Bactericidal fully human single-chain fragment variable antibodies protect mice against methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: The increasing prevalence of antibiotic-resistant Staphylococcus aureus, besides the inadequate numbers of effective antibiotics, emphasises the need to find new therapeutic agents against this lethal pathogen. METHODS: In this study, to obtain antibody fragments against S. aureus, a human single-chain fragment variable (scFv) library was enriched against living methicillin-resistant S. aureus (MRSA) cells, grown in three different conditions, that is human peripheral blood mononuclear cells with plasma, whole blood and biofilm. The antibacterial activity of scFvs was evaluated by the growth inhibition assay in vitro. Furthermore, the therapeutic efficacy of anti-S. aureus scFvs was appraised in a mouse model of bacteraemia. RESULTS: Three scFv antibodies, that is MEH63, MEH158 and MEH183, with unique sequences, were found, which exhibited significant binding to S. aureus and reduced the viability of S. aureus in in vitro inhibition assays. Based on the results, MEH63, MEH158 and MEH183, in addition to their combination, could prolong the survival rate, reduce the bacterial burden in the blood and prevent inflammation and tissue destruction in the kidneys and spleen of mice with MRSA bacteraemia compared with the vehicle group (treated with normal saline). CONCLUSION: The combination therapy with anti-S. aureus scFvs and conventional antibiotics might shed light on the treatment of patients with S. aureus infections.

The next step of neurogenesis in the context of Alzheimer's disease.

Among different pathological mechanisms, neuronal loss and neurogenesis impairment in the hippocampus play important roles in cognitive decline in Alzheimer's disease (AD). AD is a progressive and complex neurodegenerative diseases, which is very debilitating. The purpose of this paper is to review recent research into neurogenesis and AD and discuss how pharmacological drugs and herbal active components have impacts on neurogenesis and consequently improve cognitive functions. To date, despite huge research, no effective treatment has been approved for AD. Therefore, an avenue for future research and drug discovery is stimulating adult hippocampal neurogenesis (AHN). Evidence suggests that neurogenesis is regulated by the pharmacological treatment that may be recommended as a part of prophylaxis and therapeutic options for AD. However, the underlying mechanisms of regulating neurogenesis in AD are not well understood. To this point, we highlight to achieve an efficient treatment in AD by manipulating neurogenesis, it's necessary to target all steps of neurogenesis.

Analgesic Effect of Valerian Root and Turnip Extracts.

BACKGROUND: Medicinal plants are considered as one of the important sources of chemical substances with therapeutic effects. This study aimed to compare the analgesic effects of alcoholic extract of valerian root and turnip in rats. METHODS: Fifty female Wistar rats weighing 190 g were divided into 5 equal groups of control (subcutaneous injection of 2.5% formalin in the right foot), sham (subcutaneous injection of 2.5% formalin+distilled water), experimental 1 (subcutaneous injection of 2.5% formalin+200 mg/kg turnip extract), experimental 2 (subcutaneous injection of 2.5% formalin 2+200 mg/kg valerian root extract) and experimental 3 (subcutaneous injection of 2.5% formalin+200 mg/kg turnip extract+200 mg/kg valerian root extract). The time duration of 0-5 and 16-60 minutes after injection of formalin were respectively considered as acute and chronic phases. Injection of distilled water and the extracts was conducted 30 minutes before assessing the analgesic effects. RESULTS: A significant decrease in pain score in the acute phase was observed in the group received valerian root extract compared to the control group. Also, a significant reduction in pain score was noted in the acute and chronic phases of the group receiving simultaneous administration of valerian root and turnip extracts when compared to the control group. CONCLUSION: Simultaneous use of valerian root and turnip extracts is recommended for analgesic effects in both acute and chronic phases of the pain.

Enhancement of Neural Stem Cell Survival, Proliferation, Migration, and Differentiation in a Novel Self-Assembly Peptide Nanofibber Scaffold.

Considerable efforts have been made to combine biologically active molecules into the self-assembling peptide in order to improve cells growth, survival, and differentiation. In this study, a novel three-dimensional scaffold (RADA4GGSIKVAV; R-GSIK) was designed by adding glycine and serine between RADA4 and IKVAV to promote the strength of the peptide. The cell adhesion, viability, proliferation, migration, and differentiation of rat embryonic neural stem cells (NSCs) in R-GSIK were investigated and compared to laminin-coated, two-dimensional, and Puramatrix cultures. The scanning electron microscopy studies of the R-GSIK showed an open porous structure and a suitable surface area available for cell interaction. R-GSIK promoted the cell adhesion, viability, proliferation, and migration compared to the other cultures. In addition, the R-GSIK enhanced NSCs differentiation into neuronal cells. The NSCs injected in R-GSIK had a lower glial differentiation rate than in the Puramatrix. The results suggest that R-GSIK holds great promise for cell therapies and neuronal tissue repair.

Survival, proliferation, and migration of human meningioma stem-like cells in a nanopeptide scaffold.

OBJECTIVES: In order to grow cells in a three-dimensional (3D) microenvironment, self-assembling peptides, such as PuraMatrix, have emerged with potential to mimic the extracellular matrix. The aim of the present study was to investigate the influence of the self-assembling peptide on the morphology, survival, proliferation rate, migration potential, and differentiation of human meningioma stem-like cells (hMgSCs). MATERIALS AND METHODS: The efficacy of a novel method for placing hMgSCs in PuraMatrix (the injection approach) was compared to the encapsulation and surface plating methods. In addition, we designed a new method for measurement of migration distance in 3D cultivation of hMgSCs in PuraMatrix. RESULTS: Our results revealed that hMgSCs have the ability to form spheres in stem cell culture condition. These meningioma cells expressed GFAP, CD133, vimentin, and nestin. Using the injection method, a higher proliferation rate of the hMgSCs was observed after seven days of culture. Furthermore, the novel migration assay was able to measure the migration of a single cell alone in 3D environment. CONCLUSION: The results indicate the injection method as an efficient technique for culturing hMgSCs in PuraMatrix. Furthermore, the novel migration assay enables us to evaluate the migration of hMgSCs.

Third eyelid in the small Indian mongoose (Herpestes javanicus): a morphological and histological study.

The Indian mongoose (Herpestes javanicus) is native to parts of Asia, Iran. The purpose of this study was to describe the gross anatomy of the cartilage and histology of the superficial gland of the third eyelid of two adult mongooses. The animals, in terminal stages of disease and near death due to aging or unknown reasons, were referred from Park Zoo (Shiraz, Iran) to our center. By using a modified maceration technique, the morphological characteristics of the cartilage were examined. For histological examinations of the superficial gland of the third eyelid, the samples were stained with haematoxylin and eosin. Also, to detect the elastic fibers in the cartilage sections were stained with orcein and Weigert's resorcin-fuchsin. The cartilage consisted of an ovoid appendix and a mild reverse sigmoid crossbar. Elastic fibers were scattered throughout the cartilage but were more concentrated in the center. The superficial gland of the third eyelid was compound tubuloacinar with serous acini.

Alterations of the ovarian histomorphometry at pre-puberty in rat offspring from diabetic mothers.

PURPOSE: Maternal diabetes leads to increased blood glucose concentration in the mother and consequently in the foetus, causing various neonatal problems. This study was conducted to evaluate the effects of maternal diabetes on foetal ovarian structure. METHODS: Sixteen adult female rats were allocated into two equal groups. Diabetes was induced in one group by alloxan. Both groups became pregnant by natural mating. Thirty days after birth, the female offspring were terminated, the body weight and blood glucose of the animals measured and their ovaries removed. Various histological and cellular parameters were determined using histological and electron microscopy techniques. RESULTS: Results revealed a significant increase in body weight and blood glucose in the offspring of the diabetic mothers (ODM) compared to that of the controls. The weight, volume and diameter of the ovary and the ovarian capsule thickness were inclined to decrease in ODM compared to that of controls. The number and diameter of primary, pre-antral and antral follicles were decreased in ovaries in the ODM. The electro-micrographs have demonstrated the organelle alterations in oocytes and granulosa cells that suggest the apoptosis progress and oxidative stress. CONCLUSIONS: Maternal hyperglycaemia exhibited deleterious effects on the female reproductive system in the offspring.