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The compound "2-methylpyridine-1-ium-1-sulfonate" (MPS) is the active constituent of Allium hirtifolium Boiss. bulbs with potent anti-angiogenic and anti-cancer activities. Tumor microenvironment (TME) plays a key role in tumor progression via tumor derived exosome (TEX) mediated polarization of M2 type tumor associated macrophages (TAMs). In this study, we explored direct and colorectal cancer (CRC) exosome-mediated impacts of MPS on macrophage polarization to find out whether MPS could modify TEX in favor of anti-tumor M1-like macrophage polarization. After MPS isolation and characterization, first its direct anti-cancer effects were evaluated on HT-29 cells. Then, TEX were isolated from untreated (C-TEX) and MPS-treated (MPS-TEX) HT-29 cells. THP-1 M0 macrophages were incubated with MPS, C-TEX and MPS-TEX. Macrophage polarization was evaluated by flow cytometry, ELISA and gene expression analysis of several M1- and M2-related markers. MPS induced apoptosis and cell cycle arrest and reduced the migration ability of HT-29 cells. C-TEX polarized M0 macrophages toward a mixed M1-/M2-like phenotype with a high predominance of M2-like cells. Macrophage treatment with MPS was associated with the induction of M1-like phenotype. Also, MPS was demonstrated to ameliorate TEX-mediated effects in favor of M1-like polarization. In conclusion, our study addresses for the first time, the potential capability of MPS in skewing macrophages toward an anti-cancer M1-like phenotype both directly and in a TEX-dependent manner. Thus, in addition to its direct anti-cancer effects, this compound could also modify TME in favor of tumor eradication via its direct and TEX-mediated effects on macrophage polarization as a novel anti-cancer mechanism.

Natural products have well been recognized as sources of drugs in cancer treatment. Some medicinal plants contain the constituents with potent anti-angiogenic and anti-cancer effects, which have offered great hopes of being used as drugs for treating various cancers. The present study aims at identifying the anti-angiogenic effects of 2-Methylpyridine-1-ium-1-sulfonate (MPS) isolated from the ethyl acetate extract (EA) of Persian shallot ( Allium hirtifolium ). In a concentration-dependent manner, the MPS was able to inhibit endothelial cell migration and angiogenesis in both in vivo and in vitro assays, and also significantly suppressed proliferation of MCF-7 and MDA-MB-231 human breast cancer cell lines. Additionally, treatment with MPS showed a significant reduction in the vascular endothelial growth factor (VEGF) secretion level and production/activity of matrix metalloproteinases (MMP-2 and MMP-9) in the studied cells. The flow cytometry analysis indicated that MPS suppressed growth of MCF-7 and MDA-MB-231 cells at G0/G1 and S phases, respectively. Our results indicated that the induction of cell cycle arrest was correlated with the obvious changes in expression of p21, p27 and p53. According to the DNA fragmentation assay, MPS caused apoptosis in both cell lines, which confirms the results obtained with the growth assay. Moreover, the compound-mediated apoptosis accompanied with the increase in the Bax/Bcl-2 ratio and caspase-3 and −9 activities. Molecular docking results indicated that the MPS compound can surprisingly bind to VEGF and VEGF receptors and interacts with their critical amino acids. Finally, compounds with anticancer inhibitory activity (e.g. MPS) are abundant in nature and can be obtained from several sources. So, our data can be clinically developed for treating angiogenesis and cancer significantly.

To date, several new anti-CD20 monoclonal antibodies (mAbs) have been developed for potential efficacies compared with familiar mAb rituximab. Despite the recent advances in development of anti-CD20 mAbs for the treatment of B cell malignancies, the efforts should be continued to develop novel antibodies with improved properties. However, the development of mAbs against CD20 as a multi-transmembrane protein is challenging due to the difficulty of providing a lipid environment that can maintain native epitopes. To overcome this limitation, we describe a simple and efficient DNA immunization strategy for the construction of a novel anti-CD20 mAb with improved anti-tumour properties. Using a DNA immunization strategy that includes intradermal (i.d.) immunization with naked plasmid DNA encoding the CD20 gene, we generated the hybridoma cell line D4, which secretes functional mAbs against an extracellular epitope of CD20. Immunocytochemistry analysis and a cell-based enzyme-linked immunosorbent assay using a Burkitt's lymphoma cell line showed that D4 mAbs are capable of binding to native extracellular epitopes of CD20. Moreover, the binding specificity of D4 mAbs was determined by western blot analysis. Cell proliferation was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by the annexin V/propidium iodide staining and dye exclusion assay. The results showed that D4 anti-CD20 mAbs produced by DNA immunization exhibit potent growth inhibitory activity and have superior direct B-cell cytotoxicity compared to rituximab. We propose that antibody-induced apoptosis is one of the mechanisms of cell growth inhibition. Taken together, the data reported here open the path to DNA-based immunization for generating pharmacologically active monoclonal antibodies against CD20. In addition, the data support future in vivo animal testing and subsequent procedures to produce a potential therapeutic mAb.

Context: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. Objective: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. Material and methods: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p.) from the first day of cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin oligodendrocyte glycoprotein (MOG+)/caspase-3+ cells), gliosis (H&E staining, glial fibrillary acidic protein (GFAP+) and macrophage-3 (Mac-3+) cells) and inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal cell-derived factor 1 α (SDF-1α) or CXCL12] during cup intoxication were examined. Results: High dose of EA (EA-80) increased mature oligodendrocytes population (MOG+ cells, p

Soybean Bowman-Birk protease inhibitor (BBI) and genistein, two biological compounds from soybean, are well-known for their anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was designing a BBI-genistein conjugate and then investigating its protective effect on lipopolysaccharide (LPS)-induced inflammation in BALB/c mice, compared with the effects of combination of BBI and genistein. BBI was purified from soybean and the BBI-genistein conjugate was synthesized. The BALB/c mice were intraperitoneally treated 2 hours before LPS induction. Our results showed that treatment with the combination of BBI and genistein greatly led to more reduced serum levels of tumor necrosis factor (TNF)-α and interferon (IFN)-γ compared with the treatments of BBI alone, the BBI-genistein conjugate, and genistein alone, respectively. Moreover, the expression of TNF-α and IFN-γ in the splenocytes was significantly downregulated along with improving host survival against the LPS-induced lethal endotoxemia in the same way. Our data support a new combined therapy using BBI and genistein, as natural anti-inflammatory agents, to develop a new drug for inflammatory diseases.

Introduction Sulfur mustard (SM) is a potent toxic agent that cause local and systemic changes in the human body such as dysregulation of the immunological system. This gas affects different organs such as lungs, skin, eyes and the gastrointestinal tract. Methods 128 veterans with SM-induced eye injuries were examined and compared to 31 gender- and age-matched healthy controls. Serum levels of IgM, IgE, IgA, IgG, and IgG subclasses were measured using ELISA method. Results There was no significant difference in IgM level between two groups with abnormal and normal ocular conditions except for those having bulbar conjunctiva-limbal ischemia and bulbar conjunctiva-hyperemia abnormalities. There were not significant difference in IgA, IgE, and IgG levels between two groups with and without ocular problem also between study groups. IgG1 level in some ocular abnormalities were significantly lower than the healthy control groups. IgG2 level in SM-exposed participants with stromal abnormality was higher in the SM-exposed groups without this problem. IgG2 levels in the exposed group with some ocular problems were significantly increased compared with control. IgG3 level in all patients did not reveal any significant changes compared with the controls except the fundus abnormality. IgG4 level was not significantly different between two groups with normal and abnormal ocular conditions. Nonetheless, IgG4 level in the exposed participants with some ocular abnormalities significantly increased compared with the controls. Conclusion The results showed SM exposure could alter immunoglobulins level compared with healthy controls and the changes of IgG2 and IgG1 levels were associated with some ocular problems.

Angiogenesis has essential role in growth and metastasis of tumors. Development of therapies aimed to suppress angiogenesis using medicinal plants is one of the effective approaches for prevention/treatment of cancer. The current study was performed to investigate in vitro anti-angiogenic effect of Teucrium Polium (TP) extract and its fractions. The aerial part of Teucrium Polium was powdered and extracted with 50% ethanol. The extract was fractionated in to aqueous (AQ), n-butanol (BU), ethyl acetate (EA) and n-hexane (HE) fractions. Anti-angiogenic effect of TP was examined on human umbilical vein endothelial cells (HUVECs) in three-dimensional collagen matrix. The endothelial cells form capillary-like branches that can be visualized using phase contrast microscope and the number of tube-like structures can be quantified as a measure of in vitro angiogenesis. Furthermore, anti-proliferative and vascular endothelial growth factor(VEGF )suppressive effect of TP as important factors in the process of angiogenesis were assessed using3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)and quantitative ELISA, respectively. Based on our findings, among the TP fractions, EA fraction showed the highest inhibitory activity on angiogenesis. This fraction with IC50: 68 µg/mL, inhibited angiogenesis at 60 µg/mL. The crude extract and other fractions of TP inhibited angiogenesis in a dose-dependent manner at doses higher concentrations than EA fraction, significantly.TP extract and EA fraction were able to inhibit proliferation of HUVEC and inhibited VEGF secretion in a dose dependent manner. The ethyl acetate fraction at 60 µg/ml inhibited VEGF secretion perfectly. Our data indicated that ethyl acetate fraction of Teucrium Polium could be a potential candidate for the prevention of angiogenesis in cancer and other related disorders. However, this suggestion needs more quantitative and in vivo investigations for confirmation.

Angiogenesis is a process through which new capillaries are formed from pre-existing ones, which contributes significantly to the pathogenesis of numerous diseases, such as cancer and chronic inflammatory disorders. The β-D-mannuronic acid (M2000) is a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive effects and is a matrix metalloproteinase (MMP) inhibitor. This research aimed to study the anti-angiogenesis effects of M2000 under in vitro and in vivo models. The cytotoxic and anti-proliferative effects of M2000 were examined using the trypan blue method and the MTT assay, respectively. The 3D collagen-cytodex model and the chick chorioallantoic membrane (CAM) assay were then used to evaluate the anti-angiogenesis property of M2000. Cytotoxicity assay revealed that M2000 (at concentrations of less than 100 μg/mL) had no cytotoxic effect on human umbilical vein endothelial cells (HUVECs). It was also illustrated that M2000 had little or no anti-proliferative effect on HUVECs. In addition, the anti-angiogenesis effects of M2000 were shown to be marginal in the in vitro model and both significant and dose-dependent in the in vivo status. This study showed that M2000 could be considered as an anti-angiogenic molecule which more likely exerts its activity mainly via indirect effects on endothelial cells and its anti-inflammatory effects may partly be attributable to its anti-angiogenic activity. Therefore, it could be recommended as a candidate for prevention and treatment of cancer, chronic inflammatory diseases, and other angiogenesis-related disorders.

Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0.2% Cup for 6 weeks to induce detectable neuroinflammation and myelin loss. TP was administered intraperitoneally at different doses (125, 250 or 500 μg/kg/day) during the last week of the Cup challenge. Although TP substantially decreased Cup-induced NF-κB extra activation, TNF-α and IL-1 over expression, and gliosis in a dose-dependent manner, only low dose of TP (TP-125) was able to raise the number of OLGs precursor cells (NG-2+/O4+), reduce Bax/Bcl-2 ratio and improve behavioral deficits. In addition, TP-125 decreased NF-κB activation on GFAP+ astrocytes more than MAC-3+ microglial and MOG+ oligodendrocytes which suggested the possibility of specific dampening of NF-κB signaling in reactive astrocytes. Behavioral assessments by open-field and rota-rod tests showed that only TP-125 notably improved motor function and motor coordination compared to the Cup group. These findings highlight the pivotal role of NF-κB signaling in the oligodendrogenesis and lesion reduction in demyelination diseases such as MS.

OBJECTIVE Allium hirtifolium (Persian shallot) has a hypoglycemic effect on diabetic animals. The aim of this study was to assess the effect of the ethyl acetate fraction of Allium hirtifolium on the function of isolated hearts of diabetic rats. METHODS The control and diabetic animals were randomly divided into four groups: saline- or extract-treated controls (n=10 and n=6, respectively) and saline- or extract-treated diabetic rats (n=8 and n=9, respectively), which received normal saline or extract for four weeks by daily gavage. The hearts were perfused according to the Langendorff method. Cardiac function parameters, including left ventricular developed pressure (LVDP), heart rate (HR), rate pressure product (RPP; LVDP×HR), and dp/dt were measured. RESULTS The findings of this study showed that in the extract-treated diabetic rats, LVDP (94.5±9.1 mm Hg, mean±SEM), HR (249±15 beats/min), RPP (22732±1246) and +dp/dt (2598±230) at the baseline were significantly higher than those in the saline-treated diabetic animals, (71.5±4.0), (189±6), (13923±984), and (1701±124), respectively. Furthermore, RPP and HR were also significantly higher than the corresponding values obtained in the saline-treated diabetic rats after ischemia. CONCLUSION Besides blood glucose lowering action, oral administration of the ethyl acetate fraction of Allium hirtifolium significantly improved the baseline and post-ischemic cardiac function parameters in streptozotocin-induced diabetic rats.

The most important long-term morbidity problem of sulfur mustard (SM) toxicity is pulmonary complications but the pathogenesis of these complications is not clearly understood. This study evaluates the peripheral blood mononuclear sub-sets and their correlation with pulmonary function in SM exposed civilian cases 20 years post-exposure as gathered in the context of the Sardasht-Iran Cohort Study (SICS). Samples were randomly selected from two groups, SM-exposed (n=372) and control (n=128), with the same ethnicity, culture, and demography. Three color flow cytometry was applied for peripheral blood mononuclear sub-population determination. Results indicated a significant decrease in CD45+/CD3+, CD45+/CD3+/CD4+, and an increase in CD3+/CD16+56+ percentages. It was also found that absolute count of NK cells was highly increased in peripheral blood of exposed cases. There was a significant increase in NK cell count of SM exposed group with pulmonary problems as compared to the same group without pulmonary problems (p-value

Sulfur mustard (SM) is a strong toxic agent that causes acute and chronic health effects on a myriad of organs following exposure. Although the primary targets of inhaled mustard gas are the epithelia of the upper respiratory tract, the lower respiratory tract is the focus of the current study, and upper tract complications remain obscure. To our knowledge there is no study addressing the secretory IgA (S-IgA), C5a, alpha 1 antitrypsin (A1AT) in the saliva of SM-exposed victims. In this study, as many as 500 volunteers, including 372 SM-exposed cases and 128 control volunteers were recruited. A 3 ml sample of saliva was collected from each volunteer, and the level of secretory IgA, C5a, and alpha 1 antitrypsin in the samples were compared between the two groups. The SM-exposed group showed a significantly higher amount of salivary alpha 1 antitrypsin and secretary IgA compared to the control group (p

Angiogenesis is a key process in the promotion of cancer and its metastasis. Herein, the antiangiogenic activity of Salvia officinalis extract and its fractions was investigated. S. officinalis aerial parts were extracted with ethanol and its successive hexane, ethyl acetate, n-butanol and aqueous fractions were evaluated for their antiangiogenic activities using human umbilical vein endothelial cells (HUVEC) capillary tube formation and rat aorta models in a three-dimensional collagen matrix. Furthermore, antimigrative effects of the fractions were assessed using a wound healing model. The ethanol extract of S. officinalis (ESO) potently inhibited capillary tube formation in HUVEC and rat aorta models of angiogenesis, and its hexane fraction (HSO) exerted the highest inhibitory effect. In addition, the ethanol extract of S. officinalis and its hexane fraction showed a dose-dependent inhibitory activity on the migration of the endothelial cells in the wound healing model. Furthermore, ESO inhibited endothelial cell proliferation at 50-200 μg/mL in a dose-dependent manner. These findings indicated some new pharmacological activities of S. officinalis such as antiangiogenic in vitro and ex vivo, and antimigrative activity in vitro. Therefore, S. officinalis could be a candidate as a useful herb with therapeutic or preventive activity against angiogenesis related disorders.

Mustard gas, even in low doses, has the ability to inflict damage in multiple organs especially the skin, eyes, as well as the respiratory tract. This damage may cause many complications which persist during the lifespan of exposed subjects. Pro-inflammatory cytokines including TNF, IL-1alpha, IL-1beta and IL-1Ra cause systemic inflammatory reactions and numerous changes including altered cell signaling and migration, changes in cytokine production and fever. The aim of this study was to determine the serum levels of these cytokines in subjects who were exposed to mustard gas 20 years ago in comparison with an unexposed control group. In this historical cohort study 368 sulfur mustard (SM) exposed participants from Sardasht and 126 age-matched unexposed volunteers from Rabat (a nearby town) as controls were chosen by a random systematic sampling. The serum concentrations of IL-1alpha, IL-1beta, IL-1Ra and TNF were measured by a sandwich ELISA technique. Median of the serum levels of cytokines TNF, IL-1alpha, IL-1beta and IL-1Ra in the control group was 23.79, 1.89, 1.91 and 32.9 pg/ml respectively, while in the SM-exposed participants these values were 11.11, 0.81, 1.73 and 26.7 pg/ml respectively. The serum pro-inflammatory cytokine levels were significantly lower in the exposed group than in controls (p

Background 5-Aminolevulinic acid-mediated photodynamic therapy (ALA–PDT) is an effective and noninvasive modality for treatment of several types of non-melanoma skin cancers. This in-vitro study attempted to know whether the killing effect of ALA–PDT on the human melanoma cells (Mel-Rm cell line) could be increased by the presence of 5-fluorouracil (5-FU). Methods To evaluate the effect of ALA–PDT in combination with 5-FU on viability of human melanoma Mel-Rm cells, the cells incubated with 5-ALA and 5-FU for 3 h in nontoxic concentrations, and subsequently illuminated with a 630 nm light-emitting diode array. The cells viability and cytotoxicity determined by mitochondrial activity and lactate dehydrogenase assays. Results Combination of ALA–PDT and 5-FU (FU–ALA–PDT) showed a considerable growth inhibition according to the results of MTT assay compared to ALA–PDT. The results of LDH assay also showed a cytotoxicity effect in ALA–PDT; however, the FU–ALA–PDT showed no significantly enhancement in cytotoxicity compared to ALA–PDT using LDH assay. Conclusion The Mel-Rm cells incubation with 5-FU before PDT enhances the efficiency of 5-Aminolevulinic acid-mediated photodynamic therapy.

Progression of cancer cells is completely dependent on its angiogenesis. Inhibition of tumor angiogenesis has shed new light on cancer treatment. As a result, anti-angiogenesis therapy represents one of the most significant advances in clinical oncology. Peganum harmala L. (Zygophyllaceae) is a native plant from the eastern Iranian region, which is used as a traditional folk medicine. Although some biological properties of this plant are determined, its effect on angiogenesis is still unclear.We investigated the anti-angiogenic effects of heat and low pH stable hydroalcoholic extract of P. harmala seeds on endothelial cells (ECs) proliferation and VEGF secretion.Dried Peganum seeds were purchased from Kermanshah Traditional Bazar in 2011. Hydroalcoholic extract of dried seeds (0, 10, 20, 40, 60, 80, 100, 120, and 150 μg/ml) was used for in vitro evaluation of its cytotoxicity, anti-proliferative, and anti-angiogenic effects on ECs. In vitro effect of the extract on VEGF secretion was assayed using ELISA.Treatment with hydroalcoholic extract at seven different concentrations resulted in significant decrease of ECs proliferation and angiogenesis with an ID50 of ∼ 85 μg/ml. VEGF secretion was (inhibited) decreased by the extracts at concentrations higher than 10 μg/ml.Herbal plant extracts still attract attention owing to their fewer side effects comparing to synthetic drug agents. Current study indicated that hydroalcoholic extract of P. harmala seeds contains a potent anti-angiogenic component, which exerts its inhibitory effect mainly through down-regulation of essential mediators such as VEGF.

Shark cartilage has proven to have some inhibitory effects on angiogenesis, metastasis, cell adhesion and proteolysis. In this study, we wanted to study some of the effects of shark cartilage on tumor immune response. Firstly, by means of chromatographic methods and delayed type hypersensitivity (DTH) test, we optimized a procedure for isolation and purification of a shark cartilage protein fraction with most immunostimulatory effects. Then, we examined its effect on the infiltration of CD(4)(+) and CD(8)(+) lymphocytes into a murine tumor model. Our fraction was composed of two major proteins with molecular weights (MWs) of about 14 and 15 kDa. This fraction highly increases DTH response against sRBC in mice. Furthermore, intraperitoneal injection of this fraction to tumor-bearing mice could increase T-cell infiltration into the tumor. Also, there was a significant increase in the CD(4)/CD(8) ratio in tumor infiltrating lymphocytes, but no such changes were found in the peripheral blood lymphocytes. According to these results, we suppose that this fraction is a good candidate for further studies in cancer therapy. Also, we concluded that this fraction, with previously proven anti-angiogenic effects, can augment cellular immune response and T-cell infiltration into the tumor and thus, there may be a direct relationship between angiogenesis inhibition and T-cell infiltration.

Doxorubicin (DOX) is a potent, broad-spectrum chemotherapeutic drug used for treatment of several types of cancers. Despite its effectiveness, it has a wide range of toxic side effects, many of which most likely result from its inherent prooxidant activity. It has been reported that DOX has toxic effects on normal tissues, including brain tissue. In the current study, we investigated the protective effect of osthole isolated fromPrangos ferulacea(L.) Lindl. on oxidative stress and apoptosis induced by DOX in PC12 as a neuronal model cell line. PC12 cells were pretreated with osthole 2 h after treatment with different concentrations of DOX. 24 h later, the cell viability, mitochondrial membrane potential (MMP), the activity of caspase-3, the expression ratio of Bax/Bcl-2, and the generation of intracellular ROS were detected. We found that pretreatment with osthole on PC12 cells significantly reduced the loss of cell viability, the activity of caspase-3, the increase in Bax/Bcl-2 ratio, and the generation of intracellular ROS induced by DOX. Moreover, pretreatment with osthole led to an increase in MMP in PC12 cells. In conclusion, our results indicated that pretreatment with nontoxic concentrations of osthole protected PC12 cells from DOX-mediated apoptosis by inhibition of ROS production.

Respiratory complications are the foremost long term debilitating effects after sulfur mustard toxicity. The underlying immunological mechanisms of sulfur mustard induced lung damage are still poorly understood. The question of the involvement of immunoglobulin classes and subclasses in delayed pulmonary complications induced by SM was addressed in this study as a part of Sardasht-Iran Cohort Study (SICS).In SICS, 372 male participants who were exposed to SM 20 years earlier were compared with 128 unexposed age-matched controls. At the time of study (2007), the clinical evaluations and spirometry was performed for all subjects according to the American Thoracic Society Criteria, and at the same time, the sera were isolated, labeled and aliquots were kept frozen in -80°C. Serum immunoglobulin (Ig) levels including IgM, IgA, IgE, IgG, and IgG subclasses (IgG1, IgG2, IgG3 and IgG4) were measured using quantitative Elisa method. It was found that among immunoglobulin classes and IgG subclasses only IgM and IgG4 were significantly decreased in the peripheral blood of exposed cases. IgM level also positively correlated with FEV1 only in the SM exposed group. These results indicated a weak but significant role for IgA in control of the delayed pulmonary complications. There were no strong correlations between other immunoglobulin classes or IgG subclasses with pulmonary disease severity in sulfur mustard intoxicated subjects. The authors proposed that systemic levels of immunoglobulins do not exert essential roles in severity of delayed pulmonary complications following SM toxicity. However, more studies on local and systemic levels of immunoglobulins in more severe groups are suggested.

New strategies that stimulate cell-mediated immunity (CMI) against tumors and inhibit regulatory T cells are needed to improve the outcome of cancer immunotherapy. The aim of this study was to enhance the anti-tumor immunity of gp96 vaccine through naloxone administration. Therefore, we used BALB/c mouse model of fibrosarcoma tumor and analyzed the tumor size, splenocyte proliferation, spleen and tumor-infiltrated lymphocytes. Tumor and spleen CD4 + CD25 + Foxp3 + regulatory T lymphocytes, cytotoxic activity of the splenocytes, IFN-γ and IL-4 secretion were assessed to describe the anti-tumor immune response. Our findings showed that co-administration of gp96 and naloxone has resulted in a significant reduction in CD4 + CD25 + Foxp3 + regulatory T cells in the spleen. The results indicated that on days 27 and 32 the tumors in the gp96 + Nal group grew significantly slower. Moreover, co-administration of gp96 and naloxone significantly increased the intra-tumor CD8 + T cells and cytotoxic activity. In addition the results indicated a significant increase in the proliferation of splenocytes and IFN-γ production. Our results demonstrate that naloxone is an effective immunoadjuvant in cancer immunotherapy.

The selectins (L, P and E) are carbohydrate-binding membrane glycoproteins acting as adhesion molecules involved in the development of different inflammatory reactions. Various eye, skin and lung diseases are associated with induction of soluble selectins. In this study serum levels of soluble forms of selectins (sL-selectin, sP-selectin and sE-selectin) were evaluated in the sulfur mustard (SM) exposed and the control groups using ELISA method. sL-selectin was significantly lower in the SM exposed group compared to the control group (1131.5+/-16.3 and 1205.7+/-26.9 pg/ml respectively; p=0.021). The serum levels of sP-Selectin was significantly reduced in the SM exposed group in comparison to the control group (149.35+/-2.61 and 170.25+/-5.16 pg/ml respectively; p

Neovascularization of the normally avascular cornea is seen in many pathological conditions including trauma, corneal transplantation, inflammation and eye diseases. Various growth factors and proteinases are involved in corneal neovascularization. Data supporting a causal role for vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are extensive. Inhibition of angiogenesis is a main strategy for treating corneal neovascularization. Several findings have shown that corneal neovascularization can be reduced by using anti-VEGF and anti-MMPs agents. Efficacy of a propolis extract has been demonstrated for reducing angiogenesis in vitro and in vivo. Propolis extracts containing artepillin C and caffeic acid phenyl ester significantly reduced the number of newly formed vessels and expression of MMPs and VEGF production from various cells. So far, propolis extract is a potential candidate as an anti-angiogenic agent and can inhibit cell proliferation, migration and capillary tube formation. We hypothesize that topical application of propolis is potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity.

Soybean kunitz trypsin inhibitor (STI) was purified from aqueous extract of defatted soybean meal by affinity and ion exchange chromatography. In this study the effect of purified STI on cell migration and tubulogenesis in microcarrier-based fibrin gel was assayed. Purified STI had strong inhibitory effect on human umbilical vein endothelial cells migration and tubulogenesis in fibrin matrix, without toxic effects in the studied doses.

Shark cartilage has proven to have inhibitory effects on angiogenesis. In this research, we studied the effects of shark cartilage on the immune system. Firstly, we isolated and purified a shark cartilage protein fraction with the most immunostimulatory effects. Our fraction was composed of two proteins with molecular weights of about 14 and 15 kDa. This fraction highly augments delayed-type hypersensitivity response against sRBC in mice, and decreases the cytotoxic activity of Natural Killer cells. Furthermore, intraperitoneal injection of this fraction to tumor-bearing mice could increase T-cell infiltration into the tumor, and decrease the tumor lesion size. Also, this fraction has strong inhibitory effect on HBMEC proliferation and migration in fibrin matrix. According to these results, we suppose that this fraction is a good candidate for further studies in cancer therapy.