Low pH modulates lipopolysaccharide-induced tumor necrosis factor-alpha expression and macropinocytotic activity in RAW264.7 cells.

Inflammation triggers various types of diseases that need to be addressed. Macrophages play important roles in the inflammatory responses. As atherosclerosis progresses, macrophages transform into foam cells.

Survival and cognitive deterioration in elderly patients undergoing hemodialysis.

Aim: This study aimed to elucidate the 5-year changes in the cognitive function of elderly patients undergoing hemodialysis and its association with survival and related factors.

Methods: Cognitive function in patients aged ≥65 years undergoing hemodialysis at the Nagasaki Renal Center was assessed using the Mini-Mental State Examination (MMSE) in 2016. Patients were subsequently classified into normal, mild cognitive impairment (MCI) and suspected dementia groups according to their scores; MMSE was conducted at 30 and 60 months thereafter.

Poor prognosis after lower-limb amputation irrespective of diabetes status in patients undergoing hemodialysis.

Introduction: Diabetes mellitus is one of the most important risk factors for lower-limb amputation in patients undergoing hemodialysis. However, the influence of diabetes mellitus on survival after lower-limb amputation is unknown.

Methods: Patients who underwent lower-limb amputation since 1996 (amputation group) and those who underwent hemodialysis during 2011-2012 (control group) were included and were followed up until July 2022.

Ethylenediaminetetraacetic acid (EDTA) enhances cAMP production in human TDAG8-expressing cells.

Ethylenediaminetetraacetic acid (EDTA) is a chelating agent that binds tightly to metal ions. We found that cAMP response element (CRE)-driven promoter activity by protons was enhanced by EDTA in human T-cell death-associated gene 8 (TDAG8)-overexpressed HEK293T cells. The enhancing action by EDTA was also detected by proton-induced cAMP production that is located upstream from the CRE-driven promoter activity even at physiological proton concentration pH7.

Favorable Humoral Response to Third Dose of BNT162b2 in Patients Undergoing Hemodialysis.

Patients undergoing hemodialysis are known to exhibit low humoral responses to vaccines against severe acute respiratory syndrome coronavirus 2. In this study, we aimed to elucidate the humoral response to the third dose of BNT162b2 (Pfizer) in patients undergoing hemodialysis. We included 279 patients undergoing hemodialysis (69 ± 11 years, 65% male, median dialysis vintage: 69 months) and 189 healthcare workers (45 ± 13 years, 30% male) who received the third dose of BNT162b2.

Associations between components of household expenditures and the rate of change in the number of new confirmed cases of COVID-19 in Japan: Time-series analysis.

Background: Social distancing measures to prevent the spread of COVID-19 included restrictions on retail services in many countries. In some countries, the governments also subsidized consumer spending on part of retail services to help struggling businesses. To evaluate the costs and benefits of government interventions in retail services, it is necessary to measure the infectiousness of each type of consumer activity.

Metal-Stimulated Interleukin-6 Production Through a Proton-Sensing Receptor, Ovarian Cancer G Protein-Coupled Receptor 1, in Human Bronchial Smooth Muscle Cells: A Response Inhibited by Dexamethasone.

Purpose: Human bronchial smooth muscle cells (BSMCs) contribute to airway obstruction and hyperresponsiveness in patients with bronchial asthma. BSMCs also generate cytokines and matricellular proteins in response to extracellular acidification through the ovarian cancer G protein-coupled receptor 1 (OGR1). Cobalt (Co) and nickel (Ni) are occupational agents, which cause occupational asthma.

Hemodialysis Patient with Diffuse Liver Calcification After Septic Shock.

BACKGROUND Calcification in arteries is sometimes observed in patients undergoing hemodialysis; however, ectopic calcification in other organs is uncommon. In particular, diffuse liver calcification is very rare. We report a case of rapidly developing diffuse liver calcification in a patient undergoing hemodialysis.

The protective role of proton-sensing TDAG8 in the brain injury in a mouse ischemia reperfusion model.

Extracellular acidification in the brain has been observed in ischemia; however, the physiological and pathophysiological implications of the pH reduction remain largely unknown. Here, we analyzed the roles of proton-sensing G protein-coupled receptors, including T-cell death-associated gene 8 (TDAG8), ovarian cancer G protein-coupled receptor 1 (OGR1), and G protein-coupled receptor 4 (GPR4) in a mouse ischemia reperfusion model. Cerebral infarction and dysfunctional behavior with transient middle cerebral artery occlusion (tMCAO) and subsequent reperfusion were exacerbated by the deficiency of TDAG8, whereas no significant effect was observed with the deficiency of OGR1 or GPR4.

Species-Dependent Enhancement of Ovarian Cancer G Protein-Coupled Receptor 1 Activation by Ogerin.

Ogerin is a positive allosteric modulator of human and mouse ovarian cancer G protein-coupled receptors (OGR1s). In the present study, we found that ogerin differentially enhances the activation of OGR1 in various animal species. Amino acid residues of OGR1 that are associated with ogerin are conserved among the species.

Involvement of GPR4 in increased growth hormone and prolactin expressions by extracellular acidification in MtT/S cells.

Hormone-secreting pituitary adenomas show unregulated hormonal hypersecretion and cause hyperpituitarism. However, the mechanism of the unregulated hormone production and secretion has not yet been fully elucidated. Solid tumors show reduced extracellular pH, partly due to lactate secretion from anaerobic glycolysis.

Characterization of molecular mechanisms of extracellular acidification-induced intracellular Ca increase in LβT2 cells.

Extracellular acidification regulates endocrine cell functions. Ovarian cancer G protein-coupled receptor 1 (OGR1), also known as GPR68, is a proton-sensing G protein-coupled receptor and is activated by extracellular acidification, resulting in the activation of multiple intracellular signaling pathways. In the present study, we found that OGR1 was expressed in some gonadotropic cells in rat anterior pituitary and in LβΤ2 cells, which are used as a model of gonadotropic cells.

Protons Differentially Activate TDAG8 Homologs from Various Species.

Mammalian T cell death-associated gene 8 (TDAG8)s are activated by extracellular protons. In the present study, we examined whether the TDAG8 homologs of other species are activated by protons as they are in mammals. We found that Xenopus TDAG8 also stimulated cAMP response element (CRE)-driven promoter activities reflecting the activation of Gs/cAMP signaling pathways when they are stimulated by protons.

Increased luminescence of the GloSensor cAMP assay in LβT2 cells does not correlate with cAMP accumulation under low pH conditions.

Cyclic adenosine monophosphate (cAMP) plays a pivotal role in gonadotrope responses in the pituitary. Gonadotropin-releasing hormone (GnRH) mediated synthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are regulated by both the G/cAMP and G/Ca signaling pathways. Pituitary adenylate cyclase-activating polypeptide (PACAP) also regulates GnRH responsiveness in gonadotropes through the PACAP receptor, which activates the G/cAMP signaling pathway.

Metals Differentially Activate Ovarian Cancer G Protein-Coupled Receptor 1 in Various Species.

Human, mouse, and zebrafish ovarian cancer G protein-coupled receptors (OGR1s) are activated by both metals and extracellular protons. In the present study, we examined whether pig, rat, chicken, and Xenopus OGR1 homologs could sense and be activated by protons and metals. We found that all homologs stimulated serum response element (SRE)-driven promoter activities when they are stimulated by protons.

Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR4.

Mammalian ovarian G-protein-coupled receptor 1 (OGR1) is activated by some metals in addition to extracellular protons and coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebrafish OGR1, zebrafish GPR4, and human GPR4 (zOGR1, zGPR4, and hGPR4, respectively) could sense the metals and activate the intracellular signaling pathways. On one hand, we found that only manganese and cobalt of the tested metals stimulated SRE-promoter activities in zOGR1-overexpressed HEK293T cells.

Easy detection of hormone secretion from LβT2 cells by using Gaussia luciferase.

Reproduction is regulated by gonadotropins secreted from gonadotrophs. The production and secretion of gonadotropins are mainly regulated by gonadotropin-releasing hormone (GnRH). Agonists or antagonists that influence GnRH action on gonadotrophs are important to regulate reproduction; however, these factors have not been fully characterized due to the lack of simple and easy-to-use techniques to detect gonadotropin secretion from gonadotropin-producing cells.

Molasses melanoidin promotes copper uptake for radish sprouts: the potential for an accelerator of phytoextraction.

Phytoextraction has been proposed as an alternative remediation technology for heavy metal contamination, and it is well known that chelators may alter the toxicity of heavy metals and the bioavailability in plants. Our previous work demonstrated that an adsorbent-column chromatography can effectively separate melanoidin-like product (MLP) from sugarcane molasses. The aim of this study was to examine the chelating property of MLP and to evaluate the facilitatory influence on the phytoextraction efficiency of Japanese radish.

Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment.

Human G2A is activated by various stimuli such as lysophosphatidylcholine (LPC), 9-hydroxyoctadecadienoic acid (9-HODE), and protons. The receptor is coupled to multiple intracellular signaling pathways, including the Gs-protein/cAMP/CRE, G12/13-protein/Rho/SRE, and Gq-protein/phospholipase C/NFAT pathways. In the present study, we examined whether zebrafish G2A homologs (zG2A-a and zG2A-b) could respond to these stimuli and activate multiple intracellular signaling pathways.

Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1 and GPR4 homologs of zebra fish.

Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as a proton-sensing G-protein-coupled receptor coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebra fish OGR1 and GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple intracellular signaling pathways and, if so, whether the similar positions of histidine residue, which is critical for sensing protons in mammalian OGR and GPR4, also play a role to sense protons and activate the multiple signaling pathways in the zebra fish receptors. We found that extracellular acidic pH stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4 overexpressed cells.

Proton-sensing ovarian cancer G protein-coupled receptor 1 on dendritic cells is required for airway responses in a murine asthma model.

Ovarian cancer G protein-coupled receptor 1 (OGR1) stimulation by extracellular protons causes the activation of G proteins and subsequent cellular functions. However, the physiological and pathophysiological roles of OGR1 in airway responses remain largely unknown. In the present study, we show that OGR1-deficient mice are resistant to the cardinal features of asthma, including airway eosinophilia, airway hyperresponsiveness (AHR), and goblet cell metaplasia, in association with a remarkable inhibition of Th2 cytokine and IgE production, in an ovalbumin (OVA)-induced asthma model.

Effects of a multi-method discharge planning educational program for medical staff nurses.

Aim: To evaluate the effects of an educational program on discharge planning for staff nurses that was developed to improve their knowledge, attitudes, and practice as well as the organizational climate regarding discharge planning.

Methods: Quasi-experimental design was used. Participants were 256 staff nurses on general internal medicine units in a 1210-bed national university hospital in the Tokyo area.

Expansion of discharge planning system in Japan: Comparison of results of a nationwide survey between 2001 and 2010.

Background: In response to the rapid aging of the population in Japan, many care systems have been created in quick succession. Establishment of discharge planning departments (DPDs) in hospitals is one of them. In this study, we compared the distribution and characteristics of DPDs and the characteristics of the hospitals that have DPDs between 2001 and 2010 in Japan.

Ovarian cancer G-protein-coupled receptor 1 induces the expression of the pain mediator prostaglandin E2 in response to an acidic extracellular environment in human osteoblast-like cells.

Although bone pain in osteoporosis and skeletal metastasis is an expected consequence of fracture, there are other underlying causes responsible. Our study demonstrated that ovarian cancer G-protein-coupled receptor 1 detected extracellular protons in MG63 cells, and regulated osteoblast functions, such as prostaglandin E2 production, in response to acidic circumstances. In this work, we measured inositol phosphate production, intracellular Ca(2+) concentration, prostaglandin E2 production, and cyclic adenosine monophosphate accumulation in MG63 cells exposed to extracellular acidification.