Serum lncRNA LOXL1-AS1 is a diagnostic and prognostic marker for epithelial ovarian cancer.

BACKGROUND: The present study aimed to examine the levels of circulating LOXL1-AS1 in epithelial ovarian cancer (EOC) patients and to analyze its diagnostic and prognostic value. METHODS: The levels of LOXL1-AS1 in 185 EOC patients and 43 healthy volunteers were evaluated by a quantitative reverse transcriptase-polymerase chain reaction. The potential of LOXL1-AS1 as a biomarker for EOC diagnosis was determined by receiver-operating characteristic (ROC) curve assays. The associations between clinicopathological parameters and LOXL1-AS1 expression were analyzed using a chi-squared test. The influence of LOXL1-AS1 on overall survival was analyzed by the use of Kaplan-Meier. A Cox proportional hazards assays were conducted for the determination of the prognostic value of LOXL1-AS1. RESULTS: The expression of LOXL1-AS1 was dramatically higher in EOC patients compared to healthy controls (p < 0.01). LOXL1-AS1 yielded an area under the ROC curve of 0.843 with 65.3% sensitivity and 68.2% specificity in discriminating high-grade EOC from healthy controls. It was also shown that LOXL1-AS1 expression was associated with advanced FIGO stage (p = 0.004) and positively distant metastasis (p = 0.013). Kaplan-Meier assays revealed that patients with high LOXL1-AS1 expression had a shorter overall survival than those with low expression (p = 0.0006). By performing multivariate assays, LOXL1-AS1 was confirmed to be an independent prognostic factor for predicting the prognosis of EOC patients. CONCLUSIONS: We provide evidence indicating that LOXL1-AS1 expression is correlated with a poor clinical outcome in EOC patients and may act as an independent prognostic indicator, as well as a new diagnostic biomarker.

Mechanism and effects of fructose diphosphate on anti-hypoxia fatigue and learning memory ability.

This study aims to investigate the mechanisms through which fructose diphosphate (FDP) causes anti-hypoxia and anti-fatigue effects and improves learning and memory. Mice were divided into three groups: low-dose FDP (FDP-L), high-dose FDP (FDP-H), and a control group. Acute toxic hypoxia induced by carbon monoxide, sodium nitrite, and potassium cyanide and acute cerebral ischemic hypoxia were used to investigate the anti-hypoxia ability of FDP. The tests of rod-rotating, mouse tail suspension, and swimming endurance were used to explore the anti-fatigue effects of FDP. The Morris water maze experiment was used to determine the impact of FDP on learning and memory ability. Poisoning-induced hypoxic tests showed that mouse survival time was significantly prolonged in the FDP-L and FDP-H groups compared with the control group (p < 0.05). In the exhaustive swimming test, FDP significantly shortened struggling time and prolonged the time of mass-loaded swimming; the rod-rotating test showed that endurance time was significantly prolonged by using FDP (p < 0.05). FDP significantly decreased lactate and urea nitrogen levels and increased hepatic and muscle glycogen and glucose transporter-4 and Na+-K+-ATPase (p < 0.05). To conclude, FDP enhances hypoxia tolerance and fatigue resistance and improves learning and memory ability through regulating glucose and energy metabolism.

Educational Video Followed by Retelling Bowel Preparation Process to Improve Colonoscopy Bowel Preparation Quality: A Prospective Nursing Intervention Study.

BACKGROUND This study investigated the effect of a patient education video followed by retelling the process of bowel preparation on colonoscopy bowel preparation quality. MATERIAL AND METHODS This was a prospective, randomized, controlled clinical trial of outpatients undergoing colonoscopy. Patients were randomized (1: 1) to the video + retelling group or the control group. The primary endpoint was to assess the bowel preparation quality using the Ottawa Bowel Preparation Quality scale (Ottawa score). Risk factors associated with poor bowel preparation were also evaluated. RESULTS The video + retelling group had a higher percentage of patients with adequate colonoscopy bowel preparation (Ottawa score <6) than the control group (P<0.001). Mean Ottawa total scores significantly differed between the control group and the video + retelling group (4.18±1.4 vs. 3.05±1.3, P<0.001). The video + retelling group showed superior cleanliness in the right, middle, and recto-sigmoid colon segments (all Ps <0.001). Logistic regression analysis revealed that male gender (OR=2.10, 95%CI: 1.098-4.018, P=0.025), diabetes mellitus (OR=2.830, 95%CI: 1.257-6.372, P=0.012), and no educational video followed by retelling bowel preparation process (OR=3.02, 95%CI: 1.731-5.270, P<0.001) were independently associated with poor bowel preparation. CONCLUSIONS Use of an educational video followed by asking patients to retell the process of bowel preparation after receiving regular instructions is a convenient and risk-free practice that enhances the compliance with bowel preparation guidance and improves bowel preparation quality.

Sandwich-Type Polyoxotungstate Consisting of Two Different Trilacunary Keggin-Type Units.

A unique mixed W/Sb/Mn/Ag sandwich-type metal-O cluster was isolated, in which the six-membered {Ag4O3[Mn(OH2)]2}2+ cationic belt is sandwiched between two different anionic slices: the trilacunary B-ß-[SbW9O33]9- and the central-atom-lost A-α-{[Mn(OH2)]2W7O32}18-.

Urocortin attenuates myocardial fibrosis in diabetic rats via the Akt/GSK-3ß signaling pathway.

OBJECTIVE: Urocortin, a novel identified corticotropin-releasing factor-related endocrinal peptide, has been shown to play an essential role in cardioprotection. Until recently, whether urocortin can protect the heart against diabetic cardiomyopathy (DCM) remained unclear. Herein, we evaluated the cardioprotective effect of urocortin on cardiac dysfunction, inflammation, and fibrosis and demonstrated the potential mechanism in a diabetic rat model. METHODS: Diabetic rats were randomly divided into 4 groups: diabetic control group, urocortin, urocortin + astressin (a selective CRF receptor 2 antagonist) and urocortin + triciribine (an Akt pathway blocker). Cardiac catheterization was performed to evaluate cardiac function. The levels of creatine phosphokinase isoenzyme (CK-MB), plasma brain natriuretic peptide (BNP), myocardial collagen volume fraction (CVF) and left ventricular mass index (LVWI) were measured. Inflammatory factors (transforming growth factor beta 1, TGF-ß1; connective tissue growth factor, CTGF) and activation of signaling proteins (Akt, GSK-3ß) were also detected using western blot. RESULTS: DCM was successfully induced by the injection of streptozotocin (STZ) as evidenced by abnormal heart mass and cardiac function as well as the imbalance of extracellular matrix homeostasis. Rats in the DCM group showed increased mRNA and protein levels of LVWI, BNP, CK-MB, CVF, TGF-ß1 and CTGF compared to the control group, which were accompanied with diminished phosphorylation of Akt and GSK-3ß. Interestingly, myocardial dysfunction, cardiac fibrosis, and inflammation were suppressed by urocortin in the heart of diabetic rats. Moreover, inhibition of phosphorylation of Akt and GSK-3ß was also reversed by urocortin. These effects of urocortin were suppressed by astressin. In addition, triciribine partially reduced the effects of urocortin on myocardial dysfunction, inflammation, and cardiac fibrosis. CONCLUSIONS: These results suggest that urocortin exhibits a therapeutic benefit in the treatment of DCM by attenuating fibrosis and inflammation. Furthermore, inhibition of the Akt/GSK-3ß signaling pathway may be partially responsible for these effects.

Comparison between continuing midwifery care and standard maternity care in vaginal birth after cesarean.

OBJECTIVE: To determine whether continuing midwifery care has more benefits than standard maternity care in vaginal birth after cesarean (VBAC). METHODS: This study was conducted on women in labour who had history of previous cesarean section and received vaginal birth in obstetrical department of our hospital from May 2013 to November 2014. The included patients were divided randomly into observation group and control group. The women in labour allocated to the observation group received continuing midwifery care, and those to control group received standard maternity care in all the stages of labour. The duration of labor stage together with the rate of fetal distress, neonatal asphyxia, vaginal birth and postpartum bleeding were compared between the two groups. RESULTS: Ninety-six participants were included in the current study, forty-eight in each group. The length of labor was significantly longer (p<0.05), the vaginal birth rate was significantly lower (p<0.05) and the postpartum hemorrhage rate was significantly higher (p<0.05) in the control group than the observation group. In addition, the rate of fetal distress and neonatal asphyxia were higher in the control group, but there was no significant difference between the two groups (p>0.05). CONCLUSION: The continuing midwifery care has more benefits than the standard maternity care in vaginal birth after cesarean (VBAC).

pH-Dependent nanostructure based on isoquinoline-cyclodextrin conjugate for thrombosis therapy.

The modification of 3S-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQA) with ß-cyclodextrin (ß-CD) provides an oral antithrombotic agent, 6-(3'S-isoquinoline-3'-carboxylaminoethylamino)-6-deoxy-ß-CD (THIQA-ß-CD). In aqueous solution THIQA-ß-CD undergoes intermolecular inclusion complexation and forms pH-dependent nanostructures. The morphological feature of THIQA-ß-CD is a nanocloud consisting of numerous particles that are 5 nm-6 nm in diameter at pH 3.0. The nanocloud switches to a nanorod ranging from 100 nm to 385 nm in length at pH 7.2, then to nanowires of 50 nm to 530 nm in length at pH 10.1. THIQA-ß-CD, which has unusual nanostructures, offers enhanced stability in blood. Inhibition of thrombin-induced platelet aggregation in vitro and demonstrated antithrombotic efficacy in vivo. This investigation demonstrated that the modification of THIQA with ß-CD is a promising approach for clinical therapy of thrombus disease. The pH-dependent nanostructures of conjugate provide the desired in vivo antithrombotic activity and in vitro stability in blood. FROM THE CLINICAL EDITOR: This study a demonstrates that the modification of 3S-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQA) with beta-cyclodextrin, which leads to pH dependent nanostructure formation, is a promising approach for clinical therapy of thrombotic disease.

The function of calcineurin and ERK1/2 signal in the antihypertrophic effects of kappa-opioid receptor stimulation on myocardial hypertrophy induced by isoprenaline.

The aim of the present study, performed in an in vitro model of cardiac hypertrophy, was to examine the possible function of calcineurin and ERK1/2 in the inhibitory effects of kappa-opioid receptor stimulation on Ca2+ transients and myocardial hypertrophy induced by beta1-adrenoceptor stimulation. We determined the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamid methanesulfonate salt (U50,488H), a selective kappa-opioid receptor agonist, on the enhancement of spontaneous Ca2+ transients and the induction of hypertrophy by isoprenaline, a beta-adrenoceptor agonist, in cultured neonatal ventricular myocytes. Total protein content, [3H]leucine incorporation and cell size were used as indices of hypertrophy; calcineurin activity and phospho-ERK1/2 level were determined by immunoblotting. Isoprenaline (10 micromol x L(-1)) increased all the three indices of hypertrophy, Ca2+ transients, calcineurin activity and the level of phospho-ERK1/2. The effects of isoprenaline were abolished by 1 micromol x L(-1) U50,488H in the absence but not in the presence of nor-binaltorphimine, a kappa-opioid receptor antagonist. The inhibitory effects of U50,488H were reproduced by cyclosporine-A, an inhibitor of calcineurin, U0126, the inhibitor of ERK1/2 and verapamil, a L-type Ca2+ channel antagonist. In addition, suppression of calcineurin activity by cyclosporine-A was associated with modest suppression of ERK1/2 phosphorylation. Meanwhile, suppression of ERK1/2 phosphorylation by U0126 was associated with modest suppression of calcineurin activity. In conclusion, the inhibitory effects of kappa-opioid receptor stimulation involved calcineurin and ERK1/2, and the two signaling pathways showed interaction in the mechanism of antihypertrophic effects afforded by kappa-opioid receptor stimulation.

Anwulignan alleviates d-galactose induced renal damage by regulating Nrf2/ARE signaling pathway in mice.

Free radical accumulation in the body will cause oxidative stress damages including the renal damage. Schisandrae Sphenantherae Fructus (Schisandra), a traditional Chinese herbal medicine, has been used throughout the world. Anwulignan, a monomer extracted from Schisandra, has been shown in our previous studies to possess antioxidant and protective effects on the liver, brain and spleen damages in the aging mice. However, its effect on the renal damage caused by aging is not clear. This study showed that anwulignan could significantly increase the kidney index, the creatinine clearance, the activities of superoxide dismutase, catalase and glutathione peroxidase; reduce the urinary protein concentration, the serum urea nitrogen and creatinine content, the content of malondialdehyde and 8-hydroxylated deoxyguanosine in the renal tissue; and improve the renal tissue damage. Moreover, anwulignan increased the production of Nrf2, HO-1 and NQO1 proteins and decreased the production level of Keap1 protein in the renal tissue in the d-galactose induced aging mice. These results suggest that anwulignan significantly alleviates the renal damage by its antioxidant effect through regulating the production of Nrf2/ARE pathway-related proteins in the renal tissue in the d-galactose induced aging mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00951-7.

3DPhenoFish: Application for two- and three-dimensional fish morphological phenotype extraction from point cloud analysis.

Fish morphological phenotypes are important resources in artificial breeding, functional gene mapping, and population-based studies in aquaculture and ecology. Traditional morphological measurement of phenotypes is rather expensive in terms of time and labor. More importantly, manual measurement is highly dependent on operational experience, which can lead to subjective phenotyping results. Here, we developed 3DPhenoFish software to extract fish morphological phenotypes from three-dimensional (3D) point cloud data. Algorithms for background elimination, coordinate normalization, image segmentation, key point recognition, and phenotype extraction were developed and integrated into an intuitive user interface. Furthermore, 18 key points and traditional 2D morphological traits, along with 3D phenotypes, including area and volume, can be automatically obtained in a visualized manner. Intuitive fine-tuning of key points and customized definitions of phenotypes are also allowed in the software. Using 3DPhenoFish, we performed high-throughput phenotyping for four endemic Schizothoracinae species, including Schizopygopsis younghusbandi, Oxygymnocypris stewartii, Ptychobarbus dipogon, and Schizothorax oconnori. Results indicated that the morphological phenotypes from 3DPhenoFish exhibited high linear correlation (>0.94) with manual measurements and offered informative traits to discriminate samples of different species and even for different populations of the same species. In summary, we developed an efficient, accurate, and customizable tool, 3DPhenoFish, to extract morphological phenotypes from point cloud data, which should help overcome traditional challenges in manual measurements. 3DPhenoFish can be used for research on morphological phenotypes in fish, including functional gene mapping, artificial selection, and conservation studies. 3DPhenoFish is an open-source software and can be downloaded for free at https://github.com/lyh24k/3DPhenoFish/tree/master.

25-OH-PPD inhibits hypertrophy on diabetic cardiomyopathy via the PI3k/Akt/GSK-3ß signaling pathway.

The present study investigated the inhibitory effects and the associated mechanism of the compound 25-OH-PPD (PPD) on cardiac hypertrophy, fibrosis and inflammation. The signaling pathways associated with diabetic mellitus cardiomyopathy (DMCM) were investigated using a rat model. DMCM Sprague-Dawley rats were induced by injection of streptozotocin. The animals were divided into 5 groups as follows: Normal group (NG group), diabetic group, PPD treatment group, PPD/LY294002 group (inhibitor of PI3K/Akt) and PPD/LiCl group [inhibitor of glycogen synthase kinase (GSK) 3ß]. The studies were carried out during the 12 weeks following induction of diabetes and the levels of plasma brain natriuretic peptide (BNP), creatine phosphokinase isoenzyme (CK-MB) were measured. In addition, the volume of myocardial collagen fraction (CVF) was tested. The expression levels of the inflammatory cytokines, including transforming growth factor beta 1 (TGF-ß1), connective tissue growth factor (CTGF), cell adhesion molecules α-smooth muscle actin (α-SMA) and vascular adhesion molecule 1 (VCAM-1) and associated signaling proteins (Akt, GSK-3ß) were measured by biochemical analyses. The levels of BNP and CK-MB, the volume of CVF, the expression levels of TGF-ß1, CTGF, α-SMA and VCAM-1 in the diabetic group were higher compared with those of the normal control group (P<0.05). Conversely, the levels of these molecules were significantly decreased in the PPD treatment groups (P<0.05). The aforementioned effects were partially eliminated in the PPD/LY294002 and PPD/LiCl groups. In addition, PPD treatment significantly increased the expression levels of p-Akt and decreased the levels of phosphorylated GSK-3ß compared with those of the DMCM group (P<0.05). The data demonstrated that the protective effects of 25-OH-PPD against DMCM may be attributed to the PI3k/Akt/GSK-3ß signaling pathway, via the suppression of the α-SMA/VCAM axis and the downregulation of TGF-ß1 and CTGF expression.

lncRNA RHPN1-AS1 Promotes Ovarian Cancer Growth and Invasiveness Through Inhibiting miR-1299.

BACKGROUND: Ovarian cancer (OC) is a big threat for public health. However, the molecular mechanism underlying OC development and progression remains unclear. Although the importance of lncRNA in cancer has been proven, how lncRNA is involved in OC is waiting for further investigation. MATERIALS AND METHODS: qRT-PCR was performed to test expression level. CCK8 and colony formation were conducted to analyze proliferation. Transwell was conducted to measure migration and invasion. Luciferase reporter assay and pulldown assay were utilized to validate RNA interaction. RESULTS: lncRNA RHPN1-AS1 was highly expressed in OC tissues. RHPN1-AS1 was positively correlated with OC progression and its high expression indicated a low survival rate. Moreover, knockdown of RHPN1-AS1 significantly inhibited the proliferation, migration and invasion of OC cells, and bioinformatics analysis identified that miR-1299 was sponged by RHPN1-AS1 in OC cells. Knockdown of RHPN1-AS1 markedly promoted miR-1299 expression. Of note, inhibition of miR-1299 reversed the roles of RHPN1-AS1 silencing on suppressing proliferation, migration and invasion. CONCLUSION: Our study demonstrates that RHPN1-AS1 promotes OC progression via sponging miR-1299, suggesting RHPN1-AS1 may be a novel therapeutic target.

Protein kinase C mediates the effects of delta-opioid receptor stimulation on survival and apoptosis in neonatal cardiomyocytes cultured in serum-deprived condition.

The aims of the present study were to determine whether Delta opioid receptor (delta-OR) stimulation improved the survival of cardiomyocytes cultured in serum-deprived conditions, which impaired their growth. [D-Ala2, D-Leu5]-enkephalin (DADLE), a selective delta-OR agonist, at a concentration range of 0.1 micromol/L to 10 micromol/L for 48 h increased the viability of the cardiomyocyte under serum deprivation conditions. DADLE (0.1 micromol/L) also decreased the early cell apoptosis rate and the expression of Caspase-3. The effects of 0.1 micromol/L DADLE were abolished by 10 micromol x L(-1) naltrindole, a selective delta-OR antagonist, or by blockade of protein kinase C (PKC) with its blockers, 10 micromol x L(-1) GF109203X or 1 micromol/L staurosporine. Furthermore, 0.1 micromol x L(-1) DADLE increased the expression of PKC, an effect abrogated by 10 micromol x L(-1) naltrindole. The observations indicate that delta-OR stimulation improves the viability and reduces the apoptosis via PKC pathway in neonatal cardiomyocytes cultured in serum deprived conditions.

kappa-Opioid receptor stimulation inhibits augmentation of Ca(2+) transient and hypertrophy induced by isoprenaline in neonatal rat ventricular myocytes - Role of CaMKIIdelta(B).

We aimed to further define the pathway mediating the inhibitory effects of kappa-opioid receptor stimulation on Ca(2+) transients and hypertrophic responses to beta(1)-adrenoceptor stimulation. We determined the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamid methanesulfonate salt (U50,488H), a selective kappa-opioid receptor agonist, on the enhancement of spontaneous Ca(2+) transients and the induction of hypertrophy by isoprenaline, a beta-adrenoceptor agonist, in cultured neonatal ventricular myocytes. The results were compared with those found with KN93, a selective Ca(2+)/calmodulin-dependent kinase (CaMKII) inhibitor, propranolol, a beta-adrenoceptor antagonist, and verapamil, a L-type Ca(2+) channel antagonist. Hypertrophy of cardiomyocytes was characterized by increases in (i) total protein content; (ii) cell size; and (iii) [(3)H]leucine incorporation. 10 micromol/l isoprenaline increased all three parameters. We also determined the expression of nuclear CaMKIIdelta in response to U50,488H in the presence or absence of isoprenaline. To determine whether the effects of U50,488H were receptor-mediated, its effects were also measured following blockade of the kappa-opioid receptor with nor-binaltorphimine. kappa-Opioid receptor stimulation suppressed the stimulatory effect of isoprenaline on Ca(2+) transients and cardiac hypertrophy, as did KN93, propranalol and verapamil. U50,488H also suppressed the expression of nuclear CaMKIIdelta(B) in the presence, but not in the absence of isoprenaline. These results suggest that the inhibitory effect of kappa-opioid receptor stimulation on beta(1)-adrenoceptor stimulation may also involve CaMKIIdelta.

Inhibitory effects and mechanism of 25-OH-PPD on glomerular mesangial cell proliferation induced by high glucose.

OBJECTIVE: To investigate the protective effects and potential mechanism of the compound 25-OH-PPD (PPD) on the glomerular mesangial cells (GMC) under high glucose condition. METHODS: The hypertrophic GMC cells were established by DMEM containing glucose and randomly divided into five groups, including the normal control group (Control), the high glucose model group (HG, 25 mmolL(-1)), the PPD low dose group (1µmolL(-1), PPD-L), the PPD middle dose group (5µmolL(-1), PPD -M) and the PPD high dose group (10µmolL(-1), UCN-H). The GMC were incubated for 48h under different treatment factors. Total protein content was determined by Lowry method. The diameter of the single GMC and volume were measured by computer photograph analysis system. The GMC cell viability was analyzed by MTT assay. The level of malondialdehyde (MDA), the content of glutathione (GSH) and superoxide dismutase (SOD) activity were measured by ELISA. [Ca(2+)]і transient was measured by Till image system and by cell-loading Fura-2/AM. The expression of COX-1 and COX-2 were also determined using ELISA method. RESULTS: The viability of GMC and the total protein content were decreased in HG group, different dosage PPD group could increase these indexes (P<0.05). The level of MDA was increased, the content of GSH and SOD was decreased in HG group, while PPD could reduce the MDA and enhance GSH and SOD (P<0.05). Following treatment with different dosage (PPD-L, PPD-M or PPD-H), the [Ca(2+)]і transient was reduced (P<0.05 or P<0.01). Moreover, the expression of COX-1 was decreased while COX-2 expression was increased in different dosage PPD groups. CONCLUSION: The protective effects of PPD on GMC from HG-induced hypertrophy may be associated with the inhibition of [Ca(2+)]і transient and decreasing expression of COX-1 via the oxidative-stress injure pathway.

Protective effects of BAY 73-6691, a selective inhibitor of phosphodiesterase 9, on amyloid-ß peptides-induced oxidative stress in in-vivo and in-vitro models of Alzheimer's disease.

Alzheimer's disease (AD) is accompanied by enhanced oxidative stress and excess free radicals. Phosphodiesterase 9 inhibitors (PDE-9Is) showed memory improving effects in many pharmacological deficit models. However, whether BAY 73-6691 (a selective PDE-9I) may attenuate the oxidative stress during the development of AD is still unclear. For this purpose, primary cultures of SH-SY5Y cells were incubated with 20µM beta-amyloid25-35 (Aß25-35), followed by exposure to different concentrations (50, 100, 150 and 200µg/ml) of BAY 73-6691. Furthermore, the antioxidant effect of BAY 73-6691 was evaluated in mice subjected to intracerebroventricular injection of Aß25-35 (day 0) and treatment with BAY 73-6691 by intraperitoneal injection once daily (days 1-10). Our results elucidated that treatment with BAY 73-6691 attenuated the Aß25-35-induced cytotoxicity and oxidative stress in SH-SY5Y cells. In vivo, BAY 73-6691 protected Aß25-35-induced oxidative damage in hippocampus, associated with the attenuation of impairments in hippocampal neurons. Administration of BAY 73-6691 improved learning and memory in the Morris water maze test, and restored several hippocampal memory-associated proteins. Our study identified a neuroprotective role for BAY 73-6691 against Aß25-35-induced oxidative stress in vivo and in vitro, harboring therapeutic potential for the treatment of AD by alleviating the impairments in spatial memory and hippocampal neurons.

Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3ß signaling pathway.

Urocortin has been shown to exert powerful protective effects on various cardiovascular disease models. However, the role and mechanism of urocortin in protecting against diabetic cardiomyopathy (DCM) has not yet been elucidated. In the present study, the effects of urocortin on cardiac dysfunction, fibrosis, inflammation and the interrelated signaling pathways were investigated in a diabetic rat model. Diabetes mellitus (DM) was induced in the rats by intraperitoneal injection of streptozotocin. The diabetic rats were randomly divided into four groups: Diabetic control, urocortin, urocortin + astressin treatment and urocortin + triciribine treatment groups. All the experiments were conducted at 16 weeks following the induction of DM. The levels of glycosylated hemoglobin (HbA1c), creatine phosphokinase isoenzyme (CK-MB) and plasma brain natriuretic peptide (BNP), as well as the myocardial collagen volume fraction (CVF) and left ventricular mass index (LVWI), were measured. In addition, levels of inflammatory factors, including transforming growth factor (TGF)-ß1, connective tissue growth factor (CTGF) and interrelated proteins, such as Akt and glycogen synthase kinase (GSK)-3ß, were detected by biochemical analyses. In the diabetic group, the levels of BNP and CK-MB, as well as the mRNA and protein expression levels of TGF-ß1 and CTGF, and the LVWI and CVF, were higher compared with the rats in the control group (P<0.05). This was accompanied by decreased Akt and GSK-3ß phosphorylation (P<0.05). Notably, urocortin attenuated myocardial dysfunction, cardiac fibrosis and inflammation in the hearts of the diabetic rats. However, urocortin exhibited no effect on the level of HbA1c. In addition, the inhibited phosphorylation of Akt and GSK-3ß was restored with urocortin administration. However, all the effects of urocortin were eliminated with treatment of the corticotropin releasing factor receptor 2 antagonist, astressin. Triciribine, an Akt inhibitor, partially eliminated the effects of urocortin on myocardial dysfunction, inflammation and cardiac fibrosis in the hearts of the diabetic rats. These results indicated that urocortin may exhibit great therapeutic potential in the treatment of DCM by attenuating fibrosis and inflammation. Furthermore, the Akt/GSK-3ß signaling pathway may be partially involved in mediating these effects.

The effects of vasoactive peptide urocortin 2 on hemodynamics in spontaneous hypertensive rat and the role of L-type calcium channel and CRFR2.

BACKGROUND: Urocortin (UCN) is a newly identified vascular-active peptide that has been shown to reverse cardiovascular remodeling and improve left ventricular (LV) function. The effects and mechanism of urocortin 2 (UCN2) in vivo on the electrical remodeling of left ventricle and the hemodynamics of hypertensive objectives have not been investigated. METHODS: UCN2 (1 µg/kg/d, 3.5 µg/kg/d or 7 µg/kg/d) was intravenously injected for 2 weeks and its effects on hemodynamics in spontaneously hypertensive rats (SHRs) observed. The whole-cell patch clamp technique was used to explore the effects of UCN2 on the electrical remodeling of left ventricular cardiomyocytes. The flow cytometry method was used to determine the content of fluorescence calcium in myocardium. RESULTS: UCN2 improved the systolic and diastolic function of SHRs as demonstrated by decreased left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), increased +dp/dtmax and -dp/dtmax and decreased cAMP level. UCN2 inhibited the opening of L-type calcium channel and decreased the calcium channel current of cardiomyocytes. In addition, UCN2 also decreased the contents of fluorescence calcium in SHR myocardium. However, astressin2-B (AST-2B), the antagonist of corticotropin-releasing factor receptor 2 (CRFR2), could reverse the inhibitory effects of UCN2 on calcium channel. CONCLUSION: UCN2 can modulate electrical remodeling of the myocardium and hemodynamics in an experimental model of SHR via inhibition of L-type calcium channel and CRFR2 in cardiomyocytes.

The effects of neuropeptide urocortin 2 on the spontaneous discharge and glutamatergic neurotransmission of striatum neurons.

The primary cause of the neurodegenerative process that underlies Parkinson's disease (PD) is still unknown. Different mechanisms probably contribute to triggering neuronal death in the nigro-striatum pathway. The neuropeptide urocortin 2 (UCN2) plays an important role in the regulation of striatum (STR) neurons projection. We investigated the effects of UCN2 on spontaneous discharge and glutamatergic responses in STR for a better understanding of the pathogenesis of PD. The experiment used microiontophoresis method to observe the effects of UCN2 on STR neurons' firing rates in vivo. Corticotrophin releasing factor receptor 2 (CRF-R2) selective inhibitor, astressin-2B (AST-2B), was administered simultaneously with UCN2 to investigate the effects of UCN2 on CRF-R2. Moreover, we further explored the effects of UCN2 on glutamatergic responses in STR neurons. We found that UCN2 could significantly inhibit the firing rate of 84% of the tested STR neurons, and its inhibitory effect followed a concentration-dependent manner. During the microiontophoresis of GLU, the excitatory firing of glutamatergic neurons could be attenuated by the addition of UCN2, but enhanced by the application of AST-2B. The results suggest that UCN2 could regulate the effects of STR neurotransmitters (GLU) via CRF-R2 and may thereby contribute to the improvement of PD.

Insulin treatment prevents the increase in D-serine in hippocampal CA1 area of diabetic rats.

PURPOSE: Diabetes is a high risk factor for dementia. Employing a diabetic rat model, the present study was designed to determine whether the content of D-serine (D-Ser) in hippocampus is associated with the impairment of spatial learning and memory ability. METHODS: Diabetes was induced by a single intravenous injection of streptozotocin (STZ). The insulin treatment began 3 days after STZ injection. RESULTS: We found that both water maze learning and hippocampal CA1 long-term potentiation (LTP) were impaired in diabetic rats. The contents of glutamate, D-Ser, and serine racemase in the hippocampus of diabetic rats were significantly higher than those in the control group. Insulin treatment prevented the STZ-induced impairment in water maze learning and hippocampal CA1-LTP in diabetic rats and also maintained the contents of glutamate, D-Ser, and serine racemase at the normal range in hippocampus. CONCLUSIONS: These results suggest that insulin treatment has a potent protection effect on CA1-LTP, spatial learning and memory ability of the diabetic rats in vivo. Furthermore, insulin may take effect by inhibiting the overactivation of N-methyl-d-aspartate receptors, which play a critical role in neurotoxicity.