Modified Quick Change Method for Norepinephrine Syringe Exchange in Critically Ill Patients: A Quasi-randomized, Non-inferiority Trial.

Background: This study aimed to verify that the modified quick change (mQC) method of syringe exchange in critically ill patients receiving a continuous intravenous norepinephrine infusion is not inferior to the conventional double pumping (DP) method.

Methods: This non-blinded, quasi-randomized, non-inferiority trial was conducted in a single hospital from August 1, 2023 to February 29, 2024. Adult patients aged 18 years or older who were admitted to the emergency ward and received a continuous intravenous norepinephrine infusion were eligible for inclusion.

DLiP-PPI library: An integrated chemical database of small-to-medium-sized molecules targeting protein-protein interactions.

Protein-protein interactions (PPIs) are recognized as important targets in drug discovery. The characteristics of molecules that inhibit PPIs differ from those of small-molecule compounds. We developed a novel chemical library database system (DLiP) to design PPI inhibitors.

Discovery of a New STAT3 Inhibitor Acting on the Linker Domain.

Signal transducer and activator of transcription 3 (STAT3) is a latent transcription factor that contributes to tumor cell growth and survival and is often constitutively active in several types of cancers, which makes it an attractive target for cancer therapy. We identified 5,5'-(pentane-1,5'-diyl)bis(2-methyl-1,4-benzoquinone) (BPMB) as a new STAT3 inhibitor. BPMB inhibited the transcriptional activities of STAT3, despite its inability to reduce the phosphorylation and nuclear translocation of STAT3.

Virtual screening and further development of novel ALK inhibitors.

Anaplastic lymphoma kinase (ALK) has been in the spotlight in recent years as a promising new target for therapy of non-small-cell lung cancer (NSCLC). Since the identification of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene in some NSCLC patients was reported in 2007, various research groups have been seeking ALK inhibitors. Above all, crizotinib (PF-02341066) has been under clinical trial, and its therapeutic efficacy of inhibiting ALK in NSCLC has been reported.

Antitumor activity of a novel small molecule STAT3 inhibitor against a human lymphoma cell line with high STAT3 activation.

Signal transducer and activator of transcription (STAT)3, a member of a family of DNA-binding molecules mediating numerous physiological and oncogenic signaling pathways, is a novel target in cancer cells which show high phosphorylation of STAT3. Recently, we identified a novel small-molecule inhibitor of STAT3 dimerization, STX-0119, as a cancer therapeutic. We investigated the mechanisms responsible for the antitumor activity in vitro and in vivo through numerous biochemical and biological assays.

Evaluation of docking calculations on X-ray structures using CONSENSUS-DOCK.

We are participating in the challenge of identifying active compounds for target proteins using structure-based virtual screening (SBVS). We use an in-house customized docking program, CONSENSUS-DOCK, which is a customized version of the DOCK4 program in which three scoring functions (DOCK4, FlexX and PMF) and consensus scoring have been implemented. This paper compares the docking calculation results obtained using CONSENSUS-DOCK and DOCK4, and demonstrates that CONSENSUS-DOCK produces better results than DOCK4 for major X-ray structures obtained from the Protein Data Bank (PDB).

Identification of a New Series of STAT3 Inhibitors by Virtual Screening.

The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a novel STAT3 dimerization inhibitor by a virtual screen using a customized version of the DOCK4 program with the crystal structure of STAT3. In addition, we used in vitro cell-based assays such as the luciferase reporter gene assay and the fluorescence resonance energy transfer-based STAT3 dimerization assay.

[In-silico approaches for fragment-based drug design].

An important step to promote fragment-based drug design (FBDD) is to find high-quality fragment molecules. Therefore the design of the fragment library is the most crucial stage. In our fragment library, the main considerations are ligand efficiency (LE), diversity, and solubility with drug-like properties.

Relationship between aortic calcification and stroke in a mass screening program using a mobile helical computed tomography unit.

Background: It is reported that there is a significant relationship between the calcification of the aortic arch detected by chest X-ray examination and stroke. However, the relationship between stroke and aortic calcification (AoC) detected during a mass screening using a mobile helical computed tomography (CT) unit remains unknown.

Methods And Results: The study population consisted of 2,618 subjects (1,345 men, and 1,273 women; mean age, 52.

Aortic calcification detected in a mass chest screening program using a mobile helical computed tomography unit. Relationship to risk factors and coronary artery disease.

Background: There is a significant relationship between calcification of the aortic arch (Arch) detected by chest X-ray examination and coronary artery disease (CAD), but the relationship between risk factors, CAD and aortic calcification detected during a mass screening program using a mobile helical computed tomography (CT) unit remains unknown.

Methods And Results: In total 2,623 subjects (1,347 men, and 1,276 women; mean age, 52.9+/-13.

Comparison between nicorandil and magnesium as an adjunct cardioprotective agent to percutaneous coronary intervention in acute anterior myocardial infarction.

Background: It has been reported that both nicorandil and magnesium have a cardioprotective effect in experimental ischemia - reperfusion models. In the present study, the cardioprotective effects of nicorandil and magnesium as an adjunct to reperfusion therapy in patients with acute myocardial infarction (AMI) were compared.

Methods And Results: Forty consecutive patients with AMI caused by occlusion of anterior descending coronary artery were randomized into 3 groups: (1) Group N: nicorandil was given as 4 mg iv and 4 mg ic before reperfusion, followed by continuous infusion at 4 mg/h for 24 h; (2) Group M: magnesium was administered at 10 mmol iv before reperfusion, followed by continuous infusion at 0.

Induction of apoptosis and ubiquitin hydrolase gene expression by human serum factors in the early phase of acute myocardial infarction.

The physiologic events leading to apoptosis in myocardial infarction and the molecules involved in the death process have not been clarified unequivocally. We developed a method to search for serum factors that induce apoptosis of human cells, using serum obtained from patients within 1 day of the onset of acute myocardial infarction (AMI). Serum factors were found to have the ability to increase the caspase-3 activity levels in human RSa cells, which are susceptible to apoptosis inducers.

Improvement of left ventricular dysfunction during exercise by walking in patients with successful percutaneous coronary intervention for acute myocardial infarction.

A growing body of evidence suggests that walking reduces the incidence of coronary events, so the present study investigated whether walking influences left ventricular function in 30 patients with acute myocardial infarction (AMI) who had undergone successful percutaneous coronary intervention (PCI). The patients were randomly assigned to either a 3-month exercise training program of walking (group W, n=15) or a control group (group C, n=15). At both the beginning and end of the study, patients underwent exercise stress echocardiography to determine left ventricular ejection fraction (LVEF) at rest and during exercise.

Antibody binding to fas ligand attenuates inflammatory cell infiltration and cytokine secretion, leading to reduction of myocardial infarct areas and reperfusion injury.

Fas ligand (FasL) induces apoptotic cell death when bound to Fas antigen. The engagement of FasL has anti-inflammatory effects through the prevention of cell proliferation and cytokine secretion. However, the role of FasL in myocardial ischemia/reperfusion (MI/R) injury is unclear.

Long-term endothelin a receptor blockade inhibits electrical remodeling in cardiomyopathic hamsters.

Background: The endothelin (ET) system is activated in failing hearts. Congestive heart failure frequently is associated with ventricular arrhythmias, which may result from electrical remodeling such as changes of ionic current density and heterogeneous action potential prolongation. We examined the effects of long-term ET(A) receptor blockade on the electrophysiological properties of ventricular cells, the surface ECG, and the survival in BIO 14.

Peroxisome proliferator-activated receptor gamma plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo.

Background: Peroxisome proliferator-activated receptors (PPARs) are transcription factors of the nuclear receptor superfamily. It has been reported that the thiazolidinediones, which are antidiabetic agents and high-affinity ligands for PPARgamma, regulate growth of vascular cells. In the present study, we examined the role of PPARgamma in angiotensin II (Ang II)-induced hypertrophy of neonatal rat cardiac myocytes and in pressure overload-induced cardiac hypertrophy of mice.

Measurement of aortic diameters and detection of asymptomatic aortic aneurysms in a mass screening program using a mobile helical computed tomography unit.

In a mass chest computed tomography (CT) screening using a mobile helical CT unit, we measured the aortic diameter at three segments to confirm standard values and also attempted to detect any asymptomatic aortic aneurysms. The population screened in the present study consisted of 6971 subjects (3847 men and 3124 women, mean age 60.3 +/- 12.