Gly Levels Research Articles

Optimization of Hydrolysis Conditions for the Isolation of Angiotensin-I Converting Enzyme (ACE) Inhibitory Peptides from Rhopilema hispidum

To obtain the maximum angiotensin-I converting enzyme (ACE) inhibitory activity, the protein hydrolysis conditions of the jellyfish Rhopilema hispidum were optimized using response surface methodology (RSM). Trypsin was selected to produce R. hispidum protein hydrolysates (RPH) with ACE inhibitory activity. The optimal parameters for producing protein hydrolysates with the highest ACE inhibitory activity were as follows: hydrolysis time 5 h, hydrolysis temperature 50°C, and the enzyme-to-substrate ratio 6%. Under these conditions, the ACE inhibitory rate of RPH could reach 64.28% ± 5.72%. In addition, RPH contained high levels of Gly, Glu, Pro, Ala, Asp and Arg, with a molecular weight distribution range of 0.32–6.84 kDa. The following three novel ACE inhibitory peptides were isolated and identified: Ile-Gly-Glu-Thr-Gly-Pro, Gly-Ala-Thr-Gly-Pro-Ala-Gly-Tyr-Val and Gly-Ala-Phe-Gly-Pro-Gly-Gly-Leu-Val-Gly-Arg-Pro. The IC50 values of the ACE inhibitory activity of these three purified peptides were 19.07, 27.42 and 31.26 μmol L−1, respectively. These results suggested that proteins and peptides isolated from R. hispidum could be utilized as antihypertensive functional food sources.

Different Pain States of Trigeminal Neuralgia Make Significant Changes in the Plasma Proteome and Some Biochemical Parameters: a Preliminary Cohort Study.

Trigeminal neuralgia (TN) with chronic and severe neuropathic pain leads to remarkable interference in daily living activities of patients. Unknown molecular mechanisms involved in TN pathophysiology are a challenge for complete treatment of the disease. The present study was conducted to investigate changes in the plasma proteome beside biochemical parameters, including calcitonin gene-related peptide (CGRP), nitric oxide (NO), amino acids, and vitamin D (Vit D) in different pain states in TN patients. Plasma samples were obtained from the control group (#13) and patients with purely paroxysmal type of classical TN (#13) before and after microvascular decompression (MVD). We analyzed plasma proteome using two-dimensional gel electrophoresis (2-DE) and identified altered proteins by applying MALDI-TOF/TOF mass spectrometry. The plasma levels of neurotransmitters (CGRP, NO, and amino acids) and Vit D were investigated by ELISA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pain-rating index (PRI) was specified using a McGill pain questionnaire, which indicated a significant pain reduction after MVD. Plasma proteome analysis showed upregulated expression of transthyretin (TTR), retinol-binding protein 4 (RBP4), and alpha-1-acid glycoprotein 2 (AGP2) in TN patients compared to control group; whereas, TTR and RBP expression was downregulated after surgery. Moreover, the elevated NO and CGRP and decreased Vit D concentrations were observed in patients. After surgery, NO, Arg, Cit, and Gly levels were decreased along with pain relief. Our findings support the role of altered proteins in TN pathophysiology and suggest involvement of the evaluated neurotransmitters and Vit D in pain pathway sensitization during the disease.

Effect of dietary methionine levels on growth performance, amino acid metabolism and intestinal homeostasis in turbot (Scophthalmus maximus L.)

Methionine is one of the most limited factors in plant-based feed for fish. It plays critical roles in fish growth performance and feed utilization. However, little is known about its effects on amino acid metabolism and intestinal homeostasis in turbot. In this study, an 8-week feeding trial was conducted to examine the nutritional physiology of turbot fed with diets containing deficient (0.85%, LM), adequate (1.82%, MM) or excess (2.80%, HM) levels of methionine respectively. After the feeding trial, fish growth and feed efficiency were significantly reduced by LM diet while no significant difference was observed between MM group and HM group. Methionine deficiency diet also led to a reduction of free Met, Cys, Thr, Arg and His levels in plasma, while an elevation of Gly, Lys and Ala concentrations. The Asp and Gly levels in HM group were significantly lower than other groups. The mRNA expression of cystathionine β-synthase (cbs) and s-adenosylmethionine decarboxylase (samdc) in LM group were up-regulated while the expression of methionine synthase (ms) in LM group was depressed. The expression of ornithine decarboxylase (odc) was not affected by dietary methionine levels. Furthermore, methionine deficiency decreased the height of intestinal villus and microvilli, as well as the number of goblet cells. The mRNA expression of proliferating cell nuclear antigen (pcna) and mucin-2 (muc-2), as well as the content of glutathione, were also induced with the methionine level in the diets. These results provide important new clues in methionine function in teleost.

Worm wounding increases levels of pollen-related food allergens in soybean (Glycine max)

The levels of food allergens in worm-wounded or non-wounded green soybeans (edamame) and mature soybeans were investigated by immunoblotting and enzyme-linked immunosorbent assay (ELISA), using allergen-specific antibodies. Non-wounded and worm-wounded soybeans showed similar total protein profiles after Coomassie brilliant blue staining, but some protein bands were observed to have been changed by worm wounding. Immunoblotting with specific antibodies for major soybean allergens (Gly m 5, Gly m 6, Gly m Bd 30K, and Kunitz soybean trypsin inhibitor) revealed that protein band profiles and intensities were not significantly changed by worm wounding. In contrast, levels of the pollen-related soybean allergens Gly m 4 and Gly m 3 were strongly increased by worm wounding in both green and mature soybeans, as detected by immunoblotting and ELISA. These results suggested that the pollen-related food allergen risk (i.e., oral allergy syndrome; OAS) from soybeans might be enhanced by worm wounding of soybeans.

Changes in nitrogen availability lead to a reprogramming of pyruvate metabolism

BackgroundLow availability of nitrogen (N) severely affects plant growth at different levels, which can be reverted by the resupply of N. To unravel the critical steps in primary metabolism underlying the growth adjustment in response to changes in N availability, transcriptomic and comprehensive metabolite analyses were performed in barley using primary leaves at early and later stages of N deprivation, and after N resupply to N-deficient plants.ResultN deficiency in leaves caused differential regulation of 1947 genes, mostly belonging to the functional classes photosynthesis, cell wall degradation, lipid degradation, amino acid degradation, transcription factors, phytohormone metabolism and receptor-like kinases. Interestingly, 62% of the genes responding to low N were regulated in the opposite direction after two days of N resupply. Reprogramming of gene transcription was linked to metabolic rearrangements and affected the metabolism of amino acids and sugars. The levels of major amino acids, including Glu, Asp, Ser, Gln, Gly, Thr, Ala, and Val, decreased during primary leaf age and, more pronounced, during low N-induced senescence, which was efficiently reverted after resupply of N. A significant decrease was observed for pyruvate and metabolites involved in the TCA cycle under low N, and this was reverted to initial levels after 5 days of N resupply. Correspondingly, transcript levels of genes coding for pyruvate kinase, pyruvate dehydrogenase, and pyruvate orthophosphate dikinase followed the same trend as related metabolites.ConclusionOur results show that upon N limitation a specific pathway for remobilization at the link between glycolysis and TCA cycle in barley is established that is at least partly regulated by a strict reprogramming of the gene coding for pyruvate orthophosphate dikinase. Further analysis of this pathway, its regulatory levels and biochemical changing of pyruvate metabolism enzymes in response to N availability is needed to determine the link between N status and primary metabolism.

Xylazine regulates the release of glycine and aspartic acid in rat brain

Abstract Introduction Xylazine, a type of α2-adrenoceptors, is a commonly used drug in veterinary medicine. Xylazine-induced changes in the content of amino acid neurotransmitters – glycine (Gly) and aspartic acid (Asp), in different brain regions and neurons were studied. Material and Methods Wistar rats were administered 50 mg/kg or 70 mg/kg of xylazine by intraperitoneal injection. In addition, in vitro experiments were conducted, in which neurons were treated with 15 μg/mL, 25 μg/mL, 35μg/mL, and 45 μg/mL of xylazine. Test methods were based on the enzyme-linked immunosorbent assays (ELISA). Results During anaesthesia, Asp levels in each brain area were significantly lower compared to the control group. Except for the cerebrum, levels of Gly in other brain areas were significantly increased during the anaesthesia period. In vitro, xylazine-related neuron secretion of Gly increased significantly compared to the control group at 60 min and 90 min. Moreover, xylazine caused a significant decrease in the levels of Asp secreted by neurons at 20 min, but gradually returned to the level of the control group. Conclusion The data showed that during anaesthesia the overall levels of Asp decreased and overall levels of Gly increased. In addition, the inhibitory effect of xylazine on Asp and the promotion of Gly were dose-dependent. Our data showed that different effects of xylazine on excitatory and inhibitory neurotransmitters provided a theoretical basis for the mechanism of xylazine activity in clinical anaesthesia.

Xylazine Regulates the Release of Glycine and Aspartic Acid in Rat Brain.

IntroductionXylazine, a type of α2-adrenoceptors, is a commonly used drug in veterinary medicine. Xylazine-induced changes in the content of amino acid neurotransmitters – glycine (Gly) and aspartic acid (Asp), in different brain regions and neurons were studied.Material and MethodsWistar rats were administered 50 mg/kg or 70 mg/kg of xylazine by intraperitoneal injection. In addition, in vitro experiments were conducted, in which neurons were treated with 15 μg/mL, 25 μg/mL, 35μg/mL, and 45 μg/mL of xylazine. Test methods were based on the enzyme-linked immunosorbent assays (ELISA).ResultsDuring anaesthesia, Asp levels in each brain area were significantly lower compared to the control group. Except for the cerebrum, levels of Gly in other brain areas were significantly increased during the anaesthesia period. In vitro, xylazine-related neuron secretion of Gly increased significantly compared to the control group at 60 min and 90 min. Moreover, xylazine caused a significant decrease in the levels of Asp secreted by neurons at 20 min, but gradually returned to the level of the control group.ConclusionThe data showed that during anaesthesia the overall levels of Asp decreased and overall levels of Gly increased. In addition, the inhibitory effect of xylazine on Asp and the promotion of Gly were dose-dependent. Our data showed that different effects of xylazine on excitatory and inhibitory neurotransmitters provided a theoretical basis for the mechanism of xylazine activity in clinical anaesthesia.

Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study

BackgroundGlyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length.MethodUrine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. GLY measurements were performed using liquid chromatography-tandem mass spectrometry. Demographic and survey information relating to food and water consumption, stress, and residence were obtained by questionnaire. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length.ResultsThe mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5–7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths (r = − 0.28, p = 0.02).ConclusionsThis is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized.

Cynanbungeigenin C and D, a pair of novel epimers from Cynanchum bungei, suppress hedgehog pathway-dependent medulloblastoma by blocking signaling at the level of Gli

Uncontrolled excessive activation of Hedgehog (Hh) signaling pathway is linked to a number of human malignant tumorigenesis. To obtain valuable Hh pathway inhibitors from natural product, in present study, a pair of novel epimers, Cynanbungeigenin C (CBC) and D (CBD) from the plant Cynanchum bungei Decne were chemically characterized by multiple spectroscopic data and chemical derivatization, and evaluated for their inhibition on Hh pathway. Mechanistically, CBC and CBD block Hh pathway signaling not through targeting Smo and Sufu, but at the level of Gli. In addition, both eipmers significantly suppress Hh pathway-dependent Ptch+/−; p53−/− medulloblastoma in vitro and in vivo. Furthermore, both CBC and CBD inhibited two Smo mutants induced Hh pathway activation, which suggested that they are potential compounds for the treatment of medulloblastoma with primary or acquired resistance to current Smo inhibitors. These results highlight the potential of CBC and CBD as effective lead compounds in the treatment of medulloblastoma and other Hh-dependent malignancy.

Neurotransmitters and Receptors Changes in Medial Nucleus of the Trapezoid Body (MNTB) of Early-Developmental Rats with Single-Side Deafness.

BackgroundCongenital single-side deafness (SSD) affects sound localization even after cochlear implantation (CI) in some conditions. The medial nucleus of the trapezoid body (MNTB) plays an important role in binaural benefit and sound localization, but little is known about intrinsic molecular changes in MNTB with SSD. We aimed to observe changes in MNTB in early-developmental SSD rats, including the key neurotransmitters (GABA, Gly, Glu) and major receptors (GABAa-R/GABAb-R for GABA, Gly-R for Gly, and AMPA/NMDA for Glu).Material/MethodsThe model of early-developmental SSD was acquired by right cochlear ablation at P12 and confirmed by ABR. High-performance liquid chromatography fluorescence detection (HPLC-FLD) was performed to measure the levels of neurotransmitters in MNTB. The relative expression of neurotransmitter receptors was tested by quantitative real-time PCR analysis.Results(1) The right MNTB of experimental rats had an increase in GABA, Gly, and Glu at 4 weeks after right cochlear ablation (P<0.05). (2) At 2 weeks, the left MNTB of experimental rats showed increases in GABAa-R, GABAb-R, Gly-R, and AMPA, while the right MNTB showed lower expression of NMDA (P<0.05). The higher receptors in left MNTB decreased to a level at which we found no difference at 1 week for GABAa-R and GABAb-R (P>0.05), and was even reversed for Gly-R and AMPA (P<0.05). (3) Gly level was significantly increased at 2 weeks bilaterally and continued to 4 weeks in the left MNTB (P<0.05).ConclusionsEarly-developmental SSD can lead to asymmetric distribution of neurotransmitters and receptors in MNTB, which can be the fundamental cause of defective sound localization after cochlear implantation.

The Impairment of Trans Fatty Acids on Learning, Memory and Brain Amino Acid Neurotransmitters in Mice.

The aim of the study was to demonstrate the impairment of trans fatty acids (TFAs) in neurological disorders in mice. Forty-eight male Kunming mice were randomly divided into four groups with twelve in each group, namely a control group (corn oil group), and TFA groups with low, middle and high dosages. The tested chemicals were given by gavage, once a day, for 12 wk in total, with the volume of the intragastric liquid as 0.1 mL/10 g of body weight. The mice in the control group were given corn oil only. The mice in the TFA groups were given TFA solution (doses were 25, 50 and 100 mg/kg of body weight, respectively). The Morris circle water maze was used to test learning and memory of mice. The activity of acetylcholinesterase (AChE), nitric oxide synthase (NOS) and the level of brain amino acid neurotransmitters were tested. In the Morris water maze task, and compared to the control group, TFAs showed no obvious effect on learning or memory. TFA intake led to a significant decrease of AChE in all TFA groups, and the increase in levels of NOS in the high-dose group. Meanwhile, intake of TFAs increased the levels of Asp, Glu, Gly, and Tau in all TFA groups. The results suggest that long-term intake of TFAs probably impairs learning, memory and brain neurotransmitters in mice.

In Vivo Brain Glycine and Glutamate Concentrations in Patients With First-Episode Psychosis Measured by Echo Time–Averaged Proton Magnetic Resonance Spectroscopy at 4T

BackgroundAccumulating evidence suggests the involvement of abnormal glutamateric neurotransmission and N-methyl-D-aspartate receptor hypofunction in the pathophysiology of psychotic disorders. The purpose of this study was to quantify in vivo glutamate (Glu) and glycine (Gly) levels in patients with first-episode psychosis as well as age-matched healthy control subjects with magnetic resonance spectroscopy (MRS). MethodsThe subjects were 46 patients with first-episode psychosis (20 with a schizophrenia spectrum disorder, 26 with bipolar disorder) and 50 age-matched healthy control subjects. Glu and Gly levels were measured in vivo in the anterior cingulate cortex and posterior cingulate cortex of the subjects by using the echo time–averaged proton MRS technique at 4T (i.e., modified point resolved spectroscopy sequence: 24 echo time steps with 20-ms increments). Metabolite levels were quantified using LCModel with simulated basis sets. ResultsSignificantly higher Glu and Gly levels were found in both the anterior cingulate cortex and posterior cingulate cortex of patients with first-episode psychosis as compared with healthy control subjects. Glu and Gly levels were positively correlated in patients. Patients with a schizophrenia spectrum disorder and bipolar disorder showed similar abnormalities. ConclusionsOur findings demonstrate abnormally elevated brain Glu and Gly levels in patients with first-episode psychosis by means of echo time–averaged proton MRS at 4T. The findings implicate dysfunction of N-methyl-D-aspartate receptor and glutamatergic neurotransmission in the pathophysiology of the acute early phase of psychotic illnesses.

Measurement of glycine in healthy and tumorous brain by triple-refocusing MRS at 3T in vivo.

Glycine (Gly) has been implicated in several neurological disorders, including malignant brain tumors. The precise measurement of Gly is challenging largely as a result of the spectral overlap with myo-inositol (mI). We report a new triple-refocusing sequence for the reliable co-detection of Gly and mI at 3 T and for the evaluation of Gly in healthy and tumorous brain. The sequence parameters were optimized with density-matrix simulations and phantom validation. With a total TE of 134 ms, the sequence gave complete suppression of the mI signal between 3.5 and 3.6 ppm and, consequently, well-defined Gly (3.55 ppm) and mI (3.64 ppm) peaks. In vivo 1 H magnetic resonance spectroscopy (MRS) data were acquired from the gray matter (GM)-dominant medial occipital and white matter (WM)-dominant left parietal regions in six healthy subjects, and analyzed with LCModel using in-house-calculated basis spectra. Tissue segmentation was performed to obtain the GM and WM contents within the MRS voxels. Metabolites were quantified with reference to GM-rich medial occipital total creatine at 8 mM. The Gly and mI concentrations were estimated to be 0.63 ± 0.05 and 8.6 ± 0.6 mM for the medial occipital and 0.34 ± 0.05 and 5.3 ± 0.8 mM for the left parietal regions, respectively. From linear regression of the metabolite estimates versus fractional GM content, the concentration ratios between pure GM and pure WM were estimated to be 2.6 and 2.1 for Gly and mI, respectively. Clinical application of the optimized sequence was performed in four subjects with brain tumor. The Gly levels in tumors were higher than those of healthy brain. Gly elevation was more extensive in a post-contrast enhancing region than in a non-enhancing region. The data indicate that the optimized triple-refocusing sequence may provide reliable co-detection of Gly and mI, and alterations of Gly in brain tumors can be precisely evaluated.

Effects of feeding male and female broiler chickens on low-protein diets fortified with different dietary glycine levels under the hot and humid tropical climate

This study was conducted to evaluate the effect of sex and level of glycine (Gly) fortification to low-protein diets on growth performance, selected serum metabolites, carcass yield and litter characteristics in broiler chickens under tropical climate. Day-old male (n = 400) and female (n = 400) broiler chicks were assigned to five isocaloric diets (positive control, PC; negative control, NC; and more three diets obtained by fortifying NC diet with higher Gly concentrations). No significant diet × sex interaction was observed for all the parameters measured. Comapered to NC group, weight gain (WG) significantly increased (p<.0001) by feeding Gly fortified low-CP diets throughout the experiment; however, WG and feed intake (FI) of birds fed NC or NC + Gly diets were significantly lower (p<.0001) compared to PC group. During the overall period, fortification of NC diet with Gly significantly improved (p<.0001) the feed conversion ratio (FCR) compared to NC group, and resulted in FCR similar to those birds fed the PC diet. Diet effect was significant (p<.0001) for performance parameters, proportional liver and abdominal fat weights, serum triglycerides (TG) and uric acid (UA) and litter moisture and nitrogen contents; with no Gly level effect (linear and quadratic, p > .05). The sex effect was significant for performance parameters, abdominal fat, and litters’ moisture and nitrogen contents. In conclusion, it is likely that additional Gly fortification to low-CP diets under tropical climate may have a better effect on broiler chickens after the starter phase. Moreover, feeding Gly fortified low-CP diets may improve the FCR and reduce the nitrogen excretion.

Synergistic Inhibitory Effect of Arsenic Trioxide Combined with Itraconazole on Hedgehog Pathway of Multiple Myeloma NCI-H929 Cells

To investigate the antitumor effect of arsenic trioxide (ATO) combined with itraconazole (ITRA) on human multiple myeloma NCI-H929 cells by synergistically inhibiting Hedgehog (HH) signaling pathway. The inhibitory rate of NCI-H929 cells was assayed by MTT method. Tumor weight, tumor weight inhibition rate, and tumor volume of mouse model with multiple myeloma were examined. The ELISA were appled to detect the M-protein, qPCR and Western blot were used respectively to detect the expression level of Ptch, SMO, Gli and downstream target genes, the survival rate of tumor-bearing mice was analyzed. ATO combined with ITRA significantly inhibited NCI-H929 cell proliferation as compared with a single administration. The combination of ATO and ITRA could synergistically inhibit tumor growth and obviously reduced tumor burden, survival time of tumor-bearing mice was significantly prolonged. qPCR and Western blot results confirmed that the ATO combined with ITRA could significantly down-regulated expression of Gli1, leading to significantly decrease of cyclinD1 and BCL-2 expression levels. ATO combined with ITRA can more strongly suppress the growth of multiple myeloma NCI-H929 cells, as compared with a single administration. The synergistic effect of ATO and ITRA significantly down-regulates expression of Gli1 in HH signaling pathway, moreover the inhibition of target gene overexpression may be one of two drug mechanisms.

The study of the adductor muscle-shell interface structure in three Mollusc species

The adductor muscle scar (AMS) is the fixation point of adductor muscle to the shell. It is an important organicinorganic interface and stress distribution area. Despite recent advances, our understanding of the structure and composition of the AMS remain limited. Here, we report study on the AMS of three bivalves: Mytilus coruscus, Chlamys farreri and Ruditapes philippinarum. Results showed that there were significant differences among their AMS structures. Both M. coruscus and C. farreri were found to have a columnar layer above the nacreous platelet shell structure at the AMS and this layer was more organized in M. coruscus. There was no distinguishable twolayer structure in R. philippinarum. Atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FT-IR) results showed that the AMS was much smoother than the nacreous inner shell in all the three species and the AMS had minor different compositions from the nacreous shell layer. SDS-PAGE (sodium dodecyl-sulfate polyacrylamide gel electophoresis) study of the proteins isolated from the interface indicated that there was a 70 kDa protein which seemed to be specifically located to the highly organized columnar AMS structure in Mytilus coruscus. Further analysis of this protein showed it contained high level of Asx (Asp+Asn), Glx (Glu+Gln) and Gly. The special structure and composition of the AMS might play important roles in the stability, adhesion and function at this stress distribution site.

Sodium para-aminosalicylate protected cultured basal ganglia astrocytes from manganese-induced DNA damages and alteration of amino acid neurotransmitter levels.

Sodium para-aminosalicylate (PAS-Na) was first applied successfully in clinical treatment of two manganism patients with good prognosis. However, the mechanism of how PAS-Na protects against Mn-induced neurotoxicity is still elusive. The current study was conducted to explore the effects of PAS-Na on Mn-induced basal ganglia astrocyte injury, and the involvement of amino acid neurotransmitter in vitro. Basal ganglia astrocytes were exposed to 500 μM manganese chloride (MnCl2) for 24 hr, following by 50, 150, or 450 μM PAS-Na treatment for another 24 hr. MnCl2 significantly decreased viability of astrocytes and induced DNA damages via increasing the percentage of tail DNA and Olive tail moment of DNA. Moreover, Mn interrupted amino acid neurotransmitters by decreasing Gln levels and increasing Glu, Gly levels. In contrast, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects on basal ganglia astrocytes. Taken together, our results demonstrated that excessive Mn exposure may induce toxic effects on basal ganglia astrocytes, while PAS-Na could protect basal ganglia astrocytes from Mn-induced neurotoxicity.

Czy istnieją jakieś kliniczne zależności między stężeniami homocysteiny i glicyny u pacjentów z migotaniem przedsionków?

Introduction. Atrial fibrillation (AF) is constantly associated with a complex of various factors that create a diversity of pathophysiological variants due to phenomenon of atrial remodelling. The aim of the study was to investigate clinical associations with plasma homocysteine (Hcy) and glycine (Gly) levels in patients with paroxysmal and persistent AF. Materials and methods. The study included 94 patients with ischaemic heart disease and/or hypertension without significant structural myocardial damage — 48 subjects with paroxysmal AF (group 1) and 27 subjects with persistent AF (group 2). Control group consisted of 19 patients without history of AF. Echocardiography was performed to assess left atrium (LA) size and function. Plasma levels of Hcy and Gly were measured. Results. Patients with AF had significantly increased total plasma Hcy level. In group 2 there was a significant correlation between Hcy plasma level and LA-size. The Gly level > 349 μ mol/L was found to be associated with a greater AF duration and was significantly more often in patients with AF existing for more than four years. Patients with Gly plasma level > 309 μ mol/L and total Hcy plasma > 11.02 μ mol/L showed significantly increased frequency of AF. Patients without AF showed Hcy plasma level < 11 μ mol/L significantly more frequently (0% vs 29%) (р = 0.005). Conclusion. There is an association between Hcy and Gly levels, atrial remodelling and the clinical course in patients with AF. It can be assumed that in a higher level of Hcy, increased Gly level may serve as a predictor of more pronounced structural and functional changes in the atria, but in such case it acts as a protective mechanism.

PI3K/AKT/mTOR and sonic hedgehog pathways cooperate together to inhibit human pancreatic cancer stem cell characteristics and tumor growth.

Cancer stem cells (CSCs) play major roles in cancer initiation, progression, and metastasis. It is evident from growing reports that PI3K/Akt/mTOR and Sonic Hedgehog (Shh) signaling pathways are aberrantly reactivated in pancreatic CSCs. Here, we examined the efficacy of combining NVP-LDE-225 (PI3K/mTOR inhibitor) and NVP-BEZ-235 (Smoothened inhibitor) on pancreatic CSCs characteristics, microRNA regulatory network, and tumor growth. NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting pancreatic CSC's characteristics and tumor growth in mice by acting at the level of Gli. Combination of NVP-LDE-225 and NVP-BEZ-235 inhibited self-renewal capacity of CSCs by suppressing the expression of pluripotency maintaining factors Nanog, Oct-4, Sox-2 and c-Myc, and transcription of Gli. NVP-LDE-225 co-operated with NVP-BEZ-235 to inhibit Lin28/Let7a/Kras axis in pancreatic CSCs. Furthermore, a superior interaction of these drugs was observed on spheroid formation by pancreatic CSCs isolated from Pankras/p53 mice. The combination of these drugs also showed superior effects on the expression of proteins involved in cell proliferation, survival and apoptosis. In addition, NVP-LDE-225 co-operated with NVP-BEZ-235 in inhibiting EMT through modulation of cadherin, vimentin and transcription factors Snail, Slug and Zeb1. In conclusion, these data suggest that the combined inhibition of PI3K/Akt/mTOR and Shh pathways may be beneficial for the treatment of pancreatic cancer.

Effects of sublethal doses of glyphosate on honeybee navigation

Glyphosate (GLY) is a herbicide that is widely used in agriculture for weed control. Although reports about the impact of GLY in snails, crustaceans and amphibians exist, few studies have investigated its sublethal effects in non-target organisms such as the honeybee Apis mellifera, the main pollen vector in commercial crops. Here, we tested whether exposure to three sublethal concentrations of GLY (2.5, 5 and 10 mg l(-1): corresponding to 0.125, 0.250 and 0.500 μg per animal) affects the homeward flight path of honeybees in an open field. We performed an experiment in which forager honeybees were trained to an artificial feeder, and then captured, fed with sugar solution containing traces of GLY and released from a novel site either once or twice. Their homeward trajectories were tracked using harmonic radar technology. We found that honeybees that had been fed with solution containing 10 mg l(-1) GLY spent more time performing homeward flights than control bees or bees treated with lower concentrations. They also performed more indirect homing flights. Moreover, the proportion of direct homeward flights performed after a second release from the same site increased in control bees but not in treated bees. These results suggest that, in honeybees, exposure to levels of GLY commonly found in agricultural settings impairs the cognitive capacities needed to retrieve and integrate spatial information for a successful return to the hive. Therefore, honeybee navigation is affected by ingesting traces of the most widely used herbicide worldwide, with potential long-term negative consequences for colony foraging success.