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Avicennia marina, the gray mangrove, is an herbal source of bioactive anticancer compounds. In the current study, the anticancer activity of ethanol and ethyl acetate extracts of A. marina leaves were aimed to be evaluated. To do that, some assessments including phytochemical, GC-MS, cell proliferation, viability, cycle, western blot and computational modeling analysis were performed for evaluation of their anticancer activity on breast, ovarian and cervical cancer cell lines. The results demonstrated ethanol and ethyl acetate extracts of A. marina leaves had high phenolic and flavonoid contents. In GC-MS analysis of the extracts, anticancer compounds were detected. Moreover, the MTT and cell viability assays showed anti-proliferative activity and decrease in cell viability after treatment of MCF-7, OVCAR3, and HeLa cell lines with both extracts, separately. In addition, in the cell cycle analysis the cell cycle arrest was observed in MCF-7. Moreover, the western blot analysis showed that the pro-apoptotic cell effectors such as Bax and caspase-1, -3, and -7 increased. Computational results of affinity of ligands detected by GC-MS compounds and stimulated apoptosis effectors detected by western blot showed five molecules in A. marina leaves playing role in OVCAR3 and HeLa apoptosis. In conclusion, the ethanol and ethyl acetate extracts of A. marina leaves have anticancer effects. The ethanol extract induced cell cycle arrest in the breast cancer cell line and the ethyl acetate extract induced apoptotic mechanisms in ovarian and cervical cancer cell lines; that’s how they decreased cancer cells’ survival and viability.

Chimeric virus-like particles (VLPs) were developed as a candidate for allergen-specific immunotherapy. In this study, hepatitis B core antigen (HBcAg) that genetically fused to Chenopodium album polcalcin (Che a 3)-derived peptide was expressed in E. coli BL21, purified, and VLP formation was evaluated using native agarose gel electrophoresis (NAGE) and transmission electron microscopy (TEM). Chimeric HBc VLPs were characterized in terms of their reactivity to IgE, the induction of blocking IgG and allergen-specific IgE, basophil-activating capacity, and Th1-type immune responses. Results from IgE reactivity and basophil activation test showed that chimeric HBc VLPs lack IgE-binding capacity and basophil degranulation activity. Although chimeric HBc VLPs induced the highest level of efficient polcalcin-specific IgG antibody in comparison to those induced by recombinant Che a 3 (rChe a 3) mixed either with HBc VLPs or alum, they triggered the lowest level of polcalcin-specific IgE in mice following immunization. Furthermore, in comparison to the other antigens, chimeric HBc VLPs produced a polcalcin-specific Th1 cell response. Taken together, genetically fusion of allergen derivatives to HBc VLPs, in comparison to a mix of them, may be a more effective way to induce appropriate immune responses in allergen-specific immunotherapy. KEY POINTS: • The insertion of allergen-derived peptide into major insertion region (MIR) of hepatitis B virus core (HBc) antigen resulted in nanoparticles displaying allergen-derived peptide upon its expression in prokaryotic host. • The resultant VLPs (chimeric HBc VLPs) did not exhibit IgE reactivity with allergic patients' sera and were not able to degranulate basophils. • Chimeric HBc VLPs dramatically improved protective IgG antibody response compared with those induced by allergen mixed either with HBc VLPs or alum. • Chimeric HBc VLPs induced Th1 responses that were counterparts of Th2 responses (allergic). • Chimeric HBc VLPs increased IgG2a/ IgG1 ratio and the level of IFN-γ compared to those induced by allergen mixed with either HBc VLPs or alum. Graphical Abstract.

Background: The sea cucumber potentials for stem cell proliferation induction and their mechanisms of bioactive compounds in its extract have been studied. Human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs) were exposed to aqueous extract of Holothuria parva body wall. Methods: Using GC-MS analysis on aqueous extract of H. parva, proliferative molecules were detected. The extract concentrations of 5, 10, 20, 40, and 80 µg/mL and 10 and 20 ng/mL of human epidermal growth factor (EGF) as positive controls were used. MTT proliferation, cell count, viability, and cell cycle assays were performed. Using Western blot analysis, effects of aqueous extract of H. parva and EGF on cell proliferation markers were detected. Computational modeling done to detect effective proliferative compounds in aqueous extract of H. parva. Results: MTT assay showed that the 10, 20, and 40 µg/mL aqueous extract of H. parva had proliferative effects on hUC-MSCs. Count of the cells treated with the 20 µg/mL of the extract was increased faster and higher than the control group (P0.05). Expression of the cyclin D1, cyclin D3, cyclin E, HIF-1α, and TERT were increased comparing with the control group. Moreover, expression of the p21 and PCNA decreased after treating hUC-MSCs with the extract. However, the CDC-2/cdk-1 and ERK1/2 had almost the same expression as the control group. The expression of the cdk-4 and cdk-6 was decreased after treatment with the extract. Between the detected compounds, 1-methyl-4-(1-methylethenyl)-benzene showed better affinity to cdk-4 and p21 than tetradecanoic acid. Conclusions: The H. parva aqueous extract showed proliferative potential on the hUC-MSCs.

Background: Avicennia marina, the gray mangrove, is an herbal source of bioactive anti-cancer compounds.Purpose: The present study aimed to evaluate phytochemical compositions of ethanol and ethyl acetate extracts of A. marina leaves and experimental study and computational modeling of their anti-cancer activity on breast, ovarian and cervical cancer cell lines.Study design: Phytochemical analysis, computational modeling and experimental in vitro evaluationMethods: Phytochemical analysis and GC-MS analysis were used to detect phenolic and flavonoid contents in ethanol and ethyl acetate extracts of A. marina leaves. Cell proliferation, viability, cycle and western blot assays of the extracts were performed on MCF-7, OVCAR3, and HeLa. Computational modeling done to detect effective compounds.Results: The extracts of A. marina leaves had high phenolic and flavonoid contents. In GC-MS analysis of the extracts, anti-cancer and anti-proliferative compounds were detected. Moreover, after treatment of MCF-7, OVCAR3, and HeLa, separately, the MTT assay, cell proliferation assay, and cell viability assays showed anti-proliferative activity, decreasing of cell population and decreasing cell viability, respectively. In addition, the cell cycle analysis showed that the S phase of the cell cycle increased in MCF-7. Moreover, the western blot analysis showed that the pro-apoptotic cell effectors such as Bax and caspase-1, -3, and -7 increased. Computational results of affinity of ligands detected by GC-MS compounds and stimulated apoptosis effectors detected by western blot showed five molecules in A. marina leaves playing role in OVCAR3 and HeLa apoptosis.Conclusion: The extracts of A. marina leaves have anti-cancer effects on breast, ovarian and cervical cancer cells via cell cycle arrest or apoptotic mechanisms.

Introduction: Many antioxidant agents have been studied for prevention and treatment of the kidney stone disease in animals and humans. Parkinsonia aculeate (P. aculeate) has a wide range of pharmacological and biological activities, particularly antioxidant properties. The goal of this research was to investigate the anti-urolithiatic effect of P. aculeate extract on ethylene glycol induced renal calculi.Materials and methods: A total of 42 male Wistar rats were randomly divided into six equal groups with seven rats in each group: Group A served as healthy control group and received distilled water for 30 days. Group B served as ethylene glycol control group and received 1% v/v ethylene glycol in distilled water for 30 days. Group C, D, and E animals (preventive groups) concurrently received 1% v/v ethylene glycol in distilled water along with extract of P. aculeata orally for 30 days in doses of 100 mg/kg (low dose), 200 mg/kg (moderate dose), and 300 mg/kg (high dose), respectively. Group F (treatment groups) received 1% v/v ethylene glycol in distilled water for the first 30 days along with extract of P. aculeata 300 mg/kg orally from 15th to 30th days. At the end of study period, 24-hour urine and serum samples were collected and analyzed. All rats were sacrificed and both kidneys were removed, weighed and histopathologically evaluated for calcium oxalate crystals.Results: Ethylene glycol significantly decreased serum calcium, urinary levels of creatinine, calcium and uric acid. On the contrary, it significantly increased 24-hour urine volume, kidney weight, and calcium oxalate deposits. The highest number of calcium oxalate crystal depositions were in the high dose preventive group (76.6%), which is statistically significant difference with other groups including ethylene glycol control (70%), low dose preventive (72%), treatment (38%), and moderate dose preventive (42%) groups (P value < 0.05). Administration of extract of P. aculeata significantly reduced the production of calcium oxalate stones in moderate dose preventive and treatment group. However, P. Aculeata extract was not effective in reducing the formation of calcium oxalate stones in low dose and high dose preventive groups. Interestingly, the number of calcium oxalate deposits in the renal tubules of high dose preventive group was significantly more than the ethylene glycol control group.Conclusions: Extract of P. aculeata has preventive and therapeutic effects in ethylene glycol induced renal calculi in Wistar rat. Further studies are necessary to clarify the mechanism underlying this effect.

Induction of tumor-specific CD8 + T cell responses is known as a major challenge for cancer vaccine development; here we presented a strategy to improve peptide nanofibers-mounted antitumor immune responses. To this end, peptide nanofibers bearing class I (Kb)-restricted epitope (Epi-Nano) were formulated with polyethylene imine backbone (Epi-Nano-PEI), and characterized using morphological and physicochemicalcharacterizationtechniques. Nanofibers were studied in terms of their uptake by antigen-presenting cells (APCs), antigen cross-presentation capacity, and cytotoxic activity. Furthermore, nanofibers were assessed by their potency to induce NLRP3 inflammasome-related cytokines and factors. Finally, the ability of nanofibers to induce tumor-specific CD8 T cells and tumor protection were investigated in tumor-bearing mice. The formulation of Epi-Nano with PEI led to the formation of short strand nanofibers with a positive surface charge, a low critical aggregation concentration (CAC), and an increased resistancetoproteolytic degradation. Epi-Nano-PEI was significantly taken up more efficiently by antigen-presenting cells (APCs), and was more potent in cross-presentation when compared to Epi-Nano. Moreover, Epi-Nano-PEI, in comparison to Epi-Nano, efficiently up-regulated the expression of NLRP3, caspase-1, IL-1b, IL18 and IL-6. Cell viability analysis showed that formulation of PEI with Epi-Nano not only abolished its cytotoxic activity, but surprisingly induced macrophage proliferation. Furthermore, it demonstrated that Epi-Nano-PEI triggered robust antigen-specific CD8

Natural compounds from marine organisms have been rarely studied for their acetylcholinesterase inhibitory activities. The aim of this study was to isolate novel compounds with antiAChE activity from the venom of upside-down jellyfish Cassiopea andromeda Forskål, 1775. The compounds of the fractionated venom on gel filtration chromatography were identified by analyzing gas chromatography–mass spectroscopy data. The structure of the isolated compound that showed the most potent antiAChE activity in a docking study was elucidated by different spectral data, including 1H NMR and 13C NMR. Three compounds, including a neurosteroidal alkaloid androtoxin B, were identified from two venom fractions. This neurosteroidal alkaloid showed strong acetylcholinesterase inhibitory activity (IC50 2.24 ± 0.1 μM) compared with the reference standard, galantamine. The results obtained by a docking study demonstrated that Androtoxin B had close contact with two of the three amino acid residues of the catalytic triad of acetylcholinesterase gorge and was accommodated within a peripheral hydrophobic pocket composed of numerous aromatic site chains. In conclusion, the isolated neurosteroidal alkaloid from Cassiopea andromeda was a potent antiAChE agent with strong binding to both the catalytic and peripheral sites of acetylcholinesterase that correlated well with the experimental data. Further studies are required to determine whether androtoxin B could be a potential treatment for Alzheimer's disease. Keywords: Upside-down jellyfish, Antiacetylcholinesterase activity, Androtoxin B, Alzheimer's disease, Neurosteroidal alkaloid, GABA-A receptor

It is well understood that patients with different diseases may have a variety of specific proteins (e.g., type, amount, and configuration) in their plasmas. When nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may incorporate some of the disease-specific proteins. Using gold (Au) NPs with different surface properties and corona composition, we have developed a technology for the discrimination and detection of two neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a variety of techniques, including UV-visible spectra, colorimetric response analyses and liquid chromatography-tandem mass spectrometry, we found the corona-NP complexes, obtained from different human serums, had distinct protein composition, including some specific proteins that are known as AD and MS biomarkers. The colorimetric responses, analyzed by chemometrics and statistical methods, demonstrate promising capabilities of the technology to unambiguously identify and discriminate AD and MS. The developed colorimetric technology might enable a simple, inexpensive and rapid detection/discrimination of neurodegenerative diseases.

The corrosion inhibition of Tetracycline and Streptomycin on the carbon-steel, Fe (110), in seawater was evaluated using weight loss, Tafel polarization, electrochemical impedance spectroscopy and SEM morphometric methods. The surface adsorption of inhibitors follows the Langmuir adsorption isotherm and acts as spontaneous mixed-type corrosion inhibitors on the carbon-steel surface. The related thermodynamic parameters (Ea, Kads, ∆ Gads, ∆ H≠ and ∆ S≠) were evaluated and the interaction energy for Streptomycin was more than the Tetracycline. The SEM morphometric showed a good protection effect of inhibitors on carbon-steel in the presence of seawater and this was more efficient for Streptomycin. To emphasize the further insight into the efficiency of inhibitors, the Quantum chemical analysis and molecular dynamics simulations were used to find the most stable configuration and adsorption energies for inhibitors on the carbon-steel surface. The theoretical quantum chemical data such as EHOMO, η, χ, molecular surface area, MV, μ, α and ΔN were in agreement with inhibition efficiencies (IE %) that were obtained experimentally. Also, the molecular dynamics simulation showed the most stable configuration and adsorption energies of Streptomycin and Tetracycline on the carbon-steel and this follows the order of Streptomycin > Tetracycline, as verified by the experimental data.

Burn injury is one of the most destructive events in the world. The Pergularia tomentosa L. is a medicinal plant that traditionally, applies for treatment of burning, in Bushehr province, Iran. Various bioactive compounds such as steroid glycosides, tannins, various vitamins, saponins, cardenolides and anthraquinones were identified into extract of the plant, which can be effective in burn wound healing. Twenty-one rats weighting every one 200±5 grams were divided equally into three groups. The second-degree burning induced on all groups. One of groups did not receive any treatment (The control group) and was treated locally with saline and eucerin. The Second group received the P. tomentosa L. as a topical ointment, and the third group received locally, a thin layer of silver sulfadiazine ointment 3% after washing the wound with saline. Afterward treatment period, the microscopic slides from histological sections were prepared. At that point, amounts of the fibroblast cells, blood vessels, wound area, necrotic tissues, and diameter of epidermis rate of wound healing were determined. Also the exterior status of wound in different days was considered. Results obtained from current study have revealed that the extract of P. tomentosa L. can significantly, cause qualitative and quantitative acceleration in healing of second degree burn wounds, due to their bioactive and vasoactive properties. In conclusion the P. tomentosa L. can is used as an overborne medicine with lower cost and side effect than the similar chemical medicines. Although, the further studies are needed on these plants, due to their some toxic effects.

The aim of the present article was to study the healing of wounds using spider silk. Eight New Zealand female rabbits were selected as animal model. First, 3 identical wounds with length of 15 mm and a depth of 4 mm on the back of each rabbit were created. The first group, as standard control, did not receive any special treatment, they were treated only with saline and Vaseline locally. The second group, as positive control, received a thin film of phenytoin 1% ointment locally. The third group, as treated group, received a thin film of spider silk protein. At the end of the study, a biopsy of skin was done. After tissue preparation, all sections were evaluated. Some morphometrical parameters such as counting cells, fibroblasts, blood vessels, determination of the area of the wound closure, necrotic tissue, speed of wound healing, and epidermal thickness were done, and for data statistical analysis, SPSS software and Excel software were used. The results of this study showed that spider silk dressing may benefit as a possible effect of nanoparticles in the test preparation in wound healing.

Antimicrobial peptides (AMPs) have attracted attentions as a novel antimicrobial agent because of their unique activity against microbes. In the present study, we described a new, previously unreported AMP, moronecidin-like peptide, from Hippocampus comes and compared its antimicrobial activity with moronecidin from hybrid striped bass. Antibacterial assay indicated that gram-positive bacteria were more sensitive to moronecidin and moronecidin-like compared with gram-negative bacteria. Furthermore, both AMPs were found to exhibit effective antifungal activity. Comparative analysis of the antimicrobial activity revealed that moronecidin-like peptide has higher activity against Acinetobacter baumannii and Staphylococcus epidermidis relative to moronecidin. Both moronecidin-like and moronecidin peptides retained their antibacterial activity in physiological pH and salt concentration. The time-killing assay showed that the AMPs completely killed A. baumannii and S. epidermidis isolates after 1 and 5 h at five- and tenfold above their corresponding MICs, respectively. Anti-biofilm assay demonstrated that peptides were able to inhibit 50% of biofilm formation at sub-MIC of 1/8 MIC. Furthermore, moronecidin-like significantly inhibited biofilm formation more than moronecidin at 1/16 MIC. Collectively, our results revealed that antimicrobial and anti-biofilm activities of moronecidin-like are comparable to moronecidin. In addition, the hemolytic and cytotoxic activities of moronecidin-like were lower than those of moronecidin, suggesting it as a potential novel therapeutic agent, and a template to design new therapeutic AMPs.

Today air pollution as a very important issue nationally and internationally known. The annual air pollution leads to disease and death of thousands of people around the world. Although some countries take measures in order to minimize the amount of environmental pollutants, but there are still an increase in morbidity and mortality caused by air pollution. Scientific findings have shown a wide range of air pollution effects on the. Air pollution can have devastating effects on children's health, this article tries to explore the effects of oil contamination and pollutants in the air of Assaluyeh on pancreas and ovary of maternal and neonatal rats.

Burns are the most damaging kind of injuries, major global public health crisis and the fourth most common types of trauma. Decision making in the treatment of burns remains a challenge despite existence of improved assessment techniques and treatment procedures. One of the most complications in healing of burn tissues is necrosis. Several medicinal plants were used to treat skin disorders as burn wounds and necrosis so far. In our traditional medicine, one of the non-surgical methods for debridement of necrotic tissues is using toasted barley in sesame oil. Animal was used, because of the lack of previous scientific research about this herbal mixture for debridement of necrotic tissue. After being anesthetized, the second-degree burns were created in rats. Animals were divided into group I, not treated (control group) and group II treated with fibrinolysin ointment 3% (positive control group). Groups III, IV and V were treated with 1, 3 and 5% w/w doses of toasted barley in sesame oil, respectively. Histopathological and clinical findings showed that treated tissues, especially at dose of 5% w/w were more debrided. Therefore, with respect to our results, this herbal based compound can be used as remedy for debridement of necrotic tissue. Key words: Burn, debridement, necrosis, sesame oil, toasted barley.

Micronutrient interactions give rise to complex issues that have an impact on preventive strategies when multiple micronutrient deficiencies coexist. The aim of this population-based study was to determine the prevalence of vitamins A and E and iron deficiencies among women 15 to 49 years of age in the northern Persian Gulf region. We hypothesized that serum retinol levels may show correlations with hemoglobin (Hb) concentrations, independent of iron status. A total of 1242 nonpregnant women of reproductive age were selected via a multistage stratified random cluster sampling technique. Serum ferritin and soluble transferrin receptor levels were measured using enzyme immunoassay techniques. Serum retinol (vitamin A) and α-tocopherol (vitamin E) were determined for 727 women by high-performance liquid chromatography. The prevalence of anemia (Hb

The aim of the present study was morphological and morphometric investigation of burn healing impacts of an honey, milk, and Aloe vera (HMA) ointment on experimentally induced second-degree burns, to approve the medicinal basis of its use in Iranian traditional medicine. A total of 21 male Albino rats weighing 200 to 300 g were divided into 3 groups of 7, including (1) control group, (2) positive control group, and (3) the treatment group that were treated with eucerin, silver sulfadiazine 3% and HMA ointment 5% respectively.After anesthetizing, the second-degree burns (1 cm2 areas) were made on the back of the animals using a digital controlled hot plaque, and each group was treated topically, based on the time scheduled. Then, skin punch biopsies were obtained on the 1st, 14th, and 28th days of post–burn induction; processed; and stained using hematoxylin and eosin and Masson’s trichrome methods. The results showed that HMA ointment induces cell proliferation, increasing the wound closure rate, blood vessel counts, and collagen fiber density in treated animals. It also reduced the wound secretions, inflammation, and scar formation. According to the obtained morphological, morphometric results, we concluded that the traditional HMA ointment, which is rich in therapeutic biomaterials and minerals, has multiple healing effects on burn wounds in rats.

Dactylyne is an acetylenic dibromochloro ether from the Persian Gulf sea hare, Aplysia dactylomela. As a result of its unique structure and nontoxic nature; it has been known as a promising pharmacological substance of marine origin. A theoretical study of dactylyne and its stereoisomers, initiated in the hope of understanding more details of its action, is reported here. In the present research, for the first time, a density functional theory (DFT) calculation has been performed on the stereoisomers of dactylyne to determine the most stable configurations in gas phase. The HOMO–LUMO gap, global softness, chemical potential, and electrophilicity index have been calculated for the most stable stereoisomers at the B3LYP level of theory. These DFT-based global reactivity descriptors have been applied to demonstrate the reactive nature of compounds. Moreover, results from the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis have been employed to support the finding of more reactive stereoisomers. The investigation has indicated that the configuration of stereoisomers has some effects on their electronic and structural properties which control their global reactivity. It is also shown that the most probable interaction sites of dactylyne are in its unsaturated region. In the second part of our study, the effects of some typical substituents on dactylyne reactivity have been investigated theoretically and it has been shown that the strong electron donor groups increase the reactivity of dactylyne more than withdrawing substituent. However, creation of an ionic compound highly influences on reactivity descriptors.

Although it has been shown that osteocalcin functions as a hormone in the regulation of glucose metabolism and fat mass, no population-based study to date has addressed serum osteocalcin levels in relation to energy metabolism concurrent with bone metabolism in postmenopausal women. In a population-based study, cardiovascular risk factors, high-sensitivity C-reactive protein (hs-CRP), osteoprotegerin, receptor activator of nuclear factor-κB ligand, osteocalcin, CrossLaps, alkaline phosphatase, and bone mineral density (BMD) at the lumbar spine (L2–L4) and the proximal femur were measured in 382 Iranian postmenopausal women. In multiple logistic regression analysis, lower osteocalcin and CrossLaps levels were associated with a higher odds ratio (OR) of having type 2 diabetes mellitus when adjustments were made for age, hs-CRP, cardiovascular risk factors, BMD, and markers of bone metabolism [OR 5.17, CI (2.66–10.04), p

It has been suggested that adipose-derived cytokines act as insulin sensitizers/insulin-mimetics and some others may induce insulin resistance. In order to elucidate the potential role of novel adipocytokines in the pre-diabetes states, circulating levels of novel adipocytokines were evaluated in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs).Serum omentin-1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179 subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods.There was no significant difference between the two groups regarding serum RBP4 concentrations. However, serum omentin-1 (median [interquartile range], 6.18 [4.06-11.52]ng/ml versus 10.50 [4.30-20.60]ng/ml, p=0.004) and adiponectin (mean±SD, 10.07±4.0 μg/ml versus 20.66±8.12 μg/ml, p0.0001) levels were significantly lower in FDRs when compared with the controls. In multiple logistic regression analysis, FDRs showed a significant association with lower circulating omentin-1 and adiponectin levels, even after adjustments were made for age, sex, body mass index, blood pressure measures, and biochemical parameters including glucose status, lipid profile, insulin levels and HOMA-IR (OR=0.49, CI [0.30-0.79]; p=0.004 and OR=0.74, CI [0.67-0.82]; p0.0001, respectively). However, FDRs did not show a significant association with serum RBP4 levels in different models of regression analyses.The FDRs showed significant associations with lower omentin-1 and adiponectin levels. A potential role for these adipokines in the FDRs' increased risk of diabetes needs to be further elucidated.

Shark cartilage has been used for its beneficial effects on various diseases. There are evidences, that shark cartilage stimulates cellular and humoral immune responses, which makes it an anti-tumor and immunomodulator candidate.The immunostimulatory effect of shark cartilage derived proteins on the cytotoxic activity of natural killer (NK) cells from healthy human peripheral blood mononuclear cells was studied.The shark cartilage was extracted and its bioactive proteins were purified using ion-exchange chromatography (DE-52) and sequential fractionation on Amicon ultrafiltration membranes. The effect of each protein fraction on the modulation of cytotoxic activity of NK cells, as effectors, against K562, as target cells, was assayed by enzymatic lactate dehydrogenase test.The most immunostimulatory effect on the cytotoxic activity of NK cells was observed for AR10 fraction, containing proteins with molecular weight of about 14.5 kDa on the reducible discontinuous sodium dodecyl sulfate polyacrylamide gel electrophoresis.Among the examined shark cartilage derived proteins, the most immunostimulatory effects on the NK cells cytotoxicity was found for AR10 fraction with molecular weight of about 14 kDa. We propose-the direct interactions of shark cartilage derived proteins with NK cells surface receptors may lead to the enhancing in the cytotoxic activity of NK cells.Thus AR10 fraction, proteins of about 14.5 kDa, has a novel immunostimulatory effect on the NK cells activity in vitro and if confirmed by in vivo trials, it may lead to its future clinical applications as, immunotherapy of cancer, HIV, and augmentation of host immune system related immunodeficiency disorders.

Development of therapies based on the growth inhibition of new blood vessels is among the most intensively studied approaches to the treatment of cancer and other angiogenesis-related diseases. Shark cartilage has been proven to have inhibitory effects on the endothelial cell angiogenesis, metastasis, cell adhesion and MMP (matrix metalloprotease) activity. In the present study, we have used a chromatography-based procedure for the isolation and partial purification of a shark cartilage protein fraction containing anti-angiogenesis activity. Proteins were extracted in 4 M guanidinium chloride, followed by sequential anion- and cation-exchange column chromatography. Angiogenesis assays were performed using the rat aortic ring and chick CAM (chorioallantoic membrane) assay models. The results show that the final fraction contains two proteins with molecular masses of 14.7 and 16 kDa. The protein fraction is able to block microvessel sprouting in the collagen-embedded rat aortic ring assay in vitro and inhibition of capillary sprouting in the CAM assay in vivo. It is suggested that these are partially purified anti-angiogenesis proteins, which have further biotechnological or biomedical applications.

Background: Lead has been widely used in different industries for ages. It is one of the heavy metals, highly poisonous even at low doses, and has biochemical, physiological and behavioral side effects on human and animals. It has been shown that lead has toxic effects on different tissues such as neural and genitourinary tissues, cardiovascular systems and blood. Therefore, high attention has been paid to its environmental pollutions. Objectives: Although many histological and biochemical studies have reported about the effects of lead on the renal tissue, there are a few studies about the ultrastructure and morphometric effects of lead on the kidney. Hence, the aim of this study was the evaluation of morphology and morphometrics of rabbit renal urinary barrier ultrastructure following long-term exposure to lead acetate. Materials and Methods: In this experimental study, 20 male New Zealand rabbits were divided into control and test groups (10 in each). The test group was injected intraperitoneally with chronic dose (8.5 mg/kg of body weight) of lead acetate and for the control group the same volume of normal saline was used, every other day for 10 weeks. After anesthetizing, the biopsies of renal tissues were taken for light and electron microscopic morphometric and morphologic analyses. Results: Long-term exposure to lead acetate caused histopathology effects including dilatation, congestion, nuclei heterochromatic effects, increase in diameter of renal tubules and urinary barrier thickness in rabbit renal tissue. Conclusions: Quantitative and qualitative results of long-term lead acetate exposure showed many histopathology side-effects, especially in the urinary barrier.

Many studies have focused on the effect of noise stress on the health. So far, few studies have been conducted on the effect of noise on reproductive system. The aim of study was to investigate the effect of noise pollution on morphometric parameters of testicular tissue and hormonal assessment (ACTH, cortisol and testosterone). In this study, 40 male rats were exposed to control, 95, 105 and 115 dB noise intensity for sixty days. At the end of study, blood sampling was performed and ACTH, cortisol and testosterone concentrations were assessed. The results showed that noise stress decreased testosterone levels in the 115 dB-treated group, while it increased the ACTH and cortisol levels. Histological sections of testis showed that the mean diameter of the seminiferous tubules and thickness of the germinal epithelium reduced compared to the control group. Also the ratio of the interstitial tissue area to the total testicular tissue area was increased significantly. Our study shows that noise stress may have negative influences on male fertility.

Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of β-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats.

Cartilage was considered as a possible natural source of anti-angiogenesis compounds due to its known avascular nature. In this study, a low-molecular-weight protein with an anti-angiogenesis activity was isolated from shark cartilage using a mild extraction procedure. The protein was purified to homogeneity by gel filtration and electroelution techniques and its N-terminal amino acid sequence was determined. The purified protein, designated as SCP1, represented a molecular weight of 13.7 kDa, pI of 6.9-7 and its N-terminal sequence revealed sequence similarity to alpha parvalbumin family. The protein inhibited angiogenesis when subjected to microvessel sprouting of collagen-embedded rat aortic ring assay. It is suggested that SCP1 could be considered as a new angiogenesis inhibitor derived from shark cartilage.

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.