The pyruvate-GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells.

The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated.

Tissue-resident memory T cells: decoding intra-organ diversity with a gut perspective.

Tissue-resident memory T cells (T) serve as the frontline of host defense, playing a critical role in protection against invading pathogens. This emphasizes their role in providing rapid on-site immune responses across various organs. The physiological significance of T is not just confined to infection control; accumulating evidence has revealed that T also determine the pathology of diseases such as autoimmune disorders, inflammatory bowel disease, and cancer.

Distress of Educators Teaching Nursing Students with Potential Learning Disabilities: A Qualitative Analysis.

Clinical training at Japanese nursing universities has an increasing need for individualized learning support for students with potential learning disabilities. Despite a high interest in student support, educators' difficulties are neglected. This study clarified the difficulties encountered by practical training instructors in delivering clinical training to nursing students with potential learning disabilities.

Identification of a unique subset of tissue-resident memory CD4 T cells in Crohn's disease.

T cells differentiate into highly diverse subsets and display plasticity depending on the environment. Although lymphocytes are key mediators of inflammation, functional specialization of T cells in inflammatory bowel disease (IBD) has not been effectively described. Here, we performed deep profiling of T cells in the intestinal mucosa of IBD and identified a CD4 tissue-resident memory T cell (Trm) subset that is increased in Crohn's disease (CD) showing unique inflammatory properties.

Molecular Mechanisms Underlying the Bioactive Properties of a Ketogenic Diet.

The consumption of a high-fat, low-carbohydrate diet (ketogenic diet) has diverse effects on health and is expected to have therapeutic value in neurological disorders, metabolic syndrome, and cancer. Recent studies have shown that a ketogenic diet not only pronouncedly shifts the cellular metabolism to pseudo-starvation, but also exerts a variety of physiological functions on various organs through metabolites that act as energy substrates, signaling molecules, and epigenetic modifiers. In this review, we highlight the latest findings on the molecular mechanisms of a ketogenic diet and speculate on the significance of these functions in the context of the epigenome and microbiome.

Epithelial miR-215 negatively modulates Th17-dominant inflammation by inhibiting CXCL12 production in the small intestine.

MicroRNAs are a class of non-coding short-chained RNAs that control cellular functions by downregulating their target genes. Recent research indicates that microRNAs play a role in the maintenance of gut homeostasis. miR-215 was found to be highly expressed in epithelial cells of the small intestine; however, the involvement of miR-215 in gut immunity remains unknown.

Midwifery scale to support shared decision-making for unplanned pregnancies: A cross-sectional study.

Midwives significantly support women with unplanned pregnancies-promoting a shared perspective on the decision-making process. This study aimed to develop a scale to support midwives to self-assess their practice of this vital role. Following the derivation of scale items and pilot testing, the final version of the scale was administered to 531 midwives to establish internal consistency and construct criterion-related validity.

Total synthesis of pyrrolo[2,3-]quinoline alkaloid: trigonoine B.

The first total synthesis of the pyrrolo[2,3-]quinoline alkaloid trigonoine B () was accomplished via a six-step sequence involving the construction of an -substituted 4-aminopyrrolo[2,3-]quinoline framework via electrocyclization of 2-(pyrrol-3-yl)benzene containing a carbodiimide moiety as a 2-azahexatriene system. The employed six-step sequence afforded trigonoine B () in 9.2% overall yield.

TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes.

B cells produce high amounts of cytokines and immunoglobulins in response to lipopolysaccharide (LPS) stimulation. Calcium signaling cascades are critically involved in cytokine production of T cells, and the cytosolic calcium concentration is regulated by calcium-activated monovalent cation channels (CAMs). Calcium signaling is also implicated in B cell activation; however, its involvement in the cytokine production of LPS-stimulated B cells remains less well characterized.

[Early Detection of and Initial Response to Oxaliplatin-Related Hypersensitivity Reactions].

Oxaliplatin(L-OHP)-related hypersensitivity reactions(HSRs)may be fatal due to bronchospasm, dyspnea, and hypotension. Therefore, management of HSRs is extremely important, and a prompt and appropriate response is required when HSRs develop. To clarify the importance of early detection and an appropriate initial response to HSRs, we retrospectively investigated the expression of HSRs and subsequent response in patients using L-OHP from April 2016 to December 2017 at the outpatient chemotherapy center of Nagasaki Medical Center.

The Circadian Clock as an Essential Molecular Link Between Host Physiology and Microorganisms.

Advances in high-throughput sequencing technologies in the past decade has led to a tremendous growth in knowledge about the role played by microorganisms on our body health. Trillions of microbes live in close symbiosis with their host, and have impacts on various aspects of host physiology as well as predisposition to disease. This is a consequence of the direct interaction between host cells and microbes or their signaling molecules, such as metabolites, which can reach and exert their effects in distal tissues.

Low-frequency and low-intensity ultrasound increases cardiac parasympathetic neural activity and decreases clinic hypertension in elderly hypertensive subjects with type 2 diabetes.

Background: The aims of the present study were to determine the effects of an ultrasound irradiation on clinic hypertension and the heart rate variability in elderly hypertensive subjects with type 2 diabetes.

Methods: We examined the effects of ultrasound (800 kHz, 25 mW/cm) applied to the forearm for 10 min on the autonomic nerve activity and the difference between BP at home and at a clinic visit in Japanese subjects with type 2 diabetes and hypertension.

Results: In 108 subjects who displayed systolic BP (SBP) >140 mm Hg at a clinic visit, 75 subjects (69%) had a mean SBP <135 mm Hg at home and 33 subjects (31%) had a mean SBP >135 mm Hg at home in the morning for 14 days.

Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells.

Foxp3 regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming.

Interplay between Microbes and the Circadian Clock.

Circadian rhythms influence virtually all life forms on our planet, a notion that opens the question on how the circadian cycles of individual organisms may interplay with each other. In mammals, a potentially dangerous environmental stress is represented by encounters with infectious agents. Microbial attack is a major risk for organismal homeostasis and therefore needs to be efficiently counteracted by mechanisms implemented by the host immune system.

Distinct Circadian Signatures in Liver and Gut Clocks Revealed by Ketogenic Diet.

The circadian clock orchestrates rhythms in physiology and behavior, allowing organismal adaptation to daily environmental changes. While food intake profoundly influences diurnal rhythms in the liver, how nutritional challenges are differentially interpreted by distinct tissue-specific clocks remains poorly explored. Ketogenic diet (KD) is considered to have metabolic and therapeutic value, though its impact on circadian homeostasis is virtually unknown.

Low-frequency and low-intensity ultrasound irradiation to the forearm improves an index of arterial stiffness in subjects with type 2 diabetes and hypertension.

Objectives: The arterial pressure-volume index (API) is a non-invasive assessment of arterial stiffness, and is suggested as a useful predictor of future cardiovascular events. The aim of the present study was to determine the effects of low-frequency and low-intensity ultrasound applied to the forearm for 10 min on the API in Japanese subjects with type 2 diabetes and hypertension.

Methods: We examined the effects of low-frequency and low-intensity ultrasound (800 kHz, 25 mW/cm) applied to the forearm for 10 min on the API, blood pressure (BP) and pulse rate in 40 Japanese subjects (13 men and 27 women; mean age ± SE, 70 ± 2 years) with type 2 diabetes and hypertension, who had the API > 30 and systolic BP > 140 mmHg at a clinic visit.

Treatment with FGFR2-IIIc monoclonal antibody suppresses weight gain and adiposity in KKA mice.

Expression of β-Kotho, fibroblast growth factor receptor (FGFR)-1c and 2c, which bind FGF21, is decreased in the white adipose tissue of obese mice. The aim of the present study was to determine the role of FGFR2c in the development of obesity and diabetes in KKA mice. Treatment with mouse monoclonal FGFR2-IIIc antibody (0.

Gut microbiota directs PPARγ-driven reprogramming of the liver circadian clock by nutritional challenge.

The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high-fat diet, the gut microbiota drives PPARγ-mediated activation of newly oscillatory transcriptional programs in the liver.

Low-frequency and very low-intensity ultrasound decreases blood pressure in hypertensive subjects with type 2 diabetes.

Background: Despite lifestyle interventions and various types of anti-hypertension agents, hypertension remains difficult to control in some patients with type 2 diabetes. As a noninvasive device-based approach for the treatment of clinic hypertension, we examined the effects of low-frequency and low-intensity ultrasound (500 or 800kHz, 25mW/cm(2)) applied to the forearm on blood pressure (BP) and pulse rate in Japanese subjects with type 2 diabetes and hypertension.

Methods: We examined the effects of low-frequency and low-intensity ultrasound (500 or 800kHz, 25mW/cm(2)) applied to the forearm on BP, pulse rate, and pulse pressure in 212 Japanese subjects (82 men and 130 women; mean age±SE, 65±1years) with type 2 diabetes and hypertension (systolic BP>140mmHg).

The Circadian Clock in the Ventromedial Hypothalamus Controls Cyclic Energy Expenditure.

Organismal homeostasis relies on coherent interactions among tissues, specifically between brain-driven functions and peripheral metabolic organs. Hypothalamic circuits compute metabolic information to optimize energetic resources, but the role of the circadian clock in these pathways remains unclear. We have generated mice with targeted ablation of the core-clock gene Bmal1 within Sf1-neurons of the ventromedial hypothalamus (VMH).

Pharmacologic stimulation of central GLP-1 receptors has opposite effects on the alterations of plasma FGF21 levels induced by feeding and fasting.

Fibroblast growth factor 21 (FGF21) functions as an endocrine hormone to regulate energy metabolism. Circulating FGF21 is derived from the liver and is produced in response to alterations of nutritional status. Here we show the effects of liraglutide, a human glucagon-like-peptide-1 (GLP-1) receptor agonist, injected into the third cerebral ventricle on body weight and plasma FGF21 levels in free-feeding mice, food-deprived mice, and mice provided 1g after the injection.

Ingestion of eicosapentaenoic acid in the early stage of social isolation reduces a fibroblast growth factor 21 resistant state independently of body weight in KKA(y) mice.

Fibroblast growth factor (FGF) 21 is a mediator of glucose and lipid metabolism. Although exogenous administration of FGF21 exerts beneficial effects on glucose and lipid metabolism, circulating FGF21 levels are elevated in ob/ob and db/db mice, diet-induced obese mice and obese human. Here we show that ingestion of eicosapentaenoic acid (EPA) for 6 days after individually-housing significantly suppressed the hyperglycemia and hypertriglyceridemia associated with decreases in plasma insulin and FGF21 levels in KKA(y) mice while having no effects on food intake, body weight or plasma active GLP-1 levels.

Development of a Neonatal End-of-Life Care Education Program for NICU Nurses in Japan.

We developed the first end-of-life care education program for neonatal intensive care unit (NICU) nurses in Japan. It focused on ethical decision making, care of dying neonates, bereavement, and cultural communication. The program improved nurses' knowledge, F(2.

Taste uncoupled from nutrition fails to sustain the reinforcing properties of food.

Recent findings suggest the reward system encodes metabolic value independent of taste, provoking speculation that the hedonic value of taste could be derived from nutritional value as a secondary appetitive property. We therefore dissociated and compared the impact of nutrition and taste on appetitive behavior in several paradigms. Though taste alone induces preference and increased consumption, in the absence of nutritional value its reinforcing properties are greatly diminished and it does not, like sucrose, induce increased responding over time.