Objective Neurophysiological Indices for the Assessment of Chronic Tinnitus Based on EEG Microstate Parameters.

Chronic tinnitus is highly prevalent but lacks precise diagnostic or effective therapeutic standards. Its onset and treatment mechanisms remain unclear, and there is a shortage of objective assessment methods. We aim to identify abnormal neural activity and reorganization in tinnitus patients and reveal potential neurophysiological markers for objectively evaluating tinnitus. By way of analyzing EEG microstates, comparing metrics under three resting states (OE, CE, and OECEm) between tinnitus sufferers and controls, and correlating them with tinnitus symptoms. This study reflected specific changes in the EEG microstates of tinnitus patients across multiple resting states, as well as inconsistent correlations with tinnitus symptoms. Microstate parameters were significantly different when patients were in OE and CE states. Specifically, the occurrence of Microstate A and the transition probabilities (TP) from other Microstates to A increased significantly, particularly in the CE state (32-37%, p ≤ 0.05 ); and both correlated positively with the tinnitus intensity. Nevertheless, under the OECEm state, increases were mainly observed in the duration, coverage, and occurrence of Microstate B (15-47%, ), which negatively correlated with intensity ( [Formula: see text]-0.513, ). Additionally, TPx between Microstates C and D were significantly reduced and positively correlated with HDAS levels ( [Formula: see text] 0.548, ). Furthermore, parameters of Microstate D also correlated with THI grades ( [Formula: see text]-0.576, ). The findings of this study could offer compelling evidence for central neural reorganization associated with chronic tinnitus. EEG microstate parameters that correlate with tinnitus symptoms could serve as neurophysiological markers, contributing to future research on the objective assessment of tinnitus.

Transcriptome-based nutrigenomics analysis reveals the roles of dietary taurine in the muscle growth of juvenile turbot (Scophthalmus maximus).

The present study explored transcriptomics and gene regulation variations in the muscle of turbot fed with dietary taurine. A 70-day feeding trial was conducted using turbot (initial body weight: 3.66 ± 0.02 g) fed with different levels of dietary taurine: 0 % (C), 0.4 % (T2), 1.2 % (T4) and 2.0 % (T6). Two methods were used to analyze and verify the taurine effects on muscle growth: (1) real-time quantitative PCR (qRT-PCR) for the key muscle growth-related genes and (2) transcriptomic analysis by next-generation sequencing (NGS). The results showed that 1.2 % of dietary taurine supplementation significantly increased the expression of muscle growth stimulatory genes, including TauT, myoD, Myf5, myogenin and follistatin. And also, the 1.2 % level significantly decreased the expression of the muscle growth-restricting gene (myostatin). Meanwhile, transcriptomics analysis found that 1.2 % dietary taurine supplementation significantly increased the number of up-regulated genes linked to metabolic pathways. In contrast, taurine significantly enriched the actin cytoskeleton and metabolic pathways in the T4 and T2 groups, respectively. These findings align with the gene ontology (GO) analysis, which indicated a higher number of cellular component (CC) gene expressions at a 1.2 % of dietary taurine compared to a 0.4 % of dietary taurine supplementation. In conclusion, dietary taurine had positive impacts on the growth-stimulatory genes. Moreover, 1.2 % of dietary taurine supplementation is important to the metabolic pathway enrichment.

Comparative analysis of glucose metabolism responses of large yellow croaker Larimichthys crocea fed diet with fish oil and palm oil.

In order to study the effects of dietary fatty acid compositions on glucose metabolism, large yellow croaker juveniles Larimichthys crocea (initial weight, 36.80 ± 0.39 g) were fed with two experiment diets for 12 weeks. The two diets contained 6.5% of fish oil (FO) and palm oil (PO), respectively. Results showed that the contents of saturated fatty acids in liver and muscle, levels of glucose, triglyceride (TG), non-esterified fatty acid (NEFA), and leptin in blood were significantly higher in PO group, while the hepatic glycogen and muscle glycogen significantly decreased (P < 0.05). There were no significant differences in blood insulin and adiponectin levels between the two groups (P > 0.05). Compared with the FO group, the expressions of glucokinase (GK), glucose-6-phosphate dehydrogenase, glycogen synthase (GYS), glucose transporter 2 (GLUT2), insulin receptor 1 (IR1), insulin receptor substrate 1 (IRS1), insulin receptor substrate (IRS2), and protein kinase B (AKT2) were significantly decreased, and the expressions of phosphoenolpyruvate carboxykinase (PEPCK) in liver were significantly increased in the PO group. Meanwhile, the expressions of GK, phosphofructokinase, GYS, GLUT4, and insulin receptor 2 (IR2) were significantly reduced, and the expressions PEPCK, fructose-1 and 6-diphosphatase in muscle were significantly increased in the PO group. In conclusion, palm oil in diet could inhibit the utilization of glucose and promote the endogenous glucose production in large yellow croaker by reducing the sensitivity of insulin, so as to increase the blood glucose level.

Forkhead box O1 in turbot Scophthalmus maximus: Molecular characterization, gene structure, tissue distribution and the role in glucose metabolism.

Forkhead box O1 (foxo1) is a transcription factor and plays important roles in glucose metabolism. In the present study, foxo1 in turbot Scophthalmus maximus was cloned and characterized. The siRNA of foxo1 was used to investigate the functions of foxo1 in turbot hepatocytes glucose metabolism. After that, a 10-week feeding trial with two different dietary carbohydrate levels (15% and 21%, respectively) was conducted to analyze the function of foxo1 in glucose metabolism in vivo. Results showed that the foxo1 was identified as 2176 bp (base pair) with a 2025 bp open reading frame, which encoded 675 amino acids. Sequence analysis showed that foxo1 of turbot was highly homologous to most of fishes. Tissue distribution analysis revealed that the highest expression of foxo1 was in liver. After in vitro analysis, foxo1-specific small interfering RNA (sifoxo1) treatment significantly decreased the expressions of cytosolic phosphoenolpyruvate carboxykinase (cpepck) and glucose-6-phosphatase1(g6pase1) in primary hepatocytes. Expression of mitochondrial phosphoenolpyruvate carboxykinase (mpepck) was not significantly inhibited. In contrast, the expression of glucose-6-phosphatase2 (g6pase2) increased significantly. After the in vivo study (feeding trial), with the decreased expression of foxo1 in turbot due to high dietary carbohydrate level (21%), the expression of g6pase2 was significantly upregulated. However, the expression of glucokinase (gk) was not changed significantly. These increased the level of blood glucose and hepatic glycogen. In conclusion, data from both in vitro (primary hepatocytes) and in vivo (feeding trial) showed that downregulated foxo1 in turbot could not result in significant depression of gluconeogenesis and activation of glycolysis. This could be one of the reasons why intake of high level of carbohydrate resulted in prolonged hyperglycemia in turbot.

Responses of glucosensing system to glucose in Japanese flounder Paralichthys olivaceus fed diets with different carbohydrate content.

A 10-week feeding trial was conducted to investigate the response of glucosensing system to glucose in Japanese flounder Paralichthys olivaceus (initial body weight: 7.14 ±â€¯0.10 g) fed diets with different carbohydrate content. Two experimental diets were designed as carbohydrate free (CF) and suitable carbohydrate (SC) supplementation, respectively. The dietary carbohydrate contents were 0.93% and 15.6%, respectively. After a 10-week feeding trial, a glucose tolerance test (GTT) was performed. Results showed that after the last meal in the feeding trial, the blood glucose of fish fed with diet CF peaked at 3 h (4.64 ±â€¯0.29 mM), the duration of hyperglycemia was about 5 h (1-6 h). The blood glucose in SC group peaked at 9 h (3.28 ±â€¯0.66 mM), and the duration of hyperglycemia was approximately 6 h (6-12 h). After GTT, blood glucose reached the first peak at 6 h both in the two groups, and the duration of hyperglycemia was obvious 24 h. During the 3-12 h after injection, blood glucose level in SC group was significantly higher than that in CF group. However, blood glucose level in group SC was significantly lower than that in group CF at 24 h. The blood glucose level decreased to half of the peak at 10.97 h after injection of glucose in SC group and at 27.26 h in CF group. The 6-24 h clearance ability in SC group (6.57 ±â€¯1.68%/h) was significantly higher than that in CF group (2.81 ±â€¯1.11%/h). Compared with CF diet, SC diet significantly increase the expression of glucosensing-related genes including glucose facilitative transporter type 2, glucokinase, inward rectifier K+ channel pore type 6.2, sulfonylurea receptor, carnitine palmitoyltransferase 1b, hydroxyacyl-CoA dehydrogenase, cytochrome c oxidase subunit 4, mitochondrial uncoupling protein 2a, liver X receptor, sodium/glucose co-transporter 1, a heterodimer of type 1 receptor subunits depending on T1R2 + T1R3 in liver and intestine. Meanwhile, activities of glucokinase, pyruvate kinase and glycogen synthase in liver, and hepatic glycogen content were also increased. In conclusion, glucosensing systems in Japanese flounder are responsive to dietary carbohydrate levels, especially the suitable dietary carbohydrate level, at which the glucose tolerance capacity of Japanese flounder was improved.

High level of dietary soybean oil affects the glucose and lipid metabolism in large yellow croaker Larimichthys crocea through the insulin-mediated PI3K/AKT signaling pathway.

The present study was conducted to investigate the metabolic responses of glucose and lipid in large yellow croaker Larimichthys crocea (initial weight, 36.80 ±â€¯0.39 g) to high level of dietary soybean oil. Three isonitrogenous (46% crude protein) and isolipidic (13% crude lipid) experimental diets were designed, with 100% fish oil (FO), 50% fish oil and 50% soybean oil (FS) and 100% soybean oil (SO), respectively. After a 12-week growth trial, the results showed that compared with FO group, contents n-6 PUFAs increased while the n-3 PUFAs decreased significantly both in liver and muscle in FS and SO groups. Concentrations of blood glucose, leptin, free fatty acid and total triglyceride reached the highest values in SO group, while blood insulin showed no significant difference among all groups. The gene expressions of insulin receptor substrate-2, glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, fatty acid synthetase, and lipoprotein lipase increased, and the insulin receptor substrate-1, phosphotidylinsositol-3-kinase (PI3K), hexokinase, glycogen synthetase and glucose transporter 2 in liver decreased significantly in SO group. Meanwhile, the phosphorylation of protein kinase B (AKT) also decreased significantly in this group. These results suggested that high level of dietary soybean oil depressed PI3K/AKT signaling pathway, and then affected glucose and lipid metabolism by glycolysis, gluconeogenesis, glucose transportation, glycogenesis and lipogenesis.

Chronic stress of high dietary carbohydrate level causes inflammation and influences glucose transport through SOCS3 in Japanese flounder Paralichthys olivaceus.

Carnivorous fish is thought to be high-glucose intolerance. But the reasons were still unclear. The aim of the present study is to investigate the effects of high level of dietary carbohydrate on the survival, growth and immune responses of Paralichthys olivaceus, and the underlying molecular mechanism related to the immune and glucose metabolism. P. olivaceus were fed with 8%, 16% and 24% of dietary carbohydrate for 10 weeks, respectively. After that, a glucose tolerance test (GTT) was conducted. Results showed that excessive (24%) dietary carbohydrate significantly decreased the growth and glucose tolerance ability according to the GTT. It significantly increased hepatic NADPH oxidase activity and malondialdehyde content and serum contents of IL-6 and advanced glycation end products. The expressions of glucose transport-relevant genes in liver and the content of related hormones in serum were analyzed. In conclusion, it was confirmed that IL-6 increased the expression of suppressor of cytokine signaling 3 (SOCS3) and regulated the downstream targets of PI3K-AKT mediated signal transduction, and then downregulated the glucose transporter 2 activity in liver of P. olivaceus fed diet with excessive carbohydrate level. It was suggested that SOCS3 served as a bridge between immune response and glucose metabolism in P. olivaceus.

Comparatively study on the insulin-regulated glucose homeostasis through brain-gut peptides in Japanese flounder Paralichthys olivaceus after intraperitoneal and oral administration of glucose.

The present study comparatively analyzed the blood glucose and insulin concentration, the temporal and spatial expression of brain-gut peptides and the key enzymes of glycolysis and gluconeogenesis in Japanese flounder by intraperitoneal injection (IP) and oral administration (OR) of glucose. Samples were collected at 0, 1, 3, 5, 7, 9, 12, 24 and 48 h after IP and OR glucose, respectively. Results showed that the hyperglycemia lasted for about 10 h and 21 h in OR and IP group, respectively. The serum insulin concentration significantly decreased at 3 h (1.58 ±â€¯0.21 mIU/L) after IP glucose. However, it significantly increased at 3 h (3.37 ±â€¯0.341 mIU/L) after OR glucose. The gene expressions of prosomatostatin, neuropeptide Y, cholecystokinin precursor and orexin precursor in the brain showed different profiles between the OR and IP group. The OR not IP administration of glucose had significant effects on the gene expressions of preprovasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide and gastrin in intestine. In conclusion, brain-gut peptides were confirmed in the present study. And the serum insulin and the brain-gut peptides have different responses between the IP and OR administration of glucose. The OR could stimulate the brain-gut peptide expressions, which have effects on the insulin secretion and then regulate the blood glucose levels. However, in IP group, there is little chance to stimulate brain-gut peptide expression to influence the insulin secretion, which leads to a longer hyperglycemia.