The autologous pericardial aortic valve repair technique developed by Ozaki et al., using glutaraldehyde-treated autologous pericardium, has demonstrated superior durability to bioprosthetic valves. However, this technique has certain limitations, including excessive cusp height and cusp fluttering due to leaflet redunduncy.
View Article and Find Full Text PDFNon-canonical DNA structures, such as the G-quadruplex (G4) and i-motif (iM), are formed at guanine- and cytosine-rich sequences, respectively, in living cells and involved in regulating various biological processes during the cell cycle. Therefore, the formation and resolution of these non-canonical structures must be dynamically regulated by physiological conditions or factors that can bind G4 and iM structures. Although many G4 binding proteins responsible for tuning the G4 structure have been discovered, the structural regulation of iM by iM-binding proteins remains enigmatic.
View Article and Find Full Text PDFHepatocytes play important roles in the liver, but in culture, they immediately lose function and dedifferentiate into progenitor-like cells. Although this unique feature is well-known, the dynamics and mechanisms of hepatocyte dedifferentiation and the differentiation potential of dedifferentiated hepatocytes (dediHeps) require further investigation. Here, we employ a culture system specifically established for hepatic progenitor cells to study hepatocyte dedifferentiation.
View Article and Find Full Text PDFThe T7 gene 3 product, T7 endonuclease I, acts on various substrates with DNA structures, including Holliday junctions, heteroduplex DNAs and single-mismatch DNAs. Genetic analyses have suggested the occurrence of DNA recombination, replication and repair in Escherichia coli. In this study, T7 endonuclease I digested UV-irradiated covalently closed circular plasmid DNA into linear and nicked plasmid DNA, suggesting that the enzyme generates single- and double-strand breaks (SSB and DSB).
View Article and Find Full Text PDFAnamorelin (ANAM) is a novel ghrelin receptor agonist for the treatment of cancer cachexia. In clinical trials of ANAM, glucose metabolism disorders as adverse effects were relatively frequent, however, when and how they occur remains unclear. Moreover, the safety in patients with pancreatic cancer and/or diabetes has not been clarified because most previous studies focused on patients with non-small cell lung cancer and had excluded patients with poorly controlled diabetes.
View Article and Find Full Text PDFThe European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for idiopathic inflammatory myopathies (IIM) have been widely used in recent times. However, no studies have focused on electromyography (EMG) findings of IIM, considering the criteria. This study aimed to elucidate the frequency of EMG abnormalities, particularly fibrillation potentials and positive sharp waves (Fib/PSW), the most objective EMG findings of IIM.
View Article and Find Full Text PDFPhotolyases, a ubiquitous class of flavoproteins, use blue light to repair DNA photolesions. In this work, we determined the structural mechanism of the photolyase-catalyzed repair of a cyclobutane pyrimidine dimer (CPD) lesion using time-resolved serial femtosecond crystallography (TR-SFX). We obtained 18 snapshots that show time-dependent changes in four reaction loci.
View Article and Find Full Text PDFThe global coronavirus disease 2019 (COVID-19) pandemic has caused myriad adverse effects on the pathology of other diseases. Numerous studies on COVID-19 have reported that, in patients with type 2 diabetes mellitus (T2DM) who have contracted severe COVID-19, glucose metabolism is exacerbated by multiple factors, such as severe inflammation, beta-cell dysfunction caused by the SARS-CoV-2 infection itself, corticosteroid therapy, vasopressor administration, and enteral or parenteral nutrition. Very high doses of insulin are often required in the acute phase of such patients; however, the factors that affect insulin requirements and to what extent remain unclear.
View Article and Find Full Text PDFThe enhancement of insulin secretion and of the proliferation of pancreatic β cells are promising therapeutic options for diabetes. Signals from the vagal nerve regulate both processes, yet the effectiveness of stimulating the nerve is unclear, owing to a lack of techniques for doing it so selectively and prolongedly. Here we report two optogenetic methods for vagal-nerve stimulation that led to enhanced glucose-stimulated insulin secretion and to β cell proliferation in mice expressing choline acetyltransferase-channelrhodopsin 2.
View Article and Find Full Text PDFAn animal-like cryptochrome derived from Chlamydomonas reinhardtii (CraCRY) is a bifunctional flavoenzyme harboring flavin adenine dinucleotide (FAD) as a photoreceptive/catalytic center and functions both in the regulation of gene transcription and the repair of UV-induced DNA lesions in a light-dependent manner, using different FAD redox states. To address how CraCRY stabilizes the physiologically relevant redox state of FAD, we investigated the thermodynamic and kinetic stability of the two-electron reduced anionic FAD state (FADH) in CraCRY and related (6-4) photolyases. The thermodynamic stability of FADH remained almost the same compared to that of all tested proteins.
View Article and Find Full Text PDFA 66 year-old male was admitted to our clinic suffering from dyspnea on effort. Cardio thoracic ratio (CTR) was 62%. Electrocardiogram showed atrial fibrillation.
View Article and Find Full Text PDFWe repaired the bicuspid aoric valve( BAV) with aortic regurgitation( AR) by bicuspidization. However, repaired fused cusp does not open full, and shows doming. Between 1997 and 2023 we repaired 30 BAV with AR.
View Article and Find Full Text PDFTopoisomerases are enzymes that relax DNA supercoiling during replication and transcription. Camptothecin, a topoisomerase 1 (TOP1) inhibitor, and its analogs trap TOP1 at the 3'-end of DNA as a DNA-bound intermediate, resulting in DNA damage that can kill cells. Drugs with this mechanism of action are widely used to treat cancers.
View Article and Find Full Text PDFCell proliferation processes play pivotal roles in timely adaptation to many biological situations. Herein, we establish a highly sensitive and simple strategy by which time-series showing the proliferation of a targeted cell type can be quantitatively monitored in vivo in the same individuals. We generate mice expressing a secreted type of luciferase only in cells producing Cre under the control of the Ki67 promoter.
View Article and Find Full Text PDFAim: Although sarcopenia is common in patients with Alzheimer's disease (AD), the neural substrates involved remain unclear. We investigated the relationship between sarcopenia, as well as its definition components, and regional cerebral blood flow (rCBF) in older adults with progression of normal cognition to AD.
Methods: Tc-ethyl-cysteinate-dimer single-photon emission computed tomography was carried out in 95 older adults with progression of normal cognition to AD (40 men and 55 women, mean ± SD age 80.
Aims/introduction: Whether basal β-cell proliferation during adulthood is involved in maintaining sufficient β-cell mass, and if so, the molecular mechanism(s) underlying basal β-cell proliferation remain unclear. FoxM1 is a critical transcription factor which is known to play roles in 'adaptive' β-cell proliferation, which facilitates rapid increases in β-cell mass in response to increased insulin demands. Therefore, herein we focused on the roles of β-cell FoxM1 in 'basal' β-cell proliferation under normal conditions and in the maintenance of sufficient β-cell mass as well as glucose homeostasis during adulthood.
View Article and Find Full Text PDFFlavin coenzymes are universally found in biological redox reactions. DNA photolyases, with their flavin chromophore (FAD), utilize blue light for DNA repair and photoreduction. The latter process involves two single-electron transfers to FAD with an intermittent protonation step to prime the enzyme active for DNA repair.
View Article and Find Full Text PDF(6-4) Photolyases ((6-4) PLs) are ubiquitous photoenzymes that use the energy of sunlight to catalyze the repair of carcinogenic UV-induced DNA lesions, pyrimidine(6-4)pyrimidone photoproducts. To repair DNA, (6-4) PLs must first undergo so-called photoactivation, in which their excited flavin adenine dinucleotide (FAD) cofactor is reduced in one or two steps to catalytically active FADH via a chain of three or four conserved tryptophan residues, transiently forming FAD/FADH ⋯ TrpH pairs separated by distances of 15 to 20 Å. Photolyases and related photoreceptors cryptochromes use a plethora of tricks to prevent charge recombination of photoinduced donor-acceptor pairs, such as chain branching and elongation, rapid deprotonation of TrpH or protonation of FAD.
View Article and Find Full Text PDFAuris Nasus Larynx
October 2022
Objective: To investigate changes in the clinical state of taste disorders between 1990, 2003, and 2019 using the same methodology as that in previous studies.
Materials And Methods: In June 2019, we mailed a questionnaire to 1100 otolaryngologists belonging to the Japan Society of Stomato-pharyngology and investigated three question categories: "Institution", "Number of patients for 3 months", and "Treatment". In addition, we analyzed some results by the class of institution.
Photolyases (PHRs) repair ultraviolet (UV)-induced DNA photoproducts into normal bases. In this study, we measured the conformational changes upon photoactivation and photorepair processes of a PHR and its specific substrates, (6-4)PHR and a pyrimidine(6-4)pyrimidone photoproduct ((6-4)PP), by light-induced difference Fourier transform infrared (FT-IR) spectroscopy. The single-stranded DNA with (6-4)PP (ss(6-4)PP) was used as a substrate and the resultant FT-IR spectra were compared with the previous results on double-stranded DNA with (6-4)PP (ds(6-4)PP).
View Article and Find Full Text PDFBackground/objectives: Isothiocyanate (ITC) is formed via the hydrolysis of glucosinolates by myrosinase, found in cruciferous vegetables. Although myrosinase is inactivated by the cooking process, no studies have incorporated the effect of cooking into the estimation of dietary ITC intake or evaluated the validity. We evaluated the validity of dietary ITC intake estimated from a food frequency questionnaire (FFQ), and urinary ITC levels using 24 h urine samples or a WFR (weighed food record), and evaluated the reproducibility of dietary ITC in two FFQs administered at an interval of 1-year.
View Article and Find Full Text PDFPhotolyases are flavoenzymes responsible for light-driven repair of carcinogenic crosslinks formed in DNA by UV exposure. They possess two non-covalently bound chromophores: flavin adenine dinucleotide (FAD) as a catalytic center and an auxiliary antenna chromophore that harvests photons and transfers solar energy to the catalytic center. Although the energy transfer reaction has been characterized by time-resolved spectroscopy, it is strikingly important to understand how well natural biological systems organize the chromophores for the efficient energy transfer.
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