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Wound healing is a complex pathophysiological process, highlighting the importance of effective and thorough wound care along with the prevention of wound infection, a major barrier that can slow down or even disrupt the healing process. To date, there are plenty of herbal plants well known and historically supernatural, showing profound wound healing effects. Application of such herbal extracts/ingredients in electrospun nanofiber platforms has shown promising outcomes in improving wound healing process. Based on these facts, we loaded Calendula officinalis extract (CO) in chitosan/polyethylene oxide scaffolds (CS/PEO) by electrospinning. Using SEM, morphology of electrospun scaffolds showed a narrow range of fiber diameter, around 143–-252 nm, with uniform and bead-free appearance. FT-IR spectroscopy confirmed the presence of CO extract in nanofibrous scaffolds. Of importance, incorporation of CO extract improved mechanical properties of CS/PEO nanofibers. A 1602 cP reduction in viscosity and a 0.892 ms/cm increase in the conductivity of the solution was observed after addition of the CO extract. CO extract showed strong antibacterial properties with 96% and 94% reduction in Gram positive and Gram negative bacteria, respectively. In vitro studies with fibroblast cells confirmed enhanced proliferation, growth and attachment of the cells. The in vivo and histological analysis of rat wounds, revealed excellent wound healing ability of CS/PEO/CO dressings (87.5 % wound closure after 14 days) via improving collagen synthesis, re-epithelization and remodeling of the tissue. In sum, our findings show that CS/PEO/CO scaffolds can be used as a promising dressing for the treatment of skin wounds.

Glioblastoma is a lethal and incurable cancer. Tumor suppressor miRNAs are promising gene therapy tools for cancer treatment. In silico, we predicted miR-424 as a tumor suppressor. It had several target genes from the epidermal growth factor receptor (ERBB) signaling pathway that are overactive in most glioblastoma cases. We overexpressed miR-424 by lentiviral transduction of U-251 and U-87 glioblastoma cells confirmed with fluorescent microscopy and real-time quantitative PCR (qRT-PCR). Then the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) proliferation assay and scratch wound migration assay were performed to investigate the miR-424 tumor suppressor effect in glioblastoma. miR-424's effect on glioblastoma apoptosis and cell-cycle arrest was verified using Annexin V- phosphatidylethanolamine (PE) and 7-minoactinomycin D (7-AAD) apoptosis assay and cell-cycle assay. miR-424 predicted target genes mRNA and protein level were measured after miR-424 overexpression in comparison to the control group by qRT-PCR and western blotting, respectively. We confirmed miR-424 direct target genes by dual-luciferase reporter assay. miR-424 overexpression significantly suppressed cell proliferation and migration rate in glioblastoma cells based on the MTT and scratch assays. Flow cytometry results confirmed that miR-424 promotes apoptosis and cell-cycle arrest in glioblastoma cells. Predicted target genes of miR-424 from the ERBB pathway were downregulated by miR-424 overexpression. qRT-PCR and western blotting showed that KRAS, RAF1, MAP2K1, EGFR, PDGFRA, AKT1, and mTOR mRNA expression levels and KRAS, RAF1, MAP2K1, EGFR, and AKT1 protein level, respectively, had significantly decreased as a result of miR-424 overexpression in comparison to the control group. Dual-luciferase reporter assay confirmed that miR-424 directly targets RAF1 and AKT1 oncogenes. Overall, miR-424 acts as tumor suppressor miRNA in glioblastoma cells.

Summary By screening 27,000 publicly available prokaryotic genomes, we recovered ca. 6300 type I and ca. 5200 type II putative L-asparaginase highlighting the vast potential of prokaryotes. Caspian water with similar salt composition to the human serum was targeted for in silico L-asparaginase screening. We screened ca. three million predicted genes of its assembled metagenomes that resulted in annotation of 87 putative L-asparaginase genes. The L-asparagine hydrolysis was experimentally confirmed by synthesizing and cloning three selected genes in E. coli. Catalytic parameters of the purified enzymes were determined to be among the most desirable reported values. Two recombinant enzymes represented remarkable anti-proliferative activity (IC50, Graphical Abstract, Highlights • In silico screening finds 87 putative L-asparaginases from brackish Caspian Sea • Three candidate genes, cloned and expressed in E. coli, showed the desired activity • In silico screening coupled with functional validation bypasses cultivation bottleneck, Biological Sciences; Cell Biology; Cancer; In Silico Biology

Cardiovascular diseases, among all diseases, are taking the most victims worldwide. Coronary artery occlusion, takes responsibility of about 30% of the yearly global deaths in the world (Heart Disease and Stroke Statistics 2017 At-a-Glance, 2017), raising the need for viable substitutes for cardiovascular tissues. Depending on a number of factors, blocked coronary arteries are now being replaced by autografts or stents. Since the autografts, as the gold standard coronary artery replacements, are not available in adequate quality and quantity, the demand for small diameter vascular substitute comparable to native vessels is rapidly growing. Synthetic grafts have been successfully approved for developing vascular replacements but regarding the special conditions in small-caliber vessels, their use is limited to large-diameter vascular tissue engineering. The major problems associated with the vascular tissue engineered grafts are thrombosis and intimal hyperplasia. Heparin, a negatively charged natural polysaccharide has been used in fabricating vascular grafts since it prevents protein fouling on the surfaces and most importantly, impeding thrombosis. Herein, we focused on heparin, as a multifunctional bioactive molecule that not only serves as an anticoagulant with frequent clinical use but also acts as an anti-inflammatory and angiogenic regulatory substance. We summarized heparin incorporation into stents and grafts and their applicability to restrain restenosis. Also, the applications of heparinzation of biomaterials and heparin mimetic polymers and different approaches invoked to improve heparin bioactivity have been reviewed. We summarized the methods of adding heparin to matrices as they were explained in the literature. We reviewed how heparin influences the biocompatibility of the scaffolds and discussed new advances about using heparin in small-diameter vascular tissue engineering.

Cell therapy has proven to be a highly promising method in clinical applications, raising so much hope for the treatment of injured tissues with low, if any, self regeneration potential such as central and peripheral nervous system. Neurally induced bone marrow derived mesenchymal stem cells (NIMSCs) as well as olfactory ensheathing cells (OECs) were transplanted in a rat model of sub-acute spinal cord injury and the behavioral and histological analyses were conducted. A balloon-compression technique was used to produce an injury at T8-T9 level of spinal cord. After a week post injury, rats were injected with either NIMSCs or OECs at the center of developing lesion cavity, 3mm cranial and 3mm caudal to the cavity. Weekly behavioral assessment using BBB score was done over five-week period post transplantation and finally histological assessment was performed to locate labeled cells in the tissue in order to evaluate the reduction of cavity formation and axonal regeneration. Evaluation of locomotor performance showed significant behavioral improvement in NIMSC group over OEC and control groups. The histological analyses revealed the presence of transplanted cells in the spinal cord parenchyma. Volume of injured area that was occupied with syrinx cavity in NIMSC group was significantly less than control group. In addition, meanwhile neurofilament-positive axons significantly showed higher expression in rats receiving NIMSC compared to the other two groups. In conclusion NIMSC caused both behavioral and histological improvement that potentially makes them a promising candidate for cell therapy approaches of spinal cord injuries.

Among the 49 strains of moderately halophilic bacteria isolated from the salty environments of Iran, a Gram-positive coccus designated as strain QW6 showed high capacity in the removal of toxic oxyanions of tellurium in a wide range of culture medium factors including pH (5.5-10.5), temperature (25-45 degrees C), various salts including NaCl, KCl, and Na(2)SO(4) (0.5-4 M), selenooxyanions (2-10 mM), and at different concentrations of potassium tellurite (0.5-1 mM) under aerobic condition. Phenotypic characterization and phylogenetic analyses based on 16S rDNA sequence comparisons indicated that this strain was a member of the genus Salinicoccus. The maximum tellurite removal was exhibited in 1.5M NaCl at 35 degrees C, while the activity reduced by 53% and 47% at 25 and 45 degrees C, respectively. The optimum pH for removal activity was shown to be 7.5, with 90% and 83% reduced removal capacities at the two extreme values of 5.5 and 10, respectively. The impact of different concentrations of selenooxyanions (2-10 mM) on tellurite removal by strain QW6 was evaluated. The ability of strain QW6 in the removal of tellurite in the presence of 6mM selenite increased by 25%. The concentration of toxic potassium tellurite in the supernatant of the bacterial culture medium decreased by 99% (from 0.5 to 0.005 mM) after 6 days and the color of the medium changed to black due to the formation of less toxic elemental tellurium.