Noscapine modulates neuronal response to oxygen-glucose deprivation/reperfusion injury via activation of sigma-1 receptor in primary cortical cultures

In the present study, we investigated the effects of noscapine (0.5-2 μM), an alkaloid from the opium poppy (Papaver somniferum), on primary murine cortical neurons exposed to 60 min oxygen�glucose deprivation (OGD) in the presence of 5 μM BD-1047, a selective sigma-1 receptor antagonist. The experiments were performed on cortical neurons after 11�16 days of culture. To initiate oxygen�glucose deprivation, the culture medium was transferred to glucosefree DMEM, and placed in a humidified incubation chamber containing a mixture of 95 N2 and 5 CO2 at 37 °C for 60 min. In order to explore the effect on neurons under oxygen�glucose deprivation in this condition, some cultures were pretreated with noscapine and BD1047 together, 24 h prior to OGD followed by 24 h recovery. Cell viability, nitric oxide (NO) production and intracellular calcium concentration (Ca2+i) levels were evaluated by MTT assay, the modified Griess method, and Fura-2, respectively. Pretreatment of the cultures with noscapine in the presence of BD1047 significantly increased cell viability and decreased NO generation in a dosedependent manner compared to BD1047 alone. Pretreatment with 2 μM noscapine and BD-1047 was shown to decrease the rise in Ca2+i induced by sodium azide (NaN3) and glucose deprivation. We concluded that noscapine in the presence of BD1047 could protect primary cortical neurons after oxygen�glucose deprivation-induced cell injury but this effect was not complete. Our results indicate that neuroprotective effects of noscapine could be mediated partially through activation of sigma-1 receptor and by decreasing NO production and Ca2+i levels. © 2020, Iranian Journal of Pharmaceutical Research. All rights reserved

The effect of noscapine on oxygen-glucose deprivation on primary murine cortical neurons in high glucose condition

In the present work we set out to investigate the neuroprotective effects of noscapine (0.52 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen� glucose deprivation/24 h. recovery. Cell viability, nitric oxide production and intracellular calcium ((ca2+)i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100 mM D-glucose could, in a concentration dependent manner, improve cell viability and decrease NO production and (ca2+)i level in neuronal cells after ischemic insult. Moreover, pre-incubation of cells with noscapine, noticeably enhanced protective effects of 25 and 100 mM D-glucose compared to similar conditions without noscapine pretreatment. In fact, noscapine attenuated NO production in a dose-dependent fashion, after 30 minutes (min) OGD, during high-glucose (HG) condition in cortical neurons. Pretreatment with 2 μM noscapine and 25 or 100 mM D-glucose, was shown to decrease the rise in (ca2+) induced by Sodium azide/glucose deprivation (chemical OGD) model. These effects were morei pronounced than that of 25 or 100 mM D-glucose alone. The present study demonstrated that the neuroprotective effects of HG before an ischemic insult were augmented by pre-treatment with noscapine. Our results also suggested that the neuroprotection offered by both HG and noscapine involve attenuation of NO production and (ca2+)i levels stimulated by the experimental ischemia in cortical neurons. © 2016 by School of Pharmacy

Evaluation of the neuroprotective effects of electromagnetic fields and coenzyme Q 10 on hippocampal injury in mouse

Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q 10 (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25–30 g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5 mg/kg). The experimental groups were exposed to EMF at a frequency of 50 Hz and intensity of 5.9 mT for 7 hr daily over 1 week or treated with CoQ10 (10 mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ1

Neighbourhood Transformation via Multiscale Urban Optimization

Energy, emissions cutting and sustainabledevelopment are the main urban issues. The urban settlementforms could have a disproportionately large effect over theenergy consumption, and consequently, on any effective longtermstrategy for reducing C02 emission in the atmosphere.Hence, this paper demonstrates how it could be possible totransform an existing urban context into a lower energyconsumption system, using the IMM® methodology. Assumingthat the total energy consumption of the city is different from thesum of the whole building’s consumption, this theory considersthat the energy efficiency of the urban system has to be optimizedby its form. A specific case study, located in Australia (GoldCoast), shows that morphology plays a significant role for a longterm energy-saving strategy as well as for urban efficiency, life’squality and, generally, for any sustainable urban environmentpolicy

Neuroprotective effect of noscapine on cerebral oxygen-glucose deprivation injury

Methods Cells were transferred to glucose-free DMEM and were exposed to hypoxia in a small anaerobic chamber. Cell viability and nitric oxide production were evaluated by MTT assay and the Griess method, respectively. Results The neurotoxicities produced by all three hypoxia durations tested were significantly inhibited by 0.5 μM noscapine. Increasing noscapine concentration up to 2.5 μM produced a concentration-dependent inhibition of neurotoxicity. Pretreatment of cells with MK-801 (10 μM), a non-competitive NMDA antagonist, and nimodipine (10 nM), an L-type Ca2+ channel blockers, increased cell viability after 30 min OGD, while the application of NBQX (30 μM), a selective AMPA-kainate receptor antagonist partially attenuated cell injury. Subsequently, cells treated with noscapine in the presence of thapsigargin (1 μM), an inhibitor of endoplasmic reticulum Ca2+ ATPases. After 60 min OGD, noscapine could inhibit the cell damage induced by thapsigargin. However, noscapine could not reduce cell damage induced by 240 min OGD in the presence of thapsigargin. Noscapine attenuated nitric oxide (NO) production in cortical neurons after 30 min OGD. Conclusions We concluded that noscapine had a neuroprotective effect, which could be due to its interference with multiple targets in the excitotoxicity process. These effects could be mediated partially by a decrease in NO production and the modulation of intracellular calcium levels. Background The present study aims to investigate the effect of noscapine (0.5-2.5 μM), an alkaloid from the opium poppy, on primary murine fetal cortical neurons exposed to oxygen-glucose deprivation (OGD), an in vitro model of ischemia. © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved

Evaluation of effects of morphine and ionizing radiation in cancer cell lines

Purpose: Breast and cervical cancers are the two most common cancers among women worldwide. Morphine is a potent analgesic for cancer pain, and radiation therapy is a conventional treatment for cancer. Unfortunately, the combined adjuvant cellular effects of morphine and ionizing radiation in cancer cells are largely unknown. Materials and Methods: In this study, we examined the effects of morphine and single radiation dose of 2 Gy on viability and survival fraction of human breast cancer cell line MDA-MB 231 and human cervical cancer cell line HeLa, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. We were also interested in evaluating these effects in human umbilical vein endothelial cells as well. Results: We found that morphine did not have a dose- and time-dependent manner in endothelial, breast, and cervical cancer cells in vitro. It seems that pretreatment of breast and cervical cancer cells with morphine at some doses before irradiation reduces the cytotoxic effect of radiation. We also observed that endothelial cells were less sensitive than breast and cervical cancer cells to radiation or morphine + radiation. Based on the results of endothelial cells, morphine or radiation might not have a selective effect on the viability and clonogenic survival of different cell lines. Conclusions: Our data may suggest that morphine and radiotherapy could not be administered together to breast and cervical cancer patients if additional and in vivo studies confirm our results. © 2019 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow

The case study of Timisoara (Romania). IMM design for a more sustainable, livable and responsible city.

A case study based on the re-development of an important part of Timisoara shows that morphology plays an essential role for any energy-saving policy, urban efficiency, quality of life and, generally, for any sustainable urban environment. This project based on the innovative IMM® methodology applies a multi-layered design approach working in the areas of energy, water, urban green spaces, mobility, landscapes, natural resource management, participation and social cohesion. In terms of sustainability, the study defined the main catalyst for nowadays most profiting urban changes – transportation; emphasizing the transposition from “driving – in” or car dependent society to “green moving – in” concept of bicycle and public transport dependence. Furthermore applying this in a domino effect style the paper elaborates a thorough program for smaller scales such as district sustainable development. The research set the opportunity to incorporate a wide range of issues to improve the metabolism of the city as well as its livability, and energy performances

A guided tour in metasurface land: Discontinuity conditions, design and applications

The paper presents an overview of the recent research on metasurfaces performed in the author's group. This covers the introduction of bianistropic Sheet Transition Conditions (STCs), the subsequent elaboration of a general synthesis technique based on surface susceptibility tensors, the complementary elaboration of Finite Difference (FD) and Finite Element (FE) computational schemes for analysis, and, based upon this solid foundation, the development of a host of novel applications across the whole microwave to optical range of the electromagnetic spectrum.</p

Evaluation of metformin effects in the chronic phase of spontaneous seizures in pilocarpine model of temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the �ketogenic diet�. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB). We have shown that this reduced expression pattern is mediated by the transcriptional co-repressor CtBP (C-terminal binding protein). Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway. Our findings have been shown that metformin has anticonvulsant and antiepileptic properties, and suggesting that antiglycolytic compounds such as metformin may represent a new class of drugs for treating epilepsy. © 2017, Springer Science+Business Media, LLC

Comparative phenotypic characterization of human colostrum and breast milk-derived stem cells

There is a diverse population of stem cells in human breast milk that can be employed for therapeutic purposes as a reservoir of cells. The current study mainly aimed to determine the nature markers expressing on stem cells. For this aim, the expression of embryonic stem cell markers, as well as the expression of endothelial, mesenchymal, neural, and hematopoietic markers were evaluated by the flow cytometry analysis in fresh colostrum, breast milk, and cultured colostrum samples. The results showed that the embryonic (OCT4, SOX2, HLA-DR), hematopoietic (CD33, CD45, CD117), neural (CD133, Nestin), and mesenchymal (CD44, SCA1) stem cell markers present in colostrum had higher expression in comparison with their counterpart markers in fresh breast milk. The expression markers of stem cells in colostrum following a 2-week culture period were significantly increased compared with their counterpart markers in colostrum before the culture process. In the culture of breastmilk, cells were not observed adherent cells and colonies. Our findings form flow cytometry and cell culture suggest that the lactation stage could be one of the factors influencing the stem cell population and, consequently, the cultivation of breastmilk cells. The present study indicates that colostrum is a tremendous source of stem cells that could be applied in cell-based research. © 2020, Japan Human Cell Society and Springer Japan KK, part of Springer Nature