The GR-FKBP51 interaction modulates fear memory but not spatial or recognition memory.

The glucocorticoid receptor (GR) forms a protein complex with FKBP51 that is increased in post-traumatic stress disorder (PTSD) and by fear conditioned learning. Disrupting the GR-FKBP51 complex with a synthetic peptide can block the storage or retrieval of fear conditioned memories, which could be a novel approach to the alleviate fear associated memory in PTSD. However, a potential unacceptable side effect could be the impairment of other types of memory.

ROCK2 promotes ryanodine receptor phosphorylation and arrhythmic calcium release in diabetic cardiomyocytes.

Background: Diabetes is associated with an increased risk of heart failure, cardiac arrhythmias and sudden cardiac death. We previously showed that ROCK2 expression is elevated in diabetic rat hearts, and that ROCK inhibition acutely improves their contractile function. In the present study we investigated whether inhibition of ROCK or partial deletion of ROCK2 improves impaired Ca handling in the diabetic heart.

Quantitative proteomics reveals mitochondrial respiratory chain as a dominant target for carbon ion radiation: Delayed reactive oxygen species generation caused DNA damage.

Heavy ion radiotherapy has shown great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required to explore measures of overcoming devastating side effects. Here, we performed a quantitative proteomic analysis to investigate the mechanism of carbon ion irradiation on human AHH-1 lymphoblastoid cells.

Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine-dependent epilepsy using CRISPR-Cas9 technology.

Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features.

Melatonin Receptor Agonist Piromelatine Ameliorates Impaired Glucose Metabolism in Chronically Stressed Rats Fed a High-Fat Diet.

Modern lifestyle factors (high-caloric food rich in fat) and daily chronic stress are important risk factors for metabolic disturbances. Increased hypothalamic-pituitary-adrenal (HPA) axis activity and the subsequent excess production of glucocorticoids (GCs) in response to chronic stress (CS) leads to increases in metabolic complications, such as type 2 diabetes and insulin resistance (IR). Melatonin (MLT), which protects several regulatory components of the HPA axis from GC-induced deterioration, might improve glucose homeostasis.

Neu-P11, a novel MT1/MT2 agonist, reverses diabetes by suppressing the hypothalamic-pituitary-adrenal axis in rats.

Excessive glucocorticoid (GC) in type 2 diabetes mellitus (T2DM) reduces insulin sensitivity, impairs β-cell function, increases gluconeogenesis and glycogenolysis, impairs glucose uptake and metabolism, and reduces the insulinotropic effects of glucagon-like peptide 1. Melatonin, which serves as a physiological regulator of the hypothalamic-pituitary-adrenal (HPA) axis, has been suggested to have anti-diabetic effects. The objective of the present study was to investigate the effect of the MT1/MT2 melatonin agonist Neu-P11 on glucose and lipid metabolism in T2DM rats induced by a high fat diet combined with low doses of streptozotocin.

[Effect of hypoxia on expressions of MDR1 and MRP2 in rats].

Objective: To study the changes in the physiological parameters and gene expression of two drug efflux transporters MDR1 and MRP2 in the small intestine, liver and kidney of rats exposed to acute hypoxia.

Methods: Eighteen Wistar rats were randomly divided into control group, hypoxia for 24 h group and hypoxia for 72 h group. Blood samples were obtained from the abdominal aorta of the rats after the exposure for analyzing the physiological indexes.

[Changes of P-gp expression in rats’ small intestine and effects on uptake of levofloxacin after acute exposure to hypoxia].

The drug transporter play a key role in the absorption of drugs. Investigation of the changes of drug transporters in response to hypoxia will provide insight into the mechanism of drug absorption. In this study we investigated the mRNA and protein expression of the transporter P-gp after acute hypoxia, and evaluated the effects of P-gp changes on absorption of levofloxacin in the intestine.

[Effects and HPA Axis Related Mechanism of Kaixin-San and Danggui-Shaoyao-San on Glucose and Lipid Metabolism in Chronic Stress Rats with High-fat Diet].

Objective: To study the effects and potential mechanism of Kaixin-San and Danggui-Shaoyao-San on glucose and lipid metabolism in chronic stress rats fed with high-fat diet.

Methods: 50 male Wistar rats were randomly divided into normal control group (distilled water), high-fat diet with chronic stress group (distilled water), melatonin group(20 mg/kg), Kaixin-San group (445 mg/kg) and Danggui-Shaoyao-San group (3360 mg/kg). All drugs were orally administered.

[Expression of plateau adaptation gene of rat tissues after plain acute exposure to high altitude].

Objective: To detect the expression of the plateau adaptablity gene(EPAS1, EGLN1 and PPARα) and proteins(HIF-2, PHD2 and PPARα) in rats blood, heart, liver, lung and kidney tissue after the rats exposed to high altitude.

Methods: The Wistar rats were randomly divided into plain group(Shanghai, 55 m), acute exposure to high altitude 3400 m group, acute exposure to high altitude 4300 m group. Blood and organs of rats were collected in 1, 3, 5 days after arrival.

Light exposure before learning improves memory consolidation at night.

Light is recently recognized as a modulator able to activate the hippocampus and modulate memory processing, but little is known about the molecular mechanisms. Here, we report that in mice, a short pulse of white light before learning dramatically improves consolidation of contextual fear memory during the night. The light exposure increases hippocampal active p21-activated kinase 1 (PAK1) and CA1 long-term potentiation (LTP).

Effects of High Altitude Exposure on Physiology and Pharmacokinetics.

Background: High-altitude environments are known to result in a broad range of physiological changes in human body, which may influence various pharmacological processes and pharmacokinetics. A series of physiological systems reacting to a high-altitude stressor and the effects of these physiological alterations on pharmacokinetics have been investigated for decades.

Methods: In this review, we summarized the effects of high altitude on human physiological alterations (including those in the gastrointestinal system, cardiovascular system, pulmonary system, hematocrit, drug metabolism enzyme system, and renal excretory system), as well as subsequent changes of pharmacokinetics (such as absorption, distribution, metabolism, and excretion of drugs).

[Chemical Constituents with Anti-hypoxia Activity from Saussurea involucrata].

Objective: To investigate the chemical constituents with anti-hypoxia activity from Saussurea involucrata.

Methods: The chemical constituents, isolated and purified by column chromatography from Saussurea involucrata, were identified by several spectroscopic methods. The anti-hypoxic activities of these compounds were examined using the normobaric hypoxic model of mice.

In search for better pharmacological prophylaxis for acute mountain sickness: looking in other directions.

Despite decades of research, the exact pathogenic mechanisms underlying acute mountain sickness (AMS) are still poorly understood. This fact frustrates the search for novel pharmacological prophylaxis for AMS. The prevailing view is that AMS results from an insufficient physiological response to hypoxia and that prophylaxis should aim at stimulating the response.

Protective effect of apigenin on ischemia/reperfusion injury of the isolated rat heart.

Apigenin (Api), a mainly bioactive component of Apium graveolens L. var. dulce DC.

[Detection of plasma and urine furosemide based on online enrichment and restricted- access media coupled with high-performance liquid chromatography].

Objective: To establish a method based on restricted access media-high performance liquid chromatography for direct online sample injection and detection of plasma and urine furosemide in rats.

Methods: The column of restricted access media was used as the pre-treatment column and a C18 column as the analytical column. The mobile phase of the pre- treatment column was water-methanol (95:5, V/V) with a volume percentage of formic acid of 0.

[Protective effect and action mechanism of petroleum ether extracts from Saussurea involucrate on brain tissues of hypoxia rats].

Objective: To investigate the protective effect and action mechanism of petroleum ether extracts from Saussurea involucrate on brain tissues of hypoxia rats under constant pressure and closed conditions.

Method: The PESI dosage-dependent experiment for hypoxia rats was conducted under constant pressure and closed conditions by intraperitoneally injecting 125, 250, 500 mg x kg(-1) to finalize that the optimum dosage is the high dose of PESI. Afterwards, 90 Wistar rats were randomly divided into the hypoxic model group, the acetazolamide 250 mg x kg(-1) group and the PESI high dose group.

[Isolation and identification of nine iridoid glycosides from Lamiophlomis rotata by HPLC combining PDA and MS].

Objective: To establish a rapid chromatographic method to separate the iridoid glycosides from Lamioplomis rotata, and to identify the target compounds with PDA and MS.

Methods: Methanol-water gradient elution was used to separate and analyze the target compounds. The fluid fractions were gathered according to the chromatogram and dried with the nitrogen airflow.

[Effect of ethanol extract from Saussurea involucrata on biochemical indicators of simulated high-altitude hypoxia induced mice].

Objective: To estimate the effect of ethanol extract from Saussurea involucrata (EES) on biochemical indicators of simulated high-altitude hypoxia induced mice and its mechanism.

Methods: The oxidative stress indicator( MDA content, SOD activity) and metabolism parameters (LD content, LDH activity, ATP content, Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity) in both brain and heart of the simulated high-altitude hypoxia induced mice were detected.

Results: Compared with the model group, the ESS group could significantly increase the activity of SOD and LDH and decrease the content of MDA and LD in both brain and heart, the content of ATP and the activity of Na+ -K -ATPase and Ca2+ -Mg2+ -ATPase were also elevated.