Imaging analytical technique to assess gastrointestinal motility in vivo using zebrafish larvae with diabetes mellitus-like traits.

In diabetes mellitus (DM), the prevalence of gastrointestinal (GI) complications, including constipation, diarrhoea, gastroparesis, and/or enteropathy, can be up to ~75%. In this study, we compared three zebrafish larvae models of DM and established an analytical protocol for GI motility. Larvae were fed with either a standard diet (SD; control), or one of three diets to induce a DM-like phenotype: excessive feeding of SD food (ED), a high-fat diet (HFD), or exposing SD-fed larvae to 30 mmol/L glucose (SDG).

Action of cocaine- and amphetamine-regulated transcript (CART) peptide to attenuate cisplatin-induced emesis in Suncus murinus (house musk shrew).

Cocaine- and amphetamine-regulated transcript (CART) peptide is a brain-gut neuropeptide that has been implicated in a range of physiological functions including appetite, which is disturbed during chemotherapy. The aims of the present study were to identify the distribution and expression of CART mRNA and CART peptide, and to examine the potential of CART (55-102) to attenuate cisplatin-induced emesis in Suncus murinus. CART mRNA and peptide were detected throughout the entire brain, including the forebrain, hypothalamus, and brainstem, and also in the gut wall and stomach.

The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets: Anamorelin also exhibits anti-emetic effects via a central mechanism.

This study investigated whether ghrelin mimetics, namely anamorelin and ipamorelin, can alleviate weight loss and inhibition of feeding observed during acute and delayed phases of cisplatin-induced emesis in ferrets. The potential of anamorelin to inhibit electrical field stimulation (EFS)-induced contractions of isolated ferret ileum was compared with ipamorelin. In other experiments, ferrets were administered anamorelin (1-3 mg/kg), ipamorelin (1-3 mg/kg), or vehicle intraperitoneally (i.

Exploring the role of ghrelin and des-acyl ghrelin in chemotherapy-induced nausea and vomiting.

Ghrelin and its mimetics have been shown to reduce cisplatin-induced emesis in preclinical studies using ferrets and shrews. This study investigated the effectiveness of ghrelin and des-acyl ghrelin (DAG) in antagonizing cisplatin-induced emesis and physiological changes indicative of nausea in Suncus murinus. Animals implanted with radiotelemetry devices were administered ghrelin (0.

Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice.

Glial cell-mediated neuroinflammation and neuronal attrition are highly correlated with cognitive impairment in Alzheimer's disease. YKL-40 is a secreted astrocytic glycoprotein that serves as a diagnostic biomarker of Alzheimer's disease. High levels of YKL-40 are associated with either advanced Alzheimer's disease or the normal aging process.

Predicting drug adverse effects using a new Gastro-Intestinal Pacemaker Activity Drug Database (GIPADD).

Electrical data could be a new source of big-data for training artificial intelligence (AI) for drug discovery. A Gastro-Intestinal Pacemaker Activity Drug Database (GIPADD) was built using a standardized methodology to test drug effects on electrical gastrointestinal (GI) pacemaker activity. The current report used data obtained from 89 drugs with 4867 datasets to evaluate the potential use of the GIPADD for predicting drug adverse effects (AEs) using a machine-learning (ML) approach and to explore correlations between AEs and GI pacemaker activity.

Regional differences of tachykinin effects on smooth muscle and pacemaker potentials of the stomach, duodenum, ileum and colon of an emetic model, the house musk shrews.

Background And Aims: The contractile effects of tachykinins on the gastrointestinal tract are well-known, but how they modulate slow-waves, particularly in species capable of emesis, remains largely unknown. We aimed to elucidate the effects of tachykinins on myoelectric and contractile activity of isolated gastrointestinal tissues of the Suncus murinus.

Methods: The effects of substance P (SP), neurokinin (NK)A, NKB and selective NK (CP122,721, CP99,994), NK (SR48,968, GR159,897) and NK (SB218,795, SB222,200) receptor antagonists on isolated stomach, duodenum, ileum and colon segments were studied.

The Actions of Centrally Administered Nesfatin-1 on Emesis, Feeding, and Locomotor Activity in (House Musk Shrew).

Nesfatin-1 is an anorectic peptide expressed in both peripheral tissues and brain areas involved in the regulation of feeding, emotion and emesis. The aim of the present study is to characterize the distribution of NUCB2/nesfatin-1 in and to investigate the actions of nesfatin-1 to affect gastrointestinal contractility, emesis, food and water intake, and locomotor activity. The deduced amino acid sequence of nesfatin-1 using cloning showed high homology with humans and rodents.

Mechanisms of Chemotherapy-Induced Neurotoxicity.

Since the first clinical trials conducted after World War II, chemotherapeutic drugs have been extensively used in the clinic as the main cancer treatment either alone or as an adjuvant therapy before and after surgery. Although the use of chemotherapeutic drugs improved the survival of cancer patients, these drugs are notorious for causing many severe side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life. Many widely used chemotherapy drugs including platinum-based agents, taxanes, vinca alkaloids, proteasome inhibitors, and thalidomide analogs may cause direct and indirect neurotoxicity.

Insights Into Acute and Delayed Cisplatin-Induced Emesis From a Microelectrode Array, Radiotelemetry and Whole-Body Plethysmography Study of (House Musk Shrew).

Cancer patients receiving cisplatin therapy often experience side-effects such as nausea and emesis, but current anti-emetic regimens are suboptimal. Thus, to enable the development of efficacious anti-emetic treatments, the mechanisms of cisplatin-induced emesis must be determined. We therefore investigated these mechanisms in , an insectivore that is capable of vomiting.

Experimental evidence for recovery of mercury-contaminated fish populations.

Anthropogenic releases of mercury (Hg) are a human health issue because the potent toxicant methylmercury (MeHg), formed primarily by microbial methylation of inorganic Hg in aquatic ecosystems, bioaccumulates to high concentrations in fish consumed by humans. Predicting the efficacy of Hg pollution controls on fish MeHg concentrations is complex because many factors influence the production and bioaccumulation of MeHg. Here we conducted a 15-year whole-ecosystem, single-factor experiment to determine the magnitude and timing of reductions in fish MeHg concentrations following reductions in Hg additions to a boreal lake and its watershed.

A pipeline for phase-based analysis of in vitro micro-electrode array recordings of gastrointestinal slow waves.

Motility of the gastrointestinal tract (GI) is governed by an bioelectrical event termed slow waves. Accurately measuring the characteristics of GI slow waves is critical to understanding its role in clinical applications. High-resolution (HR) bioelectrical mapping involves placing a spatially dense array of electrodes directly over the surface of the GI wall to record the spatiotemporal changes in slow waves.

Involvement of TRPV1 and TRPA1 in the modulation of pacemaker potentials in the mouse ileum.

Background: The roles of transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and subfamily A, member 1 (TRPA1) in mechanisms of gastrointestinal motility are complex. This study aimed to clarify the effects of several TRPV1 and TRPA1 ligands on the electrical potentials generated by pacemaker cells in the mouse-isolated ileum.

Method: The pacemaker potentials of ileal segments of mice were recorded extracellularly using a 60-channel microelectrode array.

Sulprostone-Induced Gastric Dysrhythmia in the Ferret: Conventional and Advanced Analytical Approaches.

Nausea and emesis resulting from disease or drug treatment may be associated with disrupted gastric myoelectric activity (GMA). Conventional analytical techniques can determine the relative degrees of brady-, normo-, and tachygastric power, but lose information relative to the basic slow wave shape. The aim of the present study was to investigate the application of advanced analytical techniques in the analysis of disrupted GMA recorded after administration of sulprostone, a prostaglandin E agonist, in ferrets.

COVID-19, nausea, and vomiting.

Exclusion of nausea (N) and vomiting (V) from detailed consideration as symptoms of COVID-19 is surprising as N can be an early presenting symptom. We examined the incidence of NV during infection before defining potential mechanisms. We estimate that the overall incidence of nausea (median 10.

GLP-1 receptors are involved in the GLP-1 (7-36) amide-induced modulation of glucose homoeostasis, emesis and feeding in Suncus murinus (house musk shrew).

GLP-1 receptor agonists are used for the treatment of type 2 diabetes but they may reduce appetite and cause nausea and emesis. We investigated if GLP-1 (7-36) amide can modulate glucose homoeostasis, emesis and feeding via an exendin (9-39)-sensitive mechanism in Suncus murinus. The effect of GLP-1 (7-36) amide on glucose homeostasis was examined using an intraperitoneal glucose tolerance test.

Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer's disease pathology.

Key Points: Alzheimer's disease (AD) patients and transgenic mice have beta-amyloid (Aβ) aggregation in the gastrointestinal (GI) tract. It is possible that Aβ from the periphery contributes to the load of Aβ in the brain, as Aβ has prion-like properties. The present investigations demonstrate that Aβ injected into the GI tract of ICR mice is internalised into enteric cholinergic neurons; at 1 month, administration of Aβ into the body of the stomach and the proximal colon was observed to partly redistribute to the fundus and jejunum; at 1 year, vagal and cerebral β-amyloidosis was present, and mice exhibited GI dysfunction and cognitive deficits.

Acetylcholine exerts inhibitory and excitatory actions on mouse ileal pacemaker activity: role of muscarinic versus nicotinic receptors.

The effect of acetylcholine (ACh) on pacemaking and spontaneous contractions in the gastrointestinal tract is not well characterized. The current study aims to profile the effect of several muscarinic and nicotinic receptor agonists and antagonists on pacemaker potentials in the ICR mouse ileum. Pacemaker potentials of whole thickness mouse ileal segments were recorded extracellularly using a 60-channel microelectrode array (MEA) platform.

Soy flavonoids prevent cognitive deficits induced by intra-gastrointestinal administration of beta-amyloid.

Background: In Alzheimer's diseases, beta-amyloid may act as prion-like protein and migrate from the gastrointestinal tract towards the brain. Soy flavonoids have been identified as neuroprotective against cognitive loss in human. Diet with soy flavonoids may be used to slow down the progression of Alzheimer's diseases.

The brain-penetrating, orally bioavailable, ghrelin receptor agonist HM01 ameliorates motion-induced emesis in Suncus murinus (house musk shrew).

Background And Purpose: HM01, a novel, orally bioavailable, brain-penetrating agonist of ghrelin receptors, ameliorates emesis in Suncus murinus. This study compared HM01's activity against motion sickness with that of the less brain-penetrating ghrelin receptor agonist, HM02.

Experimental Approach: The potential of HM01 and HM02 to relax isolated mesenteric arteries and to increase feeding was investigated.

Transplantation of Retinal Ganglion Cells Derived from Male Germline Stem Cell as a Potential Treatment to Glaucoma.

Glaucoma is characterized by retinal ganglion cell (RGC) degeneration and is the second leading cause of blindness worldwide. However, current treatments such as eye drop or surgery have limitations and do not target the loss of RGC. Regenerative therapy using embryonic stem cells (ESCs) holds a promising option, but ethical concern hinders clinical applications on human subjects.

Use of a microelectrode array to record extracellular pacemaker potentials from the gastrointestinal tracts of the ICR mouse and house musk shrew (Suncus murinus).

Background: The rhythmic contraction and relaxation of smooth muscles in the gastrointestinal (GI) tract is governed by pacemaker electrical potentials, also termed slow waves, which are calcium currents generated by interstitial cells of Cajal (ICCs). Malfunction of pacemaker rhythms contributes to a number of clinically challenging gastrointestinal motility disorders.

Method: A microelectrode array (MEA) was used to record slow waves in vitro from intact GI tissues freshly isolated from the ICR mouse and Suncus murinus.

Localization of estrogen receptor ERα, ERβ and GPR30 on myenteric neurons of the gastrointestinal tract and their role in motility.

Estrogen is well known to have a modulatory role on gastrointestinal tract, particularly through its interaction with nuclear estrogen receptors (ERs), alpha and beta (ERα/β). Recent functional studies also indicate that estrogen can activate a G-protein coupled estrogen receptor, GPR30, or GPER1. The present study was designed to identify either the presence or absence of nuclear ERs and GPR30 in the myenteric plexus of the stomach, duodenum, jejunum, ileum and colon of female and male mice.