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Background: There is no effective and safe preventive/therapeutics vaccine against HIV-1 worldwide. Different viral proteins such as Nef, and two regions of Env including; variable loop of gp120 (V3) and membrane proximal external region of gp41 (MPER) are particularly important for vaccine development in different strategies and they are also the primary targets of cellular and humoral immune responses. On the other side, LDP12 is a new cell-penetrating peptide (CPP) which is capable of therapeutic application and cargoes delivery across the cellular membrane. Objective: In current study, we designed and produced Nef-MPER-V3 fusion protein harboring LDP12 that has the capability of being used in future vaccine studies. Methods: The CPP-protein was expressed in E. coli Rosseta (DE3) strain and purified through Ni-NTA column. Characterization of cellular delivery and toxicity of the recombinant protein were evaluated by western blotting and MTT assay. Results: Our results showed that the CPP-protein was successfully expressed and purified with high yield of 5 mg/L. Furthermore, non-cytotoxic effect was observed and specific band (~ 37 KDa) in western blotting indicated the capability of LDP12 to improve the rate of penetration into HEK-293T cells in comparison with a control sample. Conclusion: Altogether, the data indicated that LDP12 CPP could be utilized to internalize HIV-1 Nef-MPER-V3 protein into eukaryotic cell lines without any toxicity and represented a valuable potential vaccine candidate and this guarantees the further evaluation towards the assessment of its immunogenicity in mice, which is currently under process.

Aim As a natural compound, docosahexaenoic acid (DHA) exerts anti-cancer and anti-angiogenesis functions through exosomes; however, little is known about the molecular mechanisms. Main methods Breast cancer (BC) cells were treated with DHA (50 μM) and then tumor cell-derived exosomes (TDEs) were collected and characterized by electron microscopy, dynamic light scattering, and western blot analyses. By the time the cells were treated with DHA, RT-qPCR was used to investigate the expression of vascular endothelial growth factor (VEGF) and the selected pro- and anti-angiogenic microRNAs (miRNAs). The quantification of secreted VEGF protein was measured by enzyme-linked immunosorbent assay (ELISA). The effects of TDEs on endothelial cell angiogenesis were explored by transwell cell migration and in vitro vascular tube formation assays. Key findings DHA treatment caused a significant and time-dependent decrease in the expression and secretion of VEGF in/from BC cells. This also increased expression of anti-angiogenic miRNAs (i.e. miR-34a, miR-125b, miR-221, and miR-222) while decreased levels of pro-angiogenic miRNAs (i.e. miR-9, miR-17-5p, miR-19a, miR-126, miR-130a, miR-132, miR-296, and miR-378) in exosomes derived from DHA-treated BC cells, TDE (DHA+). While treatment with exosomes (100 μg/ml) obtained from untreated BC cells, TDE (DHA−), enhanced the expression of VEGF-A in human umbilical vein endothelial cells (HUVECs), incubation with DHA or TDE (DHA+) led to the significant decrease of VEGF-A transcript level in these cells. We indicated that the incubation with TDE (DHA+) could significantly decrease endothelial cell proliferation and migration and also the length and number of tubes made by HUVECs in comparison with endothelial cells incubated with exosomes obtained from untreated BC cells. Significance DHA alters angiogenesis by shifting the up-regulation of exosomal miRNA contents from pro-angiogenic to anti-angiogenic, resulting in the inhibition of endothelial cell angiogenesis. These data can help to figure out DHA's anti-cancer function, maybe its use in cancer therapy.

Background & Aims of the Study: Household Hazardous Waste (HHW) are the wastes can potentially increase the hazardous properties of municipal solid waste in the landfill, incineration, or composting. The lack of information about their generation and composition hinders the creation of special programs for their collection and treatment, making these wastes a potential threat to human health and the environment. Therefore the aim of this study was to determine the quantity, quality and to be able to compare the results of four seasons, regarding consumption patterns and solid waste generation rates. Materials & Methods: A cross-sectional study was done in 2015-2016 years in Isfahan compost plant (waste receipt place) and the analyses were performed on household hazardous waste in four seasons of the year. The Shapiro–Wilk test was used to evaluate the normality of the quantitative data. Results: HHW comprised 0.6% of municipal solid waste (MSW). The largest percentage of HHW in total HHW were home cleaners in spring (37.53%), summer (26.82%), and fall (39.78%), because home cleaners are the daily necessities of residential households but in winter medical products (34.70%) were more than others. Probably cause of the high percentage of medical products is disease outbreaks in winter. Generally, the most hazardous materials in MSW included home cleaning (0.2%), medical products (0.19%) and self-care equipment (0.11%) and the lowest were biological infection materials. Conclusions: This study demonstrated that the production of HHW in Isfahan is independent of different seasons of the year. Household cleaners and personal protective equipment and medicine had formed the highest percentage of household hazardous waste.