Dehydroepiandrosterone stimulates nerve growth factor and brain derived neurotrophic factor in cortical neurons

Due to the increasing cases of neurodegenerative diseases in recent years, the eventual goal of nerve repair is very important. One approach for achieving a neuronal cell induction is by regenerative pharmacology. Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are neurotrophins that play roles in neuronal development, differentiation, and protection. On the other hand, dehydroepiandrosterone (DHEA) is a neurosteroid which has multiple actions in the nervous system. DHEA could be an important agent in regenerative pharmacology for neuronal differentiation during tissue regeneration. In this study, we investigated the possible role of DHEA to modulate NGF and BDNF production. The in vivo level of neurotrophins expression was demonstrated by ELISA in rat harvested brain cortex. Also neurotrophins expression after DHEA treatment was revealed by the increased neurite extension, immunostaining, and BrdU labeling in rats. Anti-NGF and anti-BDNF antibodies were used as suppressive agents on neurogenesis. The results showed that NGF and BDNF are overproduced after DHEA treatment but there is not any overexpression for NT-3 and NT-4. Also DHEA increased neurite extension and neural cell proliferation significantly. Overall, DHEA might induce NGF and BDNF neurotrophins overproduction in cortical neurons which promotes neural cell protection, survival, and proliferation. © 2013 Anahita Rahmani et al

Preclinical studies of166Ho-chitosan for treatment of hepatocellular carcinoma

Introduction: Recently, due to the special characteristics of166Ho and chitosan,166Ho-chitosan complex was developed for treatment of tumors such as hepatocellular carcinoma. This complex has been lately prepared with high radiochemical purity in our lab. The preclinical studies of the complex however should be performed to evaluate the tracer concentration in target and normal tissues before human use. Methods: In this study,166Ho-chitosan was prepared and its preclinical studies for treatment of hepatocellular carcinoma was carried out by injection of the radiopharmaceutical into the rabbit's liver via two different methods, surgery and venography. Leakage of the injected activity from the injection site in the rabbit organs was investigated using SPECT and SPECT-CT imaging up to 24 hours. Results: Both SPECT and SPECT-CT imaging of the rabbits showed that there was no significant leakage of the injected activity. Almost all the activity would remain in the injection site at least 24 h post injection. Conclusion: Considering all of the excellent features of the complex, this radiopharmaceutical is suggestive for treatment of hepatocellular carcinoma by radioembolization method

The greater effect of high-intensity interval training versus moderate-intensity continuous training on cardioprotection against ischemia-reperfusion injury through Klotho levels and attenuate of myocardial TRPC6 expression

Background: Myocardial ischemia-reperfusion (IR) injury is a leading cause of death all over the world, so developing practical approaches to promote cardioprotection against IR injury is essential. Exercise training is an effective strategy to improve cardioprotection. Hence, the purpose of this study was to investigate the effect of short-Term preconditioning with two types of high-intensity interval training (HIIT) and moderate intensity continuous training (MICT) on klotho and TRPC6 mechanisms in cardioprotection. Methods: Eighty Male Wistar rats (250-300 g) were randomly divided into 7 groups, including Control, HIIT, MICT, Sham, IR, HIIT+IR, and MICT+IR. Training was performed in 5 consecutive days. HIIT protocol consisted of running on the treadmill at intervals 85-90 vo 2 max that separated by slow intensity periods at 50-60 vo 2 max. MICT program was performed at 70 VO 2 max at the same running distance with HIIT groups. The cardiac IR injury was induced by LAD occlusion followed by reperfusion. ELISA kit was used in order to measure the plasma levels of klotho, LDH and CK-MB, and TRPC6 expression was determined using the western blot technique. Data were analyzed using one way ANOVA and Tukey's post hoc tests. Results: The results of this study showed that both types of exercise training programs significantly increase plasma levels of klotho and reduce the infarct size and heart injury. In addition, the exercise training decreased the amount of TRPC6 channels expression during IR. However, the effect of HIIT on increasing the klotho and cardioprotection was greater compared to MICT. Conclusions: Based on the results, even a short-Term of aerobic exercise training, especially HIIT, promotes cardioprotection against IR injury and decreases infarct size via an increase in klotho and attenuate of protein expression of myocardial TRPC6 during IR. © 2019 The Author(s)

99mTc-anionic linear globular dendrimer-G2-phenylalanine conjugate: Novel brain tumor SPECT imaging

The purpose of this study was the investigation of the targeting potential of99mTc-Labeled dendrimer-phenylalanine conjugate for brain tumor SPECT imaging. L-Type amino acid transporters (LAT1) are highly expressed in the blood-brain barrier as well as in brain cancer cells; thus, targeting LAT1 using phenylalanine could improve the sensitivity and specificity of radiosynthesis nanocarrier. In this study, the dendrimer G2�phenylalanine conjugate was synthesized and characterized by Fourier transform infrared spectroscopy, atomic force microscopy, particle size, and zeta potential. MTT assay was done for cell viability measurement in different concentrations of nanoparticles (0.125, 0.25, 0.5 mg/ml) on C6 glioma cell lines; the uptake study was evaluated using fluorescence-activated cell sorter (FACS) instrument; finally, SPECT scintigraphy in glioma tumor-bearing Wistar rats was done. The dendrimer-phenylalanine conjugate particle size was found in the range of 74.14±2.2 to 109±3.1 nm, with a slightly negative surface charge. Also, phenylalanine present on the dendrimer's surface� phenylalanine conjugate enhanced the dendrimer's cellular uptake�phenylalanine conjugate on the C6 glioma cell line. Results of SPECT imaging and fluorescence studies revealed that dendrimer� phenylalanine conjugate accumulated into the brain tumor cells, and it can be suggested as a promising brain-targeting probe with no toxicity in brain tumor imaging. © 2020 by the authors

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 < 0.001). Fraction shortening in HF group was increased from 27/53 � 8/58 into 45/55 � 6/91 in SCT group (p value < 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 < 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

Targeting necroptotic cell death pathway by high-intensity interval training (HIIT) decreases development of post-ischemic adverse remodelling after myocardial ischemia / reperfusion injury

Regulated necrosis (necroptosis) plays a pivotal role in the extent of cardiomyocyte loss and the development of post-ischemic adverse remodelling and cardiac dysfunction following myocardial I/R injury. Although HIIT has been reported to give rise to cardioprotection against MI, but the detailed knowledge of its molecular targets for treatment of MI is still not available. The LAD of Male Wistar rats was occluded to induce MI for 30 min and reperfusion for eight weeks. We investigated the effect of long-term HIIT for eight weeks on lipid peroxidation, SOD activity and GSH content using ELISA assay. Cardiac function, fibrosis, and infarct size were assessed by echocardiography, Masson�s trichrome and Evans Blue/TTC dual staining respectively. The expressions of gene markers of myocardial hypertrophy, fibrosis and key mediators of necroptosis were measured using RT-PCR and western blotting assay respectively. The results indicated that HIIT reduced lipid peroxidation, infarct size and improved endogenous antioxidant system and heart function. Significant decreases in mRNA levels of procollagen α1(I), α1(III), and fibronectin1were observed following HIIT. Moreover, that HIIT significantly decreased the expression of key mediators of necroptosis induced by MI (P < 0.05). There were no significant differences in β-MHC mRNA level in different groups. The findings of study suggest that HIIT might exert cardioprotective effects against post-ischemic adverse remodeling through targeting necroptosis process. Likewise, cardioprotective effects of HIIT in coping with myocardial I/R injury may be associated with RIP1-RIP3-MLKL axis. These findings establish a critical foundation for higher efficiency of exercise-based cardiac rehabilitation post�MI and future research. © 2018, The International CCN Society

Synthesis and labeling of p-NH2-Bn-DTPA-(Dabcyl-Lys6,Phe7)-pHBSP with 99mTc as a radiopeptide scintigraphic agent to detect cardiac ischemia

Myocardial ischemia and infarction represent a major health burden worldwide, but their immediate diagnosis can reduce mortality and healthcare costs. Pyroglutamate helix B surface peptide (pHBSP) derived from erythropoietin have shown tissue-protective effects in the ischemic situation by binding to erythropoietin receptor�Beta common receptors)EPOR�βcR(. This research aimed to synthesize and biologically evaluate p-NH2-Bn-DTPA-(Lys-Dabcyl6,Phe7)-pHBSP for cardiac ischemia imaging. Radiolabeling yielded more than 97, and radiolabeled peptide showed significant binding affinity to H9c2 hypoxic cells (p &lt; 0.001). A considerable accumulation of 99mTc-p-NH2-Bn-DTPA-(Lys-Dabcyl6,Phe7)-pHBSP was detected in the ischemic region by biodistribution study and SPECT/CT scintigraphy (3.84 ID/g at 30 min). © 2020, Akadémiai Kiadó, Budapest, Hungary

Outcome improvement of cellular cardiomyoplasty using triple therapy: Mesenchymal stem cell+erythropoietin+vascular endothelial growth factor

To improve cellular cardiomyoplasty efficacy after myocardial infarction (MI), we postulated that combining mesenchymal stem cells (MSCs) transplantation with anti-apoptotic and angiogenic effects of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) may provide better prognosis in an infarcted heart 48 rats, underwent left anterior descending artery ligation, were divided into eight groups and treated as follows: Group 1: MSC+EPO+VEGF, Group 2: MSC+EPO, Group 3: MSC+VEGF, Group 4: MSC, Group 5: EPO+VEGF, Group 6: EPO, Group 7: VEGF and Group 8: Control. After MI induction, EPO and VEGF were injected subcutaneously at the dose of 3000 U/kg and 3 mg/kg respectively. MSCs were transplanted one week after MI. In the fourteenth and sixteenth days after infarction, EPO was injected again. Echocardiography demonstrated that all treatments improved left ventricular function significantly (before vs. after treatment) but in control group ejection fraction deteriorated over the 2-months period. Percent of ejection fraction recovery in all treatment groups were significantly greater than control (P<0.05). Compared with the control group, all treatments attenuated cell death in peri-infarct areas significantly, except groups 6 and 7. Vascular density of all treatment groups were more than control group but this superiority was statistically significant only in group1 (P<0.01). All of our treatments had beneficial effects to some extent but MSC transplantation combined with EPO and VEGF administration resulted in superior therapeutic outcome in enhancing cell survival and neovascularization. © 2013 Elsevier B.V. All rights reserved