Oscillation-Specific Nodal Differences in Parkinson's Disease Patients with Anxiety.

Background: Parkinson's disease (PD) is a common neurodegenerative disorder that is predominantly known for its motor symptoms but is also accompanied by non-motor symptoms, including anxiety. Objective: The underlying neurobiological substrates and brain network changes associated with comorbid anxiety in PD require further exploration. Methods: An analysis of oscillation-specific nodal properties in patients with and without anxiety was conducted using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory. We used a band-pass filtering approach to differentiate oscillatory frequency bands for subsequent functional connectivity (FC) and graph analyses. Results: The study included 68 non-anxiety PD (naPD) patients, 62 anxiety PD (aPD) patients, and 64 healthy controls (NC). Analyses of nodal betweenness centrality (BC), degree centrality (DC), and efficiency were conducted across multiple frequency bands. The findings indicated no significant differences in BC among naPD, aPD, and NC within the 0.01-0.08 Hz frequency range. However, we observed a specific reduction in BC at narrower frequency ranges in aPD patients, as well as differing patterns of change in DC and efficiency, which are believed to reflect the neurophysiological bases of anxiety symptoms in PD. Conclusions: Differential oscillation-specific nodal characteristics have been identified in PD patients with anxiety, suggesting potential dysregulations in brain network dynamics. These findings emphasize the complexity of brain network alterations in anxiety-associated PD and identify oscillatory frequencies as potential biomarkers. The study highlights the importance of considering oscillatory frequency bands in the analysis of brain network changes.

Dietary Methionine Restriction Improves Gastrocnemius Muscle Glucose Metabolism through Improved Insulin Secretion and H19/IRS-1/Akt Pathway in Middle-Aged Mice.

Methionine restriction (MR) improves glucose metabolism. In skeletal muscle, H19 is a key regulator of insulin sensitivity and glucose metabolism. Therefore, this study aims to reveal the underlying mechanism of H19 upon MR on glucose metabolism in skeletal muscle. Middle-aged mice were fed MR diet for 25 weeks. Mouse islets ß cell line ß-TC6 cells and mouse myoblast cell line C2C12 cells were used to establish the apoptosis or insulin resistance model. Our findings showed that MR increased B-cell lymphoma-2 (Bcl-2) expression, deceased Bcl-2 associated X protein (Bax), cleaved cysteinyl aspartate-specific proteinase-3 (Caspase-3) expression in pancreas, and promoted insulin secretion of ß-TC6 cells. Meanwhile, MR increased H19 expression, insulin Receptor Substrate-1/insulin Receptor Substrate-2 (IRS-1/IRS-2) value, protein Kinase B (Akt) phosphorylation, glycogen synthase kinase-3ß (GSK3ß) phosphorylation, and hexokinase 2 (HK2) expression in gastrocnemius muscle and promoted glucose uptake in C2C12 cells. But these results were reversed after H19 knockdown in C2C12 cells. In conclusion, MR alleviates pancreatic apoptosis and promotes insulin secretion. And MR enhances gastrocnemius muscle insulin-dependent glucose uptake and utilization via the H19/IRS-1/Akt pathway, thereby ameliorating blood glucose disorders and insulin resistance in high-fat-diet (HFD) middle-aged mice.

Eugenol improves high-fat diet/streptomycin-induced type 2 diabetes mellitus (T2DM) mice muscle dysfunction by alleviating inflammation and increasing muscle glucose uptake.

Eugenol has been used in dietary interventions for metabolic diseases such as diabetes and obesity. However, the protective effect of eugenol on muscle function in diabetes is unclear. In this study, a high-fat diet (HFD) with a streptozocin (STZ) injection induced type II diabetes mellitus in a mouse model. Oral eugenol lowered blood glucose and insulin resistance of HFD/STZ-treated mice. Eugenol reduced HFD/STZ-induced muscle inflammation and prevented muscle weakness and atrophy. Eugenol administration significantly increased GLUT4 translocation and AMPK phosphorylation in skeletal muscle, thereby enhancing glucose uptake. By silencing the transient receptor potential vanilloid channel 1 (TRPV1) gene in C2C12 myotube cells, eugenol was found to increase intracellular Ca2+ levels through TRPV1, which then activated calmodulin-dependent protein kinase-2 (CaMKK2) and affected AMPK protein phosphorylation. In conclusion, eugenol is a potential nutraceutical for preventing high-glucose-induced muscle impairments, which could be explained by its mediating effects on glucose absorption and inflammatory responses in the muscle.

Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in Middle-Aged Insulin-Resistant Mice.

LncRNA H19 has been reported to regulate apoptosis and neurological diseases. Hippocampal neuron apoptosis damages cognitive ability. Methionine restriction (MR) can improve cognitive impairment. However, the effect of MR on hippocampal neuronal apoptosis induced by a high-fat diet (HFD) in middle-aged mice remains unclear. For 25 weeks, middle-aged mice (C57BL/6J) were given a control diet (CON, 0.86% methionine + 4.2% fat), a high-fat diet (HFD, 0.86% methionine + 24% fat), or an HFD + MR diet (HFMR, 0.17% methionine + 24% fat). The HT22 cells were used to establish the early apoptosis model induced by high glucose (HG). In vitro, the results showed that MR significantly improved cell viability, suppressed the generation of ROS, and rescued HT22 cell apoptosis in a gradient-dependent manner. In Vivo, MR inhibited the damage and apoptosis of hippocampal neurons caused by a high-fat diet, reduced hippocampal oxidative stress, improved hippocampal glucose metabolism, relieved insulin resistance, and enhanced cognitive ability. Furthermore, MR could inhibit the overexpression of H19 and caspase-3 induced by HFD, HG, or H2O2 in vivo and in vitro, and promoted let-7a, b, e expression. These results indicate that MR can protect neurons from HFD-, HG-, or H2O2-induced injury and apoptosis by inhibiting H19.

Sevoflurane induces microRNA-18a to delay rat neurodevelopment via suppression of the RUNX1/Wnt/ß-catenin axis.

Sevoflurane anesthesia is reported to repress neurogenesis of neural stem cells (NSCs), thereby affecting the brain development, but the underlying mechanism of sevoflurane on the proliferation of NSCs remains unclear. Thus, this study aims to discern the relationship between sevoflurane and NSC proliferation. Bioinformatics tools were employed to predict the expression of microRNA-18a (miR-18a) in 9-day-old neonatal rat hippocampal tissues after sevoflurane treatment and the downstream genes of miR-18a, followed by a series of assays to explore the relationship among miR-18a, runt related transcription factor 1 (RUNX1), and ß-catenin in the hippocampal tissues. NSCs were isolated from the hippocampal tissues and subjected to gain-/loss-of-function assays to investigate the interactions among miR-18a, RUNX1, and ß-catenin in NSCs and their roles in NSC development. Bioinformatics analysis and experimental results confirmed high expression of miR-18a in rat hippocampal tissues and NSCs after sevoflurane treatment. Next, we found that miR-18a downregulated RUNX1 expression, while RUNX1 promoted NSC proliferation by activating the Wnt/ß-catenin signaling pathway. The behavioral experiments also showed that sevoflurane caused nerve injury in rats, whilst RUNX1 overexpression protected rat neurodevelopment. Our findings uncovered that sevoflurane attenuated NSC proliferation via the miR-18a-meidated RUNX1/Wnt/ß-catenin pathway, thereby impairing rat neurodevelopment.

Oxidized Pork Induces Hepatic Steatosis by Impairing Thyroid Hormone Function in Mice.

SCOPE: Recent studies have linked high consumption of red and processed meats to an increased risk of non-alcoholic fatty liver disease, and cooking-induced oxidation of proteins and amino acids might be contributing factors. Herein, this study investigates the influence of oxidized pork and the protein oxidation biomarker dityrosine (Dityr) on hepatic steatosis in mice. METHODS AND RESULTS: Low- and high-oxidative injury pork (LOP and HOP) are freeze-dried to prepare mouse diets. Mice are fed a diet of either the control, LOP, HOP, LOP+Dityr, or Dityr for 12 weeks. HOP and Dityr intake induced oxidative stress and inflammation that impaired thyroid function and peripheral metabolism (reduced type 1 deiodinase activity) of thyroid hormones (THs). These lead to a decrease in the circulating as well as liver THs and induced hepatic steatosis. This process might be regulated through reduced TH levels and altered TH target genes and proteins related to hepatic lipid metabolism that ultimately inhibited hepatic energy metabolism, as indicated by increased hepatic lipid synthesis, decreased hepatic lipid catabolism, and fatty acid oxidation. CONCLUSION: HOP intake could induce hepatic steatosis by impairing TH function. Dityr plays an important role in the HOP-induced harmful effects.

Sea Cucumber Peptides Improved the Mitochondrial Capacity of Mice: A Potential Mechanism to Enhance Gluconeogenesis and Fat Catabolism during Exercise for Improved Antifatigue Property.

Sea cucumber promotes multifaceted health benefits. However, the mechanisms of sea cucumber peptides (Scp) regulating the antifatigue capacity is still unknown. The present study is aimed at further elucidating the effects and mechanisms of Scp on the antifatigue capacity of mice. At first, C57BL/6J mice were assigned into four groups named Con, L-Scp, M-Scp, and H-Scp and received diets containing Scp (0%, 0.15%, 0.3%, and 0.5%, respectively) for continuous 30 days. On the 21th day, a fore grip test was conducted on mice. On the 25th day, a rotating rod test was conducted on mice. On the 30th day, the quantities of glycogen and mitochondrial DNA (mtDNA) were determined in 8 random mice and another 8 mice were forced to swim for 1 hour before slaughter for detecting biochemical indicators. It was observed that the Scp groups significantly prolonged the running time in rotarod, increased forelimb grip strength, improved lactic acid (LD) and urea nitrogen (BUN) levels in the serum, decreased lactic dehydrogenase (LDH) and glutamic oxalacetic transaminase (GOT) activities in the serum, increased blood glucose (BG) and glycogen (GN) levels in the liver and skeletal muscle after swimming, increased the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the skeletal muscle and heart, and improved antioxidant capacity. Furthermore, Scp treatment significantly elevated the mRNA and protein relative levels of power-sensitive factors, lipid catabolism, and mitochondrial biogenesis and significantly upregulated mRNA levels of gluconeogenesis. Besides, mtDNA before the swimming test was increased in the three Scp groups. These results show that Scp treatment has antifatigue capacity. Furthermore, these results suggest that improved energy regulation and antioxidant capacity may be the result of improved mitochondrial function.

Dietary methionine restriction improves the impairment of cardiac function in middle-aged obese mice.

Dietary methionine restriction (MR) has been reported to extend lifespan, reduce obesity and decrease oxidative damage to mtDNA in the heart of rats, and increase endogenous hydrogen sulfide (H2S) production in the liver and blood. H2S has many potential benefits in the pathophysiology of the cardiovascular system. MR also increases the level of homocysteine (Hcy) in the liver and plasma, but elevated plasma Hcy is a risk factor for cardiovascular disease. Therefore, this study aimed to determine the effect of MR on cardiac function and metabolic status in obese middle-aged mice and its possible mechanisms. C57BL/6J mice (aged approximately 28 weeks) were divided into six dietary groups: CON (0.86% methionine + 4% fat), CMR40 (0.52% methionine + 4% fat), CMR80 (0.17% methionine + 4% fat), HFD (0.86% methionine + 24% fat), HMR40 (0.52% methionine + 24% fat) and HMR80 (0.17% methionine + 24% fat) for 15 consecutive weeks. Our results showed that 80% MR improves systolic dysfunction in middle-aged obese mice and enhances myocardial energy metabolism. 80% MR also reduces myocardial oxidative stress and improves inflammatory response. In addition, 80% MR increased mice Hcy levels and activated remethylation and transsulfur pathways of Hcy and promoted endogenous H2S production in the heart. 40% MR has the same trend, but is not significant. Moreover 40% MR at variance with 80% MR, did not decrease the body weight in both control and high-fat diet mice. These findings suggest that MR can improve myocardial energy metabolism, reduce heart inflammation and oxidative stress by increasing cardiac H2S production, and improve cardiac dysfunction in middle-aged obese mice.

Dityrosine suppresses the cytoprotective action of thyroid hormone T3 via inhibiting thyroid hormone receptor-mediated transcriptional activation.

Dityrosine (Dityr) is the most common oxidized form of tyrosine. In the previous studies of mice treated with dityrosine, cell death in the pancreas, kidneys, and liver was detected in the presence of enhanced plasma triiodothyronine (T3) content. Due to its structural similarity with the thyroid hormone T3, we hypothesized that dityrosine might disrupt T3-dependent endocrine signaling. The cytotoxic effect of dityrosine was studied in C57BL/6 mice by gavage with a dityrosine dose of 320 µg per kg per day for 10 weeks. Cell death in the liver was detected in the presence of enhanced plasma thyroid hormone content in mice treated with dityrosine. The antagonistic effect of dityrosine on T3 biofunction was studied using HepG2 cells. Dityrosine incubation reduced T3 transport ability and attenuated the T3-mediated cell survival via regulation of the PI3k/Akt/MAPK pathway. Furthermore, dityrosine inhibited T3 binding to thyroid hormone receptors (TRs) and suppressed the TR-mediated transcription. Dityrosine also downregulated the expressions of T3 action-related factors. Taken together, this study demonstrates that dityrosine inhibits T3-dependent cytoprotection by competitive inhibition, resulting in downstream gene suppression. Our findings offer insights into how dityrosine acts as an antagonist of T3. These findings shed new light on cellular processes underlying the energy metabolism disorder caused by dietary oxidized protein, thus contributing to a better understanding of the diet-health axis at a cellular level.

Dietary methionine restriction improves the gut microbiota and reduces intestinal permeability and inflammation in high-fat-fed mice.

Methionine-restricted diets (MRD) have been shown to prevent high fat diet (HFD) induced complications including fat accumulation, insulin sensitivity decrease, oxidative stress and inflammation increase. We hypothesized that intestinal microbiota changes may mediate these effects, and this study aims to prove this hypothesis. Mice were fed a normal diet (ND, 0.86% methionine + 4% fat), a HF diet (HFD, 0.86% methionine + 20% fat), or a MRD (0.17% methionine + 20% fat) and euthanized at week 22. Our results showed that the HFD induced fat accumulation and gut microbiota dysbiosis; reduced short-chain fatty acid (SCFA) production; and increased intestinal permeability, inflammatory response, and oxidative stress. The MRD decreased the body weight, body fat rate, and blood glucose and plasma lipid levels; increased the abundance of putative SCFA-producing bacteria Bifidobacterium, Lactobacillus, Bacteroides, Roseburia, Coprococcus, and Ruminococcus and inflammation-inhibiting bacteria Oscillospira and Corynebacterium; and decreased the abundance of inflammation-producing bacteria Desulfovibrio in colonic contents. Moreover, the MRD improved intestinal barrier function, inflammatory response, and oxidative stress, and altered the metabolite levels of colonic contents (such as increasing SCFA and bile acid concentrations); the latter may have contributed to the prevention of HFD-induced obesity. In conclusion, the MRD can improve gut health by regulating the intestinal microbiota and its metabolite profiles in the HFD mice. Reducing methionine intake by simple dietary adjustment may be an effective method to improve intestinal health in animals and humans.

Spatial Learning and Memory Impairment in Growing Mice Induced by Major Oxidized Tyrosine Product Dityrosine.

This study focused on the effects of oxidized tyrosine products (OTPs) and major component dityrosine (DT) on the brain and behavior of growing mice. Male and female mice were treated with daily intragastric administration of either tyrosine (Tyr; 420 µg/kg body weight), DT (420 µg/kg body weight), or OTPs (1909 µg/kg body weight) for 35 days. We found that pure DT and OTPs caused redox state imbalance, elevated levels of inflammatory factors, hippocampal oxidative damage, and neurotransmitter disorders while activating the mitochondrial apoptosis pathway in the hippocampus and downregulating the genes associated with learning and memory. These events eventually led to growing mice learning and memory impairment, lagging responses, and anxiety-like behaviors. Furthermore, the male mice exhibited slightly more oxidative damage than the females. These findings imply that contemporary diets and food-processing strategies of the modern world should be modified to reduce oxidized protein intake.

[γ-aminobutyric acid fortified rice alleviated oxidative stress and pancreatic injury in type 2 diabetic mice].

OBJECTIVE: To investigate the effects of gamma aminobutyric acid(GABA) fortified rice diet intervention on oxidative stress and pancreatic injury in type 2 diabetes mellitus(T2 DM) mice. METHODS: Of the 70 male ICR mice, 10 were randomly selected as blank control group and they were always fed with the normal white rice feed. The remaining 60 mice were fed with high-fat white rice for 9 weeks. They were fasted for 12 h and injected intraperitoneally with streptozocin(STZ) at a dose of 50 mg/kg body weigh for two consecutive days. The control group was injected with the corresponding volume of normal saline. Subsequently, 50 T2 DM mice with successful modeling were randomly divided into 5 groups according to blood glucose, 10 in each group: T2 DM model control group, germinated brown rice positive control group(GABA content is 0. 2 g/kg feed), GABA-fortified rice low, medium and high dose group(GABA content was 0. 02, 0. 1 and 0. 2 g/kg feed respectively) and each target diet was fed for 6 weeks. Oral glucose tolerance test was performed one week before the end of the experiment to observe the hypoglycemic effect of different doses of GABA fortified rice. After the end of the experiment, HE staining was used to observe the morphology of pancreas. At the same time, the redox indicators from plasma and pancreas of reactive oxygen species(ROS), malondialdehyde(MDA), total antioxidant capacity(T-AOC), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) were examined in each group; The mRNA expressions of oxidative stress-related genes including glycogen synthase kinase-3ß(GSK-3ß), nuclear transcription factor 2(Nrf2), heme oxygenase 1(HO-1) and NAD(P)H: quinone oxidoreductase1(NQO1), insulin secretion related genes including pancreatic and duodenal homeobox 1(PDX-1), mus musculus v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A(MafA), glucokinase(GCK), glucose transporter 2(GLUT2) and the apoptosis associated genes including b-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax) and caspase-3 in pancreas were assayed by real-time fluorescent quantitative PCR. RESULTS: The intervention of GABA fortified rice could alleviate the improvement of the blood glucose level and the lack of insulin secretion in T2 DM mice and relieve plasma and pancreatic oxidative stress. besides, The intervention of GABA fortified rice could up-regulate the expression of insulin secretion-related genes PDX-1, GCK, GLUT2, inhibit the expression of pro-apoptotic gene caspase-3 and promote the expression of anti-apoptosis gene Bcl-2. There was a dose-response relationship between the above result and the 0. 2 g/kg dose group was the most significant, which achieved similar result to germinated brown rice. CONCLUSION: GABA-fortified rice can significantly improve the plasma and pancreatic redox status of STZ-induced T2 DM mice, regulate the expression levels of oxidative stress-related genes and apoptosis-related genes, thereby protect pancreatic tissue morphology, improve pancreatic insulin secretion and thereby alleviate glucose metabolism.

Dietary methionine restriction improves glucose metabolism in the skeletal muscle of obese mice.

Dietary methionine restriction (MR) has many positive effects on metabolic health. Recent studies have indicated that overall insulin sensitivity is improved by dietary MR. This study aimed to determine the effects of MR on insulin signalling and glucose utilisation in the skeletal muscle of obese mice. First, male C57BL/6J mice in the CON group were fed a control diet (0.86% methionine + 4% fat) for 34 weeks, and others were fed a high-fat (HF) diet (0.86% methionine + 20% fat) for 10 weeks to induce obesity. Then, the mice were divided into four dietary groups: the HF group (maintained on the HF diet), HF + MR group (0.17% methionine + 20% fat), C* group (changed to a control diet, 0.86% methionine + 4% fat), and C* + MR group (0.17% methionine + 4% fat) for 24 weeks. Mice were euthanised at 8, 16 or 24 weeks. The results indicated that MR ameliorated obesity-induced hyperglycaemia and hyperinsulinemia. Moreover, MR up-regulated the gene expression of disulfide-bond A oxidoreductase-like protein and cystathionine-γ-lyase and promoted adiponectin and H2S production in inguinal white adipose tissue. Furthermore, MR activated AMP-activated protein kinase and inhibited its downstream signalling and up-regulated insulin signalling-related molecules in gastrocnemius muscle. Overall, MR improved glucose metabolism via increasing glycogen synthesis, glycolysis, and aerobic oxidation. Interestingly, most parameters were equivalent between the HF + MR group and C* + MR group. These findings suggest that dietary MR can improve glucose metabolism in obese mice.

Dietary methionine restriction ameliorates the impairment of learning and memory function induced by obesity in mice.

Dietary methionine restriction (MR) has been reported to extend lifespan, improve insulin sensitivity, reduce adiposity and inflammation response, and in particular, increase endogenous hydrogen sulfide (H2S) production. H2S is a critical anti-inflammatory molecule in the central nervous system and a gaseous signal molecule that mediates learning and memory function. Hence, the present study aimed to investigate whether MR can ameliorate the impairment of learning and memory function induced by obesity, and to clarify its possible mechanisms. C57BL/6J mice were fed a control diet or a high-fat (HF) diet to induce obesity, and were then fed a control diet (CON group, 4.2% fat, 0.86% methionine), a HF diet (HF group, 24% fat, 0.86% methionine), or an MR diet (MR group, 24% fat, 0.17% methionine) for 16 consecutive weeks. Our results showed that HF-induced obesity impaired learning and memory function, reduced H2S production in the hippocampus, cortex, and plasma, and increased plasma and hippocampal inflammation response in the mice. MR improved the impairment of learning and memory function accompanied by selective modulation of the expression of multiple related genes, reduced plasma and hippocampal inflammatory response, normalized H2S levels in the hippocampus, cortex, and plasma, up-regulated the mRNA and protein expression levels of cystathionine ß-synthase in the hippocampus, and reduced hippocampal homocysteine level. These findings suggest that MR can ameliorate the impairment of learning and memory function, likely by increasing H2S production in the hippocampus.

Analgesic effects of TLR4/NF-κB signaling pathway inhibition on chronic neuropathic pain in rats following chronic constriction injury of the sciatic nerve.

OBJECTIVE: Chronic neuropathic pain (CNP) is attributed to a lesion or disease of the somatosensory system, may be derived from the peripheral and central system. Recent study revealed that spinal cord stimulation attenuated CNP by inhibiting TLR4/NF-κB signaling pathway. The present study focuses on the potential analgesic effects of TLR4/NF-κB signaling pathway on CNP in a rat model of chronic constriction injury (CCI). METHODS: We successfully established the rat model of CCI by Bennett method, and then inhibited the TLR4/NF-κB signaling pathway in rat models. Next, we measured the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) 0D, 2D, 6D, 8D and 12D after operation respectively. MTS510 100 mg/kg, an inhibitor of TLR4, was intrathecal injected into rats after 6D, 8D and 12D after operation. The experiment lasted for 12 days, and then the rats were sacrificed to collect the spinal cord tissues. Protein and mRNA expression levels of toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB), glial cell line-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) were detected by western blot analysis and RT-qPCR, respectively. Immunohistochemistry was performed to detect GDNF, GFAP and NGF expression. RESULTS: With the prolongation of MTS510 treatment time, MWT and TWL were increased and finally, the MWT and TWL were close to the baseline level. The levels of TLR4, NF-κB, GDNF, and GFAP as well as NGF increased in rats treated with CCI + Immunoglobulin G1 (IgG1) or CCI + MTS510, suggesting the model establishment was successful. Besides, with the prolongation of MTS510 treatment time, the protein level and mRNA expression of NF-kB, GDNF, GFAP and NGF decreased in rats treated with CCI + IgG1 or CCI + MTS510. Moreover, the GDNF, GFAP and NGF expression in spinal cord tissue in rats treated with CCI + IgG1 or CCI + MTS510 increased obviously, while the GDNF, GFAP and NGF expression decreased in spinal cord tissue in rats treated with CCI + IgG1 or CCI + MTS510 after MTS510 treatment. CONCLUSIONS: Collectively, this study defines the role of TLR4 and NF-κB, and inhibition of TLR4/NF-κB signaling pathway might contribute to the alleviation of CNP and improvement of MWT and TWL in a rat model of CCI. Additionally, the results obtained from the study provided a promising basis that could aid as an experimental basis for the potential treatment of TLR4/NF-κB signaling pathway.

Propofol postconditioning protects H9c2 cells from hypoxia/reoxygenation injury by inducing autophagy via the SAPK/JNK pathway.

Propofol postconditioning (P­PostC) offers cardioprotection in mice, and the upregulation of autophagy protects cardiac cells against ischemia/reperfusion injury. The present study aimed to examine the effects of P­PostC on the induction of autophagy and its potential roles in hypoxia/reoxygenation (H/R) injury. Rat heart­derived H9c2 cells were exposed to H/R, comprising 6 h of hypoxia followed by 4 h of reoxygenation, as well as postconditioning with various concentrations of propofol at the onset of reperfusion. Lactate dehydrogenase (LDH) activity and the rate of cell apoptosis were measured to evaluate the degree of cardiomyocyte H/R injury. The induction of autophagy in myocytes subjected to H/R injury and P­PostC was detected by western blotting and immunofluorescence. Furthermore, the activation of c­Jun N­terminal kinase (JNK) in cells treated with P­PostC with or without co­treatment with SP600125, an inhibitor of JNK, was also determined by western blotting. P­PostC reduced the activity of LDH in the culture medium and the percentage of apoptotic cells compared with cells in the untreated H/R group. In addition, P­PostC induced autophagy and promoted survival signaling in H9c2 cardiac myoblast cells. The inhibition of autophagy by 3­methyladenine treatment diminished the cardioprotective effects of P­PostC. These results indicated that propofol postconditioning promoted cell survival through the induction of autophagy in H9c2 cardiac cells, and that the stress­activated protein kinase/JNK survival pathway may be partly involved in P­PostC­induced autophagy.

[Effects of pri ming different low-dose rocurium on pharmacodynamics of mivacurium].

OBJECTIVE: To explore the effects of pri ming rocuronium on neuromuscular blockade produced by mivacurium. METHODS: Ethical approval was granted by the medical ethics committee of our hospital with a reference number of C-2013-018-01. A total of 120 ASA physical status I and II patients undergoing selective otorhinolaryngologic surgery under general anesthesia signed the form of informed consent. And they were randomly divided by a random number table into 4 groups. After a standardized imidazole-propofol-fentanyl induction, they received a saline placebo injection (GroupI) and a pri ming dose of rocuronium 0.06 mg/kg (GroupII) , rocuronium 0.075 mg/kg (Group III) and rocuronium 0.1 mg/kg (Group IV). An intubating dose of mivacurium 0.15 mg/kg was offered 3 minutes later. Anesthesia was maintained with propofol and remifentanyl continuous infusion. Neuromuscular block was monitored with train of four (TOF) stimulation. The onset time, reappearance of T1 (DUR TOFc 1), times of T1 25% and 75% recovery, recovery index and times of TOF25%, 75% and 90% recovery were recorded. RESULTS: The onset time of mivacurium was significantly shorter and the times of T1 25% and 75% recovery were significantly longer in groups of II, III and IV than those in groupI. No significant difference existed in recovery index among 4 groups. The onset time of mivacurium became progressively shorter with the growing pri ming dose of rocurium among three experiment groups. And it was not statistically significant. CONCLUSIONS: Pri ming rocuronium decreases the onset and intubating times of mivacurium without effect on recovery index. No significant difference exists in drug effect among 3 experiment groups.

Increased expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain.

In attempt to understand the underlying mechanisms of cancer-induced bone pain, we investigated the presence of two tetrodotoxin-resistant sodium channels, Nav1.8 (SNS/PN3) and Nav1.9 (SNS2/NaN), in dorsal root ganglia (DRG) neurons in an animal model of bone cancer pain. Thirty-six female Sprague-Dawley rats were randomized into three groups: Sham operation group (Sham), cancer-bearing animals killed after 7 days (C7) and cancer-bearing animals killed after 14 days group (C14). After establishment of bone cancer pain model, behavioral tests were carried out to determine the paw withdrawal threshold (PWT) of mechanical and thermal hyperalgesia, respectively. Real-time RT-PCR, Western bolt and Immunofluorescence were used to determine the mRNA and protein expression of Nav1.8 and Nav1.9 in ipsilateral lumbar 4-5 DRG. Compared to Sham group, PWT of mechanical and thermal hyperalgesia in C14 group displayed a significant decrease (P<0.01) from post-operation day (POD) 5 and POD7 to the end point of the observation, respectively. Compared to Sham group, the relative mRNA expression of Nav1.8 and Nav1.9 exhibited a significant up-regulation in C14 group (8.9 times and 9 times, respectively, P<0.01) but not C7 group (1.5 times and 2.4 times, respectively). Western blot and Immunofluorescence revealed an apparent increase of Nav1.8 (P<0.05) and Nav1.9 (P<0.05) protein in C14 group compared with Sham group. The up-regulation of mRNA and protein levels of Nav1.8 and Nav1.9 suggested their potential involvement in the development and maintenance of bone cancer pain.

[Studies of potassium channel in pulmonary artery smooth muscle cells derived from renal hypertensive rat].

AIM: To investigate the differences of membrane capacitance, membrane current, current density and I-V curves between smooth muscle cells isolated from RHR and NTR pulmonary arteries. METHODS: Under antiseptic conditions, the left renal artery was exposed through a retroperitoneal flank incision and carefully dissected free of the left renal vein. A silver clip with an internal diameter of 0.2-0.3 mm was placed around the left renal artery, resulting in partial occlusion of renal perfusion. SBP was observed by tail blood pressure. Whole cell recordings were made from smooth muscle cells freshly isolated from pulmonary arteries derived from RHR or NTR. RESULTS: The average membrane capacitance was (3.43 +/- 1.16) pF, decreased by 31.1%; membrane current was (0.54 +/- 0.26) nA, decreased by 68.2%; current density was (180 +/- 90) pA/pF, decreased by 48.6%; membrane potential was (-26.96 +/- 7.23) mV, decreased by 2.5%, all compared with that of NTR respectively. Iptakalim hydrochloride at the concentration of 0.1-100 micromol/L can significantly increased NTR potassium currents. Iptakalim hydrochloride 1-100 micromol/L can significantly increased RHR potassium currents. CONCLUSION: Membrane capacitance, membrane current, membrane potential were decreased, I-V curves were shift downward, compared with that of NTR. Iptakalim hydrochloride might significantly increase NTR and RHR potassium currents.