Publications by authors named "Zen K"

Background: Emerging evidence has revealed that PKM2 has oncogenic functions independent of its canonical pyruvate kinase activity, serving as a protein kinase that regulates gene expression. However, the mechanism by which PKM2, as a histone kinase, regulates the transcription of genes involved in triple-negative breast cancer (TNBC) metastasis remains poorly understood.

Methods: We integrated cellular analysis, including cell viability, proliferation, colony formation, and migration assays; biochemical assays, including protein interaction studies and ChIP; clinical sample analysis; RNA-Seq and CUT&Tag data; and xenograft or mammary-specific gene knockout mouse models, to investigate the epigenetic modulation of TNBC metastasis via NONO-dependent interactions with nuclear PKM2.

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Cuproptosis represents a new type of cell death that intricately associated with copper homeostasis and protein lipoylation. The cuproptosis suppression has been characterized in the hypoxic tumor microenvironment (TME). Here we reveal that hypoxia inducible factor-1α (HIF-1α) is a driver of cuproptosis resistance in solid tumor.

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Silencing resistance genes of pathogenic bacteria by RNA interference (RNAi) is a potential strategy to fight antibiotic-resistant bacterial infections. Currently, RNAi cannot be achieved in bacteria due to the lack of RNA-induced silencing complex machinery and the difficulty of small interfering RNA (siRNA) delivery. Here, we show that exosomal siRNAs can be efficiently delivered into bacterial cells and can silence target genes primarily through translational repression without mRNA degradation.

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Background: Alternative access approaches are required for transcatheter aortic valve replacement (TAVR) cases wherein the transfemoral approach is restrictive with severe calcification. We aimed to examine the safety of the external iliac artery (EIA) as an alternative access site by evaluating the calcification distributions from the common iliac artery (CIA) to the common femoral arteries (CFA).

Methods: We retrospectively enrolled 402 patients who underwent TAVR.

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Shiga toxin (Stx)-induced hemolytic uremic syndrome (HUS) poses a life-threatening complication for which a definitive treatment remains elusive. To exert its cytotoxic effect on renal cells, Stx must be delivered from the infected intestines to the kidney. However, the mechanism underlying Stx delivery remains unclear.

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Background: The clinical outcomes of percutaneous coronary intervention (PCI) using drug-coated balloons (DCB) for de novo coronary artery lesions with eruptive calcified nodules remain unclear.

Methods And Results: This retrospective study analyzed the long-term outcomes of 308 consecutive patients (389 lesions) treated with PCI using DCB under optical coherence tomography guidance for de novo coronary artery lesions between September 2018 and November 2020. Patients were classified into 2 groups: those with an eruptive calcified nodule in the culprit lesion (CN group) and those without (non-CN group).

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Endovascular treatment (EVT) for patients with lower extremity artery disease is widely used as a less invasive alternative to surgical bypass. Recently, transradial artery intervention has gained popularity owing to its minimally invasive nature. The distance from the radial artery to the target vessel is critical for success; however, effective pre-assessment methods have not yet been established.

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Objective: Diabetic nephropathy (DN), characterized by a complex and multifaceted pathogenesis, stands as the foremost catalyst behind end-stage renal disease (ESRD). This study aims to analyze the level and non-metabolic role of glomerular aldolase B (ALDOB) in DN progression.

Methods: Glomerular proteomics and transcriptome are analyzed from 50 DN patients and 25 controls, respectively.

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Background: macrophage-targeting therapy of ischemic disease has made progress in clinic trial. However, the role and underlying mechanism of pro-inflammatory or anti-inflammatory polarized macrophages in modulating ischemic diseases remain incompletely understood.

Results: here we examine the effect of pro-inflammatory (LPS) and anti-inflammatory (IL-4) macrophage on ischemic diseases in a mouse ischemic hindlimb and heart model, and identify that signal regulatory protein α (Sirpα) modulates macrophage polarization induced angiogenesis via promoting phagocytosis or activating HIF1α nucleus relocation in macrophages, respectively.

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Article Synopsis
  • - Podocyte injury is a key factor in developing diabetic nephropathy, influenced by high blood sugar, oxidative stress, and inflammation.
  • - The protein SIRPα is crucial for maintaining the health of podocytes; its deletion worsens damage while overexpression helps protect against injury in experimental models.
  • - SIRPα regulates processes involving pyruvate kinase M2 (PKM2) that lead to oxidative stress and impaired cell metabolism; a compound called shikonin can reduce this damage by blocking harmful PKM2 activity and restoring normal metabolism.
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Background: Despite the widespread use of drug-coated balloons (DCBs) for femoropopliteal (FP) lesions, there is still no consensus on treatment strategies for DCB restenosis. This study aimed to determine the risk factors for recurrent restenosis after repeat DCB therapy for DCB restenosis in FP lesions.

Methods: This multicenter retrospective study assessed 1176 consecutive limbs in 860 patients who successfully received initial DCB therapy for FP lesions at four cardiovascular centers between May 2018 and December 2022.

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Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018 and updated in 2022. Recently, the European Society of Cardiology (ESC) published the guidelines for the management of acute coronary syndrome in 2023.

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Objective: The recommended revascularisation methods for acute limb ischaemia (ALI), which is caused by embolism and atherosclerotic thrombosis, include endovascular therapy (EVT) and open surgical revascularisation (OSR); however, treatment choices based on patient characteristics remain controversial. This retrospective analysis from the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination database (April 2012 to March 2020) evaluated differences in clinical outcomes and identified prognostic predictors in patients with ALI.

Methods: This study analysed 10 977 patients with lower limb ALI.

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Objective: Although urinary extracellular vesicles (uEVs) have been extensively studied in various cancers, their involvement in breast cancer (BC) remains largely unexplored. The non-invasive nature of urine as a biofluid and its abundant protein content offer considerable potential for the early detection of breast cancer.

Methods: This study analyzed the proteomic profiles of uEVs from BC patients and healthy controls (HC).

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Background: Balloon aortic valvuloplasty (BAV) has gained renewed interest as a bridge to transcatheter aortic valve replacement (TAVR) for patients with aortic stenosis (AS). However, it is unclear whether they patients should undergo TAVR directly or receive a staged bridge to BAV before TAVR is unclear. We used a national database to examine the association between BAV and TAVR in patients with TAVR and its effect on in-hospital mortality.

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Article Synopsis
  • This study evaluated the effectiveness of endovascular therapy (EVT) versus open surgical revascularization (OS) for acute superior mesenteric artery occlusion in 746 patients using data from a Japanese registry.
  • In-hospital mortality and bowel resection rates were similar between the two treatment groups, but the EVT group had a shorter hospital stay and lower costs.
  • Predictive factors for in-hospital mortality included advanced age and chronic kidney disease, while diabetes was linked to increased likelihood of bowel resection post-revascularization.
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Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non-invasive source for disease diagnosis through liquid biopsy.

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Article Synopsis
  • Signal-regulatory protein alpha (SIRPα) is crucial for podocyte function and is significantly downregulated in lupus nephritis (LN), impacting renal health.
  • The absence of SIRPα in podocytes leads to worse kidney disease in lupus-prone mice, marked by increased T cell infiltration and activation.
  • SIRPα inhibits spleen tyrosine kinase (Syk) phosphorylation, and its deletion enhances podocyte antigen presentation, suggesting that targeting Syk could help reduce T cell activation and alleviate renal disease symptoms.
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Pulmonary vein stenosis might be caused by mediastinal migration into the vacated pleural space after pneumonectomy. In a patient complaining of worsening dyspnea in the left lateral decubitus position after left pneumonectomy, transthoracic echocardiography during different postures revealed pulmonary vein stenosis that worsened in the left lateral position.

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Background: Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates.

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Zinc and ring finger 3 (ZNRF3) is a negative suppressor of Wnt signal and newly identified as an important regulator in tumorigenesis and development. However, the pan-cancer analysis of ZNRF3 has not been reported. We found that ZNRF3 was significantly decreased in six tumors including CESC, KIRP, KIRC, SKCM, OV, and ACC, but increased in twelve tumors, namely LGG, ESCA, STES, COAD, STAD, LUSC, LIHC, THCA, READ, PAAD, TGCT, and LAML.

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For successful viral propagation within infected cells, the virus needs to overcome the cellular integrated stress response (ISR), triggered during viral infection, which, in turn, inhibits general protein translation. This paper reports a tactic employed by viruses to suppress the ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus and hepatovirus within their respective host cells induces PNPT1 expression.

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Mono-methylation of histone H3 on Lys 4 (H3K4me1), which is catalyzed by histone-lysine N-methyltransferase 2D (KMT2D), serves as an important epigenetic regulator in transcriptional control. In this study, the authors identify early B-cell factor 2 (EBF2) as a binding protein of H3K4me1. Combining analyses of RNA-seq and ChIP-seq data, the authors further identify killin (KLLN) as a transcriptional target of KMT2D and EBF2 in pancreatic ductal adenocarcinoma (PDAC) cells.

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