundongos , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proteína 7 com Repetições F-Box-WD/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteólise , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismoRESUMO
Identification of unique gene markers of normal and cancer stem cells is an effective strategy to study cells of origin and understand tumor behavior. Lineage tracing experiments using the Cre recombinase driven by a stem cell-specific promoter in the CreERT2 reporter mouse model enables identification of adult stem cells and delineation of stem cell activities in vivo. In our recent research on the mouse stomach, Iqgap3 was identified as a homeostatic stem cell marker located in the isthmus of the stomach epithelium. Lineage tracing with the Iqgap3-2A-CreERT2;Rosa26-LSL-tdTomato mouse model demonstrated stem cell activity in Iqgap3-expressing cells. Using the Iqgap3-2A-CreERT2 mouse model to target oncogenic KrasG12D expression to Iqgap3-expressing cells, we observed the rapid development of precancerous metaplasia in the stomach and proposed that aberrant Iqgap3-expressing cells may be critical determinants of early carcinogenesis. In this chapter, we detail a lineage tracing protocol to assess stem cell activity in the murine stomach. We also describe the procedure of inducing KrasG12D expression in Iqgap3-expressing homeostatic stem cells to explore their role as cells of origin and to trace the early cellular changes that precede neoplastic transformation.
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Células-Tronco Adultas , Neoplasias Gástricas , Camundongos , Animais , Camundongos Transgênicos , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Gástricas/patologia , Mucosa Gástrica/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Adultas/metabolismoRESUMO
The relationship between severity of calcification and clinical outcomes after endovascular therapy (EVT) for femoropopliteal lesions is well known. We often encounter dense calcifications in our daily practice, which are darker than normal calcifications on angiography. Accordingly, we named it "black rock" (BR), and investigated its impact on clinical outcomes after EVT. We retrospectively analyzed 677 lesions in 495 patients who underwent EVT for de novo calcified femoropopliteal lesions at our hospital between April 2007 and June 2020. BR is defined as a calcification which is 1 cm or more in length, occupies more than half of the vessel diameter, and appears darker than the body of the femur on angiography. Propensity score matching analysis was performed to compare clinical outcomes between lesions with BR [BR (+) group] and without BR [BR (-) group]. A total of 119 matched pairs of lesions were analyzed. Primary patency at 2 years was significantly lower in the BR (+) group than in the BR (-) group (48% vs. 75%, p = .0007). Multivariate analysis revealed that the presence of BR [hazard ratio (HR) = 2.23, 95% confidence interval (CI); 1.48-3.38, p = .0001], lesion length (HR = 1.03, 95%CI; 1.00-1.06, p = .0244), and no scaffold use (HR = 1.58, 95%CI; 1.06-2.36, p = .0246) were predictors of restenosis. The presence of BR is independently associated with clinical outcomes after EVT for de novo calcified femoropopliteal lesions.
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Procedimentos Endovasculares , Doença Arterial Periférica , Calcificação Vascular , Humanos , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Stents , Fatores de Risco , Artéria Femoral/diagnóstico por imagem , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/terapia , Grau de Desobstrução VascularRESUMO
OBJECTIVE: In subjects with chronic kidney disease (CKD), the effect of low-protein diet (LPD) is expected to alleviate uremic symptoms. However, whether LPD is effective in preventing loss of kidney function is controversial. The aim of this study was to evaluate the association between LPD and renal outcomes. METHODS: We conducted a multicenter cohort study of 325 patients who suffered CKD stage 4 and 5 with eGFR ≥10 mL/min/1.73 m,2 between January 2008 and December 2014. The primary diseases of the patients were chronic glomerulonephritis (47.7%), nephrosclerosis (16.9%), diabetic nephropathy (26.2%), and others (9.2%). The patients were divided into four groups, based on the mean protein intake (PI)/day, group 1 (n = 76): PI < 0.5 g/kg ideal body weight/day, group 2 (n = 56): 0.5 ≤ PI < 0.6 g/kg/day, group 3 (n = 110): 0.6 ≤ PI < 0.8 g/kg/day, group 4 (n = 83): PI ≥ 0.8 g/kg/day. Dietary supplementation with essential amino acids and ketoanalogues was not used. The outcome measure was occurrence of renal replacement therapy (RRT) (hemodialysis, peritoneal dialysis, renal transplantation (excluding preemptive transplantation)) and all-cause mortality until December 2018. Cox regression models were used to examine whether LPD was associated with the risk of outcomes. RESULTS: During a mean follow-up of 4.1 ± 2.2 years. Thirty-three patients (10.2%) died of all causes, 163 patients (50.2%) needed to start RRT, and 6 patients (1.8%) received a renal transplant. LPD therapy of 0.5 g/kg/day or less was significantly related to a lower risk of RRT and all-cause mortality [Hazard ratio = 0.656; 95% confidence interval, 0.438 to 0.984, P = .042]. CONCLUSIONS: These results suggest that non-supplemented LPD therapy of 0.5 g/kg/day or less may prolong the initiation of RRT in stage 4 and 5 CKD patients.
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Dieta com Restrição de Proteínas , Insuficiência Renal Crônica , Humanos , Japão , Estudos de Coortes , Progressão da Doença , Terapia de Substituição RenalRESUMO
We present a detailed protocol to identify and validate IGF2BP1 target genes in pluripotent human embryonic carcinoma cells (NTERA-2). We first identify the target genes through RNA-immunoprecipitation (RIP) sequencing. We then validate the identified targets through the use of RIP-qPCR assays, determine the m6A status of target genes by m6A-IP, and perform functional validation by quantifying changes in mRNA or protein expression levels upon knockdown of IGF2BP1 or methyltransferases in NTERA-2. For complete details on the use and execution of this protocol, please refer to Myint et al. (2022).1.
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PURPOSE: To investigate whether the severity of calcification assessed by the peripheral artery calcification scoring system (PACSS) was associated with clinical outcomes of drug-coated balloon (DCB) angioplasty for femoropopliteal lesions. MATERIALS AND METHODS: We retrospectively analyzed 733 limbs with intermittent claudication of 626 patients, who underwent DCB angioplasty for de novo femoropopliteal lesions between January 2017 and February 2021 at seven cardiovascular centers in Japan. The patients were categorized using the PACSS classification (grades 0-4: no visible calcification of the target lesion, unilateral wall calcification < 5 cm, unilateral calcification ≥ 5 cm, bilateral wall calcification < 5 cm, and bilateral calcification ≥ 5 cm, respectively). The main outcome was primary patency at 1 year. The Cox proportional hazards analysis was used to explore whether the PACSS classification was an independent predictor of clinical outcomes. RESULTS: The distribution of PACSS was grade 0 in 38%, grade 1 in 17%, grade 2 in 7%, grade 3 in 16%, and grade 4 in 23%. The 1-year primary patency rates in these grades, respectively, were 88.2%, 89.3%, 71.9%, 96.5%, and 82.6%, respectively (p < 0.001). Multivariate analysis disclosed that PACSS grade 4 (hazard ratio: 1.82, 95% confidence interval 1.15-2.87, p = 0.010) was associated with restenosis. CONCLUSION: The PACSS grade 4 calcification was independently associated with poor clinical outcomes after DCB angioplasty for de novo femoropopliteal lesions.
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Angioplastia com Balão , Doença Arterial Periférica , Calcificação Vascular , Humanos , Artéria Femoral/diagnóstico por imagem , Artéria Poplítea/diagnóstico por imagem , Estudos Retrospectivos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Resultado do Tratamento , Fatores de Risco , Angioplastia com Balão/efeitos adversos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/terapia , Materiais Revestidos Biocompatíveis , Grau de Desobstrução VascularRESUMO
Kα,ß X-ray lines from photon excitation were measured in selected elements from Mg to Cu using a high-resolution double-crystal X-ray spectrometer with a proportional counter, and the Kß/Kα intensity ratio for each element was obtained, after correcting for self-absorption, detection efficiency, and crystal reflectance. This intensity ratio increases rapidly from Mg to Ca but, in the 3d elements region, the increase becomes slower. This is related to the intensity of the Kß line involving valence electrons. The slow increase of this ratio in the 3d elements region is thought to be due to the correlation between 3d and 4s electrons. Moreover, the chemical shifts, FWHM, asymmetry indices, and Kß/Kα intensity ratios of the Cr compounds, due to different valences, were also investigated using the same double-crystal X-ray spectrometer. The chemical effects were clearly observed, and the Kß/Kα intensity ratio was found to be compound-dependent for Cr.
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Elétrons , Raios XRESUMO
The runt-related transcription factors (RUNX) play prominent roles in cell cycle progression, differentiation, apoptosis, immunity and epithelial-mesenchymal transition. There are three members in the mammalian RUNX family, each with distinct tissue expression profiles. RUNX genes play unique and redundant roles during development and adult tissue homeostasis. The ability of RUNX proteins to influence signaling pathways, such as Wnt, TGFß and Hippo-YAP, suggests that they integrate signals from the environment to dictate cell fate decisions. All RUNX genes hold master regulator roles, albeit in different tissues, and all have been implicated in cancer. Paradoxically, RUNX genes exert tumor suppressive and oncogenic functions, depending on tumor type and stage. Unlike RUNX1 and 2, the role of RUNX3 in stem cells is poorly understood. A recent study using cancer-derived RUNX3 mutation R122C revealed a gatekeeper role for RUNX3 in gastric epithelial stem cell homeostasis. The corpora of RUNX3R122C/R122C mice showed a dramatic increase in proliferating stem cells as well as inhibition of differentiation. Tellingly, RUNX3R122C/R122C mice also exhibited a precancerous phenotype. This review focuses on the impact of RUNX3 dysregulation on (1) stem cell fate and (2) the molecular mechanisms underpinning early carcinogenesis.
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Subunidades alfa de Fatores de Ligação ao Core , Neoplasias , Animais , Camundongos , Biologia , Subunidades alfa de Fatores de Ligação ao Core/genética , Subunidades alfa de Fatores de Ligação ao Core/metabolismo , Mamíferos/metabolismo , Mutação , Neoplasias/genética , Transdução de Sinais , HumanosRESUMO
The Task Force on Rotational Atherectomy of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed the expert consensus document to summarize the techniques and evidences regarding rotational atherectomy (RA) in 2020. Because the revascularization strategy to severely calcified lesions is the hottest topic in contemporary percutaneous coronary intervention (PCI), many evidences related to RA have been published since 2020. Latest advancements have been incorporated in this updated expert consensus document.
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Aterectomia Coronária , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Calcificação Vascular , Humanos , Aterectomia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Consenso , População do Leste Asiático , Resultado do Tratamento , Calcificação Vascular/cirurgiaRESUMO
PURPOSE: Chronic limb-threatening ischemia due to isolated below-the-knee lesions is a factor associated with wound recurrence. However, there is a lack of data regarding wound recurrence in such cases. This study aimed to determine the predictors of wound recurrence in patients with chronic limb-threatening ischemia undergoing endovascular treatment. PATIENTS AND METHODS: This was a single-center, retrospective, observational study. We enrolled 152 consecutive patients with chronic limb-threatening ischemia (172 limbs) who achieved complete wound healing after undergoing endovascular treatment for isolated below-the-knee lesions between February 2008 and December 2017. Of these, the wound had recurred in 56 limbs (33%), and we divided the patients into 2 groups based on wound recurrence. We evaluated the recurrence rate of chronic limb-threatening ischemia and predictors of wound recurrence. Wound recurrence was defined as recurrence of the wound within 2 years of complete wound healing. RESULTS: Patients' backgrounds were similar in both groups, including mean age (72±9 vs 72±11; p=0.76) and hemodialysis (43% vs 40%; p=0.66). Pre-pedal arch type 2 (52% vs 8%; p<0.01), infrapopliteal grade 4 of the Global Limb Anatomic Staging System (77% vs 59%; p=0.02), and Wound, Ischemia, and foot Infection criteria stage 4 (43% vs 28%; p=0.04) were more common in the wound recurrence group. Multivariate Cox proportional hazard analysis identified pre-pedal arch type 2 (hazard ratio, 5.28; 95% confidence interval, 3.08-9.10; p<0.01) and Wound, Ischemia, and foot Infection criteria stage 4 (hazard ratio, 1.98; 95% confidence interval, 1.15-3.36; p=0.01) as predictors of wound recurrence after complete wound healing. CONCLUSION: Pre-pedal arch type 2 and Wound, Ischemia, and foot Infection classification system stage 4 were associated with wound recurrence in patients with chronic limb-threatening ischemia who achieved complete wound healing after undergoing endovascular treatment for isolated below-the-knee lesions.