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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.

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

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.

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.

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.

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.