نوروز دلیرژ

 A fourth of all cancers in women in the country are breast cancer, making it the most common and fatal cancer in women. Some novel approaches are being implemented to reduce the impact of cancer. Thus, this study was conducted to treat breast cancer using dendritic cells in mice.

The study used the 4T1 cell line to induce breast cancer in Balb/C mice. After tumor induction, the mice were divided into three groups: healthy control, tumor control, and dendritic cell-treated groups. After developing palpable tumors, each group was treated with one million dendritic cells twice at a two-week interval. Body weight, tumor weight, and breast tissue samples were taken for pathological examination. Cells were photographed during the 9-day dendritic cell culture period. One-way analysis of variance (ANOVA) and Duncan's test were used in SPSS V.24 to analyze the data at the 0.05 significance level.

In the dendritic cell treatment group, the ratio of tumor weight to body weight went down, and the amount of tumor weight loss was balanced out compared to the tumor control group. The dendritic cell receiving group also had a lot more tumor growth inhibition. The dendritic cell-treated group showed an increase in the number of immune cells in the tumor tissue.

Treatment with dendritic cells for the treatment of breast tumors enhances the immune response against the tumor.

Nanotechnology mainly shows its inhibitory effect on the tumor microenvironment by modulating the immune suppression mechanism. Success in this field largely depends on the physicochemical characterization of nanoparticle vaccines. The goal of this study was to produce anti PD-L1 monoclonal antibody decorated nanoparticles containing linrodostat mesylate with desirable properties and to investigate their physicochemical characterization . Nanoparticles were prepared using double emulsion-solvent_evaporation method. Size and morphology of the particles were investigated using the FESEM microscope method and polydispersity index and zeta potential of the particles using the DLS method, as well as release rate and encapsulation efficiency. The research results showed that nanoparticles had a suitable uniform dispersion. In the group of nanoparticles containing linrodostat mesylate, the polydispersity index of particles was 0.06 and after the binding of anti-PDL1 monoclonal antibody was 0.24. All particles were spherical with a smooth surface. The ideal particle size for nanoparticles containing linrodostat mesylate was estimated to be 210.14 nm, and it was estimated to be about 270.35 nm after binding anti-PDL1 monoclonal antibody to nanoparticles. Binding of anti-PDL1 monoclonal antibody decreased the amount of encapsulated linrodostat mesylate. The release of linrodostat mesylate was biphasic, it has an initial phase with a steep slope and the next phase is a slow and controlled release. The results showed that the vaccine based on nanoparticles produced by the double emulsion-solvent-evaporation method containing linrodostat mesylate and decorated with anti-PDL-1 monoclonal antibody has very suitable physicochemical characterization to be used as an immunotherapy vaccine.

Mesenchymal stem cells (MSCs) are multipotent, non-hematopoietic precursor cells that can be found in many adult tissues. The multipotency and immunomodulatory potential of MSCs make these cells a remarkable tool for the treatment of some diseases. It seems that stimulation of toll-like receptors expressed on the surface of mesenchymal stem cells may potentiate the immunomodulatory potential of these cells. This study was conducted to investigate the effects of polarized bone marrow-derived mesenchymal stem cells from mice on the cytotoxic activity of natural killer (NK) cells.

MSCs were isolated from the bone marrow of the femur and tibia of NMRI mice. The third passage of cells was treated with LPS and Poly I-C, then the effects of polarized MSCs, as well as their culture supernatant, on the cytotoxic activity of NK cells against lymphoid cancer cells Yac-1 (as target cells), were evaluated using flow cytometry after 12, 24, and 72 hours.

MSCs treated with LPS and Poly I-C, and their respective culture supernatants, decreased the percentage of dead cells (necrosis and apoptosis) (38% and 35% respectively) compared to untreated MSCs (44%). In the case of cell viability, this effect was the opposite; that is, the untreated cells showed higher viability.

Previous studies indicated that MSCs inhibit the expansion and cytotoxicity of NK cells on tumor cells; however, our results revealed that MSCs treated with LPS potentiated the inhibitory effects of MSCs on NK cell activity.

Caffeine, a natural substance found in coffee and tea, can have anticancer effects by reducing cell proliferation and inducing apoptosis. On the other hand, nanocarriers can be used as a suitable method for properly delivering drugs at the tumor site, protecting drugs, targeting specific organs, and high durability. This study aimed to produce caffeine nanoemulsions and evaluate its anticancer effects on leukemia cells.

In this experimental study after producing caffeine nanoemulsion and evaluating its physicochemical properties, K562 cancer cells were treated with different concentrations of these caffeine nanoemulsions and free caffeine, and then, the viability of cancer cells was determined using Neutral Red and Trypan Blue methods. The AO/PI test was also used to evaluate the rate of apoptosis and necrosis. Data were analyzed by one-way ANOVA and Tukey's test using SPSS v.16 software.

The results showed that the decrease in the viability of cells treated with different concentrations of caffeine nanoemulsion and free caffeine was both concentration- and time-dependent, and caffeine nanoemulsion has more cytotoxic effects on cancer cells than free caffeine. The results also showed that caffeine nanoemulsion caused more apoptosis-type cell death in treated cancer cells.

The present study indicated a decrease in the viability and induction of apoptosis in K562 cells as a chronic myeloid leukemia cancer cell line after exposure to caffeine nanoemulsion, and caffeine nanoemulsion can be suggested as an adjuvant therapy along with other treatments for the treatment of chronic myeloid leukemia cancer.

 The present study aimed to assess the effects of spleen-cell-conditioned medium treated with different concentrations of adenosine on the 4T1 breast cancer cell line.

For this purpose, mouse spleens were isolated in completely sterile conditions, and splenocytes were then isolated for culture. Different concentrations of adenosine (25, 50, and 100 μM doses), phytohemagglutinin solution, and culture medium containing Fetal Bovine Serum (FBS) were added to splenocytes and incubated for 72 h. Thereafter, splenocytes were incubated by adding fresh culture medium without serum for 24 h. This fluid was collected and stored in a freezer at -80 for further assessment. The conditioned medium was mixed with an equal volume of the culture medium containing 4T1 cancer. The studied groups included control containing untreated 4T1 cancer cells, spleen-cell-conditioned medium untreated with adenosine, spleen-cell-conditioned medium treated with adenosine ∼25 μM, spleen-cell-conditioned medium treated with adenosine ∼5 μM, and the fifth group: spleen-cell-conditioned medium treated with adenosine ∼10 μM. After 48 h, the viability of 4T1 cells was measured by MTT and NR tests, and the amount of apoptosis in the cells was evaluated by vital dye staining.

The spleen-cell-conditioned medium is able to damage cancer cells and causes a significant reduction in neutral red uptake or damage to the cancer cell membrane. In the MTT test, a decrease was observed in the mitochondrial power; that is to say, a decrease in cell viability of cancer cells compared to the control group. In the apoptosis test, a percentage of cancer cells changed color from green to red. This function of the conditioned medium was strengthened by adding adenosine ∼25 μM to the spleen cell conditioned medium so that the amount of neutral red uptake was markedly reduced and caused a further decrease in the mitochondrial power of cancer cells. It also increased apoptosis in cancer cells so that most cancer cells changed color to red. The beneficial effect of the spleen-cell-conditioned medium decreased by increasing the concentration of adenosine to 5 µM so that there was no statistically significant difference with the untreated spleen-cell-conditioned medium. When we increased the concentration of adenosine to 10 µM, the killing efficacy disappeared, and there was no significant difference with the control group.

Based on the results, the spleen-cell-conditioned medium was able to kill a percentage of cancer cells. When we treat the spleen-cell-conditioned medium with low concentrations of adenosine, we observe a marked improvement in the killing efficacy of cancer cells, as well as an interaction between immune cells and cancer cells. Nonetheless, when the concentration of adenosine increases, the killing efficacy of cancer cells is lost and completely reversed, resulting in the growth of cancer cells.

Colorectal cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer related death for both men and women in the United States of America (US) and also, is the third and fourth common cancer in Iranian men and women, respectively. It is curable in its early stages; we hypothesized” the inflammatory gene expression level of the peripheral monocytes of CRC patients is different from control healthy persons”. Therefore, this research was done with the aim of finding of the role of inflammation in the formation of CRC to help diagnosis and treatment of CRC in its early stages on the basis of its immunopathological view.

Inthis case-control study, the expression level of TLR2, TLR4, NLRP3 and NOS2 genes was compared following RNA extraction and cDNA synthesis from isolated monocytes of stage II CRC patients (confirmed by TNM method and before any chemotherapyand radiotherapy n=12) versus non-CRC healthy/controls (referred for CRC screening n=12) by qPCR method. The β- actin gene was used as the reference gene in this research.

In CRC patients’ monocytes, the expression levels of TLR2 and TLR4 genes were significantly less than those of healthy controls (p < 0.05). The NLRP3 gene expression level in CRC group was slightly higher but, not significant. In contrast, the expression level of NOS2 gene in CRC group was significantly higher than that of in healthy controls (p < 0.05).

On the basis of the variations of the gene expression levels of TLR2, TLR4 and NOS2 in monocytes of stage II CRC patients and the role of inflammation in its formation, it is possible using this variations as CRC prognosis and in time treatment along with other methods; though, it needs more investigations.

The influenza virus causes hundreds of deaths in the world. Despite the availability of some authorized vaccines for all age groups and its approved beneficial effects, the influenza is still a major problem for public health.

In this study, the adjuvant of MF59 was developed by methylglycol-chitosan. The physico-chemical characteristics and immune response stimulation of novel adjuvant were measured in combination with the influenza virus.

The new adjuvant was produced with a nano-droplet diameter of 156 and Zeta potential of 29. The pH of adjuvant was not significantly changed for two years. Immunization of mice with developed adjuvant makes more HAI titer than MF59 adjuvant.

The favorable characteristics of physico-chemical properties and lack of local side effects of developed adjuvant as well as its strong humoral immunity can introduce it as a novel MF59 adjuvants.

Asthma is a chronic inflammatory disease of the airways that is associated with excessive irritation and airway obstruction. The aim of the present study was to investigate the immunomodulatory effects of betaine on experimental model of asthma in Balb/c mice.

The statistical population consisted of 32 Balb/c mice that were randomly divided into four groups (n=8 per group). One group (control) was not sensitized with ovalbumin to induce experimental asthma. Experimental asthma was induced in other three groups by injecting ovalbumin. These groups were treated with saline phosphate buffer, betaine (1% w/w), and prednisolone (3 mg/kg) in drinking water, for 81 days after induction of the disease, respectively. Then, blood and spleen samples were collected for biochemical studies.

Betaine treatment of ovalbumin-sensitized mice significantly reduced IgE antibody production, spleen cell proliferation, IL-5 and IL-17 levels, and significantly increased TGF-β and INF-γ levels (P<0.05).

Betaine as a naturally occurring chemical in the body has significant effects on IgE production and levels of some key cytokines of asthma. So, this substance could be considered as as a possible candidate for modulating immune responses in asthma.

Allergic diseases have increased in the last decade worldwide and researchers have been trying to introduce new strategies and drugs to treat these types of diseases. Nicotine shows anti-inflammatory properties and the studies have revealed that it can reduce the inflammation and the allergic responses. The mammalian target of rapamycin (mTOR) is a multifunctional protein kinase that forms two complexes in the signaling pathway. It has been shown that mTOR Complex 2 (mTORC2) tends to promote the immune response toward Th2. Also, the studies have indicated that the signal transducer and activator of transcription 3 (STAT3) is an essential transcription factor in anti-inflammatory responses and nicotine exert its anti-inflammatory effects using the STAT3 signaling pathway In this experimental Study, we investigated the effects of nicotine on the expression RICTOR-mTORC2 and STAT3 genes in a mouse model of allergic asthma. The mice were sensitized using ovalbumin and alum and 2 weeks later treated tree times with nicotine in the concentration of 10 mg/kg every other day. The mice were challenged with ovalbumin aerosols on days 35, 38 and 41 and sacrificed the next day Our results showed that nicotine treatment resulted in down-regulation of RICTOR-mTORC2 expression. Also, the results indicated that nicotine could up-regulate the expression of STAT3 Such data proposed that nicotine administration may decrease allergic responses and the inflammation in the airways of the allergic mice by down-regulating the expression of RICTOR-mTORC2 and up-regulating the expression of STAT3 genes.

The anti-inflammatory effects of cabergoline have been documented in various studies. The purpose of the present study was to evaluate the effects of cabergoline administration (as a potent D2 agonist) on clinical aspects and immune responses in rheumatoid arthritis (RA) induced in Wistar rats. In the present experimental study, the population consisted of 40 male Wistar rats with a weight range of 160 to 180 g. Animals were randomly allocated into four groups of 10, including the control group (healthy), RA group treated with PBS (100 mg/kg orally), RA group treated with cabergoline (50 µg/kg-orally) and ultimately RA group treated with Prednisolone (10 mg/kg orally). Changes in severity of disease and changes in temperature were recorded every three days. All treatments were initiated at day 7, after induction and observation of the first symptoms of foot inflammation in all rats. Finally, the serum of rats was isolated to evaluate the levels of nitric oxide (Griess assay) and myeloperoxidase (evaluation of the ability to the reduction of hydrogen peroxide). Spleen cells were isolated in sterile conditions in order to evaluate the lymphocyte proliferation rate (MTT reduction assay), the intensity of the respiratory burst (NBT reduction assay), and the potential of neutral red phagocytosis. Data were analyzed using Kruskal-Wallis statistical tests and one-way ANOVA and Tukey tests. The cabergoline drug was similar to prednisolone, which led to a reduction in the severity of the disease and the swelling of soles of the feet (p=0.15). The serum levels of nitric oxide (p=0.0001) and myeloperoxidase (p=0.0001), the intensity of the respiratory burst of splenic phagocytic cells (p=0.002) and the proliferation rate of splenic lymphocytes (p=0.02) were significantly decreased in both treatment groups. Prednisolone indicated a more profound effect than cabergoline in reducing the lymphocyte proliferative index (p=0.001), while cabergoline effectively reduced respiratory burst activity (p=0.002). Moreover, cabergoline significantly revealed a more profound effect than prednisolone in reducing the increased levels of neutral red uptake by splenic phagocytic cells (p=0.01). Considering the appropriate results in the animal model, the use of cabergoline may be considered as a useful approach to control RA.

Cancer immunotherapy, despite its many benefits, faces major challenges. Nanoparticles are drug delivery systems that may address these challenges. The goal of this study was to produce the tumor cell lysate and Poly-IC loaded nanoparticles with desirable properties and evaluation of their therapeutic effects in mouse model of breast cancer. Nanoparticles were prepared by the double emulsion solvent-evaporation method, using poly (vinyl alcohol) (PVA) as a surfactant. Effects of molecular weight variation and the degree of hydrolyzation of PVA were investigated for the particle size, polydispersity index, encapsulation efficiency and the residual surfactant percentage of nanoparticles. 4T1 Cell line was used to induce the breast tumor in mice. To evaluate the effectiveness of the vaccine, tumor growth rate, proliferation of splenic cells by MTT assay and Delayed Type Hypersensitivity (DTH) reaction were evaluated. These results showed that the use of polyvinyl alcohol with a molecular weight of 13-23 kDa and 87-89% hydrolysis, produced nanoparticles with desirable properties. Although injection of nanoparticles containing tumor cell lysate with or without poly-IC to mice, caused a significant decrease in tumor growth, increased splenic lymphocyte proliferation, and delayed type hypersensitivity response in these two groups. But these changes, in the group that received nanoparticles containing the tumor cell lysate with Poly-IC were more significant than other groups. The results showed that the co-encapsulation of tumor cell lysate and poly-IC in one nanoparticle, due to the effects of Poly-IC on the maturation and activation of dendritic cells, enhance anti-tumor immune responses and can be considered as an effective therapeutic strategy for the treatment of breast cancer.

Several studies have shown that pentoxifylline is an antioxidant and anti-inflammatory agent. Pentoxifylline (PTX), has been shown to exert protective effects on autoimmune disorders. The objective of the present study was to examine the effect of pentoxifylline on histopathology of pancreas in diabetic mice.
Diabetes was induced by multiple injection of low-dose streptozotocin (40 mg/kg/day for 5 consecutive days) in male C57BL/6 mice. After induction of diabetes, mice were treated with pentoxifylline (100 mg/kg/day i.p.) for 21 days. The nitric oxide levels were evaluated in spleen cell culture supernatant. Pancreases were isolated and stained by hematoxylin & eosin (H&E) and Gomori aldehyde fuchsin (GAF).
Pentoxifylline treatment significantly inhibited the production of nitric oxide (p These findings indicated that pentoxifylline might have a therapeutic effect against the autoimmune destruction of the pancreatic beta-cells during the development of STZ-induced type 1 diabetes in mice.

Backgrounds & Type 1 diabetes is an auto-immune disease and caused by insufficient insulin production by the body. All-trans Retinoic Acid (ATRA) is an antioxidant, anti-cancer and anti-inflammatory agent. The objective of the present study was to investigate the effects of ATRA on histopathology of pancreas in diabetic mice.
Material & Diabetes was induced by multiple low-dose of streptozotocin injection (40 mg/kg/day for 5 consecutive days) in male C57BL/6 mice. After induction of diabetes, mice were treated with ATRA (20 mg/kg/day i.p.) for 21 days. On the last day, pancreases were isolated and stained with hematoxylin &eosin (H&E) and Gomeri aldehyde fuchsin (GAF) for histological analyses (the number of islets and β cells, diameter of islets) of pancreas.
ATRA treatment in streptozotocin-induced diabetic mice was increased the mean diameter of islets and the number of islets and beta cells compared to the diabetic group. (p The administration of ATRA improved pancreas tissue during destruction of the pancreatic beta-cells in STZ-induced type 1 diabetes in mice.

The positive effect of mesenchymal stem cells in healing of various types of tissue damage such as burn has been reported. The therapeutic potential effects of mesenchymal stem cells influenced by certain agonists from their surface called Toll like receptor (TLR) can be modified into proinflammatory and anti-inflamation phenotypes. It is believed that modification of phenotypes of mesenchymal stem cells can affect their therapeutic function. Therefore, the aim of this study was to assess the influence of Poly(I:C) (TLR3 agonist) versus LPS (TLR4 agonist) in stimulating mesenchymal stem cells and alteration of the therapeutic potential of these cells for the treatment of third-degree skin burns in mice which was performed at institute of Bio-technology, Urmia University, Urmia, Iran.
Total 36 male mice aged 7-8 weeks with 25-30 gr average weights were selected. Based on burn standard method, a stainless-metal rod was heated to 100 in boiling water and burn wounds of 9 second duration were created on each mouse. Within an hour of burn induction, the mice were randomly assigned to four groups, control group with daily application of silver sulfadiazine gel, treatment 1 was treated by receiving subcutaneously 106 unstimulated mesenchymal cells, treatment 2 was treated by receiving subcutaneously 106 lipopolysaccharide (LPS)-stimulated mesenchymal cells, treatment3 was treated by receiving subcutaneously 106 Poly (I:C)-stimulated mesenchymal cells. Biopsies were taken from wounds and some normal tissues around it on days 7, 14 and 21 after burn induction. All samples were examined histopathologically by Hematoxilin-Eosin and masson trichrome stains in terms of thickness of the granulation tissue, tissue repair process, array of granulation tissue and deposition of collagen fibers in the repairing area. Checking normality test was processed using SPSS 18.0 Software (SPSS Inc, Chicago, IL, USA) and data then were analyzed using one-way ANOVA, Tukey and post hoc test.
Thickness of the granulation tissue on day 7 differed significantly between the control group and treatment 1 (P Increased therapeutic potential of LPS -stimulated mesenchymal stem cells versus reduced therapeutic potential of Poly (I:C)-stimulated mesenchymal stem cells can be as a result of attaining the proinflammatory versus anti-inflammatory phenotype in mesenchymal stem cells in response to the respective agonists, respectively.

Cancer is a complex genetic disease which basically caused by environmental factors. Nowadays, nanometrials with various techniques used in all human daily applications such as medicine, pharmaceutical, drug and cancer therapy. MgO-NP is an important inorganic oxide. The aim of this study is investigation of K562 cell line growth inhibition by MgONP. The effect of magnesium oxide nanoparticles has not been studied on these types of cancer cells.
K562 cells were cultured in RPMI medium containing 10% FBS supplemented with 0, 25, 50,100 and 200 mg/l of MgO-NP for 24 hours. The toxicity was evaluated using MTT assay and acridine orange and propidium iodide double staining.
MgO NPs had no effects on cell viability of K562 cancer cells and peripheral blood mononuclear cell (normal cells) in MTT assay. The MgO NPs did not induce apoptosis which was confirmed through acridine orange and propidium iodide double staining.
The MgO-NP did not exert any impact on viability of K562 cells under our experimental conditions. This observation indicates that MgO-NPs may have no anti cancerous effect on K562 cell line.

The regulatory role of the mesenchymal stem cells on the cells of immune system such as neutrophil has been investigated in several studies. On the other hand, estrogen hormone is one kind of immunomodulatory agents. This study was designed to investigate the effect of mesenchymal cells treated with estrogen on the neutrophil function.
Having isolated the mesenchymal stem cells from bone marrow of rats, the researchers treated the cells with 10 or 20 nM concentrations of estrogen for 72 hours. In the next stage, the MSC cells were co-cultured with neutrophil cells and incubated for 1 hour. Then, the neutrophil functions were assessed (P The results of the study clearly showed that the percentage of phagocytosis and the respiratory burst in co-cultured neutrophil with mesenchymal stem cells treated with estrogen had increased compared to that of the control group. Moreover, the rate of apoptosis in neutrophils treated with estrogen significantly decreased in both estrogen concentrations compared to that of the control group (P It seems that estrogen can modify the interaction of the mesenchymal stem cells and neutrophil.

It is necessary to potentiate the immune system of fishes against stresses in farms.
This study was carried out to address the potential effect of Levamisole on immune system of rainbow trout against density stress.
1500 fish (average weight of 50 g) were divided into 5 test groups, in which each test group was repeated three times with average density of 33 kg/m3. They were fed with commercial diet supplemented with Levamisole at concentrations of 0 (control), 100, 250, 500 and 1000 mg / kg for a period of 45 days. The fishes of all groups were then fed with Levamisole free diet and exposed to 2 and 3-fold density stress for the following 15 days. Blood samples were collected on days 0, 15, 30, 45 and 60 to evaluate the serum compliment and lysozyme activity as well as total immunoglobulins.
The results showed that all used concentrations of Levamisole just had significant effect on compliment activity after 45 days feeding period (p Our results revealed that using 0/1% Levamisole as an immunostimulator in commercial diet could potentiate rainbow trout against outbreak of high density stresses and increase its overall survival.

Burning provides irreparable effects on the affected patient. Several studies show that these cells may contribute to tissue regeneration whether through producing a variety of bioactive growth factors and/or by differentiation into mesoderm lineage. Several studies demonstrate that stimulated mesenchymal stem cells have more therapeutic potential than unstimulated cell in accelerate tissue wound healing. The aim of the present study was to investigate the effect of subcutaneous administration of stimulated bone marrow-derived mesenchymal stem cells with lipopolysaccharide in repairing or regeneration of skin wounds induced by third-degree burn and to compare it with unstimulated Mesenchymal stem cell in mouse model.
The third-degree skin burn was induced on male mice (N=27). After 1 hour, based on the equal physical condition mice were randomly divided into three separate groups which included control, mesenchyme and LPS groups and then respectively subcutaneously administered with phosphate buffered saline (PBS; 400 µl), mesenchymal stem cells and stimulated mesenchymal stem cells with LPS (106 cell in 400µl PBS) at the burn site. In order to check the speed of the process of 21-days wound repair, tissue section at days 7, 14, and 21 after induction of burn were prepared and stained with hematoxylin/eosin and Massons trichrome.
Considering investigated parameters including formation of granulation tissue, angiogenesis, fibroblast proliferation, collagen deposition and the rate and quality of healing of third-degree thermal burns were significantly accelerated in mesenchyme and LPS groups when compared to the control group (P The results demonstrate that stimulate cells whit LPS improve BMScʼs therapeutic effect in some factors of burn wound healing.

All-trans retinoic acid (ATRA) has a variety of biological activities, including immunomodulatory action in a number of inflammatory and autoimmune diseases. The purpose of this study was to investigate the effects of all-trans retinoic acid on the treatment of autoimmune diabetes in mice and its effects on expressions of Peroxisome Proliferator-Activated Receptor gamma (PPARγ) gene.
Diabetes was induced by multiple low-dose of streptozotocin (MLDS) injection (40mg/kg/day for 5 consecutive days) in male C57BL/6 mice. After induction of diabetes, mice were treated with ATRA (20mg/kg/day i.p.) for 21 days. Blood glucose level was measured in 0, 7, 14 and 21 days after Streptozotocin induction induced diabetes. Splenocytes were tested for cytokines production by ELISA and Immune changes in spleens were tested by semi-quantitative RT-PCR. One-way analysis of variance (ANOVA) followed by Tukeys test were used for comparisons between groups. P ATRA treatment prevented hyperglycemia in the diabetic mice. ATRA treatment also significantly inhibited the production of proinflammatory cytokines interleukin 17 (IL-7) as well as interferon gamma (IFN-γ) while increased the level of anti-inflammatory cytokine IL-10 and upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) gene expression in spleens as compared with those in diabetic control group.
In conclusion, these findings indicate that ATRA may have a therapeutic effect against the autoimmune destruction of the pancreatic beta-cells during the development of MLDS-induced type 1 diabetes in mice.

Linterleukine (IL) -17 est exclusivement produite par les cellules T auxiliaires CD4 après activation. LIL-17 agit le plus souvent comme une cytokine pro-inflammatoire capable de stimuler la libération dautres cytokines pro-inflammatoires (IL-6, IL-8, TNF-α) ainsi que les facteurs de stimulation des colonies de granulocytes-macrophage (GM-CSF). Dans cette étude, nous avons étudié la réponse in vitro IL-17 vis-à-vis dantigènes spécifiques et dune série de substances mitogènes. La réponse IL-17 a été ensuite comparée à celles dautres cytokines, en loccurrence lIL-2, IL-4, IL-5, IL-6, IL-10, et lIFN-γ. Dans ce but, les antigènes spécifiques du vaccin de la fièvre aphteuse (foot and mouth disease vaccine, FMDV) et des substances mitogènes comme la phytohémagglutinine (PHA), lagent mitogène de la phytolaque (pokeweed mitogen, PWM) ainsi que la concanavaline A (Con A) ont été utilisés dans le but de stimuler les cellules mononucléées du sang périphérique (PBMC) des veaux vaccinés. Le surnageant des cultures cellulaires a été prélevé et son contenu en cytokines analysé en utilisant des kits ELISA bovins commerciaux. Selon nos résultats, les agents mitogènes induisent une hausse significative de la libération dIL-17. Des taux élevés de cette cytokine sont effectivement produits à la suite dune stimulation des cellules T par la PHA et la Con A alors que la réponse au mitogène PWM semble moins importante. En revanche, letaux dIL-17 généré en réponse des antigènes spécifiques du FMDV est bien inférieur comparé à ceux induits par les mitogènes. Les antigènes FMDV et les substances mitogènes testées augmentent donc de façon significative la production IL-17. Il ny a cependant pas de corrélation entre la libération dIL-17 et la concentration des cytokines de type 1 «IFN-γ, et IL-2», contrairement au cas des cytokines de type 2 «IL-4 et IL-5» dont la production par les PBMC est stimulée par les antigènes FMDV. De plus, un lien direct a été établi entre les taux des cytokines IL-17 et IL-6 libérés lors des différentes stimulations.

Because of existing different stresses in fish farms, there is necessary to corroborate immune system of fishes against stresses. In the present study effects of Levamisole on immune responses of rainbow trout were evaluated. For this purpose 1000 pieces fish (average weight of 150 g) were obtained from a local fish farm of Urmia and were divided in 5 test groups (33 kg/m3 density) and were fed on diet supplemented with Levamisole at 0, 100, 250, 500 and 1000 mg per kg of diet for a period of 45 days. Then the fishes of all groups were fed on commercial diet without Levamisole and were exposed density stress by 2-3 folds for the following 15 days. Blood samples were collected from all groups on days 0, 15, 30, 45 and 60 to evaluate the serum total immunoglobulin, complement system activity and lysozyme activity. The results showed that, at the end of trial (day 60) Significantly (P

Fish are the major dietary source of the polyunsaturated fatty acid for humans. Therefore, protection of fish against all types of oxidative corruption seems to be necessary. Lycopene is the source of natural antioxidant. The present study was conducted to evaluate antioxidant properties of lycopene (using the method of DPPH) and the combined effect of its various doses (1.5 and 3%) and chitosan on fat oxidation parameters and fatty acids composition of Rainbow trout fillet. The analysis was performed after 0, 8 and 16 days of storage of the samples at 4°C to determine peroxide value (PV) and free fatty acid content (FFA). In addition, fatty acid compositions was determined by Gas chromatography assay. In control treatment, the fatty acid composition of Rainbow trout fillet was consisted of %20.6±0.03 saturated fatty acids (SFA), %43.81±0.04 monounsaturated fatty acid (MUFA) and %32.83±0.03 polyunsaturated fatty acids (PUFAs) in 0 day. Statistical analysis showed that there were fewer changes in PV, FFA and proportion of fatty acids between chitosan and lycopene-chitosan treatment in regard to control sample during 16 days of refrigeration storage. Chitosan coated samples enriched with lycopene exhibited less rapidly lipid damages than all the other samples (p

Background and Tretinoin is the most active metabolite of Retinoic acid (RA) in the body. It has a variety of biological activities, including antioxidant and immunomodulatory effects on a number of inflammatory and autoimmune conditions. The purpose of this study was to investigate the effects of tretinoin on plasma insulin and nitric oxide levels in streptozotocin-induced diabetes in mice.
In this experimental study, 15 male C57BL/6 mice were divided into 3 groups (n= 5 per group) including a normal group, diabetic control group (streptozotocin: 40 mg/kg/day for 5 consecutive days) and treatment group (tretinoin: 20 mg/kg/day i.p. for 21 days after induction of diabetes).Then, the levels of nitric oxide in spleen cell culture supernatant and insulin level of plasma were evaluated. Data was analyzed by One-way analysis of variance (ANOVA) and Tukeys test in Microsoft Excel.
Tretinoin prevented the STZ-induced reduction in plasma insulin, indicating a possible protective effect of tretinoin against β-cell damage. Also, nitric oxide production significantly reduced in treatment group (P These findings indicate that tretinoin may have a therapeutic effect against the autoimmune destruction of the pancreatic beta-cells during the development of STZ-induced type 1 diabetes in mice.

Olive has a protective effect against chronic inflammatory conditions. However, it is not clear weather this effect is due to its immunomodulatory or antioxidant property. The aim of this study was to investigate the effect of olive leaf extract on serum levels of Th-17 related cytokines and its antioxidant properties. 40 male rats divided into 5 groups, and were treated by placebo (Control group), vitamin C (as a known and potent antioxidant) and different doses of olive leaf extract. Four test groups, received vitamin C 10 mg/kg and olive leaf extract which contained 5, 10 and 15 mg/kg Oleuropein. All treatments were applied for 10 consecutive days orally via gavage. After this period, cardiac puncture was performed to retrieve blood from animals in order to determine interleukin 17, 23 and TGFβ levels in their serum by ELISA method. Glutathione peroxidase (GPx), Superoxide dismutase (SOD), Catalase (CAT) activities and thiobarbituric acid reactive substances (TBARS, as a lipid peroxidation marker) were assayed in right brain hemisphere of treated animals. TBARS increased significantly in control group when compared to the other groups (p<0.05). GPx and SOD enzymes indicated higher activity in the animal group which was treated with 15mg/kg Oleuropein, in comparison with control group and a group who treated with 5mg/kg Oleuropein (p<0.05). Although there were no significant difference in IL-23 and IL-17 levels among control and test groups (p>0.05), TGFβ concentration was significantly lower in animals which treated by 5 and 15 mg/kg of Oleuropein. Olive leaf extract, which contains Oleuropein, had a significant antioxidant effect on the brain of studied animals, while it was not able to change the Th-17 cell-related cytokines (Except TGFβ) significantly. Therefore, it could conclude that the protective role of olive against chronic degenerative diseases is related to its antioxidant properties rather than its effects on pathogenic cytokine profile of Th17 cells.

Mesenchymal stem cells (MSCs) were introduced as multipotent non-hematopoietic precursor adult cells. Pre or anti-inflammatory features of these cells appear on immune responses by activating specific tool like receptors (TLRs). The aim of this study was to evaluate the effect of Lipopolysaccharide and Polyribocytidylic Acid on different concentration and times of incubation on nitric oxide production and apoptosis induction in activated T-cells.

Suspension cells were prepared through the femural and tibial bones by flushing method; and Mesenchymal cells were isolated by plastic adhesion technique. When the cultures reached % 70 confluence, cells treated with TLR agonists, Poly: IC (1 and 5 µg/ml), LPS (10 and 20 ng/ml) and the lowest combination concentrations (Poly: IC 1µg/ml and LPS 10ng/ml) (LP) at two different times, 1 and 12hr. Nitric oxide of cell surface liquid were measured by Griess (year) method. Apoptosis percentage in T cells was assayed by flowcytometry in the presence of Achridin orange/propidium iodide (AO/PI).

The results showed that Poly: IC could induce the highest T cells apoptosis at low concentration (1 µg/ml) after 12hr incubation. But, LPS could cause T cells apoptosis at high concentration (20 ng/ml) after 1hr incubation (P<0.05). Also, an increase in T cells apoptosis could be related to nitric oxide production.

These findings suggest that the concentration of agonist and treatment period of the stem cells could affect nitric oxide production and apoptotic activity in MSCs.