mohammadraman moloudi

Huntington's disease is a chronic hereditary disorder that causes cognitive and movement defects in affected individuals by progressive destruction of neurons in the cerebral cortex, striatum and the hippocampus. Studies have shown that increased activity of cyclin-dependent kinase-5 (CDK5) plays an important role in the pathogenesis and occurrence of memory impairment in Huntington's disease. Recently, alpha-pinene has been reported to improve learning and memory performance in Alzheimer's and Parkinson's models. Therefore, the aim of this study was to investigate the effect of alpha-pinene on passive avoidance memory and CDK5 gene expression in Huntington's animal model induced by 3-nitro-propionic acid (3-NP).

In this study, 40 male rats were randomly divided into 5 groups: sham, 3-NP (10 mg/kg),and 3 other groups receiving 3-NP (10 mg/kg) + alpha-pinene at doses of 1, 5 and 10 mg/kg (for 3 weeks,via intraperitoneal injection). Passive avoidance memory was assessed through the shuttle box device. Then, the expression level of CDK5 gene was measured by RT-qPCR method in brain cortex and hippocampus.

3-NP injection caused memory impairment by decreasing step through latency (STL). Alpha-pinene at all three doses improved passive avoidance memory performance. Also, 3-NP injection caused a significant increase in CDK5 gene expression level in the brain cortex and hippocampus compared to that in the sham group. The groups which received alpha-pinene at doses of 5 and 10 mg/kg in brain cortex and 1 mg/kg in hippocampus showed decreased expression level of this gene compared to the group that received 3-NP.

The results of this study showed that alpha-pinene improves passive avoidance memory performance probably by reducing the CDK5 gene expression level in Huntington's animal model induced by 3-NP.

This study aimed to compare the effect of different physical training on the mechanism of ceramidedependent insulin resistance in the flexor hallucis longus (FHL) muscle of diabetic rats.

In this experimental study, 7 healthy as a healthy control (HC) group, and 21 diabetics (55 mg/ kg Streptozotocin) Wistar rats (200-220 g; 8-10 weeks old) divided into the diabetic control (DC), moderate continuous training (MCT), and moderate intensity interval training (MIIT) groups. Both MCT (55-70% of maximal oxygen uptake (VO2max), and MIIT (85% VO2max) groups trained for 10-25 minutes at a speed of 10-20 m/minutes. The changes in the expression of blood glucose, insulin, insulin resistance, lipid profile and total ceramide were measured as well as ceramide synthase-1, Glucose transporter type 4 (GLUT4), Protein kinase B known as Akt, phosphorylated protein kinase B known as pAkt, protein kinase C (PKC), and tumour necrosis factor α (TNFα).

Blood glucose, triglyceride (TG) and ceramide synthase-1 (CS1) expression levels in the MCT group decreased in comparison with the DC group. FHL protein expression of GLUT4 in the MCT group was higher than the DC group. FHL expression of GLUT4, pAKT, AKT/pAKT, PKC, CS1 and total ceramide in the MIIT group were higher than the DC group. Cholesterol, low-density lipoprotein (LDL), TG, and TNF-α protein expression in the MIIT group were lower than the DC group. GLUT4, PKC, pAKT, AKT/pAKT in the MIIT group were higher, and total ceramide and TNF-α were lower in the MIIT group than the MCT group.

It seems that both training plan MIIT and MCT have favorable effects on the metabolism of glucose, insulin, lipids, and the decrease of TNFα level in the diabetes, but in connection with the improvement of the ceramides mechanism, it seems that the MIIT training plan is more optimal than MCT training plan.

Oxidative stress is an important factor in the development of memory and learning disorder which can cause neuronal damage in the hippocampus. Alpha-pinene is a polyphenolic compound from the terpene family that has shown important anti-inflammatory, anti-anxiety, antioxidant and neuroprotective effects in the central nervous system and can affect memory. The aim of the present study was to investigate the effect of alpha-pinene on the improvement of working and spatial memory in rats. 

In this study, 24 male rats were randomly divided into 3 groups: control and 2 alpha-pinene groups (5 and 10 mg/kg IP) for 3 weeks. Spatial and working memories were assessed by Morris water maze and Y maze, respectively. Then, malondialdehyde level and total antioxidant capacity in hippocampal tissue were measured. Data were analyzed using one-way analysis of variance and Tukey's post hoc test.

The percentage of alternation in the Y maze increased in the group which had received 10 mg/kg alpha-pinene group compared to those in the control group and the group which had received 5 mg/kg alpha-pinene. The time spent in the target area at the dose of 10 mg/kg of alpha-pinene showed a significant increase compared to that in the control group, but there was no significant difference among the groups in terms of the time to reach the target platform. Alpha-pinene at the dose of 10 mg/kg decreased the level of malondialdehyde in hippocampal tissue compared to the control group, but no significant difference was observed between the groups in terms of total antioxidant capacity.

Alpha-pinene increased spatial and working memory performance in rats. One of the possible mechanisms of memory improvement in the present study could be due to the reduction of malondialdehyde in the hippocampal tissue, as one of the important indicators of oxidative stress in the central nervous system.

Non-alcoholic fatty liver disease, characterized by abnormal fat accumulation in the liver, is associated with obesity and insulin resistance. Vaspin is an adipokine secreted by adipose tissue, and its gene expression increases when insulin sensitivity is reduced. In this study, we made a comparison between 3D and 2D cultures in regard to the effects of vaspin on fatty acid metabolism.

The steatosis model was induced by oleic and palmitic acid in HepG2 cell line in two- and three-dimensional cultures (collagen gel). Then, the cells were treated with 100 ng/ml vaspin for 24 hours. We used Real time PCR for measurement of the expressions of FABP4, MCAD, FAS and ApoB100 genes.

In two- and three-dimensional cultures, we found significant decrease in the expression of FABP4 and FAS genes. There was no significant difference between the expression of these genes in the two- and three-dimensional cultures. We detected significant increase in the expression of MCAD and ApoB100 genes in 2D and 3D cultures. We did not find any significant difference in the expressions of MCAD and ApoB100 genes between two- and three-dimensional cultures.

Alteration of the expressions of the genes involved in uptake, lipogenesis, oxidation and secretion of fatty acids occurred in the group treated with vaspin compared to the control group in the 2-D and 3-D cultures. But, we did not find any significant difference in the expressions of these genes between the 2-D and 3-D cultures.

Probiotics, including lactobacilli, have immunomodulatory activities with promising effects on inflammatory diseases. In this study, we evaluate the effect of Enterococcus durans (Edu) and three various strains of lactobacilli (Lacto-mix), including L. rhamnosus, L. casei, and L. plantarum, to prevent Experimental Autoimmune Encephalomyelitis (EAE) features

C57BL/6 female mice were inoculated with Myelin Oigodendrocyte Glycoprotein (MOG35-55) in CFA (complete Freund’s adjuvant) to induce EAE. Five groups (n=6 in each group) of animals received saline or probiotics by oral gavage with 200 µL of lactobacilli (1.5×108 CFU/mL) for 2 weeks before the immunization and during the test for one month.

Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but a decrease in inflammatory cells in the probiotic-treated animals. Pro-inflammatory cytokines (Interleukin [IL]-17 and Interferon [IFN]-γ) concentration in the supernatant of the brain and spinal cord tissues showed a significant increase in the EAE compared with the normal saline group (P<0.01). While in the spinal cord tissue, there was a decrease in IL-17 in those animals treated with the Lacto-mix and Edu + Lacto-mix (P<0.01) and a significant decrease in IFN-γ in those animals that received Edu (P<0.05). Western blot analysis of matrix metalloproteinase-9 and myelin basic protein showed a decrease and increase in treatment and EAE groups, respectively, compared to the normal control group. 

Our data suggest that probiotic Enterococcus durans and Lacto-mix prevents EAE, but further studies are needed to clarify the exact mechanisms and their application in preclinical and clinical trials.

Trimethylamine N-oxide (TMAO) is emerging as a new generation of metabolites related to the activation of inflammatory reactions in the macrophages during atherosclerosis. Stress-activation of cell surface toll-like receptors (TLRs) as well as nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) is also assumed to be involved in TMAO-induced inflammatory reaction in the macrophages. To elucidate the possible contribution of TLRs and NOX to the mentioned signaling pathway, we aimed to simultaneously evaluate the expression level of TLR2, TLR6, and NOX2 in TMAO-treated macrophages.

2.5 × 106 cells of U937-derived macrophages were treated in triplicates with different concentrations (37.5, 75, 150, and 300 μM) of TMAO for 24 hours. The cells were also treated with tunicamycin (TUN), as a positive control of stress. Normal control group (CTR) cells received no treatment. The viability of treated cells was checked by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole (MTT) assay. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was also used to evaluate the relative expression (fold change) of TLR2, TLR6, and NOX2 at messenger ribonucleic acid (mRNA) levels. One-way analysis of variance (ANOVA) with post-hoc Dunnett’s test was performed to compare every mean with that of the control.

No cell death occurred because of treatments. Dose of 300 μM of TMAO significantly increased the relative expression of both TLR2 and NOX2 compared to the CTR cells (P < 0.001 for both). The elevation of TLR6 was not statistically significant in all groups of TMAO-treated cells (P > 0.050).

Our results provide documentation supporting contribution of TLR2 and NOX2 to previously described inflammatory reactions induced by TMAO in macrophages. In addition, they may clarify the proatherogenic role of TMAO in foam cell formation as well as abnormal activation of macrophages during atherosclerosis.

Depression is one of the most common mood disorders. Considering the evidence on the effect of Cinnamomum on mood disorders, this study investigatedthe effect of hydroalcoholic extract of Cinnamomum (HEC) in an animal model of depression.

Thirty-two male rats were selected and divided into four groups (n=8) including: control, depressed, and depressed treated with200 and 400 mg/kg HEC. Depression induction protocol was conducted in all groups except for the control group. Sucrose preference test (SPT) and forced swimming test (FST) were done to analyze the depression score. After four weeks, the animals brain cortex was removed and BDNF protein and tyrosine receptor kinase B (TrkB) gene expression levels were determined by ELISA and Real Time PCR, respectively.

The results of this study showed that 400 mg/kg of HEC increased the tendency to drink the sucrose solution. Furthermore, immobility time significantly increased in the depressed group compared to the control group while it was attenuated by administration of 400 mg/kg extract on the 28th day versus the depressed group. Also the extract at both doses increased swimming time compared to the depressed group. In addition, an increase in the BDNF protein and TrkB gene expression levels was observed in the prefrontal cortex of the treatment groups.

We found that HEC ameliorated depression symptoms in rats and these effects were probably due to an increase in BDNF proteins and its receptor, TrkB, gene expressions in the prefrontal cortex.

Mood disorders such as anxiety and depression are among the most common psychiatric disorders worldwide. Existing drug therapies have various side effects on the central nervous system. Cinnamomum zeylanicum is a dietary additive and studies have shown that it has antioxidant, anti-inflammatory, analgesic, and neuroprotective effects. Also, in traditional medicine, the sedative properties of cinnamon against anxiety and obsession have been mentioned. Therefore in this study, the effect of Cinnamomum zeylanicum on mood in mice was investigated.

In this experimental study, 144 mice weighing 32±4g were divided in two anxiety (Five groups including control, diazepam 2 mg/kg, and three groups of Cinnamomum hydroalcoholic extract 100,200,400 mg/kg, in each test of the elevated plus-maze and Vogelchr('39')s conflict tests) and depression (Four groups including control and three groups of cinnamon hydroalcoholic extract 100,200,400 mg/kg, in each test of the forced swimming test and tail suspension tests) protocols. Data were analyzed using one-way ANOVA and Tukey’s post-hoc test. P <0.05 were considered significant.

In the anxiety protocol, the results of the elevated plus-maze test showed that the Cinnamomum hydroalcoholic extract at doses of 200 and 400 mg/kg significantly (P <0.01, P <0.001) reduced anxiety. In the depression protocol, the results of the forced swimming test and tail suspension test showed that the Cinnamomum hydroalcoholic extract at a dose of 400 mg/kg was significantly (P <0.05) increased swimming time and mobility compared to the control group.

The results of this study showed that the Cinnamomum hydroalcoholic extract reduced anxiety, increased mobility, and finally mood in mice.

There are reports for analgesic, anti-inflammatory, hypnotic, neuroprotective and anti-oxidative effects of safranal. The aim of this study was to investigate the analgesic effects of safranal using acute pain method in rat and determine the role of GABAergic and Opioidergic pathways.

Wistar male rats were randomly divided into six groups (n=6). Experimental groups including: Control, safranal (1, 2, 4, mg/kg, ip) and the most effective dose of safranal in combination with naloxone or flumazenil receiving groups. The analgesic effect was assessed by plantar apparatus in 30, 60 and 90 min after drugs or vehicle administration.

Our results showed that safranal injection (2 mg/kg, ip) significantly increased the time delay in response to thermal inducing pain effect at 30, 60 and 90 min after injection compared with the control group(P <0.05). While, the administration of flumazenil with the same dose, prevented analgesic effect of safranal at all three times (P <0.05).

Our findings support the analgesic effect of safranal. Considering the effects of flumazenil in preventing the safranal analgesia, it seems that GABAergic system may mediate the analgesic effect of safranal.

Ulcerative colitis (UC) is an inflammatory disease which is characterized by infiltration of inflammatory cells, crypt abscesses, distortion of the mucosal glands, and goblet cell depletion. The existence of neutrophil‑rich inflammation in colon tissues of patients with UC is one of the most significant histological features of this disease. Nonetheless, the expression of CXCR chemokine receptors which appear as the main chemical mediators governing the migration of neutrophils into the mucosal tissue of patients with UC has not been well clarified.

In this experimental study, the UC model was induced in Wistar rats by administration of 2 ml 4% acetic acid into the large colon through the rectum. Animals were anesthetized after 48 h; their colon tissue samples were isolated for macroscopic and histopathological examination. The expression of receptor1‑7 of CXC chemokine was assessed by quantitative reverse transcription‑polymerase chain reaction (qRT‑PCR) technique.

Heavy infiltration of neutrophils, coagulative necrosis, and ulcers were observed in H and E staining, which pathologically proved the UC model. qRT‑PCR results indicated that CXCR2 as one of the important ELR+ chemokine family receptors bears the highest expression in the UC group (32 fold) than the control group (P ≤ 0.05). In addition, other CXCRs of this group including CXCR1 did not possess any change (P > 0.05). In contrast, RLR negative chemokine family receptors did not show any changes with the normal group.

The results showed that CXCR2 is the only receptor for CXCL family which was remarkably upregulated in experimental UC and that CXCR2 might play a significant role in the pathogenesis of UC.

Cholestasis is characterized by blockade of bile flow from the liver to the intestine, which leads to accumulation of bile acids within liver and plasma; it is associated with metabolic disorders and cause hepatocellular necrosis and apoptosis during cholestatic liver diseases. Mitochondria are critical cellular organelles that produce most of the cellular energy. Mitochondrial morphology varies from an interconnected filamentous network to isolated dots. These processes are called mitochondrial fission and fusion. Disrupted mitochondrial morphology has been observed in cholestatic liver disease. Optic Atrophy 1 (OPA1) is one of the proteins involved in mitochondrial fusion and plays an anti-apoptotic role. The aim of this study was to evaluate the effect of α-lipoic acid (LA) on OPA1 gene expression in pancreas of rat after bile duct ligation (BDL).

Thirty-six male Wistar rats were randomly divided into six groups each containing six rats including: control, sham-operated, cholestatic, cholestatic+LA, cirrhotic, and cirrhotic+LA. After 14 days in cholestasis groups and six weeks in cirrhosis groups, serum samples and liver and pancreas tissue samples prepared for total bilirubin assays, histopathological analysis and pancreatic OPA1 gene expression evaluation by Real-time PCR technique. Total bilirubin data and gene expression data were analyzed by one-way ANOVA and Kruskal-Wallis statistical tests. 

The results revealed that serum levels of total Bilirubin were significantly increased in BDL groups as compared with the control and sham operation groups (P<0.0001). Concerning histology, the inflammation Symptoms and tissue necrosis were noted with BDL group. These symptoms were reduced by lipoic acid treatment in the cholestatic group. The result of pancreatic OPA1 gene expression showed the significant increase in cholestatic rats and significant decrease in cirrhotic groups as compared with other groups (P<0.05). In cholestatic group, restoring the expression of OPA1 gene was shown in the presence of lipoic acid.

Changing OPA1 gene expression in obstructive rat suggest the causal role of mitochondrial dynamics in pathogenesis of cholestatic disease. In this study, the effect of lipoic acid in OPA1 mRNA level reflects implications of oxidative stress in signaling pathway of cholestasis.

This study aimed to investigate sleep architecture in patients with primary snoring and obstructive sleep apnea.
In this study, we analyzed polysomnographic data of 391 clients who referred to Sleep Disorders Research Center (SDRS). These people were classified into three groups based on their Apnea-Hypopnea Index (AHI) and snoring; control, Primary Snoring (PS), and Obstructive Sleep Apnea (OSA) group. Sleep architecture variables were then assessed in all groups.
The results of this study indicated a decrease in deep sleep or Slow Waves Sleep (SWS) and increase in light sleep or stage 1 of non-REM sleep (N1) in OSA patients compared with the control and PS groups. After controlling the effects of confounding factors, i.e. age and Body Mass Index (BMI) (which was performed through multiple regression analysis) significant differences were observed among the three groups with regard to N1. However, with regard to SWS, after controlling confounding variables (age and BMI), no significant difference was found among the groups.
The results indicated that OSA, regardless of age and BMI, may increase light (N1) sleep possibly via a decline in blood oxygen saturation (SpO2). Such increase in N1 may be responsible for brain arousal. In addition, by controlling confounding factors (age and BMI), OSA did not affect SWS in OSA patients. However, further research is necessary to determine sleep architecture in more detail in the patients with OSA.

Androgenic alopecia (AGA) is one of the most common problems among men; in some societies, 50 percent of 50-years-old men are involved. In the past, opium versions of therapeutic compounds for the treatment of hair loss were used. Therefore, this study aimed to examine the relationship of opium consumption and androgenic alopecia in men.
In this case-control study, 604 men referred to the Isfahan Amin Hospital, Iran, were enrolled. The sampling method was a simple classification (convenient) and men were divided to 2 equal groups of control (non-consumer of opium) and addict (consumer of opium). The intensity of androgenic alopecia was compared on the basis of a Hamilton Norwood scale. Data were collected using physical examination and a researcher-made questionnaire. Statistical analysis was carried using chi-square, Student's t, Spearman and One-way ANOVA tests.
Findings: Percentage frequency of androgenic alopecia in addict men was significantly less than control group (P Our finding indicates that the prevalence of androgenic alopecia in opium-addict men is lower than non-consumer men.

The stimulation of neural stem cells (NSCs) differentiation into neurons has attracted great attention in management of neurodegenerative disease and traumatic brain injury. It has been reported that selegiline could enhance the morphologic differentiation of embryonic stem cells. Therefore this study aimed to investigate the effects of selegiline on NSCs differentiation with focus on the role of neurotrophic factor gene expression. The NSCs were isolated from lateral ventricle of C57 mice brain. The cells were exposed to selegiline in nano to micromolar concentrations for 24 hr or 72 hr. In order to assay the effect of selegiline on NSCs differentiation into neurons, astrocytes and oligodendrocytes, immunocytochemical techniques were utilized. Samples were exposed to specific antibodies against neurons (β tubulin), astrocytes (GFAP) and oligodendrocytes (OSP). The expression of BDNF, NGF and NT3 genes was investigated using Real-Time PCR. Our findings revealed that selegiline increased NSCs differentiation into neurons at 10-7 and 10-8 M and decreased the differentiation into astrocytes at 10-9,while oligodendrocyte did not significantly change in any of the used concentrations. In addition data analyses showed that selegiline increased BDNF, NGF and NT3 gene expression at 24 hr, but did not change them in the other time of exposure (72 hr) except 10-7 M concentration of selegiline, which increased NT3 expression. Our results indicate selegiline induced the differentiation of NSCs into neurons and in this context the role of neurotrophic factors is important and should be considered.

A known problem of chronic administration of opioid is tolerance to its analgesic effect. Co-administration of a non-opioid analgesic may help reducing the opiate dose and consequently tolerance and dependency. It is reported that repeated use of methylphenidate, one of amphetamines, increased the expression of µ opioid receptor and had antinociception. Therefore, this study aimed to evaluate the effect of methylphenidate on methadone-induced analgesia. Nine groups of 8 male rats weighting 270 ± 20 g were randomly selected; control group received 1 ml/kg oral normal saline, metylphenidate groups received 5, 10 and 15 mg/kg oral metylphenidate, methadone groups received 5, 10, 20 mg/kg oral methadone, and combined groups received 5 mg/kg methadone +5 or 15 mg/kg methylphenidate orally. Pain was measured using plantar test apparatus. Only, 15 mg/kg methylphenidate produced significant analgesic effect. In addition, co-administration of non-effective doses of methylphenidate and 5 mg/ kg methadone significantly increased the analgesic effects of methadone at 60 minutes after gavage. We found that methylphenidate potentiate the analgesic effects of methadone in rats.

Background and The exact mechanisms of morphine dependence and withdrawal syndrome remain unclear. Many studies have been performed to find a drug for prevention of withdrawal symptoms. The aim of this study was to evaluate the effect of mefloquine (a gap junction inhibitor) on morphine withdrawal symptoms in male rats. In an experimental study, adult male Wistar rats weighting 225± 275 g were randomly divided into 6 groups (n=8 per group). In order to induce dependency, additive doses of morphine were injected subcutaneously for 13 days. At day 13, after the last dose of morphine, saline (1 ml/kg: control) or mefloquine (5, 15, 30 mg/kg) were injected intraperitoneally. After 30 min, all groups received naloxone (4 mg/kg, ip) and the withdrawal signs including jumping, rearing, genital grooming, abdominal writhing, body grooming and wet dog shake, were recorded for 60 minutes. The results showed that mefloquine in all used doses decreased the withdrawal symptoms and the total withdrawal scores compared to control group. Mefloquine was found effective as a gap junction inhibitor in decreasing the symptoms of morphine withdrawal syndrome.