Vitamin D Protects Against Cardiac Hypertrophy Through the Regulation of Mitochondrial Function in Aging Rats.

Cardiac aging is defined as mitochondrial dysfunction of the heart. Vitamin D (VitD) is an effective agent in ameliorating cardiovascular disorders. In this study, we indicated the protective effects of VitD against cardiac aging. Male Wistar rats were randomly divided into four groups: control (CONT), D-galactose (D-GAL): aged rats induced by D-GAL, D-GAL + Ethanol: aged rats treated with ethanol, and D-GAL + VitD aged rats treated with VitD. Aging was induced by D-GAL at 150 mg/kg via intraperitoneal injection for 8 weeks. Aged rats were treated with VitD (D-GAL + VitD) by gavage for 8 weeks. The serum samples were used to evaluate biochemical factors, and heart tissues were assessed to determine oxidative stress and gene expression. The D-GAL rats exhibited cardiac hypertrophy, which was associated with decreased antioxidant enzyme activity, enhanced oxidative marker, and changes in the expression of mitochondrial genes in comparison with the control rats. Co-treatment with VitD ameliorated all these changes. In conclusion, VitD could protect the heart against D-GAL-induced aging via enhancing antioxidant effects, and the expression of mitochondrial genes.

Toxoplasma gondii attenuates the ethidium bromide induced demyelination lesions in multiple sclerosis model rats.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease. Since the modulation of the immune system by parasites has been proven, and there have been reports of a reduction in the clinical symptoms of MS in people with toxoplasmosis, this study aimed to investigate the effect of toxoplasmosis on MS in an animal model. MS model was induced by the ethidium bromide injection in the areas specified in the Rat's brain in the stereotaxic device and Toxoplasma gondii RH strain injection of the rat's peritoneal for creation of toxoplasmosis. The effect of acute and chronic toxoplasmosis on the MS model was evaluated by examining the development of clinical symptoms of MS, body weight, changes in the levels of inflammatory cytokines, inflammatory cell infiltration, cell density, and spongy tissue in the brain. The body weight in the acute toxoplasmosis with MS was the same as the MS group, and a significant decrease was observed, but no weight loss was observed in the chronic toxoplasmosis with MS. In the chronic toxoplasmosis, the progress of clinical signs such as Immobility of limbs, including tail, hands, and feet, was observed less compared to other groups. The histology results in the group of chronic toxoplasmosis showed high cell density and inhibition of spongy tissue formation, and the infiltration of inflammatory cells in this group was less. TNF-α and INF-γ decreased in MS with chronic toxoplasmosis compared to the MS group. Our findings showed that chronic toxoplasmosis with inhibition of spongy tissue formation and prevention of cell infiltration and. As a result, the reduction of inflammatory cytokines could reduce clinical symptoms in MS in the animal model.

The bFGF Can Improve Angiogenesis in Oral Mucosa and Accelerate Wound Healing.

Background: The role of the basic fibroblast growth factor (bFGF) has well known in the angiogenesis and ulcer healing. In this study, we aimed to evaluate the effects of bFGF on tissue repair in a rat oral mucosal wound. Methods: Musosal wound induced on the lip mucosa of rats and bFGF was injected along the edge of the mucosal defect immediately after surgery. The tissues were collected on days 3, 7 and 14 after the wound induction. The micro vessel density (MVD) and CD34 expression were done by histochemical studies. Results: The bFGF significantly accelerated granulation tissue formation and MVD was increased three days after ulcer induction but decreased 14 days after surgery. The MVD was significantly higher in the bFGF-treated group. The wound area was decreased in all groups time-dependently and a statistically significant difference (p value?) was observed between the bFGF-treated group and untreated group. The wound area was smaller in the bFGF-treated group compared to the untreated group. Conclusions: Our data demonstrated that bFGF can accelerated and facilitated wound healing.

How can nanomicelle-curcumin modulate aluminum phosphide-induced neurotoxicity?: Role of SIRT1/FOXO3 signaling pathway.

Aluminum phosphide (ALP) is among the most significant causes of brain toxicity and death in many countries. Curcumin (CUR), a major turmeric component, is a potent protective agent against many diseases, including brain toxicity. This study aimed to examine the probable protection potential of nanomicelle curcumin (nanomicelle-CUR) and its underlying mechanism in a rat model of ALP-induced brain toxicity. A total of 36 Wistar rats were randomly divided into six groups (n = 6) and exposed to ALP (2 mg/kg/day, orally) + CUR or nanomicelle-CUR (100 mg/kg/day, orally) for 7 days. Then, they were anesthetized, and brain tissue samples were dissected to evaluate histopathological alterations, oxidative stress biomarkers, gene expression of SIRT1, FOXO1a, FOXO3a, CAT and GPX in brain tissue via hematoxylin and eosin (H&E) staining, biochemical and enzyme-linked immunosorbent assay (ELISA) methods and Real-Time PCR analysis. CUR and nanomicelle-CUR caused significant improvement in ALP-induced brain damage by reducing the MDA levels and induction of antioxidant capacity (TTG, TAC and SOD levels) and antioxidant enzymes (CAT, GPX), modulation of histopathological changes and up-regulation of gene expression of SIRT1 in brain tissue. It was concluded that nanomicelle-CUR treatment ameliorated the harmful effects of ALP-induced brain toxicity by reducing oxidative stress. Therefore, it could be considered a suitable therapeutic choice for ALP poisoning.

Antimicrobial and cytotoxic properties of calcium-enriched mixture cement, Iranian propolis, and propolis with herbal extracts in primary dental pulp stem cells.

Objectives: In this study, natural substances were introduced as primary dental pulp caps for use in pulp therapy, and the antimicrobial and cytotoxic properties of these substances were investigated. Materials and Methods: In this in vitro study, the antimicrobial properties of calcium-enriched mixture (CEM) cement, propolis, and propolis individually combined with the extracts of several medicinal plants were investigated against Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Then, the cytotoxicity of each substance or mixture against pulp stem cells extracted from 30 primary healthy teeth was evaluated at 4 concentrations. Data were gathered via observation, and optical density values were obtained using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test and recorded. SPSS software version 23 was used to analyze the data. Data were evaluated using 2-way analysis of variance and the Tukey test. Results: Regarding antimicrobial properties, thyme alone and thyme + propolis had the lowest minimum inhibitory concentrations (MICs) against the growth of S. aureus, E. coli, and P. aeruginosa bacteria. For E. faecalis, thyme + propolis had the lowest MIC, followed by thyme alone. At 24 and 72 hours, thyme + propolis, CEM cement, and propolis had the greatest bioviability in the primary dental pulp stem cells, and lavender + propolis had the lowest bioviability. Conclusions: Of the studied materials, thyme + propolis showed the best results in the measures of practical performance as a dental pulp cap.

Preparation of polyvinyl alcohol hydrogel containing chlorogenic acid microspheres and its evaluation for use in skin wound healing.

Chlorogenic acid (CGA) is a phenolic compound widely found in plants. Several studies have shown that CGA possesses antioxidant, antibacterial, anti-inflammatory and wound healing properties. Because of their three-dimensional structure, good permeability, excellent biocompatibility and moisturizing properties, hydrogels are ideal candidates for wound dressing. The aim of the present study was to preparation and characterization of Polyvinyl alcohol (PVA) hydrogel containing CGA microspheres and evaluation its wound healing activity. The double-emulsion solvent evaporation technique was applied for preparing the CGA containing microspheres. The microspheres were characterized using scanning electron microscopy (SEM) and Fourier transformation infrared spectroscopy (FTIR) and subsequently incorporated in the structure of a PVA hydrogel. The effects of prepared hydrogel on NIH3T3 cell line viability were evaluated using MTT method and wound healing activity was investigated in full thickness wound model in rabbit. SEM images showed formation of homogenous CGA microspheres with diameters in the range of 1-2 µm, embedded in the porous structure of the hydrogel. Infra-red results indicated successful incorporation of CGA microspheres into PVA hydrogel. The NIH3T3 cell viability percentage in CGA 2.5% hydrogel treated group significantly (p < .05) increased after 24 h and 48 h comparing to control group. In vivo studies showed that CGA hydrogel significantly (p < .001) stimulated the rate of wounds closures. Histological studies revealed that administration of CGA hydrogel significantly increased epithelialization and production of collagen fibers compared to the control group. It can be concluded that the CGA microsphere loaded PVA hydrogel has the potential for wound healing.

Evaluation of the Cytotoxicity of Two Types of Triple Antibiotic Paste on Human Permanent Dental Apical Papilla Stem Cells: an in vitroin vitro Study.

Statement of the Problem: The use of a new antimicrobial combination in the regenerative endodontic treatment of immature teeth pulp necrosis is a well-known method. Concerns have been raised about the destructive effect of this combination on the stem cells from the apical papilla of permanent human teeth, and there is a study gap. Purpose: The main objective of the present study was to investigate the cytotoxic effect of modified triple antibiotic paste (mTAP) on stem cells from the apical papilla (SCAPs) of permanent human teeth. Materials and Method: In this in vitro study, stem cells were removed from the immature teeth. After cultivation and third passage, metronidazole, ciprofloxacin, minocycline, and clindamycin were placed in the cell culture medium alone , paired, and in combinations as triple antibiotic paste (TAP) (metronidazole, ciprofloxacin, and minocycline) and mTAP (metronidazole, ciprofloxacin, clindamycin) with doses of 25, 50, 100, 200, 400µg/ml. After 1 and 3 days, cell viability in the culture medium was assessed using the MTT method ([4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). SPSS software version 24, descriptive statistics methods, and statistical tests such as Kruskal-Wallis and Mann-Whitney tests were adopted to analyze the data. Results: Analysis of MTT findings indicated that the use of mTAP at 100µg/ml and TAP at 200µg/ml had no adverse cytotoxic effect on stem cells in the first 24 hours, compared to the control group. The cell viability decreased at higher concentrations, although it was not statistically significant. After 72 hours, the toxicity of concentrations higher than 100µg/ml of mTAP and 400 µg/ml of TAP significantly mitigated the percentage of viable cells. Conclusion: The obtained results demonstrated that the concentration of 100 µg/ml of mTAP could replace TAP in regenerative endodontic treatments at the studied time intervals without worrying about the toxicity.

Nanocurcumin Improves Lipid Status, Oxidative Stress, and Function of the Liver in Aluminium Phosphide-Induced Toxicity: Cellular and Molecular Mechanisms.

Background: The present study aimed to evaluate the effect of nanocurcumin and curcumin on liver transaminases, lipid profile, oxidant and antioxidant system, and pathophysiological changes in aluminium phosphide (ALP) induced hepatoxicity. Material and Methods. In this experimental study, thirty-six male Wistar rats were randomly divided into six groups curcumin (Cur), nanocurcumin (Nanocur), ALP, ALP+Cur, and ALP+Nanocur. All treatments were performed by oral gavage for seven days. After treatment, animals were sacrificed, and liver and blood samples were taken. Serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), total bilirubin, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were measured by photometric methods. Total antioxidant capacity (TAC) and malondialdehyde (MDA) as parameters of oxidative stress and mRNA expression of the nonenzyme protein including Sirtuin 1 (STR1), Forkhead box protein O1 (FOXO1) and protein O3 (FOXO3), catalase (CAT), and glutathione peroxidase (GPX) as the enzyme protein in homogenized tissues have been investigated. A histologist analyzed liver tissue sections after staining with hematoxylin-eosin. Results: In the aluminium phosphide group, there was a significant increase in MDA, ALT, AST, and AP and total bilirubin, cholesterol, triglyceride, LDL, and VLDL; AST, ALT, total bilirubin, LDL, VLDL, cholesterol, and MDA were significantly decreased; and HDL and TAC were significantly increased compared to ALP (P < 0.05). In the ALP+Nanocur group, ALT, AST, ALP, total bilirubin, cholesterol, LDL, VLDL, triglyceride, and MDA were significantly decreased and HDL and TAC were increased significantly (P < 0.05). The effect of nanocurcumin on controlling serum levels of LDL, VLDL, triglyceride, and MDA in ALP-poisoned rats was significantly more than curcumin (P < 0.05). The ALP group had significant changes in genes SIRT1, FOXO1a, FOXO3a, CAT, and GPX compared to healthy controls (P < 0.05). Nanocurcumin mice expressed more SIRT1, FOXO1a, CAT, and GPX genes than controls, and curcumin-treated mice expressed more SIRT1 and FOXO1a genes (P < 0.05). Histopathological findings also indicated a more significant protective effect of nanocurcumin relative to curcumin against ALP-induced hepatotoxicity. Conclusion: Nanocurcumin significantly protects the liver against aluminum phosphide toxicity. It is suggested that nanocurcumin-based drugs be developed to reduce the toxic effects of ALP in poisoned patients.

Neuroprotective effects of coenzyme Q10-loaded exosomes obtained from adipose-derived stem cells in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative disease that causes memory and learning impairments as well as dementia. Coenzyme Q10 (CoQ10) is an anti-inflammatory and anti-oxidative stress supplement that can improve inflammation and oxidative stress associated with AD. This study investigated the effects of drug delivery of COQ10 by exosomes derived from adipose-derived stem cells (ADSCs-Exo) on cognition, memory, and neuronal proliferation in a rat model of Streptozotocin (STZ)-induced AD. Since the establishment of the AD model, the rats have received intraperitoneal injections of CoQ10, Exo, or CoQ10-loaded ADSCs-Exo (Exo+ CoQ10). The passive avoidance test and the Morris water maze (MWM) were used to assess memory and cognition changes. Cell density was determined using histological methods. The expression of BDNF was measured using an ELISA kit. SOX2 expression was determined using immunohistochemistry. According to the results of the MWM and passive avoidance task, Exo+CoQ10 significantly improved STZ-induced memory impairment compared to CoQ10 and Exo groups alone. Furthermore, BDNF expression increased in the STZ-induced rats after Exo+ CoQ10, when compared to the CoQ10 and Exo groups. In addition, Exo+CoQ10 had the highest cell density and SOX2 gene expression, when compared to the CoQ10 and Exo groups. According to the findings of this study, Exo+ COQ10 enhanced cognition and memory deficiency in Alzheimer's disease by boosting BDNF and SOX2 levels in the hippocampus. Hence, the use of exosomes derived from adipose-derived stem cells as the carrier of CoQ10 may increase the therapeutic effect of CoQ10, which can possibly be due to the regenerative properties of the exosomes.

The effect of different exercise training modes on dentate gyrus neurodegeneration and synaptic plasticity in morphine-dependent rats.

Various impacts of exercise on brain performance following the induction of morphine dependence have been documented; however, the underlying neuronal mechanisms are still unclear. The present research was done to investigate the impact of different exercise training modes on apoptosis, neuronal maturation, and synaptic plasticity in the perforant pathway (PP)-dentate gyrus (DG) synapses in the morphine-dependent rats. Five groups, including a control group (Con, ten healthy rats) and forty morphine-dependent rats were considered as follows (n = 10/group): 1) sedentary-dependent (Sed-D); 2) endurance exercise-dependent (En-D); 3) strength exercise-dependent (St-D); and 4) concurrent exercise-dependent (Co-D). The exercise training groups were subjected to endurance, strength, and concurrent training five days a week for ten weeks. After training sessions, the field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude in the DG were determined in response to high-frequency stimulation (HFS) of the PP. For assessing neurogenesis and apoptosis, NeuroD and Caspase-3 expression levels were evaluated after all experiments. Concurrent training increased PS amplitude and EPSP compared to the control group. NeuroD in the morphine-dependent rats significantly decreased, but concurrent training returned the NeuroD to its levels in healthy rats. Furthermore, Caspase-3 expression levels in morphine-dependent rats remarkably increased and concurrent training significantly reduced Caspase-3 expression levels compared to the Sed-D group. Concurrent training can ameliorate synaptic plasticity impairment in morphine-dependent rats through neurogenesis promotion and apoptosis reduction. According to the results, concurrent training can be an appropriate novel candidate for treating opioid addiction.

Protective Effects of N-acetylcysteine Niosome Nanoparticles on Paraquatinduced Nephrotoxicity in Male Rats.

INTRODUCTION: Paraquat (PQ), as a bipyridyl compound, is widely used as an effective herbicide that produces reactive oxygen species (ROS), affecting the unsaturated lipids of cell membranes leading to cell mortality. N-acetylcysteine (NAC) is a medication that has a beneficial role in reducing the intoxication of kidneys caused by PQ. Niosomes are bilayer vesicles that enhance the bioavailability of drugs. This study aimed to compare the effects of NAC and niosome of NAC (NACNPs) on PQ-induced kidney toxicity concerning its antioxidant activity. METHODS: In this experimental study, after formulating NACNP, 30 Wistar male rats weighing 180 to 250 gm were classified into five groups: the control group was treated with normal saline, while the other four groups received 35mg/kg/day of PQ via intraperitoneal route and, was treated with 25mg/kg/day NAC, 25mg/kg/day niosome and 25 mg/kg/day NACNP by gavage, Then, oxidative stress biomarkers such as total antioxidant capacity (TAC), catalase activity (CAT), lipid peroxidation (LPO), and total thiol group (TTG), plus blood urea nitrogen (BUN) and creatinine levels were evaluated in kidney tissue homogenate and examined histopathologically. RESULTS: The results revealed that TTG increased significantly in NAC & NACNP groups than in the PQ group. Further, in the PQ group, LPO increased significantly compared with the control, NAC, and NACNP groups, while in the NAC and NACNP group, LPO diminished compared with the PQ group. There was no significant difference in TAC between groups. Blood urea nitrogen (BUN) and creatinine levels dropped in NACNP compared with the PQ group and the NAC. Histological studies also approved PQ-induced damage and the protective effect of NACNP. CONCLUSION: The results indicated that NACNP could modulate oxidative stress status and kidney function against PQ toxicity.

Chronic stimulation of the serotonergic 5-HT4 receptor modulates amyloid-beta-related impairments in synaptic plasticity and memory deficits in male rats.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory decline and impaired hippocampal synaptic plasticity. The serotonin 5-HT4 receptor is involved in learning and memory processes. This study explored the effects of chronic stimulation of 5-HT4R on cognition, memory, long-term potentiation (LTP), paired-pulse ratio (PPR), and neuronal apoptosis in a rat model of amyloid-beta (Aß)-induced AD. Thirty-five male Wistar rats were randomly divided into three groups as follows: the sham, Aß, and Aß + BIMU8 groups. Aß (6 µg/µl) was administrated by intracerebroventricular (icv) injection. The animals were treated with BIMU8 (1 µg/µL, ICV) as a 5-HT4R agonist for 30 days. Memory and behavioral changes were assessed by the passive avoidance learning, novel object recognition, open field, and elevated plus maze tests. Hippocampal synaptic plasticity was evaluated in the dentate gyrus (DG) in response to the stimulation applied to the perforant pathway. Furthermore, neuronal apoptosis was measured in the hippocampus. Data were analyzed by SPSS version 19 using one-way ANOVA, followed by Tukey's post hoc test. Aß induced memory deficits and neuronal loss and inhibited LTP induction. Aß also increased the normalized PPR. BIMU8 enhanced the slope of the field excitatory postsynaptic potential in LTP and improved cognition behavior. Paired-pulse inhibition or facilitation was not affected by LTP induction in Aß animals receiving the BIMU8. It can be concluded that the stimulation of the 5-HT4 receptor modulated the Aß-induced cognition and memory deficits, probably via a decrease in the hippocampal apoptotic neurons and an improvement in the hippocampal synaptic functions without involving its inhibitory interneurons.

Chitosan-coated Selenium nanoparticles enhance the efficiency of stem cells in the neuroprotection of streptozotocin-induced neurotoxicity in male rats.

Alzheimer's disease (AD) is one of the common neurodegenerative diseases characterized by memory impairment. The protective effects of stem cell-based therapy have been reported in AD. In this study, it was assumed that Chitosan-coated Selenium nanoparticles (ChSeNPs) increase the efficiency of stem cells in the attenuation of neurotoxicity in the rat AD model. The AD model was induced using Streptozotocin (STZ) and treated by the adipose-derived mesenchymal stem cells (AMSCs) and SeNPs/ChSeNPs (0.4 mg/kg). Passive avoidance learning and recognition memory were assessed using shuttle box and novel object recognition tasks. The amyloid-beta deposition, the injected cells' homing and survival, antioxidant capacity, and BDNF concentration were evaluated using the histological, biochemical, and ELISA methods. The results showed that the combined administration of ChSeNPs and AMSCs is more effective in increasing the step-through latency and discrimination index than administering SeNPs and stem cells. Combined therapy caused a significant increase in antioxidant capacity that ChSeNPs was more effective than SeNPs, while AMSCs beside SeNPs had a greater effect on BDNF levels compared to conventional treatment of nanoparticles or AMSCs alone. Ultimately, the homing and survival of the transplanted AMSCs were greater in the group that received both stem cells and ChSeNPs. Taken together, it seems that the administration of ChSeNPs enhances the efficiency of transplanted stem cells in decreasing the neurotoxicity induced by STZ through an increase in the antioxidant capacity.

Deferoxamine preconditioning enhances the protective effects of stem cells in streptozotocin-induced Alzheimer's disease.

AIMS: Stem cell-based therapy is one of the promising strategies in the treatment of Alzheimer's disease (AD), but the short lifespan and low homing of transplanted cells continue to be a major obstacle in this method. Preconditioning of stem cells before transplantation could increase cell therapy efficiency. Herein, we examined whether the treatment of stem cells with deferoxamine (DEF) prior to graft could enhance the neuroprotective effects of stem cells in the streptozotocin (STZ)-treated male rats. MATERIALS AND METHODS: After induction of the AD model, the rats were transplanted with DEF-preconditioned Adipose-derived mesenchymal stem cells (AMSCs) or untreated cells. Memory function, antioxidant capacity, cell density, and homing of transplanted cells were assessed using Morris water maze and shuttle box tasks as well as biochemical and histochemical methods. KEY FINDINGS: Transplantation of AMSCs caused a memory improvement when compared to the AD model. The injection of DEF-preconditioned AMSCs was more effective in improving learning and memory than the untreated cells through an increase in the antioxidant capacity. Moreover, the homing of transplanted cells was higher in the rats that received the preconditioned cells than that of the naïve cell-injected group. SIGNIFICANCE: It seems that the transplantation of DEF-treated cells may increase the efficiency of stem cells via an increase in the antioxidant capacity.

Protective effect of chronic administration of pelargonidin on neuronal apoptosis and memory process in amyloid-beta-treated rats.

OBJECTIVE: Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with impaired cognitive skills and learning and memory dysfunctions.  It has been suggested that pelargonidin (PG), as an antioxidant agent, has a neuroprotective effect. PG could prevent damaging effects of amyloid-beta (Aß) deposition. The aim of this study was to determine the chronic effect of PG on hippocampal neurons and memory processes in a rat model of AD. MATERIALS AND METHODS: Twenty-eight male adult rats were divided into sham, AD, AD+PG (5 µg, intracerebroventricular), and PG (5 µg, intracerebroventricular) groups. Intracerebroventricular (ICV) injection of Aß peptides (6 µg) was done using stereotaxic surgery. ICV administration of PG or saline was performed daily for 28 consecutive days. Behavioral analysis was performed using the novel object recognition (NOR) and passive avoidance tests. Neuronal apoptosis was detected using TUNEL assay in the hippocampus. RESULTS: The ICV injection of Aß reduced step-through latency and discrimination index in behavioral tests (p<0.001). Aß increased the number of apoptotic neurons (p<0.001). PG treatment decreased the time spent in the dark compartment and neuronal apoptosis in the AD+PG rats (p<0.001). PG increased the discrimination index in the NOR test (p<0.001). Although PG did not change behavioral variables, it decreased cell death in the PG group. CONCLUSION: PG attenuated neuronal apoptosis and improved cognition and memory deficiency in AD rats. The protective effect of PG against Aß may be due to its anti-apoptotic property. It is suggested that PG can be useful to treat AD.

Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats.

MDMA (3,4-Methylenedioxymethamphetamine) is a common recreational drug of abuse which causes neurodegeneration. Nicotine and modafinil provide antioxidant and neuroprotective properties and may be beneficial in the management of MDMA-induced neurotoxicity. The purpose of this study was to characterize how acute and chronic administration of nicotine and/or modafinil exert protective effects against the MDMA-induced impaired cognitive performance, oxidative stress, and neuronal loss. Adult male rats were divided into three groups, namely control, MDMA and treatment (modafinil and/or nicotine). MDMA (10 mg/kg) was administered intraperitoneally during a three-week schedule (two times/day for two consecutive days/week). The treated-groups were classified based on the acute or chronic status of treatment. In the groups which underwent acute treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected just prior to the MDMA administration (acute nicotine (NA), acute modafinil (MA), and acute nicotine and modafinil (NMA)). In the rats which received chronic treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected every day during the three week-schedule administration of MDMA (chronic nicotine (NC), chronic modafinil (MC), and chronic nicotine and modafinil (NMC)). Learning and memory performance, as well as avoidance response, were assessed by Morris water maze and Shuttle box, respectively. Our findings indicate enhanced learning and memory and avoidance response in the NMC group. By TUNEL test and Cresyl Violet staining we evaluated neuronal loss and apoptosis in the hippocampal CA1 and found increased neuronal viability in the NMC group. On the other hand, chronic administration of modafinil and nicotine significantly down-regulated the caspase 3 and up-regulated both BDNF and TrkB levels in the MDMA-received rats. The serum levels of glutathione peroxidase (GPx) and total antioxidant capacity (TAC) were evaluated and we found that the alterations of serum levels of GPx and TAC were considerably prevented in the NMC group. The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA.

Administration of Selenium Nanoparticles Reverses Streptozotocin-Induced Neurotoxicity in the male rats.

Alzheimer's disease is the most common neurodegenerative disease associated with deposition of amyloid-beta and the increased oxidative stress. High free radical scavenging ability of selenium nanoparticles (SeNPs) has been acknowledged, so in the present study, the effects of treatment with SeNPs on Streptozotocin (STZ)-induced neurotoxicity were evaluated in the male rats. Learning and memory impairment was induced by intraventricular injection of STZ. Following induction of memory impairment, the rats received 0.4 mg/kg of SeNPs daily for one month. Memory function, antioxidant capacity, and deposition of Amyloid ß (Aß) were assessed using the shuttle box task, biochemical methods, and Congo red staining. Injection of STZ caused memory impairment, a decrease in the level of total thiol group (TTG), and an increase in the malondialdehyde (MDA) content and deposition of Aß. Administration of SeNPs reversed the neurotoxicity induced by STZ. It seems that SeNPs likely had neuroprotective effects on the animal model of Alzheimer's disease through increasing antioxidants҆ capacity.

Stem Cell-Derived Exosomes: a New Strategy of Neurodegenerative Disease Treatment.

Short-term symptomatic treatment and dose-dependent side effects of pharmacological treatment for neurodegenerative diseases have forced the medical community to seek an effective treatment for this serious global health threat. Therapeutic potential of stem cell for treatment of neurodegenerative disorders was identified in 1980 when fetal nerve tissue was used to treat Parkinson's disease (PD). Then, extensive studies have been conducted to develop this treatment strategy for neurological disease therapy. Today, stem cells and their secretion are well-known as a therapeutic environment for the treatment of neurodegenerative diseases. This new paradigm has demonstrated special characteristics related to this treatment, including neuroprotective and neurodegeneration, remyelination, reduction of neural inflammation, and recovery of function after induced injury. However, the exact mechanism of stem cells in repairing nerve damage is not yet clear; exosomes derived from them, an important part of their secretion, are introduced as responsible for an important part of such effects. Numerous studies over the past few decades have evaluated the therapeutic potential of exosomes in the treatment of various neurological diseases. In this review, after recalling the features and therapeutic history, we will discuss the latest stem cell-derived exosome-based therapies for these diseases.

Synergistic effects of adipose-derived mesenchymal stem cells and selenium nanoparticles on streptozotocin-induced memory impairment in the rat.

AIMS: Memory impairment is determined to be the most well-known symptom of Alzheimer's disease (AD). Although cell therapy seems is an efficient therapeutic strategy to attenuate the AD-related memory impairment, transplanted cells have a short lifespan and do not survive long term in the recipient animals. Herein, we investigated whether the combination therapy of Selenium nanoparticles (SeNPs) and stem cells attenuates the neurotoxicity in an AD animal model. MATERIAL AND METHODS: The adipose-derived mesenchymal stem cells (AMSCs) were transplanted in the AD model. In addition to cell injections, the animals also received oral administration of SeNPs (0.4 mg/kg) for one month. Recognition memory, cell survival, and BDNF concentration were assessed using the novel object recognition task, immunofluorescence, and ELISA methods. KEY FINDINGS: Our results showed that the combined therapy was more effective in increasing the discrimination index than the administering SeNPs or AMSCs alone. Moreover, SeNPs and stem cells together had the greatest effects in reducing the deposition of Aß and increasing the concentration of BDNF. Ultimately, the survival and proliferation of transplanted cells were more in the group that received stem cells besides SeNPs. SIGNIFICANCE: Taken together, it seems that the transplantation of MSCs combined with SeNPs could achieve better results in the neuroprotection in the AD model than a conventional treatment of SeNPs or stem cells alone.

ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS

ABSTRACT Objective: A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) and ADAMTS-5 normal expression levels are essential for ovulation and subsequent fertilization. The objective of the present study was to assess expression pattern of these genes in cumulus cells (CCs) taken from patients with polycystic ovary syndrome (PCOS) and to investigate any possible relationship with the oocyte quality. Subjects and methods: ADAMTS-4 and -5 expression levels within CCs containing oocytes at the metaphase II (MII) and germinal vesicle (GV) stages, taken from 35 patients with PCOS and 35 women with normal ovarian function, were investigated using RT-qPCR. Moreover, possible correlations between ADAMTS-4, ADAMTS-5, and progesterone receptors (PRs) expression as well as oocyte quality were evaluated. Results: ADAMTS-4 and -5 expression levels were dramatically diminished in the CCs of the PCOS patients when compared to the controls. ADAMTS-4 and -5 expression levels were correlated with each other and with the oocyte quality. Furthermore, lower expression levels of ADAMTS-4 and -5 in the PCOS patients were strongly correlated with the diminished PRs expression levels. Conclusions: Downregulation of ADAMTS-4 and -5 in the human CCs of the PCOS patients correlated with the decline in the PRs expression, and impaired oocyte quality may cause lower oocyte recovery, maturation, and fertilization rate.