An 86-year-old man presented to our hospital with symptoms of diarrhea and bloody stool, which had manifested two weeks after receiving his third severe acute respiratory syndrome coronavirus 2 mRNA vaccination. Colonoscopy revealed diffuse, rough-surfaced mucosa extending from the ascending colon to the rectum. Despite attempting probiotic treatment, the patient's condition did not improve, leading to admission.
View Article and Find Full Text PDFCardiac contractility evaluation using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has recently attracted much attention as a clinical cardiotoxicity predictive model. Most studies on this were conducted under spontaneous beating conditions and involved video-based analyses. Cardiac contractility is known to be influenced by beating rates; accordingly, beating rate control is recommended to accurately analyze the effects of drugs on cardiac contractility.
View Article and Find Full Text PDFThe retinoic acid receptor-related orphan nuclear receptor γt (RORγt), a promising therapeutic target, is a major transcription factor of genes related to psoriasis pathogenesis such as interleukin (IL)-17A, IL-22, and IL-23R. On the basis of the X-ray cocrystal structure of RORγt with , an analogue of the known piperazine RORγt inverse agonist , triazolopyridine derivatives of were designed and synthesized, and analogue was found to be a potent RORγt inverse agonist. Structure-activity relationship studies on , focusing on the treatment of its metabolically unstable cyclopentyl ring and the central piperazine core, led to a novel analogue, namely, 6-methyl--(7-methyl-8-(((2,4)-2-methyl-1-(4,4,4-trifluoro-3-(trifluoromethyl)butanoyl)piperidin-4-yl)oxy)[1,2,4]triazolo[1,5-]pyridin-6-yl)nicotinamide (), which exhibited strong RORγt inhibitory activity and a favorable pharmacokinetic profile.
View Article and Find Full Text PDFMitral cells (MCs) of the mammalian olfactory bulb have a single primary dendrite extending into a single glomerulus, where they receive odor information from olfactory sensory neurons (OSNs). Molecular mechanisms for controlling dendritic arbors of MCs, which dynamically change during development, are largely unknown. Here we found that MCs displayed more complex dendritic morphologies in mouse mutants of Maml1, a crucial gene in Notch signaling.
View Article and Find Full Text PDFThe incidence of ampicillin (ABPC)-resistant Escherichia coli (E. coli) infection in very low-birthweight infants has been increasing. The rate of ABPC/sulbactam (ABPC/SBT)-resistant E.
View Article and Find Full Text PDFObesity and related metabolic disorders, such as diabetes mellitus, raise the risk of liver carcinogenesis. Metformin, which is widely used in the treatment of diabetes, ameliorates insulin sensitivity. Metformin is also thought to have antineoplastic activities and to reduce cancer risk.
View Article and Find Full Text PDFMetabolic syndrome (Mets), including diabetes and hypertension, increases the risk of colorectal cancer via the induction of chronic inflammation, acceleration of oxidative stress, and activation of the renin-angiotensin system. The present study examined the possible inhibitory effects of captopril, an angiotensin-converting enzyme (ACE) inhibitor and antihypertensive drug, on the development of azoxymethane (AOM)-induced colonic premalignant lesions, aberrant crypt foci (ACF), in SHRSP.Z- /IzmDmcr (SHRSP-ZF) diabetic and hypertensive rats.
View Article and Find Full Text PDFReelin is a secreted glycoprotein that plays essential roles in the brain. Reelin is specifically cleaved at two distinct sites, called N-t and C-t, with the former being the major one. N-t cleavage can occur both in the extracellular space and in the endosomes, although the physiological importance of endosomal N-t cleavage has not been investigated.
View Article and Find Full Text PDFJ Nutr Sci Vitaminol (Tokyo)
October 2015
The prognosis of patients with hepatocellular carcinoma (HCC) is poor and the development of effective treatments for this malignancy, including combination chemotherapy, is required. This study examined the possible combined inhibitory effects of bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, and acyclic retinoid (ACR), which can prevent the development of HCC, on the growth of Huh7 human HCC cells. Xenograft tumors were produced by subcutaneously injecting Huh7 cells into nude mice.
View Article and Find Full Text PDFBackground: A malfunction of RXRα due to phosphorylation is associated with liver carcinogenesis, and acyclic retinoid (ACR), which targets RXRα, can prevent the development of hepatocellular carcinoma (HCC). Activation of PI3K/Akt signaling plays a critical role in the proliferation and survival of HCC cells. The present study examined the possible combined effects of ACR and LY294002, a PI3K inhibitor, on the growth of human HCC cells.
View Article and Find Full Text PDFNon-alcoholic steatohepatitis (NASH), which involves hepatic inflammation and fibrosis, is associated with liver carcinogenesis. The activation of the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, promotes hepatic fibrogenesis. In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins, on the development of glutathione S-transferase placental form (GST-P)-positive (GST-P(+)) foci, a hepatic preneoplastic lesion, in SHRSP.
View Article and Find Full Text PDFMetabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats.
View Article and Find Full Text PDFObjective: The purpose of this study was to show the effects of the tracheal gas insufflation (TGI) technique on gas exchange using helium-oxygen mixtures during high-frequency oscillatory ventilation (HFOV). We hypothesized that a helium-oxygen mixture delivered into the trachea using the TGI technique (0.3 L/min) would enhance gas exchange during HFOV.
View Article and Find Full Text PDFObesity and its associated disorders, such as non-alcoholic steatohepatitis, increase the risk of hepatocellular carcinoma. Branched-chain amino acids (BCAA), which improve protein malnutrition in patients with liver cirrhosis, reduce the risk of hepatocellular carcinoma in these patients with obesity. In the present study, the effects of BCAA supplementation on the spontaneous development of hepatic premalignant lesions, foci of cellular alteration, in db/db obese mice were examined.
View Article and Find Full Text PDFNemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions "nemaline bodies" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM. We have identified recessive RYR1 mutations in a patient with severe congenital NM, through high-throughput screening of congenital myopathy/muscular dystrophy-related genes using massively parallel sequencing with target gene capture.
View Article and Find Full Text PDFSphingomyelin (SM) plays important roles in regulating structure and function of plasma membrane, but how intracellular localization of SM is regulated in neuronal cells is not understood. Here we show that two isoforms of SM synthase (SMS) are differentially expressed in neuronal subtypes and that only SMS2 proteins localize in neurites of hippocampal neurons. Moreover, SMS proteins induce Lysenin-binding SM clusters exclusively in their vicinity although neurons hardly contain such cluster under control condition.
View Article and Find Full Text PDFObesity-related metabolic abnormalities include a state of chronic inflammation and adipocytokine imbalance, which increase the risk of colon cancer. Curcumin, a component of turmeric, exerts both cancer preventive and antiinflammatory properties. Curcumin is also expected to have the ability to reverse obesity-related metabolic derangements.
View Article and Find Full Text PDFBackground: Obesity and related metabolic abnormalities, including inflammation and lipid accumulation in the liver, play a role in liver carcinogenesis. Adipocytokine imbalances, such as decreased serum adiponectin levels, are also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of pitavastatin - a drug used for the treatment of hyperlipidemia - on the development of diethylnitrosamine (DEN)-induced liver preneoplastic lesions in C57BL/KsJ-db/db (db/db) obese mice.
View Article and Find Full Text PDFReversible histone methylation and demethylation are highly regulated processes that are crucial for chromatin reorganization and regulation of gene transcription in response to extracellular conditions. However, the mechanisms that regulate histone-modifying enzymes are largely unknown. Here, we characterized a protein kinase A (PKA)-dependent histone lysine demethylase complex, PHF2-ARID5B.
View Article and Find Full Text PDFObjective: To investigate postnatal changes in the direction of blood flow through the ductus arteriosus in neonates with meconium-stained amniotic fluid, we measured preductal and postductal oxygen saturation in normal neonates, neonates with meconium-stained amniotic fluid, and a neonate with persistent pulmonary hypertension of the newborn.
Design: Prospective, observational case series report.
Setting: A single, tertiary neonatal intensive care unit.
Obesity and related metabolic abnormalities, including insulin resistance and a state of chronic inflammation, increase the risk of hepatocellular carcinoma. Abnormal activation of the insulin-like growth factor (IGF)/ IGF-1 receptor (IGF-1R) axis is also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of (-)-epigallocatechin gallate (EGCG), a major biologically active component of green tea, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-db/db (db/db) obese mice.
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