rana keyhanmanesh

Diabetes is a multifactorial disorder that involves several molecular mechanisms and is still one of the key global health challenges with increasing prevalence and incidence. Gut microbiome dysbiosis could activate and recognize receptors that trigger the inflammation response and modulation of insulin sensitivity. In addition, the intricate role of gut microbiota dysbiosis in the onset and development of T2D (Type 2 diabetes mellitus) and associated microvascular complications was identified. These complications include diabetic nephropathy (DN) and diabetic retinopathy (DR), diabetic neuropathy, cerebrovascular disorders, and coronary heart disease. A recent interesting strategy to improve these complications is probiotics administration. The safety and health effects of probiotics against various diseases have been validated by various in vitro, in vivo and clinical studies. In this review, the related mechanisms between the gut microbiome, initiation, and progression of T2D and its common microvascular complications (DN and DR) have been discussed.

 Among varied ω-3 polyunsaturated fatty acid types, the therapeutic properties of docosahexaenoic acid (DHA) have been indicated under diabetic conditions in different cell lineages. Here, we investigated the anti-diabetic properties of DHA in rats with type 2 diabetes mellitus (D2M) focusing on autophagy-controlling factors.

 D2M was induced in male Wistar rats using a single dose of streptozocin (STZ) and a high-fat diet for 8 weeks. On week 2, diabetic rats received DHA 950 mg/kg/d until the end of the study. After that, rats were euthanized, and aortic and cardiac tissue samples were stained with H&E staining for histological assessment. The expression of adhesion molecules, ICAM-1 and VCAM-1, was measured in heart samples using real-time PCR analysis. Using western blotting, protein levels of BCLN1, LC3, and P62 were measured in D2M rats pre- and post-DHA treatment.

 Data showed intracellular lipid vacuoles inside the vascular cells, and cardiomyocytes, after induction of D2M and DHA reduced intracellular lipid droplets and in situ inflammatory response. DHA can diminish increased levels of ICAM-1 in diabetic conditions (PControl vs. D2M rats=0.005) and reach near-to-control values (PControl vs. D2M rats=0.28; PD2M rats vs. D2M rats+DHA=0.033). Based on western blotting, D2M slightly increased the BCLN1 and LC3-II/I ratio without affecting P62. DHA promoted the LC3II/I ratio (P=0.303) and reduced P62 (PControl vs. D2M rats+DHA =0.0433; pD2M vs. D2M rats+DHA=0.096), leading to the completion of autophagy flux under diabetic conditions.

 DHA can reduce lipotoxicity of cardiovascular cells possibly via the activation of adaptive autophagy response in D2D rats.

Parkinson’s disease (PD) is the second most common neurodegenerative disease caused by the loss of dopaminergic neurons. Genetic factors, inflammatory responses, oxidative stress, metabolic disorders, cytotoxic factors, and mitochondrial dysfunction are all involved in neuronal death in neurodegenerative diseases. The risk of PD can be higher in aging individuals due to decreased mitochondrial function, energy metabolism, and AMP-activated protein kinase (AMPK) function. The potential of AMPK to regulate neurodegenerative disorders lies in its ability to enhance antioxidant capacity, reduce oxidative stress, improve mitochondrial function, decrease mitophagy and macroautophagy, and inhibit inflammation. In addition, it has been shown that modulating the catalytic activity of AMPK can protect the nervous system. This article reviews the mechanisms by which AMPK activation can modulate PD.

This study aimed to evaluate the effects of voluntary exercise as an anti-inflammatory intervention on the pulmonary levels of inflammatory cytokines in type 2 diabetic male rats.

Twenty-eight male Wistar rats were divided into four groups (n=7), including control (Col), diabetic (Dia), voluntary exercise (Exe), and diabetic with voluntary exercise (Dia+Exe). Diabetes was induced by a high-fat diet (4 weeks) and intraperitoneal injection of streptozotocin (35 mg/kg), and animals did training on the running wheel for 10 weeks as voluntary exercise. Finally, the rats were euthanized and the lung tissues were sampled for the evaluation of the levels of pulmonary interleukin (IL)-10, IL-11, and TNF-α using ELISA, and the protein levels of Nrf-2 and NF-κB using western blotting and tissue histopathological analysis. 

Diabetes reduced the IL-10, IL-11, and Nrf2 levels (P<0.001 to P<0.01) and increased the levels of TNF-α and NF-κB compared to the Col group (P<0.001). Lung tissue levels of IL-10, IL-11, and Nrf2 in the Dia+Exe group enhanced compared to the Dia group (P<0.001 to P<0.05), however; the TNF-α and NF-κB levels decreased (P<0.001). The level of pulmonary Nrf2 in the Dia+Exe group was lower than that of the Exe group while the NF-κB level increased (P<0.001). Moreover, diabetes caused histopathological changes in lung tissue which improved with exercise in the Dia+Exe group. 

These findings showed that voluntary exercise could improve diabetes-induced pulmonary complications by ameliorating inflammatory conditions.

This study investigated the paracrine therapeutic effects of intra-tracheal administration of bone marrow-derived c-Kit+and c-Kit- cells on the T helper (Th)1/Th2 balance in ovalbumin-induced acute asthma in male rats.

Forty male Wistar rats were randomly allocated into four experimental groups; healthy (group C) and sensitized (group S) rats received PBS (Phosphate-buffered saline); sensitized rats received PBS containing c-Kit- (group S+c-Kit- ) and c-Kit+cells (group S+c-Kit+). Total and percentages of differential leukocytes were calculated in bronchoalveolar Lavage. The lung cellular contents of interleukin (IL)-4, IL-10, and interferon gamma (IFN-γ) mRNAs were measured quantitatively. Moreover, the existence of excessive collagen deposition in pulmonary interstitial space was evaluated through Masson’s trichrome staining.

The results showed the successful homing of c-Kit+cells into the asthmatic niche. The significantly increased total number of leukocyte, eosinophil, neutrophil, and IL-4 mRNA levels, as well as decreased lymphocyte count, IL-10, IFN-γ mRNAs, and IL-4/IFN-γ ratio, were observed in asthmatic rats compared to C group (P<0.001). C-Kit+cells, but not c-Kit- cells, had the potential to participate in these changes (P<0.001 to P<0.05). The deposition of collagen fibers in the asthmatic pulmonary tissue decreased after administration of both c-Kit+and c-Kit-cells, which were more prominent in the S+c-Kit+group.

The results of the current experiment highlighted the therapeutic capacity of c-Kit+cells in the alleviation of asthmatic changes at the cellular level.

 This study investigated the paracrine therapeutic effects of intra-tracheal administration of bone marrow-derived c-Kit+and c-Kit- cells on the T helper (Th)1/Th2 balance in ovalbumin-induced acute asthma in male rats.

 Forty male Wistar rats were randomly allocated into four experimental groups; healthy (group C) and sensitized (group S) rats received PBS (Phosphate-buffered saline); sensitized rats received PBS containing c-Kit- (group S+c-Kit- ) and c-Kit+cells (group S+c-Kit+). Total and percentages of differential leukocytes were calculated in bronchoalveolar Lavage. The lung cellular contents of interleukin (IL)-4, IL-10, and interferon gamma (IFN-γ) mRNAs were measured quantitatively. Moreover, the existence of excessive collagen deposition in pulmonary interstitial space was evaluated through Masson’s trichrome staining.

 The results showed the successful homing of c-Kit+cells into the asthmatic niche. The significantly increased total number of leukocyte, eosinophil, neutrophil, and IL-4 mRNA levels, as well as decreased lymphocyte count, IL-10, IFN-γ mRNAs, and IL-4/IFN-γ ratio, were observed in asthmatic rats compared to C group (P<0.001). C-Kit+cells, but not c-Kit- cells, had the potential to participate in these changes (P<0.001 to P<0.05). The deposition of collagen fibers in the asthmatic pulmonary tissue decreased after administration of both c-Kit+and c-Kit-cells, which were more prominent in the S+c-Kit+group.

 The results of the current experiment highlighted the therapeutic capacity of c-Kit+cells in the alleviation of asthmatic changes at the cellular level.

Nephropathy is known to be the leading cause of kidney failure in diabetic patients. Troxerutin, as a flavonoid component, could provide a novel protective strategy in the prevention of diabetic nephropathy. A large number of reports on the salutary effects of troxerutin inspired us to investigate its effect on the nephropathy signaling events (i.e., expression of TGF-β, miRNA192, and SIP1) in type-1 induced diabetic rats.

50 male Wistar rats were divided into 5 groups including control group, sham group treated with troxerutin for 4 weeks, diabetic group induced by streptozotocin (STZ) injection, DI group including insulin-treated diabetic animals and DT group treated with troxerutin. Ultimately, rat kidneys were extracted, and the level of miR-192 (using qPCR), transforming growth factor-beta (TGF-β), and smad interacting protein 1 (SIP1) using an ELISA kit, was measured.

The level of TGF-β and miRNA192 significantly increased in the diabetic group. However, their expression levels decreased following the administration of troxerutin and insulin (p<0.05) compared to control group. SIP1 was down-regulated in the diabetic group, whereas a spike in the expression levels was observed after troxerutin administration compared to control and troxerutin groups (p<0.05). However, no significant difference was found in the effects of insulin and troxerutin on the level of miR-192, SIP1, and TGF- β.

According to the previous literatures, during the progression of nephropathy, TGF-β represses SIP1 (the repression region in the collagen gene) by increasing the expression of miR-192. Ultimately, in this study, diabetes led to up-regulation of TGF-β while troxerutin proved to have a protective effect on the kidney by increasing SIP and lowering miR-192 levels.

Diabetes mellitus, especially type 2, is conceived as a devastating chronic metabolic disease globally. Due to the existence of an extensive vascular network in the pulmonary tissue, it is suggested that lungs are sensitive to the diabetic condition like other tissues. This study was designed to address the possible effect of type 2 diabetes mellitus on the promotion of pathological changes via vascular injury.

Sixteen male Wistar rats were randomly allocated to the two of Control and T2D groups. To induce type 2 diabetes, rats were received high-fat and a single dose of STZ. On week 12, rats were euthanized and lungs samples were taken. Using Hematoxylin and Eosin staining, the pathological changes were monitored. The expression of vascular ICAM-1 and VCAM-1, and IL-10 was monitored using real-time PCR assay. The level of TNF-α was detected using ELISA assay. Nitrosative stress was monitored using the Griess assay.

 

 Pathological examination in bronchoalveolar discharge revealed the existence of mild to moderate interstitial bronchopneumonia and increased neutrophilic leukocytosis compared to the control. Enhanced ICAM-1 and VCAM-1 expression and suppression of IL-10 was found using real-time PCR analysis (p<0.05). The levels of TNF-α and NO were increased with diabetic changes compared to the control rats (p<0.05).

T2D could promote pulmonary tissue injury via the production of TNF-α and up-regulation of vascular ICAM-1 and VCAM-1. The inflammatory status and vascular ICAM-1 and VCAM-1 increase immune cell recruitment into the pulmonary niche.

The exact role of the progenitor cell types in the dynamic healing of asthmatic lungs is lacking. This investigation was proposed to evaluate the effect of intratracheally administered rat bone marrow-derived c-kit+ cells on ovalbumin-induced sensitized male rats. Forty rats were randomly divided into 4 groups; healthy rats received phosphate-buffered saline (PBS) (C); sensitized rats received PBS (S); PBS containing C-kitˉ cells (S+C-kit-); and PBS containing C-kit+ cells (S+C-kit+). After two weeks, circulatory CD4+/CD8+ T-cell counts and pulmonary ERK/NF-ƙB signaling pathway as well as the probability of cellular differentiation were assessed.  The results showed that transplanted C-Kit+ cells were engrafted into pulmonary tissue and differentiated into epithelial cells. C-Kit+ cells could increase the number of CD4+ cells in comparison with the S group (P<0.001); however, they diminished the level of CD8+ cells (P<0.01). Moreover, data demonstrated increased p-ERK/ERK ratio (P<0.001) and NF-ƙB level (P<0.05) in sensitized rats compared with the C group. The administration of C-kit+, but not C-Kit-, decreased p-ERK/ERK ratio and NF-ƙB level compared with those of the S group (P<0.05).  The study revealed that C-Kit+ cells engrafted into pulmonary tissue reduced the NF-ƙB protein level and diminished p-ERK/ERK ratio, leading to suppression of inflammatory response in asthmatic lungs.

Most male patients with type 2 diabetes mellitus (T2DM) experience infertility. It is well established that regular physical activity could alleviate diabetic infertility symptoms. This study was designed to determine the effect of voluntary exercise on sperm malformation.   Thirty-two male Wistar rats were randomly divided into control (C), diabetic (D), voluntary exercise (Ex), and diabetic-voluntary exercise (D-Ex) groups. Diabetes was induced by an intraperitoneal injection of streptozotocin (35 mg/kg) followed by a high-fat diet for four weeks. Voluntary exercise was performed by placing the animals in the rotary wheel cages for ten weeks. Sperm malformations were analyzed. Moreover, the hypothalamic leptin, kisspeptin, kisspeptin receptors (KissR), as well as plasma LH, FSH, testosterone, and leptin levels were evaluated.  Results showed that induction of T2DM caused increased sperm malformation, plasma, and hypothalamic leptin as well as decreased hypothalamic kisspeptin, KissR, and plasma LH levels compared with the C group (P<0.001 to P<0.01). Voluntary exercise in the Ex group increased hypothalamic KissR, plasma FSH, LH, and testosterone levels compared with the C group; however, it decreased sperm malformation and hypothalamic leptin levels (P<0.001 to P<0.05). Voluntary exercise in the D-Ex group reduced sperm malformation, hypothalamic leptin, and plasma testosterone while elevated hypothalamic kisspeptin and KissR protein levels compared with the D group (P<0.001 to P<0.01).  The results illustrated voluntary exercise reduces sperm malformations by improving the HHG axis and kisspeptin/leptin signaling in rats with T2DM.

Asthma is a chronic pulmonary inflammation occurred in response to different allergens, leading to respiratory system insufficiency. The production of different inflammatory factors and enhanced immune system response may affect the function of other organs. The aim of this study was to investigate the expression of inflammatory microRNAs in cardiac tissue in asthmatic rat model.

In this study, the animals were allocated into Control and Asthmatic rats (n=8). To induce asthma, rats were challenged with ovalbumin. 14 days after induction of asthma, rats were euthanized and Hematoxylin-Eosin staining was performed to assess pathological changes in pulmonary tissue. Serum levels of cardiac enzymes were measured using ELISA kits. Finally, transcription level of inflammatory miRNAs, miRNA-146a and -155, were measured using real-time PCR analysis.

Based on our findings, histological examination indicated the existence of pathological changes in pulmonary tissue after asthma induction. Bright-field analysis revealed an existence of inflammatory response and cytotoxicity in cardiac tissue. Also, the serum levels of CpK-MB, ALT, and AST were significantly higher in the serum of asthmatic group compared to control group (p<0.05). Finally, asthmatic condition induced the expression of (2-fold) miRNA-146a and (1.5-fold)-155 in cardiac tissue, respectively.

As a conclusion, it could be concluded that asthmatic condition induces systemic inflammation in cardiac tissue. On a more general note, we propose that therapeutical approaches directed to inflammatory pathway may be required to preserve cardiac injuries caused of asthma.

This research was designed to demonstrate the impact of voluntary exercise on sperm parameters including sperm count, morphology, motility, viability, testicular apoptosis, oxidative stress, and the mir-34a/SIRT1/p53 pathway in type 2 diabetic rats. 32 Wistar male rats were separated into four groups: control (C), voluntary exercise (VE), diabetic (D), and diabetic rats that performed voluntary exercise (VED). To induce diabetes, animals were injected with streptozotocin (35 mg/kg) after receiving a high-fat diet. The testicular protein levels of SIRT1 and P53, miR-34a expression, MDA, GPx, SOD, catalase, and sperm parameters were evaluated. Diabetes caused increased testicular MDA content, miR-34a expression, acetylated p53 protein expression, and the percent of immotile sperm (p It seems that voluntary exercise has significant positive impacts that can be employed to reduce the complications of type 2 diabetes in the testis of male rats.

The glucose-reducing effects of troxerutin was previously proven. This study was conducted to evaluate troxerutin effect on testicular structure and spermatozoid parameters in type-1 diabetic adult male rats.

Fifty male Wistar rats were randomly classified into 5 groups as follows: control (C), troxerutin (T), diabetic (DM), troxerutin-treated DM (DT) and insulin-treated DM (DI). Testicular structure, apoptosis, lipid peroxidation and antioxidant activity, and spermatozoid parameters were assessed 4 weeks after initiation of the interventions.

The results revealed that diabetes caused testicular stereological changes and significantly increased blood glucose level, testicular MDA content and apoptosis but decreased insulin level, testicular GPX activity, and sperm parameters compared to controls (p

Taken together, troxerutin, comparable to insulin, effectively improved DM-induced testicular dysfunction and sperm parameters in diabetic rats and these effects might be mediated through troxerutin’s anti-apoptotic effects.

Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on tracheal responsiveness to methacholine and insulin resistance in ovalbumin (OVA) sensitized male and female rats. The rats were divided into eight groups (n=6 per group): female with the normal diet (F+ND), male with the normal diet (M+ND), female OVA-sensitized with the normal diet (F+SND), male OVA-sensitized with the normal diet (M+SND), female with high-fat diet (F+HFD), male with high-fat diet (M+HFD), female OVA-sensitized with high-fat diet (F+SHFD), and male OVA-sensitized with high-fat diet (M+SHFD). All rats were fed for 8 weeks with high-fat diet or standard pelts, and for another 4 weeks, they were sensitized with OVA or saline. At the end of the study, the tracheal responsiveness to methacholine, serum insulin, and blood glucose levels was measured. Also, insulin resistance indexes were determined. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration response to shifting to the left. In addition, results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (p<0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (p<0.001). These results suggest that insulin resistance and metabolic syndrome may be involved in the pathogenesis of obesity associated with OVA-sensitized rats condition, especially in female animals.

Epidemiological and clinical studies have shown a close relationship between asthma and obesity. The present study examined the effect of obesity on the airway response to methacholine and the number of inflammatory cells in the bronchoalveolar fluid of ovalbumin-sensitized male rats. Twenty-four male Wistar rats were divided into 4 groups: normal diet (C+ND), OVA‐sensitized with the normal diet (S+ND), high-fat diet (C+HFD) and OVA‐sensitized with high‐fat diet (S+HFD). All animals were fed for 8 weeks with standard diet or high-fat diet, and then were sensitized with ovalbumin or normal saline for another 4 weeks while receiving the designed regimens. At the end of the study, the number of inflammatory cells in bronchoalveolar fluid (BALF) and tracheal responsiveness to methacholine were examined. In diet-induced obesity groups, weight and obesity indices increased (p<0.05 to p<0.001). The results also showed that tracheal responsiveness to methacholine in S+HFD group compared to S+ND group, was significantly increased (p<0.05). In addition, the number of inflammatory cells in the BAL, in the S+HFD group was higher than other groups (p<0.001). the results of this study suggest that the response of the airways to methacholine and the number of inflammatory cells are increased in obese-asthmatic male rats.

Diabetes can gradually cause damage to the function and structure of male gonads. This survey was conducted to investigate the effect of troxerutin on hormonal changes, serum oxidative stress indices, and testicular function and structure in prepubertal diabetic rats.

Fifty prepubertal (6 weeks old) male Wistar rats were divided into five groups including Control, Troxerutin, Diabetic, Diabetic+Troxerutin, and Diabetic+Insulin. Type I diabetes was induced by 55 mg/kg of streptozotocin intraperitoneally. The groups were treated with 150 mg/kg/day troxerutin via oral gavage or 4-6 IU/day insulin via subcutaneous injection for 4 consecutive weeks. Blood sugar (BS) and serum levels of insulin, FSH, LH, testosterone, glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC) were analyzed. Testis and epididymis were removed for histopathologic study and analysis of sperm parameters.

Troxerutin significantly reduced the BS in the diabetic group similar to insulin but could not affect insulin, FSH, or LH significantly. Troxerutin caused a significant increase in testosterone and GPX but had no significant effect on serum MDA, TAC, and SOD levels. In addition, troxerutin had a better effect than insulin on diabetes-induced testicular structural damage. Sperm analysis results also revealed that troxerutin and insulin could improve sperm number, motility, and viability in diabetic rats.

According to these results, it can be derived that administration of troxerutin is a suitable protective strategy for side effects of diabetes in testis of prepubertal diabetic male rats.

Diabetic hearts are resistant to cardioprotection by ischemic-postconditioning (IPostC). Protection of diabetic hearts and finding related interfering mechanisms would have clinical benefits. This study investigated the combination effects of vildagliptin (Vilda) and IPostC on cardioprotection and the levels of autophagy and mitochondrial function following myocardial ischemia/reperfusion (I/R) injury in type-II diabetic rats.
Diabetes was established by high fat diet/low dose of streptozotocin and lasted for 12 weeks. The diabetic rats received Vilda (6 mg/kg/day, orally) for one month before I/R. Myocardial regional ischemia was induced through the ligation of left coronary artery, and IPostC was applied immediately at the onset of reperfusion. The infarct size was assessed by a computerised planimetry and left ventricles samples were harvested for cardiac mitochondrial function studies (ROS production, membrane potential and staining) and western blotting was used for determination of autophagy markers.
None of Vilda or IPostC but combination of them could significantly reduce the infarct size of diabetic hearts, comparing to control (P

Epidemiological and clinical studies indicate a close relationship between obesity and asthma. Here, we determined the impact of diet-induced obesity on the expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA as well as IL-1β protein level and pathological changes in male Wistar rat’s lung after sensitization with ovalbumin (OVA). Twenty male Wistar rats divided into four groups, control with normal diet (C), OVA-sensitized with normal diet (S), control with high-fat diet (C᱐), and OVA-sensitized with high-fat diet (S᱐). All rats fed for 12 weeks with standard pellets or high-fat diet while sensitization and challenging with OVA or saline were done for groups in the last month. In the end of intervention, lung was isolated and tested for the expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA with real time-PCR method, and pathological changes were determined. Diet-induced obesity groups showed increased weight, obesity indexes and lipid profiles The expression levels of IL- β mRNA in OVA-sensitization groups (S and S᱐) showed a significant increase compared with other groups. Also in S᱐ group, expression level of IRAK-1 and TRAF-6 mRNA were markedly higher than other groups (p

Human and animal studies have shown a close relationship between obesity and asthma severity. Here, we examined the effects of diet-induced obesity (DIO) on the expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA in male Wistar rats tracheal after sensitization with ovalbumin (OVA).
Twenty male Wistar rats divided to four groups, included, control group with normal diet (C), OVA-sensitized group with normal diet (S), control group with high-fat diet (C᱐), and OVA-sensitized group with high-fat diet (S᱐). All animals fed for 8 weeks with standard pelts or high-fat diet, and then were sensitized and challenged with OVA or saline for another 4 weeks with designed regimens. At the end of study, trachea isolated and examined for expression levels of IL-1β, IRAK-1 and TRAF-6 mRNA with RT-PCR method.
Diet-induced obesity groups developed increased weight, obesity indexes and lipid profiles (PThe results showed that DIO causes overexpression of IL-1β, IRAK-1 and TRAF-6 mRNA in an experimental model of asthma. Our results suggested that in obese-asthmatic conditions locally production and activation of pro-inflammatory agents can be increased. These findings showed that possible mechanism for obesity-asthma relationships.

In previous studies the therapeutic effects of Nigella sativa have been demonstrated on asthmatic animals. In the present study, the preventive effect of single dose of alpha-hederin, its active constituent, has been evaluated on lung inflammation and some inflammatory mediators in lungs of ovalbumin sensitized rat in order to elicit its mechanism. Forty rats were randomly grouped in 4 groups; control (C), sensitized (S), sensitized pretreated groups with thymoquinone (3 mg/kg i.p., S+TQ) and alpha-hederin (0.02 mg/kg i.p., S+AH). Levels of IL-13 mRNA and miRNA-126 in lung tissue and its pathological changes in each group were assessed. Elevated levels of miRNA-126, IL-13 mRNA and pathological changes were observed in the sensitized group compared to the control group (p The results suggested that alpha-hederin had preventive effect on sensitized rats like thymoquinone. It may intervene in miRNA-126 expression, which consequently could interfere with IL-13 secretion pathway leading to a reduction in inflammatory responses.

Hypoxia is a condition of decreased availability of oxygen. When cells are exposed to a low oxygen environment, they impel the hypoxia responses to adapt to new situation. The hypoxia response leads to the activation of various cellular signaling pathways. The aim of this study was to evaluate the effect of ghrelin on angiogenesis, Hypoxia-Inducible-Factor-1α (HIF-1) and Vascular endothelial growth factor (VEGF) levels in normobaric hypoxia situation. Twenty four animals were divided into 4 groups (n=6): control (C), ghrelin (Gh), hypoxia (H), and hypoxic animals that received ghrelin (H+Gh). Hypoxia (11%) was induced by an Environmental Chamber System GO2 Altitude. Animals in ghrelin groups received a subcutaneous injection of ghrelin (150 μg/kg/day) for 14 days. Our results showed that hypoxia significantly (p<0.05) increased angiogenesis without any significant changes on HIF-1 and VEGF levels, whereas ghrelin significantly (p<0.05) decreased angiogenesis, expression of HIF-1 and VEGF in this condition. Ghrelin administration did not show any significant changes in normal conditions. Ghrelin had no effect on angiogenesis, expression of HIF-1 and VEGF in normal oxygen conditions but it reduced angiogenesis process in lung tissue with reducing the level of HIF and VEGF in hypoxic condition. Therefore, effect of ghrelin on angiogenesis could be related to blood oxygen level.

Nigella sativa (N. sativa) is a spice plant which has been traditionally used for culinary and medicinal purposes. Different therapeutic properties including the beneficial effects on asthma and dyspnea, digestive and gynecology disorders have been described for the seeds of N. sativa. There is evidence of the relaxant effects of this plant and some of its constituents on different types of smooth muscle including rabbit aorta, rabbit jejunum and trachea. The relaxant effect of N. sativa could be of therapeutic importance such as bronchodilation in asthma, vasodilation in hypertension and therapeutic effect on digestive or urogenital disorders. Therefore in the present article, the relaxant effects of N. sativa and its constituents on smooth muscles and its possible mechanisms as well as clinical application of this effect were reviewed.

For determining the mechanism of anti-asthmatic effect of thymoquinone, this investigation evaluated the effect of thymoquinone in the presence of selective A2A and A2B adenosine receptor antagonists (ZM241385 and MRS1706, respectively). Seventy guinea pigs were randomly divided to 7 groups; control (C), sensitized with ovalbumin (S), sensitized groups pretreated with thymoquinone (S+TQ), ZM241385 (S+Anta A2A), MRS1706 (S+Anta A2B), thymoquinone and antagonists (S+Anta A2A+TQ and S+Anta A2B+TQ). Thymoquinone and each of these antagonists with 3 mg/kg dose were injected i.p. on 10th day of sensitization protocol. Tracheal responsiveness (TR) to methacholine and ovalbumin (OA), and total and differential cell count in lung lavage fluid (LLF) in different groups were measured. Increased EC50 and LLF neutrophil count and decreased TR to methacholine and OA, LLF eosinophil and basophil counts were observed in S+TQ group compared to S group (P<0.001 to P<0.05). Significant decrease in EC50 (P<0.01), LLF neutrophil, lymphocyte and monocyte count (P<0.001 for all) and significant increase in TR to OA (P<0.01), LLF total WBC (P<0.01) and eosinophil count (P<0.001) were observed in S+A2A group compared to S+TQ group. There was significant increase in LLF eosinophil and monocyte counts in S+Anta A2B group compared with S+TQ group (P<0.001 for both). In S+TQ+Anta A2A group, there was significant increase in LLF eosinophil (P<0.001) and significant decrease in LLF neutrophil (P<0.01) and monocyte (P<0.001) counts compared with S+TQ group. Thymoquinone affects adenosine receptors, which suggest that some of its anti-inflammatory effects may be mediated by these receptors.

Previous studies have shown that study guides are effective tools that recognize students’ educational needs and help teachers to attain satisfactory results. Unfortunately, this effective learning tool has not been used in the coursework and teaching of basic sciences in Tabriz University of Medical Sciences. Therefore, this study was proposed to evaluate the effects of a study guide in an applied physiology course on the overall learning quality of dental students. In this semi-quasi experimental study, 45 dental and 63 medical students in an Applied Physiology course were included. A study guide was given to the dental students at the beginning of the course. At the end of the course, a final examination was held for both groups separately using the OSCE method. The medical and dental students’ final scores were compared using a T-test with SPSS v.16 software. A 34-question Likert-scaled questionnaire was prepared by researchers to evaluate the experimental group’s opinion about the effects of the study guide on their learning. The final exam score of the dental students was 18.01±1.57, and it was 17.94±1.42 for the medical students. The final score of both groups was not different significantly (p=0.804). Based upon the questionnaire, the dental students believed that study guide significantly improved their knowledge and skills in applied physiology (Mean= 61.12±13.7). Use of a study guide improves both the attitude and knowledge of dental students in the applied physiology course.

Hypoxia is a condition of decreased availability of oxygen. To adapt hypoxia,some changes in blood cells occur in the body. The aim of this study was to evaluate theeffect of ghrelin on different types of blood cell in normobaric hypoxia situation. Thirty-two animals were divided in 4 groups (n=8): control (C), ghrelin (G),hypoxia (H), and hypoxic animals that received ghrelin (H+G). Hypoxia (11%) was inducedby an Environmental Chamber System GO2 Altitude. Animals in ghrelin groups received asubcutaneous injection of ghrelin (150 μg/kg/day) for 14 days. Our results show that ghrelin significantly (p<0.05) increased RBC and Hct levels,whereas it significantly (p<0.05) decreased lymphocytes in the blood. RBC, Hct, Hbconcentration, platelet and MCV increased significantly (p<0.05) in hypoxic conditions butlymphocytes, monocytes and Polymorphonuclears did not show any significant changes.Platelets had a significant (p<0.05) decrease in hypoxic conditions and ghrelinadministration in hypoxic conditions could increase lymphocyte levels significantly(p<0.05). Effect of ghrelin on blood cells could be related to blood oxygen level. Ghrelinin normal oxygen conditions increases RBC and Hct