Iranian Biomedical Journal
Volume:24 Issue: 2, Mar 2020

Aging, as a major risk factor of memory deficiency, affects neural signaling pathways in hippocampus. In particular, age-dependent androgens deficiency causes cognitive impairments. Several enzymes like protein kinase C (PKC) are involved in memory deficiency. Indeed, PKC regulatory process mediates α-secretase activation to cleave APP in β-amyloid cascade and tau proteins phosphorylation mechanism.  Androgens and cortisol regulate PKC signaling pathways, affecting the modulation of receptor for activated C kinase 1. Mitogen-activated protein kinase/ERK signaling pathway depends on CREB activity in hippocampal neurons and is involved in regulatory processes via PKC and androgens. Therefore, testosterone and PKC contribute in the neuronal apoptosis. The present review summarizes the current status of androgens, PKC, and their influence on cognitive learning. Inconsistencies in experimental investigations related to this fundamental correlation are also discussed, with emphasis on the mentioned contributors as the probable potent candidates for learning and memory improvement.

Recently, modification of T cells with chimeric antigen receptor (CAR) has been an attractive approach for adoptive immunotherapy of cancers. Typically, CARs contain a single-chain variable domain fragment (scFv). Most often, scfvs are derived from a monoclonal antibody of murine origin and may be a trigger for host immune system that leads to the T-cell clearance. Nanobody is a specific antigen-binding fragment derived from camelid that has great homology to human VH and low immunogenic potential. Therefore, in this study, nanobody was employed instead of scFv in CAR construct.

In this study, a CAR was constructed based on a nanobody against PSMA (NBPII-CAR). At first, Jurkat cells were electroporated with NBPII-CAR, and then flow cytometry was performed for NBPII-CAR expression. For functional analysis, CAR T cells were co-cultured with prostate cancer cells and analyzed for IL-2 secretion, CD25 expression, and cell proliferation.

Flow cytometry results confirmed the expression of NBPII-CAR on the transfected Jurkat cells. Our data showed the specificity of engineered Jurkat cells against prostate cancer cells by not only increasing the IL-2 cytokine (about 370 pg/ml) but also expressing the T-cell activation marker CD25 (about 30%). In addition, proliferation of engineered Jurkat cells increased nearly 60% when co-cultured with LNCaP (PSMA+), as compared with DU145 (PSMA-).

Here, we describe the ability of nanobody-based CAR to recognize PSMA that leads to the activation of Jurkat cells. This construct might be used as a promising candidate for clinical applications in prostate cancer therapy.

Recent studies have shown that bone marrow mesenchymal stem cells (BMSCs) have a putative ability to promote neurogenesis and produce behavioral and functional improvement. Our previous study demonstrated that co-treatment of granulocyte colony-stimulating factor (G-CSF) and BMSCs have beneficial effects on Parkinson's models. The main purpose of this research was to investigate the effects of these two factors on oxidative stress factors in the brain of Parkinson's rat.

Adult male Wistar rats (weighing 200–250 g) were used and randomly divided into five groups of seven each. To create the Parkinson's model, 6-OHDA was injected into the left substantia nigra pars compacta. The BMSCs (2 × 106) and G-CSF (75 µg/kg) were used for treatment after creating the PD model. After four weeks, the brains of rats were removed and processed for immunohistochemical studies, such as tyrosine hydroxylase-positive neurons as well as analysis of oxidative stress factors.

The results showed that the injected BMSCs could cross the BBB. The injected cells are also able to settle in different areas of the brain. Analyses of the brain oxidative stress factors showed that G-CSF and BMSCs reduced the expression of malondialdehyde and induced the activity of superoxide dismutase, glutathione, and peroxidase ferric reducing ability of plasma.

Co-administration of G-CSF and BMSC reduced the expression of pro-inflammatory cytokines and induced the activity of antioxidant enzymes; however, neurogenesis increased in the brain.

The recent improvements in wound healing have led to new strategies in regenerative medicine. Burn wound healing is an important issue in skin regeneration and has multiple indications for stem cell therapy. Hair follicle stem cells (HFSCs) are a highly promising source of stem cells for healing use, as these cells are accessible, active and pluripotent adult stem cells.

HFSCs of the rat whisker were isolated, cultured, and labeled with DiI. Flow cytometry method was used to detect special markers of HFSCs. Deep partial-thickness burn wound was created, and labeled HFSCs were injected around the wound bed. Wound closure was recorded via digital photographs. The inflicted rats were sacrificed at 3, 7, or 14 days post burn and used for subsequent histological and tensiometry analysis.

Our results indicated that HFSCs were positive for Nestin and CD34 markers, but negative for Kr15. Morphological and histological photographs revealed that wound closure rate was accelerated in stem cell-treated group compared with other groups. In addition, faster re-epithelialization and collagen deposition were observed. The immunohistochemical analysis suggested that CD31 expression and vascular density enhanced in the stem cell-treated group. Further, tissue tensile strength increased in HFSCs-treated rats in comparison to the control group.

The present study demonstrates that HFSC could accelerate burn wound healing as well as tensile strength in rats.

Self-assembling peptides (SApeptides) have growing applications in tissue engineering and regenerative medicine. The application of SApeptide-based hydrogels depends strongly on their viscoelastic properties. Optimizing the properties is of importance in tuning the characteristics of the hydrogels for a variety of applications.

In this study, we employed statistical modeling, conducted with the response surface methodology (RSM) and particle tracking microrheology, to investigate the effects of self-assembling SPG-178 peptide and added NaCl salt concentrations and milieu type (deionized water or blood serum) on the viscoelastic properties of SPG-178 hydrogels. A central composite RSM model was employed for finding the optimum value of the parameters to achieve the highest storage modulus and the lowest tan δ.

Viscoelastic properties of each sample, including storage modulus, loss modulus, and tan δ, were determined. Storage modulus and tan δ were modeled, accounting for the impact of the SPG-178 peptide and NaCl concentrations and milieu type on the viscoelastic properties. It was found that the SPG-178 hydrogel storage modulus was positively influenced by the SPG-178 peptide concentration and the serum.

A combination of microrheology and RSM is a useful test method for statistical modeling and analysis of rheological behavior of solid-like gels, which could be applied in various biomedical applications such as hemostasis.

Ascorbic acid, known as vitamin C, has been used in combination with a number of cytotoxic agents in vitro and in vivo with contradictory results on its effectiveness. It is believed that vitamin C can sensitize different cancer cells to common therapy strategies such as chemotherapy and radiotherapy. During current research, the combination effect of vitamin C with cisplatin was evaluated against gastric cancer cells.

MTT-based proliferation assay, combination index method, and flow cytometry technique were employed for the assessment of cell cycle and determination of apoptosis/necrosis on the AGS cell line.

Co-treatment of gastric cancer cells with vitamin C in its IC50 dose in addition to cisplatin in both IC50 (10 µg/ml) and five times less (2 µg/ml) doses could increase the cytotoxicity effect of cisplatin in a synergistic manner. Moreover, the pointed co-treatment approach could induce the cell count in sub-G0 phase while reducing it in the G0/G1, G2/M, and S phases. Further findings showed that the combined dose of vitamin C and cisplatin could increase the percentage of apoptotic and necrotic cells in comparison with a single dose of cisplatin.

This study introduces a possible approach for the treatment of gastric cancer with more potency and less amount of administered cisplatin to induce toxicity.

Rotavirus infection is one of the most common gastroenteritis in the world, and a million cases are registered to enter hospital every year. Promyelocytic leukemia proteins (PMLs) are IFN-up-regulated proteins, and one of their critical functions is working as antiviral proteins. Recently, promyelocytic leukemia isoform II (PML-II) has been depicted as an isoform responsible for the antiviral function.

Rotavirus prevalence determination was achieved by PCR and Rapid Adeno/Rota Virus test, while the relative expression assay was carried out by real-time PCR technique. Blood and stool samples were collected from 34 children under five years admitted to the hospital with acute gastroenteritis showing signs of dehydration. RNA samples were extracted from blood specimens and converted to cDNA to be used in gene expression analysis of PML, PML-II, and IFN-γ in rotavirus positive or negative samples.

Rapid Adeno/Rota Virus Antigen Combo Test and PCR assay could detect the virus in stool samples in 45% and 17.6% of cases, respectively. PML in positive samples decreased to 104fold less than the level in negative ones. The same trend was noticed in the level of IFN-γ and PML-II expression as their expression reduced to 104 or 13fold in rotavirus-infected samples compared to the control, respectively.

Altogether, our data showed that the gene expression of PML, PML-II, and type II IFN considerably diminished in rotavirus-infected samples compared to the negative control.

Herpes simplex virus type 2 (HSV-2) seroprevalence has been shown to be a potential sign of infection in pregnant women, and it could be applied to check HSV-2 transmission. This study evaluated the anti-HSV-2 IgG prevalence in pregnant women who were referred to health centers in Urmia, Northwest of Iran, during 2014-2015.

Serum samples were collected from 86 pregnant women and tested for Anti-HSV-2-specific IgG using a commercial enzyme-linked immunosorbent assays kit.

Five (5.8%) pregnant women showed the presence of Anti-HSV-2-specific IgG antibodies. Previous abortion was reported in 16 (19.7%) and 2 subjects in the seronegative and seropositive groups, respectively.

Data from the present study indicate a lower number of HSV-2 seropositives among the pregnant women in Urmia. This reduction would be a result of low number of studied subjects used in the present study; hence, assessing a large sample is recommended.