On Solutions of a Nonlinear Erdélyi-Kober Integral Equation

We conduct some investigations concerning the solvability of a nonlinear integral equation of Erdélyi-Kober type. To facilitate our study we will first consider a nonlinear integral equation of Volterra-Stieltjes type. Since the mentioned Erdélyi-Kober integral equation turns out to be a special case of that of Volterra-Stieltjes type, we can apply the obtained results to the Erdélyi-Kober integral equation. Examples illustrating the obtained results will be also included

Inhibition of APE1/Ref-1 redox signaling alleviates intestinal dysfunction and damage to myenteric neurons in a mouse model of spontaneous chronic colitis

Background:Inflammatory bowel disease (IBD) associates with damage to the enteric nervous system (ENS), leading to gastrointestinal (GI)dysfunction. Oxidative stress is important for the pathophysiology of inflammation-induced enteric neuropathy and GI dysfunction. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a dual functioning protein that is an essential regulator of the cellular response tooxidative stress. In this study, we aimed to determine whether an APE1/Ref-1 redox domain inhibitor, APX3330, alleviates inflammation-inducedoxidative stress that leads to enteric neuropathy in the Winnie murine model of spontaneous chronic colitis.Methods: Winnie mice received APX3330 or vehicle via intraperitoneal injections over 2 weeks and were compared with C57BL/6 controls. Invivo disease activity and GI transit were evaluated. Ex vivo experiments were performed to assess functional parameters of colonic motility, immune cell infiltration, and changes to the ENS.Results: Targeting APE1/Ref-1 redox activity with APX3330 improved disease severity, reduced immune cell infiltration, restored GI function ,and provided neuroprotective effects to the enteric nervous system. Inhibition of APE1/Ref-1 redox signaling leading to reduced mitochondrial superoxide production, oxidative DNA damage, and translocation of high mobility group box 1 protein (HMGB1) was involved inneuroprotective effects of APX3330 in enteric neurons.Conclusions: This study is the first to investigate inhibition of APE1/Ref-1’s redox activity via APX3330 in an animal model of chronic intestinal inflammation. Inhibition of the redox function of APE1/Ref-1 is a novel strategy that might lead to a possible application of APX3330 forthe treatment of IBD

A green synthesis route to derive carbon quantum dots for bioimaging cancer cells

Carbon quantum dots (CQDs) are known for their biocompatibility and versatile applications in the biomedical sector. These CQDs retain high solubility, robust chemical inertness, facile modification, and good resistance to photobleaching, which makes them ideal for cell bioimaging. Many fabrication processes produce CQDs, but most require expensive equipment, toxic chemicals, and a long processing time. This study developed a facile and rapid toasting method to prepare CQDs using various slices of bread as precursors without any additional chemicals. This fast and cost-effective toasting method could produce CQDs within 2 h, compared with the 10 h process in the commonly used hydrothermal method. The CQDs derived from the toasting method could be used to bioimage two types of colon cancer cells, namely, CT-26 and HT-29, derived from mice and humans, respectively. Significantly, these CQDs from the rapid toasting method produced equally bright images as CQDs derived from the hydrothermal method

Bioimaging of C2C12 Muscle Myoblasts Using Fluorescent Carbon Quantum Dots Synthesized From Bread

Biocompatible carbon quantum dots (CQDs) have recently attracted increased interest in biomedical imaging owing to their advantageous photoluminescence properties. Numerous precursors of fluorescent CQDs and various fabrication procedures are also reported in the literature. However; the use of concentrated mineral acids and other corrosive chemicals during the fabrication process curtails their biocompatibility and severely limits the utilization of the products in cell bio-imaging. In this study; a facile; fast; and cost-effective synthetic route is employed to fabricate CQDs from a natural organic resource; namely bread; where the use of any toxic chemicals is eliminated. Thus; the novel chemical-free technique facilitated the production of luminescent CQDs that were endowed with low cytotoxicity and; therefore; suitable candidates for bioimaging sensors. The above mentioned amorphous CQDs also exhibited fluorescence over 360-420 nm excitation wavelengths; and with a broad emission range of 360-600 nm. We have also shown that the CQDs were well internalized by muscle myoblasts (C2C12) and differentiated myotubes; the cell lines which have not been reported before

Mechanosensitive Enteric Neurons in the Myenteric Plexus of the Mouse Intestine

BACKGROUND: Within the gut the autonomous enteric nervous system (ENS) is able to sense mechanical stimuli and to trigger gut reflex behaviour. We previously proposed a novel sensory circuit in the ENS which consists of multifunctional rapidly adapting mechanosensitive enteric neurons (RAMEN) in the guinea pig. The aim of this study was to validate this concept by studying its applicability to other species or gut regions. METHODOLOGY/PRINCIPAL FINDINGS: We deformed myenteric ganglia in the mouse small and large intestine and recorded spike discharge using voltage sensitive dye imaging. We also analysed expression of markers hitherto proposed to label mouse sensory myenteric neurons in the ileum (NF145kD) or colon (calretinin). RAMEN constituted 22% and 15% of myenteric neurons per ganglion in the ileum and colon, respectively. They encoded dynamic rather than sustained deformation. In the colon, 7% of mechanosensitive neurons fired throughout the sustained deformation, a behaviour typical for slowly adapting echanosensitive neurons (SAMEN). RAMEN and SAMEN responded directly to mechanical deformation as their response remained unchanged after synaptic blockade in low Ca(++)/high Mg(++). Activity levels of RAMEN increased with the degree of ganglion deformation. Recruitment of more RAMEN with stronger stimuli may suggest low and high threshold RAMEN. The majority of RAMEN were cholinergic but most lacked expression of NF145kD or calretinin. CONCLUSIONS/SIGNIFICANCE: We showed for the first time that fundamental properties of mechanosensitive enteric neurons, such as firing pattern, encoding of dynamic deformation, cholinergic phenotype and their proportion, are conserved across species and regions. We conclude that RAMEN are important for mechanotransduction in the ENS. They directly encode dynamic changes in force as their firing frequency is proportional to the degree of deformation of the ganglion they reside in. The additional existence of SAMEN in the colon is likely an adaptation to colonic motor patterns which consist of phasic and tonic contractions

Excitability and synaptic transmission in the enteric nervous system: Does diet play a role?

© Springer International Publishing Switzerland 2016. Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption. The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. Nonetheless, traditional research methods like intracellular electrophysiological approaches have provided the basis for our understanding of the ENS circuitry. In particular, animal models of intestinal inflammation have shown us that we can document changes to neuronal excitability and synaptic transmission. Recent studies examining diet-induced changes to ENS programming have opted to use fast imaging techniques to reveal changes in neuron function. Advances in imaging techniques using voltage- or calcium-sensitive dyes to record neuronal activity promise to overcome many limitations inherent to electrophysiological approaches. Imaging techniques allow access to a wide range of ENS phenotypes and to the changes they undergo during dietary challenges. These sorts of studies have shown that dietary variation or obesity can change how the ENS processes information-in effect reprogramming the ENS. In this review, the data gathered from intracellular recordings will be compared with measurements made using imaging techniques in an effort to determine if the lessons learnt from inflammatory changes are relevant to the understanding of diet-induced reprogramming

Analysis of purinergic and cholinergic fast synaptic transmission to identified myenteric neurons

Types and projections of neurons that received cholinergic, purinergic and other fast excitatory synaptic inputs in myenteric ganglia of the guinea-pig distal colon were identified using combined electrophysiological recording, application of selective antagonists, marker dye filling via the recording microelectrode, and immunohistochemical characterisation. Fast synaptic inputs were recorded from all major subtypes of uniaxonal neurons including Dogiel type I neurons, filamentous interneurons, circular muscle motor neurons and longitudinal muscle motor neurons. Fast excitatory postsynaptic potentials were completely blocked by the nicotinic receptor antagonists hexamethonium or mecamylamine in 62% of neurons tested and were partially inhibited in the remaining neurons. The P2 purine receptor antagonist, pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid, reduced the amplitudes of fast excitatory postsynaptic potentials in 20% of myenteric neurons. The 5-hydroxytryptamine3 receptor antagonist granisetron reduced the amplitude of fast excitatory postsynaptic potentials in only one of 15 neurons tested. In five of five neurons tested, the combination of a nicotinic antagonist, pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid, granisetron and 6-cyano-7-nitroquinoxaline-2,3-dione did not completely block the fast excitatory postsynaptic potentials. Immunohistochemical studies of the neurons that had been identified electrophysiologically and morphologically imply that P2X2 receptors may mediate fast transmission in some neurons, and that other P2X receptor subtypes may also be involved in fast synaptic transmission to myenteric neurons of the guinea-pig distal colon. Neurons with nicotinic and pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid-sensitive fast excitatory postsynaptic potentials were present in both ascending and descending pathways in the distal colon. Thus, neither cholinergic nor mixed cholinergic/purinergic synaptic responses are confined to a particular class of neuron. The results indicate that acetylcholine and ATP are the major fast excitatory neurotransmitters in guinea-pig distal colon myenteric ganglia