Magnetic resonance imaging of human-derived amniotic membrane stem cells using PEGylated superparamagnetic iron oxide nanoparticles

Objective: The label and detection of cells injected into target tissues is an area of focus for researchers. Iron oxide nanoparticles can be used to label cells as they have special characteristics. The purpose of this study is to examine the effects of iron oxide nanoparticles on human-derived amniotic membrane stem cell (hAMCs) survival and to investigate the magnetic properties of these nanoparticles with increased contrast in magnetic resonance imaging (MRI). Materials and Methods: In this experimental study, we initially isolated mesenchymal stem cells from amniotic membranes and analyzed them by?ow cytometry. In addition, we synthesized superparamagnetic iron oxide nanoparticles (SPIONs) and characterized them by various methods. The SPIONs were incubated with hAMCs at concentrations of 25-800 μg/mL. The cytotoxicity of nanoparticles on hAMCs was measured by the MTT assay. Next, we evaluated the effectiveness of the magnetic nanoparticles as MRI contrast agents. Solutions of SPION were prepared in water at different iron concentrations for relaxivity measurements by a 1.5 Tesla clinical MRI instrument. Results: The isolated cells showed an adherent spindle shaped morphology. Polyethylene glycol (PEG)-coated SPIONs exhibited a spherical morphology. The average particle size was 20 nm and magnetic saturation was 60 emu/g. Data analysis showed no signifcant reduction in the percentage of viable cells (97.86 ± 0.41) after 72 hours at the 125 μg/ml concentration compared with the control. The relaxometry results of this SPION showed a transverse relaxivity of 6.966 (μg/ml.s)-1 Conclusion: SPIONs coated with PEG used in this study at suitable concentrations had excellent labeling efficiency and biocompatibility for hAMCs

Role of morphine preconditioning and nitric oxide following brain ischemia reperfusion injury in mice

Objective(s): Morphine dependence (MD) potently protects heart against ischemia reperfusion (IR) injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day) of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg) or L-NAME (20 mg/kg) 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining) performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P<0.01) and neuronal survival (P<0.001) and decreased apoptosis (P<0.05) in region I of hippocampus (CA1 region) in mouse. Treatment with naloxone or L-NAME abolished all MD aforementioned effects. Conclusion: Results of the present study suggested that opioid receptors activation in the early hr post ischemia is crucial for MD-induced hippocampus tolerance against IR injury. Opioid receptor-dependent balance of NO production was another key factor in MD-induced protection. Further studies are required to determine the effect of MD on opioid receptor changes after ischemia and its correlation with MD-induced protection. © 2015, Mashhad University of Medical Sciences. All rights reserved

Case report: West-Nile virus infection in two Dutch travellers returning from Israel

We report about West Nile virus (WNV) infections in a symptomatic traveller returning from Israel and in her asymptomatic travel companion. Knowledge of the current epidemiological situation in Israel from where WNV cases were reported recently enabled a rapid diagnosis. The described cases serve as a reminder for physicians to consider WNV in the diagnosis of patients returning from areas with potential circulation of the virus

Protection of hippocampal CA1 neurons against ischemia/Reperfusion injury by exercise preconditioning via modulation of Bax/Bcl-2 ratio and prevention of Caspase-3 Activation

Introduction: Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia. Methods: Male rats weighing 260-300 g were randomly allocated into three groups (sham, exercise, and ischemia). The rats in exercise group were trained to run on atreadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries (CCAs) for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining . Results: The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group (P<0.001), and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P<0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group (P<0.001). Discussion: This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli

Improvement of tissue survival of skin flaps by 5α-reductase inhibitors: Possible involvement of nitric oxide and inducible nitric oxide synthase

Background: Skin flap grafting is a popular approach for reconstruction of critical skin and underlying soft tissue injuries. In a previous study, we demonstrated the beneficial effects of two 5α-reductase inhibitors, azelaic acid and finasteride, on tissue survival in a rat model of skin flap grafting. In the current study, we investigated the involvement of nitric oxide and inducible nitric oxide synthase (iNOS) in graft survival mediated by these agents. Methods: A number of 42 male rats were randomly allocated into six groups: 1, normal saline topical application; 2, azelaic acid (100 mg/flap); 3, finasteride (1 mg/flap); 4, injection of L-NG-nitroarginine methyl ester (L-NAME) (i.p., 20 mg/kg); 5, L-NAME (20 mg/kg, i.p.) + azelaic acid (100 mg/flap, topical); 6, L-NAME (20 mg/kg, i.p.) + finasteride (1 mg/flap, topical). Tissue survival, level of nitric oxide, and iNOS expression in groups were measured. Results: Our data revealed that azelaic acid and finasteride significantly increased the expression of iNOS protein and nitric oxide (NO) levels in graft tissue (P &lt; 0.05). These increases in iNOS expression and NO level were associated with higher survival of the graft tissue. Conclusion: It appears that alterations of the NO metabolism are implicated in the azelaic acid- and finasteride-mediated survival of the skin flaps. © 2015, Pasteur Institute of Iran. All rights reserved

Lavender oil (Lavandula angustifolia) attenuates renal ischemia/reperfusion injury in rats through suppression of inflammation, oxidative stress and apoptosis

Renal ischemia/reperfusion (I/R) injury following kidney transplantation has been found to be a great clinical problem owing to initiation of acute inflammatory responses and subsequently rapid loss of kidney function. It is well known that lavender oil exhibits an extensive spectrum of pharmacological and biochemical activities. The purpose of this study was to clarify molecular targets of lavender in treatment of this disease. Male Wistar rats weighing 200�250 g were divided into three major groups: sham, I/R, and I/R + different doses of lavender oil (L1:50 mg/kg, L2: 100 mg/kg, and L3: 200 mg/kg). A rat model of renal I/R (45 min ischemia and 24 h reperfusion) was created and lavender was administrated at 1 h after the beginning of reperfusion (i.p). Activities of antioxidant enzymes such as SOD, GPX, and CAT, and lipid peroxidation were evaluated. The expression of inflammatory cytokines such as TNFα IL1β and IL10 was determined by IHC and ELISA assay. Apoptosis activity and tissue damage were evaluated by TUNEL and H & E staining, respectively. Our results showed that lavender oil markedly restored activities of antioxidant enzymes and reduced lipid peroxidation (P < 0.05). Lavender significantly decreased levels of TNFα and IL1β and increased level of IL10 in a dose-dependent manner (P < 0.05). Lavender reduced TUNEL positive cells in a dose-dependent manner. However, lavender reduced damage to peritubular capillaries and contributed to preservation of normal morphology of renal cells. In sum, our findings establish a fundamental foundation for future drug industry to decrease the rates of rejection in kidney transplant patients. © 201

Human amniotic membrane mesenchymal stem cells-conditioned medium attenuates myocardial ischemia-reperfusion injury in rats by targeting oxidative stress

Objective(s): Ischemic heart diseases (IHD) are one of the major causes of death worldwide. Studies have shown that mesenchymal stem cells can secrete and release conditioned medium (CM) which has biological activities and can repair tissue injury. This study aimed to investigate the effects of human amniotic membrane mesenchymal stem cells (hAMCs)-CM on myocardial ischemia/reperfusion (I/R) injury in rats by targeting oxidative stress. Materials and Methods: Male Wistar rats (40 rats, weighing 200�250 g) were randomly divided into four groups: Sham, myocardial infarction (MI), MI + culture media, and MI + conditioned medium. MI was induced by ligation of the left anterior descending coronary artery for 30 min. After 15 min of reperfusion, intramyocardial injections of hAMCs-CM or culture media (150 μl) were performed. At the end of the experiment, serum levels of cardiac troponin-I (cTn-I), myocardial levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as cardiac histological changes were evaluated. Results: HAMCs-CM significantly decreased cTn-I and MDA levels and increased SOD and GPx activities (P<0.05). In addition, hAMCs-CM improved cardiac histological changes and decreased myocardial injury percentage (P<0.05). Conclusion: This study showed that hAMCs-CM has cardioprotective effects in the I/R injury condition. Reduction of oxidative stress by hAMCs-CM plays a significant role in this context. Based on the results of this study, it can be concluded that hAMCs-CM can be offered as a therapeutic candidate for I/R injury in the future, but more research is needed. © 2020 University of Baghdad-College of Science. All rights reserved

Improvement of heart failure by human amniotic mesenchymal stromal cell transplantation in rats

Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1-Control 2-Heart Failure (HF) 3-Sham 4-Culture media 5-Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3�106 cells in 150 μl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 � 9 to 81/25 � 6/05 in SCT group (p value &lt; 0.001). Fraction shortening in HF group was increased from 27/53 � 8/58 into 45/55 � 6/91 in SCT group (p value &lt; 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value &lt; 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters. � 2016, Tehran Heart Center. All rights reserved

Amniotic membrane mesenchymal stem cells labeled by iron oxide nanoparticles exert cardioprotective effects against isoproterenol (ISO)-induced myocardial damage by targeting inflammatory MAPK/NF-κB pathway

The aim of the present study is to investigate the protective effects of human amniotic membrane-derived mesenchymal stem cells (hAMSCs) labeled by superparamagnetic iron oxide nanoparticles (SPIONs) against isoproterenol (ISO)-induced myocardial injury in the presence and absence of a magnetic field. ISO was injected subcutaneously for 4 consecutive days to induce myocardial injury in male Wistar rats. The hAMSCs were incubated with 100 μg/ml SPIONs and injected to rats in magnet-dependent and magnet-independent groups via the tail vein. The size and shape of nanoparticles were determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Prussian blue staining was used to determine cell uptake of nanoparticles. Myocardial fibrosis, heart function, characterization of hAMSCs, and histopathological changes were determined using Masson�s trichrome, echocardiography, flow cytometry, and H&E staining, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to the expression pro-inflammatory cytokines. Immunohistochemistry assay was used to determine the expression of nuclear factor-κB (NF-κB) and the Ras/mitogen-activated protein kinase (MAPK). SPION-labeled MSCs in the presence of magnetic field significantly improved cardiac function and reduced fibrosis and tissue damage by suppressing inflammation in a NF-κB/MAPK-dependent mechanism (p < 0. 05). Collectively, our findings demonstrate that SPION-labeled MSCs in the presence of magnetic field can be a good treatment option to reduce inflammation following myocardial injury. Figure not available: see fulltext. © 2020, Controlled Release Society

The effect of leptin on prepulse inhibition in a developmental model of schizophrenia

Post-weaning social isolation is a developmental animal model of schizophrenia. Impairment of prepulse inhibition (PPI), possibly due to increased activity of the mesolimbic dopaminergic system, has frequently been reported in this model. There are some reports of increased level of leptin in schizophrenic patients. It has been shown that intracerebroventricular (ICV) injection of leptin decreases dopamine in the nucleus accumbens of rats. Here we investigated the effect of leptin on PPI impairment following social isolation. Five groups of Sprague-Dawley rats were reared post weaning in social or isolated conditions for 14 weeks. PPI was measured before treatment in week 12, and after ICV injection of vehicle or different doses of leptin (1, 5, and 10. μg/5. μl) in week 14. Results showed reduced PPI in untreated isolated compared to socially-reared rats in week 12 (p = 0.009), but not in week 14 (p = 0.45). Results also showed that leptin dose-dependently increased the basal PPI in isolated rats compared to vehicle, that was significant at a dose of 10. μg (p = 0.002). A considerable but non-significant effect of treatment with leptin on startle response (p = 0.13) was seen. In conclusion, our results reveal that leptin significantly increases PPI in socially-isolated rats. The findings of this study suggest possible antipsychotic properties for leptin. We suggest further studies on the possible disruption of leptin signaling in schizophrenia, and also the possible interaction of leptin with therapeutic effects of second generation antipsychotics. © 2013 Elsevier Ireland Ltd