Cytomodulatory characteristics of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) against cypermethrin on skin fibroblast cells (HFF-1).

The hematopoietic factor granulocyte macrophage-colony stimulating factor (GM-CSF) has been identified via its capacity to promote bone marrow progenitors' development and differentiation into granulocytes and macrophages. Extensive pre-clinical research has established its promise as a critical therapeutic target in an assortment of inflammatory and autoimmune disorders. Despite the broad literature on GM-CSF as hematopoietic of stem cells, the cyto/geno protective aspects remain unknown. This study aimed to assess the cyto/geno protective possessions of GM-CSF on cypermethrin-induced cellular toxicity on HFF-1 cells as an in vitro model. In pre-treatment culture, cells were exposed to various GM-CSF concentrations (5, 10, 20, and 40 ng/mL) with cypermethrin at IC50 (5.13 ng/mL). Cytotoxicity, apoptotic rates, and genotoxicity were measured using the MTT, Annexin V-FITC/PI staining via flow-cytometry, and the comet assay. Cypermethrin at 5.13 ng/mL revealed cytotoxicity, apoptosis, oxidative stress, and genotoxicity while highlighting GM-CSF's protective properties on HFF-1. GM-CSF markedly attenuated cypermethrin-induced apoptotic cell death (early and late apoptotic rates). GM-CSF considerably regulated oxidative stress and genotoxicity by reducing the ROS and LPO levels, maintaining the status of GSH and activity of SOD, and suppressing genotoxicity in the comet assay parameters. Therefore, GM-CSF could be promising as an antioxidant, anti-apoptotic, genoprotective and cytomodulating agent.

Polymorphism of LRP4 Gene (rs9667108) among Post Menopause Women with Osteoporosis.

Background: Many studies have been done to identify the factors that influence the development and progression of osteoporosis. One genetic factor is polymorphisms of LRP4 gene. Regarding the lack of comprehensive study on polymorphisms of LRP4 gene in the north of Iran, mainly Mazandaran Province, we decided to investigate the polymorphism of this gene in postmenopausal women with osteoporosis. Methods: This case-control study has been conducted at GhaemShahr Valiasr Hospital on 100 female patients with osteoporosis (average age of 58.1) and 90 healthy females without osteoporosis (average age of 55.2). After sampling and extraction of genomic DNA via of the salt deposition method, the genotype and SNP (rs9667108) polymorphism of LRP4 gene were evaluated with the PCR-RFLP method. Restriction enzymes cut the PCR products. In order to identify patients, their bone mineral density was tested by the DEXA method. The results of digestion (digestion enzyme) were analyzed by MedCalc, SPSS software, Hardy-Weinberg equilibrium, and Chi2. Results: The statistical analysis has shown the significant relationship between SNP (rs9667108) polymorphism and the risk of osteoporosis disease in patients and control groups (P<0.05). In SNP (rs9667108), the GC genotype, compared to GG, increased the risk of disease significantly (1.556 time). Similarly, CC genotype, compared to GG genotype, increased the risk of this disease by 2.091 time. Conclusion: The existence of mutation in the LRP4 gene could increase susceptibility to osteoporosis disease. Moreover, determining this patient's genotype in SNP (rs9667108) can be used to identify individuals who are in endanger osteoporosis.

Correction to: Evaluation of curcumin effect on Il6, Sirt1, TNFα and NFkB expression of liver tissues in diabetic mice with STZ.

[This corrects the article DOI: 10.1007/s40200-022-01090-4.].

Evaluation of curcumin effect on Il6, Sirt1, TNFα and NFkB expression of liver tissues in diabetic mice with STZ.

Background: Curcumin is active ingredient of turmeric The main purpose of this study is evaluating impact of curcumin on suger, hypoalgesia and inflammatory factors in diabetic mice. Materials and methods: Male mice divided into six groups of 6. One group as a negative and the other five groups injected with Streptozotocin (STZ) (200 mg/kg). Diabetic mice in each group given different treatments for twenty-one days.After that, blood sugar and neuroathy studies have been done and tissue samples the liver were studied for gene expression. Result: Curcumin reduced blood sugar, but the rate of hypoglycemia was significantly lower than metformin group P > 0.05, and the comparison of the synergistic effect of curcumin and metformin with metformin was not significant P > 0.05. Also, in neuropathy studies, the groups which recieved curcumin and metformin have shown a significant difference with diabetic group P < 0.01, Also, by evaluating inflammatory factors, there was a significant difference in the expression of TNF-a, IL-6 and NfkB, but there is no significant difference in the expression of Sirt1 P < 0.05. Conclusions: The analgesic effect of curcumin was quite evident, probably due to the significant impact of this herbal drug in reducing the expression of inflammatory genes NF-kB, IL6, and TNF-α. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01090-4.

The effects of Lavandula angustifolia essential oil on analgesic effects and percutaneous absorption of naproxen sodium gel; an in vivo and in vitro study.

The percutaneous bioavailability of naproxen is low and several technologies have been utilized to overcome the problem. Although, some studies have reported the permeation-enhancing properties of natural essential oils, no research has reflected the effectiveness of Lavandula angustifolia essential oil (LAEO) on increasing the percutaneous absorption of naproxen sodium from a topical gel. Therefore, the present study was designed to investigate whether LAEO increased the percutaneous absorption and the analgesic effects of naproxen sodium topical gel. In the present study, naproxen topical gel was formulated using carbopol 940 (a gelling agent) and several vehicles such as PEG 400, ethanol, and water and the properties of gels were measured. Percutaneous absorption-enhancing properties of LAEO were measured too. Based on our data, the essential oil-containing formulation of naproxen represented greater penetration into (222.19 ± 24.87 vs. 107.65 ± 6.38 µg/cm2 ), and also across (22.07 ± 4.42 vs. 13.14 ± 2.87 µg/cm2 ) skin layers compared to the naproxen gel. Additionally, a significant analgesic property was observed in the naproxen topical gel containing 0.5% essential oil during both first and late phases of formalin test, as well as the late phase of tail-flick test. It could be concluded that LAEO significantly enhanced naproxen percutaneous absorption and also its analgesic effects.

A promising technology for wound healing; in-vitro and in-vivo evaluation of chitosan nano-biocomposite films containing gentamicin.

Aim: This paper aims to study in-vitro and in-vivo evaluation of chitosan (CHI) biocomposite of gentamicin nanoparticles (GNPs) for wound healing. Methods: In this study, CHI nanoparticles (NPs) were prepared using the ionic gelation technique. GNP biocomposites were examined on the excision wound model in Wistar rats to determine the in-vivo efficiency. Results: The diameter and zeta potential of NPs were between 151-212.9 nm and 37.2 - 51.1 mV, respectively. The entrapment efficiency was in an acceptable range of 36.6-42.7% w/w. The release test information was fitted to mathematical models (Zero, First order, Higuchi, and Korsmeyer-Peppas), and according to calculations, the kinetics of drug release followed the Korsmeyer-Peppas model. A comparison of thermograms revealed that the drug was present in the formulation in a non-crystalline form. Conclusion: Histological studies of the wound showed that the rate of skin tissue repair was higher in the GNP biocomposite treatment group than in the others.

Evaluation of the Anti-apoptotic and Anti-cytotoxic Effect of Epicatechin Gallate and Edaravone on SH-SY5Y Neuroblastoma Cells.

INTRODUCTION: Parkinson disease (PD) is the second most common neurodegenerative disease affecting older individuals with signs of motor disability and cognitive impairment. Epicatechin (EC) and edaravone have neuroprotective effects most probably due to their antioxidant activity; however, a limited number of studies have considered their role in PD. This research aimed at investigating the neuroprotective effect of EC and edaravone in a neurotoxin-induced model of PD. METHODS: An in vitro model of PD was made by subjecting SH-SY5Y neuroblastoma cells to neurotoxin: 6-hydroxydopamine (6-OHDA) 100 µM/well. The cytoprotective effect of EC and edaravone in five concentrations on cell viability was tested using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The apoptotic assay was done by annexin V and propidium iodide method using flow cytometry. RESULTS: According to the MTT assay analysis, EC and edaravone had protective effects against 6-OH DA-induced cytotoxicity in SH-SY5Y neuroblastoma cells that were much more significant for edaravone and also a relative synergistic effect between EC and edaravone was observed. The apoptotic analysis showed that edaravone alone could decrease early and late apoptosis, whereas EC diminished early apoptosis, but enhanced late apoptosis and necrosis. Besides, co-treatment of edaravone and EC had a synergistic effect on decreasing apoptosis and increasing cell viability. CONCLUSION: The protective effect of edaravone on apoptosis and cytotoxicity was demonstrated clearly and EC had a synergistic effect with edaravone.

Protective effect of thymoquinone, the main component of Nigella Sativa, against diazinon cardio-toxicity in rats.

Several studies have shown that oxidative stress and cell damage can occur at very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin), against DZN cardio-toxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups: control (corn oil gavages), DZN gavages (20 mg/kg/day), Thy gavages (10 mg/kg/day) and Thy + DVN gavages (2.5, 5 and 10 mg/kg/day). Treatments were continued for 28 days, then the animals were anesthetized by ether and superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), lactate dehydrogenize (LDH) and glutathione peroxide (GPX) activity was evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) the heart tissue and creatinephosphokinase-MB (CPK-MB) and troponin (TPI) levels and cholinesterase activity in the blood were evaluated. DZN-induced oxidative damage and elevated the levels of the cardiac markers CK-MB, TPI, MDA and LDH and decreased SOD, CAT and cholinesterase activity and GSH level compared with the control group. Treatment with Thy reduced DZN cardio-toxicity and cholinesterase activity. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents. Administration of Thy as a natural antioxidant decreased DZN cardio-toxicity and improved cholinesterase activity in rats through the mechanism of free radical scavenging.

Expression of MT1 receptor in patients with gastric adenocarcinoma and its relationship with clinicopathological features.

Gastric cancer accounts 8% of the total cancer cases leading to 10% of total cancer deaths worldwide. The indoleamine N-acetyl-5-methoxytryptamine, better known as melatonin, is the principal hormone produced by the pineal gland. Recently, it has been well documented some anti-cancer roles of melatonin in some malignancies as breast and colon cancer; as well as some its protective roles in the GI tract that have been known as free radical scavenger, antimitogenic and apoptotic properties. According to the anti-cancer effects of melatonin, wide distribution of this neurohormone in GI tract and some proposed physiologic and pharmacologic roles for this neurohormone and following our previous study which has shown expression of MT2 receptor in gastric adenocarcinoma, this study initially scheduled to determine the expression of melatonin receptor MT1 in tissue samples of adenocarcinoma cancer patients. A total of 10 gastric adenocarcinoma patients and 10 normal individuals were examined for MT1 gene expression by real-time PCR. Additionally, for screening of different alleles of MT1 in our samples, the SSCP-PCR procedure was developed. Our results have shown interestingly high expression for MT1 receptor in cancer and marginal cancer groups comparing with normal group. Our findings also have shown that a remarkable association between MT1 receptor mRNA levels and grade in individuals over age 50. PCR-SSCP analysis results showed a variation between individuals which may be effective on their gene expression patterns. According to our knowledge, for the first time this study evaluated the expression of MT1 receptor gene in gastric adenocarcinoma tissues which consistent with our previous study but with some difference in comparisons between kind of tissue expression and difference in polymorphisms. Moreover, these results show the defending role of melatonin in the GI system.

Cross state-dependency of learning between tramadol and MK-801 in the mouse dorsal hippocampus: involvement of nitric oxide (NO) signaling pathway.

RATIONALE: Tramadol, an atypical µ-opioid receptor agonist, as a psychoactive drug, is frequently abused by human beings. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help prevent drug addiction and relapse. Previous study revealed that dorsal hippocampus (CA1) plays a crucial role in the retrieval of tramadol-associated memory and that its role depends on the expression of CA1 N-methyl-D-aspartate (NMDA) receptors (Jafari-Sabet et al. Can J Physiol Pharmacol 96:45-50, 2018). OBJECTIVE: To clarify the exact mechanisms involved, the activation of CA1 nitric oxide (NO) signaling pathway by L-arginine (a nitric oxide precursor) on the interaction between tramadol and MK-801 in memory retrieval was examined. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated and a single-trial step-down inhibitory avoidance apparatus was used for the assessment of memory retrieval. RESULTS: Post-training and/or pre-test microinjection of tramadol (0.5 and 1 µg/mouse) and/or a non-competitive NMDA receptor antagonist, MK-801 (0.25 and 0.5 µg/mouse), induced amnesia which were reversed when the same doses of the drugs were administered 24 h later in a pre-test session, suggesting tramadol state-dependent learning (SDL) and MK-801 SDL. The amnesia induced by post-training microinjection of tramadol (1 µg/mouse) was reversed by pre-test microinjection of MK-801 (0.25 and 0.5 µg/mouse). Pre-test microinjection of MK-801 (0.125 and 0.25 µg/mouse) with an ineffective dose of tramadol (0.25 µg/mouse) potentiated tramadol SDL. The amnesia induced by post-training microinjection of MK-801 (0.5 µg/mouse) was reversed by pre-test microinjection of tramadol (0.5 and 1 µg/mouse). Pre-test microinjection of tramadol (0.25 and 0.5 µg/mouse) with an ineffective dose of MK-801 (0.125 µg/mouse) potentiated MK-801 SDL. Pre-test microinjection of ineffective doses of L-arginine (0.125, 025, and 0.5 µg/mouse) improved amnesia induced by the co-administration of tramadol and MK-801. Pre-test microinjection of L-arginine (0.125, 025, and 0.5 µg/mouse) could not reverse amnesia induced by post-training microinjection of tramadol while same doses of L-arginine improved MK-801 response on tramadol SDL. CONCLUSION: The results strongly propose that activation of CA1 NO signaling pathway has a pivotal role in cross SDL among tramadol and MK-801.

Evidence for the Involvement of the Dopaminergic System in Seizure and Oxidative Damage Induced by Tramadol.

Tramadol (TR) is a synthetic analgesic drug with central function that can induce seizures even at therapeutic doses. The exact mechanism of TR effect on seizure generation is not clear, but inhibition of the serotonin and nitric oxide pathways and inhibitory effects on GABA receptors are the most common hypotheses about the seizure-inducing mechanism of the TR. This study aimed to evaluate the role of dopaminergic system on the seizure and oxidative damage induced by TR using agonist and antagonist drugs of this system in the Albino mice. Clonic seizure induced by TR was evaluated as seizure threshold. Haloperidol (0.2 mg/kg, IP), a predominantly D2 receptor antagonist, and cabergolin (0.5 mg/kg, IP), a dopamine agonist specific for the D2 receptors, were injected 60 minutes before the seizure induction. The seizure threshold was significantly increased by dopaminergic antagonist, but it was decreased significantly by pretreatment with the selective agonist. Oxidative stress biomarkers (reactive oxygen species, lipid peroxidation, and protein carbonyl content) significantly increased and glutathione content significantly decreased in brain mitochondria by TR compared with the control group, whereas oxidative markers were decreased significantly after pretreatment with haloperidol compared with the TR group. This study revealed that the dopaminergic system is involved in TR-induced seizure, and meanwhile, inhibition of dopamine D2 receptors can increase the TR threshold seizure and decrease the oxidative damage in the brain mitochondria. Conversely, stimulation of dopamine D2 receptors by cabergolin can decrease the TR threshold seizure and glutathione content in the brain mitochondria.

The Determination of Blood Glucose Lowering and Metabolic Effects of Mespilus germanica L. Hydroacetonic Extract on Streptozocin-Induced Diabetic Balb/c Mice.

Background: The serum glucose lowering, normalization animal body weight, and antioxidative stress effects of Mespilus germanica L. leaf extract were investigated in normal and streptozotocin-induced Balb/C mice. Methods: The phenol and flavonoid of the leaves of M. germanica were extracted by percolation and concentrated using a rotary evaporator. Its total phenol and flavonoid content was determined using folin and aluminum chloride methods, respectively. The study was conducted on 48 matured male Balb/C mice (20-30 g) divided into 6 groups (n = 8). Diabetes mellitus was induced by single intraperitoneal injection of 35 mg/kg of streptozotocin (STZ). Extracts of Mespilus germanica were used orally at the dose of 50, 100, and 200 mg/kg body weight per day for 21 days. Results: Oral administrations of the M. germanica L. leaf extract significantly decreased serum glucose, oxidative stress, and lipid peroxidation and maintained animal body weight during treatment period (p < 0.05) compared to metformin (200 mg/kg) in over 100 mg/kg, 200 mg/kg, and 50 mg/kg dosages, respectively. Conclusions: The present study indicated that the Mespilus germanica leaf extract significantly decreased serum glucose and maintained normal body weight in Balb/C diabetic mice.

Morphine pre- and post-conditioning exacerbates apoptosis in rat hippocampus cells in a model of homocysteine-induced oxidative stress.

Recent investigations indicated that morphine has protective effects in different ischemia/reperfusion models and may protect against neuronal cell death, while other evidence showed that morphine induces apoptosis in neurons. Therefore, the current study was conducted to investigate pre- and post-conditioning effects of morphine on hippocampal cell apoptosis in a rat model of homocysteine (Hcy)-induced oxidative stress. In the present study, 0.5 µmol/µl Hcy was injected into bilateral intrahipocampal in the rat brain and morphine at a therapeutic dose of 10 mg/kg was injected intraperitoneally 5 days before and after Hcy injection in rats. The left and right rat hippocampus were removed for biochemical and histopathological analysis. In addition, hippocampal cell apoptosis was assayed by the TUNEL kit. Our results indicated that malondialdehyde (MDA) and superoxide anion (SOA) levels in the Hcy group were increased significantly compared to the control group (P<0.001). In addition, morphine pre- and post-treatment increased the MDA and SOA levels significantly in rat hippocampus compared with other groups (P<0.001). It was found that Hcy alone induced apoptosis in hippocampus cells and significantly increased the number of TUNEL-positive cells in rat hippocampus compared to the other group (P<0.001). Notably, our results indicated that pre- and post-treatment by morphine increased apoptosis in hippocampus cells compared with the other group (P<0.001). In conclusion, morphine neuroprotection and neurotoxicity needs to be further investigated to determine morphine side-effects in medical applications and to identify new targets for potential therapies.

The effect of epicatechin on oxidative stress and mitochondrial damage induced by homocycteine using isolated rat hippocampus mitochondria.

Oxidative stress and mitochondrial dysfunction are the main suggested mechanisms for neurodegenerative diseases. In this study, we have evaluated the effects of epicatechin (EC) on mitochondrial damage induced by homocycteine (Hcy) using isolated rat hippocampus mitochondria in vivo. EC (50 mg/kg) was gavaged daily for a period of 10 days, starting 5 days prior to Hcy (0.5 µmol/µL) intra hippocampus injection in rats. Mitochondria were isolated from brain by different centrifuge techniques. Mitochondrial function was assayed by MTT test. Also, mitochondrial swelling and oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation and glutathione (GSH), were assayed. Hcy induced mitochondrial dysfunction and swelling. Increase in ROS formation, lipid peroxidation, and decreased GSH were observed after Hcy treatment in isolated brain mitochondria. Furthermore, oral administration of EC significantly decreased the lipid peroxidation and ROS levels and also increased GSH levels. Also, EC treatment significantly improved mitochondrial function. As EC indicated protective effects against oxidative stress and mitochondrial damage induced by Hcy, it is suggested for further trials for prevention or treatments of neurodegenerative disorders such as Alzheimer disease.

Polyphenolic Antioxidants and Neuronal Regeneration.

Many studies indicate that oxidative stress is involved in the pathophysiology of neurodegenerative diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling and ultimately leads to neuronal death by apoptosis or necrosis. To review antioxidants preventive effects on oxidative stress and neurodegenerative diseases we accumulated data from international medical journals and academic informations' sites. According to many studies, antioxidants could reduce toxic neuronal damages and many studies confirmed the efficacy of polyphenol antioxidants in fruits and vegetables to reduce neuronal death and to diminish oxidative stress. This systematic review showed the antioxidant activities of phytochemicals which play as natural neuroprotectives with low adverse effects against some neurodegenerative diseases as Parkinson or Alzheimer diseases.

Low Expression of the bcl2 Gene in Gastric Adenocarcinomas in Mazandaran Province of Iran.

BACKGROUND: Gastric cancer accounts for about 8% of the total cancer cases and 10% of total cancer deaths worldwide. It is the second lethal cancer after esophageal cancer and is considered the fourth most common cancer in north and northwest Iran. The bcl2 family has a key role in the regulation of apoptosis and change in its expression can contribute to cancer. This study initially scheduled to determine the expression of bcl2 gene in tissue samples of adenocarcinoma cancer patients. MATERIALS AND METHODS: A total of 10 samples of gastric adenocarcinoma and 10 of normal tissues from Sari hospital were selected and after DNA extraction from tissues, bcl2 gene expression assayed by real-time PCR. RESULTS: Our results demonstrated higher expression of the bcl2 gene in control compared with cancer and marginal cancer tissues. CONCLUSIONS: On one hand BCL2 plays an important role as an oncogene to inhibit apoptosis; on the other hand, it can initiate cell cycle arrest at G0 stage. Our observed association between its expression and patient survival is quite conflicting and may be tissue-specific. The data suggest expression both tumoural and non-tumoral(marginal) groups have lowered expression than controls (P>0.05). Due to the low number of samples we could not examine the relationship with clinicopathological features. However, bcl-2 expression may be important for prognostic outcome or a useful target for therapeutic intervention.

Genetic and molecular aspects of Helicobacter pylori in gastritis, pre- cancerous conditions and gastric adenocrcinoma.

Gastric adenocarcinoma is one of the most common malignancies worldwide. Many ethological causes have been introduced among which helicobacter pylori, as a gram-negative bacterium has been considered as an important pathological facilitating factor. This agent is also associated with different digestive diseases, such as gastritis, peptic ulcer, and mucosa-associated lymphoid tissue lymphoma. Recently, scientists have been described some molecular aspects that show the role of some apoptotic genes and proteins; for example: P53, Bcl2, C-Myc and Rb-suppressor systems in the H. pylori pathogenesis. Also the relationship between nitric oxide (NOSi genotype) with H. pylori infection has been shown. The aim of this mini-review is to explain better these genetically aspects of H.pylori pathogenesis.

α:Non-α and Gγ:Aγ globin chain ratios in thalassemia intermedia patients treated with hydroxyurea.

OBJECTIVES: To elucidate the possible ways by which hydroxyurea molecules affect globin chain (α or ß-like) synthesis. METHODS: A total of 23 thalassemia intermedia patients (13 male and 10 female) aged between 5 and 26 years were treated for five months with 15 mg/(kg·day) of hydroxyurea. Hemoglobins electrophoresis and globin chain electrophoresis was performed on each sample at different time points before and during the treatment. RESULTS: Fetal hemoglobin increased significantly in most patients and average episodes of transfusion decreased. Both Gγ and Aγ-globin chains increased significantly and α-globin:Nonα-globin chain as well as Gγ-globin:Aγ globin chains ratios decreased. CONCLUSIONS: Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major.

Expression of MT2 receptor in patients with gastric adenocarcinoma and its relationship with clinicopathological features.

BACKGROUND: Gastric cancer accounts 8% of the total cancer cases and 10% of total cancer deaths worldwide. The indoleamine N-acetyl-5-methoxytryptamine, better known as melatonin, is the principal hormone produced by the pineal gland. Recently, it has shown some anticancer role in some malignancies such as breast and colon cancer; also, some of its protective roles in the GI tract are as free radical scavenger and as antimitogenic and apoptotic agents. Based on the anticancer effects of melatonin and wide distribution of this neurohormone in the GI tract and some proposed physiologic and pharmacologic roles for this neurohormone, this study is initially scheduled to determine the expression of melatonin receptor MT2 in tissue samples of adenocarcinoma cancer patients. METHODS: For this aim, a total of 30 gastric adenocarcinoma patients and 30 normal individuals were selected and examined for MT2 gene expression by real-time PCR. RESULTS: Our results have shown interestingly high expression for MT2 receptor in cancer and marginal cancer tissues compared with normal people. CONCLUSIONS: According to our results, it is concluded that for the first time, the expression of MT2 receptor in gastric adenocarcinoma tissues which was in parallel with breast and colon cancer studies and high expression of this receptor in the marginal tissues indicate refractory mechanism which shows the defending role of melatonin in the GI system. Our experiments has not shown any relationship between MT2 receptor expression and grade and clinicopathological features of gastric tumor, so we cannot conclude any relationship between this receptor expression and progression of the tumor, although this expression can be considered as an etiology.

Nitric oxide in the dorsal hippocampal area is involved on muscimol state-dependent memory in the step-down passive avoidance test.

In the present study, the effects of intra-dorsal hippocampal (intra-CA1) injections of nitric oxide (NO) agents on muscimol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retrieval in adult male NMRI mice. Post-training intra-CA1 administration of a GABAA receptor agonist, muscimol (0.05 and 0.1 µg/mouse) dose dependently induced impairment of memory retention. Pre-test injection of muscimol (0.05 and 0.1 µg/mouse) induced state-dependent retrieval of the memory acquired under post-training muscimol (0.1 µg/mouse, intra-CA1) influence. Pre-test injection of a NO precursor, L-arginine (1 and 2 µg/mouse, intra-CA1) improved memory retention, although the low dose of the drug (0.5 µg/mouse) did not affect memory retention. Pre-test injection of an inhibitor of NO-synthase, L-NAME (0.5 and 1 µg/mouse, intra-CA1) impaired memory retention, although the low dose of the drug (0.25 µg/mouse) did not affect memory retention. In other series of experiments, pre-test intra-CA1 injection of L-arginine (0.25 and 0.5 µg/mouse) 5 min before the administration of muscimol (0.1 µg/mouse, intra-CA1) dose dependently inhibited muscimol state-dependent memory. Pre-test intra-CA1 administration of L-arginine (0.125, 0.25 and 0.5 µg/mouse) by itself cannot affect memory retention. Pre-test intra-CA1 injection of L-NAME (0.25 µg/mouse, intra-CA1) reversed the memory impairment induced by post-training administration of muscimol (0.1 µg/mouse, intra-CA1). Moreover, pre-test administration of L-NAME (0.125 and 0.25 µg/mouse, intra-CA1) with an ineffective dose of muscimol (0.025 µg/mouse, intra-CA1) significantly restored the retrieval and induced muscimol state-dependent memory. Pre-test intra-CA1 administration of L-NAME (0.0625, 0.125 and 0.25 µg/mouse) by itself cannot affect memory retention. It may be suggested that the nitric oxide in the dorsal hippocampal area play an important role in muscimol state-dependent memory.