Neuroprotective effects of rosemary extract on white matter of prefrontal cortex in old rats.

Objectives: During aging, cerebral structures undergo changes due to oxidative stress. The consumption of some plants seems to improve neurological health. For example, rosemary extract (RE) which is widely used as a flavoring food has anti-inflammatory and anti-oxidant activities. Therefore, we aimed to study the effect of RE on the changes related to the aging process in the prefrontal cortex (PFC). Materials and Methods: Twenty-four male Wistar rats including young and old were purchased. Each group was divided into two subgroups: vehicle and rosemary (old vehicle (OV), old rosemary (OR), young vehicle (YV), and young rosemary (YR) groups). Then, we examined the number of intact neurons, myelin base protein (MBP), white matter (WM), levels of malondialdehyde (MDA), and glutathione peroxidase (GPx) in the PFC. Results: The results showed that in the old vehicle rats compared to the young group without treatment, except for the MDA level (which increased), other variables significantly decreased (P≤0.05). Additionally, RE consumption demonstrated a significant elevation of WMA, MBP intensity, number of intact neurons, and GPx activity level, while MDA levels significantly reduced in the treated old rats compared to the old vehicle group (P≤0.05). However, there was no significant difference between the OR and YV groups (P≥0.05). Conclusion: Overall, it seems that RE can protect and improve aging damages in the PFC due to its anti-oxidant properties. So, the use of RE can be a suitable strategy to prevent aging complications in the brain.

Aerobic training and vitamin E administration ameliorates cardiac apoptosis markers in rats exposed to methamphetamine.

Methamphetamine (MA) abuse is related to risks to the cardiovascular system. The present study aimed to compare the effects of moderate-intensity aerobic training (MIAT) and vitamin E (Vit.E) supplementation on markers of cardiac apoptosis following MA exposure. Fifty-four rats were randomly divided into six groups. CON group did not receive MA, while the others received MA alone or in combination with MIAT, Vit. E, MIAT+Vit E, or paraffin (PAR). These groups received MA incrementally for 23 consecutive days. Vit.E and MIAT+Vit.E groups received vitamin E three times a week for six weeks. MIAT and MIAT+Vit.E groups exercised for 25-40 min. Immunohistochemical and gene expression analyses were performed on the heart tissues. Bax and TGF-ß expression was significantly higher, while Bcl-2 and VEGF expression was significantly lower in the MA and PAR groups than in the other groups (p < 0.05). Bcl-2 and VEGF expression was higher, and Bax and TGF-ß expression was significantly lower in the MIAT and MIAT+Vit.E groups than in the other groups (p < 0.05). In Vit.E treated groups, Bax and TGF-ß expression were lower, and VEGF was higher than that in the MA and PAR groups, but higher than those in the CON, MIAT and MIAT+Vit.E groups. MA increased the expression of Bax and TGF-ß, and decreased the expression of Bcl-2 and VEGF, suggesting increased cardiac apoptosis. In contrast, MIAT and Vit.E decreased the expression of Bax and TGF-ß, suggesting a reduction in cardiac apoptosis induced by MA.

Dual role of Exosome in neurodegenerative diseases: a review study.

INTRODUCTION: Extracellular vesicles (EVs) are one of the crucial means of intercellular communication, which takes many different forms. They are heterogeneous, secreted by a range of cell types, and can be generally classified into microvesicles and exosomes depending on their location and function. Exosomes are small EVs with diameters of about 30-150 nm and diverse cell sources. METHODS: The MEDLINE/PubMed database was reviewed for papers written in English and publication dates of recent years, using the search string "Exosome" and "Neurodegenerative diseases." RESULTS: The exosomes have attracted interest as a significant biomarker for a better understanding of disease development, gene silencing delivery, and alternatives to stem cell-based therapy because of their low-invasive therapeutic approach, repeatable distribution in the central nervous system (CNS), and high efficiency. Also, they are nanovesicles that carry various substances, which can have an impact on neural plasticity and cognitive functioning in both healthy and pathological circumstances. Therefore, exosomes are conceived as nanovesicles containing proteins, lipids, and nucleic acids. However, their composition varies considerably depending on the cells from which they are produced. CONCLUSION: In the present review, we discuss several techniques for the isolation of exosomes from different cell sources. Furthermore, reviewing research on exosomes' possible functions as carriers of bioactive substances implicated in the etiology of neurodegenerative illnesses, we further examine them. We also analyze the preclinical and clinical research that shows exosomes to have therapeutic potential.

Evaluation of the Negative Effects of Opium Tincture on Memory and Hippocampal Neurons in the Presence of Chicory Extract.

Background: Due to the high prevalence of addiction in society and the need to its attention, various methods are used for addiction withdrawal. The side effects of some methods restrict their use and increase the risk of recurrence. One of the Iranian useful methods is consumption of opium tincture (OT) that may cause brain structure and memory defects. Hence, this study aimed the effects of different doses of OT on memory and hippocampal neurons with the use of an antioxidant such as various concentrations chicory. Materials and Methods: In the present study, 70 Wistar rats were randomly divided into 10 groups and the effect of various doses of chicory extract and OT were assessed on memory by the passive avoidance test. The neurons and astrocyte cells numbers in dentate gyrus were investigated, using histological examination. Results: In passive avoidance test, the total time in dark compartment was significantly more in groups with 100 and 75 µl OT compared with control and normal saline groups (P < 0.001). Traffic number results showed that there was a significant difference between T100 and control groups (P > 0.05). Moreover, initial latency time was significantly shorter in groups with 75 and 100 µl of OT compared with control and normal saline groups (P < 0.05). However, the presence 250 mg/kg of chicory increases granular layer thickness of dentate gyrus and number of neurons. Conclusion: The use of 250 mg/kg of chicory extract may be promising strategy for inducing neurogenesis and this dose could prevent neural damage.

Comparing the Effects of Rosemary Extract and Treadmill Exercise on the Hippocampal Function and Antioxidant Capacity in Old Rats.

INTRODUCTION: A sequence of time-dependent changes can affect the brain's functional capacity.This study aimed at investigating the effects of Forced Aerobic Exercise (FAE) versus the Rosemary Extract (RE) on the learning abilities and oxidative stress modulation in rats. METHODS: Young and old rats received daily FAE and RE for 3 months. Using the Passive Avoidance (PA) test, we evaluated the learning and memory of the rats by Step-Through Latency (STL) score. We measured the Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Catalase (CATA), Malondialdehyde (MDA) enzymes levels, and Total Antioxidant Capacity (TAC) in the hippocampus. RESULTS: FAE could significantly increase the STL score (P<0.001) among old rats similar to the rosemary extract consumption. The SOD, GPx, and CATA enzyme activities and the level of TAC significantly increased by the treatments (exercise: P<0.001 for SOD and TAC and P<0.05 for CATA, exercise/rosemary: P<0.001 for all enzymes, and rosemary: P<0.01 for SOD and TAC). Furthermore, the MDA level significantly decreased by the treatments (exercise and exercise/rosemary: P<0.001, rosemary: P<0.01). The partial Pearson test revealed the significant positive correlations between the score of STL (day 2) with the SOD (P<0.01) and TAC (P<0.05) levels and negative correlations between the MDA level and STL score in both days (P<0.05 for the first day and P<0.001 for the second day). CONCLUSION: Similar to the rosemary extract, FAE could increase the working memory and antioxidants activity in old rats in 3 months.

Cell Sources in Cardiac Tissue Engineering: Current Choices.

The past decade has evidenced numerous developments in the treatment of heart diseases; however many patients with chronic heart failure suffer from low quality of life. Therapeutic methods, including drug-delivery as well as heart transplantation, have been used to improve quality of life. Cell therapy and tissue engineering have been recently introduced to the field of medicine as a novel therapeutic approach. Treatment of heart diseases has seen novel development through the introduction of cell therapy approaches. Based on the evidence, cell therapy has emerged as a promising therapeutic strategy for the treatment of cardiac diseases. Since the first cell transplant to patients, different types of (stem) cells have been studied. This study aims to provide a comprehensive review of different types of cells and their roles in cardiac cell-based therapy.

High porous electrospun poly(ε-caprolactone)/gelatin/MgO scaffolds preseeded with endometrial stem cells promote tissue regeneration in full-thickness skin wounds: An in vivo study.

In the current study, electrospun poly(ε-caprolactone)-gelatin (PCL-Gel) fibrous scaffolds containing magnesium oxide (MgO) particles and preseeded with human endometrial stem cells (hEnSCs) were developed to use as wound care material in skin tissue engineering applications. Electrospun fibers were fabricated using PCL-Gel (1:1 [wt/wt]) with different concentrations of MgO particles (1, 2, and 4 wt%). The fibrous scaffolds were evaluated regarding their microstructure, mechanical properties, surface wettability, and in vitro and in vivo performances. The full-thickness excisional wound model was used to evaluate the in vivo wound healing ability of the fabricated scaffolds. Our findings confirmed that the wounds covered with PCL-Gel fibrous scaffolds containing 2 wt% MgO and preseeded with hEnSCs have nearly 79% wound closure ability while sterile gauze showed 11% of wound size reduction. Our results can be employed for biomaterials aimed at the healing of full-thickness skin wounds.

Effect of short-term and long-term traffic noise exposure on the thyroid gland in adult rats: a sexual dimorphic study.

OBJECTIVES: Traffic noise, as one of the noise types, is a widespread feature of the urban environments. Traffic noise exposure can lead to hearing loss, hypertension, obesity and ischemic heart diseases. Thyroid hormones involved in the physiological and pathological conditions of the body. Therefore, this study was designed to aim the evaluation of traffic noise effects on thyroid hormones secretion and thyroid tissue structure. METHODS: Seventy two males and females wistar rats were used in this study. After one week adaptation, they divided randomly into 12 groups; the control, short term (one day) and long term (one, two, three and four weeks) groups. Traffic sound was recorded, adjusted and played (86 dB) for animals. Female rats' cycle estrus was matched. At the end of experiment, the animals were anesthetized and cardiac blood sample was drawn. Thyroid tissue was then removed. Levels of the T3, T4, TSH, corticosterone and H&E staining were measured. p<0.05 considered to be statistically significant. RESULTS: Findings showed that in the one-day group, T3 levels increased and T3 levels decreased in the long term groups (p<0.05). In the same way, concentration of TSH decreased in the one day, while they increased in the one, two, three and four weeks' groups (p<0.05). Histopathological evaluations showed that in the female and male animals, long-term traffic noise increased the full follicles and decreased empty follicles (p<0.05). CONCLUSIONS: This study revealed that traffic noise exposure led to increase of T3 plasma concentration and decrement of TSH level, although in the long term, they return to basal status. It may be due to adaptation to traffic noise.

Encapsulation of curcumin loaded chitosan nanoparticle within poly (ε-caprolactone) and gelatin fiber mat for wound healing and layered dermal reconstitution.

Hybrid electrospun fiber containing bioactive molecules, which offer the ability to deliver the cells into the wound bed, will help to achieve a high therapeutic effect. In this study, an electrospun polycaperlactone (PCL) and gelatin (Gela) scaffold containing curcumin loaded chitosan nanoparticle (NCs/Cur) was used to evaluate in vivo wound healing ability of the fabricated scaffolds. The electrospun hybrid scaffold seeded with human endometrial stem cells (EnSCs) showed desirable biocompatibility with the host immune system and wound healing ability in a full-thickness excisional animal model. The constructs were characterized for structural, mechanical and biochemical properties. Fourier transform infrared spectroscopy (FTIR) confirmed all typical absorption characteristics of PCL and Gela polymers as well as NCs and Cur. The results showed the perfect contact angle, wettability and degradability of hybrid fiber scaffolds with the good mechanical and structural characteristics including shape uniformity, pore size and porosity. The cell attachment and proliferation on the PCL/Gela/NCs/Cur was higher than PCL and PCL/Gela scaffolds. In term of the capability of hybrid scaffold and EnSCs in histological analysis, this novel tissue-engineered construct could be suggested as a skin substitute to repair injured skin and regenerative medicine application.

Transplantation of Adipose Tissue-Derived Stem Cells into Brain Through Cerebrospinal Fluid in Rat Models: Protocol Development and Initial Outcome Data.

BACKGROUND: Cell therapy is an important strategy for the treatment of incurable diseases including those that occur in the Central Nervous System (CNS). Among different strategies, the method of delivering or transplantation of cells into the brain has shown significant effects on regeneration. In this study, a new protocol has been developed for the transplantation of adipose tissuederived stem cells into the brain through Cerebrospinal Fluid (CSF) in rat models. METHODS: For this purpose, a wide range of ages (7-30 days old) of male neonates of Wistar rats was used. Moreover, human adipose tissue was obtained from a superficial layer of abdomen through liposuction surgery. The size of the inserted part of needle to access middle cranial fossa and subarachnoid space in animals with an average weight of 10-80 g was determined. In addition, to confirm the entrance of needle into the subarachnoid space, CSF was aspirated slowly and then injection was done within two minutes. RESULTS: The findings showed the presence of transplanted human Adipose-Derived Stem Cells (hADSC) in the cerebellum and basal ganglia following three days and also after two months that confirmed the entrance of transplanted cells into the cerebrospinal fluid and migration of them into the brain tissue. All the animals survived after the transplantation process, with the lowest side effects compared to the available conventional methods. CONCLUSION: It can be concluded that the cells could be efficiently transplanted into CSF through subarachnoid space by injection via superior orbital fissure with a minimally invasive technique.

Allantoin improves methionine-choline deficient diet-induced nonalcoholic steatohepatitis in mice through involvement in endoplasmic reticulum stress and hepatocytes apoptosis-related genes expressions.

OBJECTIVES: Non-alcoholic steatohepatitis (NASH) is defined by steatosis and inflammation in the hepatocytes, which can progress to cirrhosis and possibly hepatocellular carcinoma. However, current treatments are not entirely effective. Allantoin is one of the principal compounds in many plants and an imidazoline I receptor agonist as well. Allantoin has positive effects on glucose metabolism and inflammation. In this study, the effects of allantoin on the NASH induced animals and the pathways involved have been evaluated. MATERIALS AND METHODS: C57/BL6 male mice received saline and allantoin as the control groups. In the next group, NASH was induced by the methionine-choline-deficient diet (MCD) for eight weeks. In the NASH+allantoin group, allantoin was injected four weeks in the mice feeding on an MCD diet. Histopathological evaluations, serum analysis, ELISA assay, and real-time RT-PCR were performed. RESULTS: Allantoin administration decreased serum alanine aminotransferase (ALT), cholesterol, low-density lipoprotein (LDL), hepatic lipid accumulation, and liver tumor necrosis factor (TNFα) level. Also, treatment with allantoin down-regulated the gene expression of glucose-regulated protein 78 (GRP78), activating transcription factor 6 (AFT6), TNFα, sterol regulatory element binding proteins 1c (SREBP1c), fatty acid synthase (FAS), Bax/Bcl2 ratio, caspase3, and P53. On the other hand, peroxisome proliferator-activated receptor alpha (PPARα), apolipoprotein B (Apo B), and acetyl-coenzyme acetyltransferase 1 (ACAT1) gene expression increased after allantoin injection. CONCLUSION: This study indicated that allantoin could improve animal induced NASH by changes in the expression of endoplasmic reticulum stress-related genes and apoptotic pathways.

The Effect of Amygdalin on Endoplasmic Reticulum (ER) Stress Induced Hepatic Steatosis in Mice.

BACKGROUND: Endoplasmic reticulum (ER) stress creates abnormalities in the insulin action, inflammatory responses, lipoprotein B100 degradation, and hepatic lipogenesis. Hepatic steatosis leads to a broad spectrum of hepatic disorders such as nonalcoholic fatty liver disease (NAFLD) and NASH. Amygdalin has beneficial effects on asthma, bronchitis, diabetes, and atherosclerosis. We designed this study to evaluate the effect of amygdalin on the ER stress induced hepatic steatosis. METHODS: Inbred mice received saline, DMSO and amygdalin, as control groups. ER stress was induced by tunicamycin (TM) injection. Amygdalin was administered 1 h before the TM challenge (Amy + TM group). Mice body and liver weights were measured. Hematoxylin and eosin (H&E) and oil red O staining from liver tissue, were performed. Alanin aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride and cholesterol levels were measured. RESULTS: Histological evaluation revealed that amygdalin was unable to decrease the TM induced liver steatosis; however, ALT and AST levels decreased [ALT: 35.33(2.15) U/L versus 92.33(6.66) U/L; (57.000, (50.63, 63.36), P < 0.001) and AST: 93(5.09) U/L versus 345(97.3) U/L, (252, (163.37, 340.62), P < 0.001)]. Amygdalin also decreased triglyceride and cholesterol plasma levels in the Amy + TM group [TG: 42.66(2.15) versus 53.33(7.24) mg/dL; (10.67, (3.80, 17.54), P = 0.006) and TC: 9.33(3.55) versus 112.66(4.31) mg/dL, (103.33, (98.25, 108.40) P < 0.001)]. CONCLUSION: Amygdalin improved the ALT, AST, and lipid serum levels after the TM challenge; however, it could not attenuate hepatic steatosis.

Migration of Bone Marrow-Derived Very Small Embryonic-Like Stem Cells toward An Injured Spinal Cord.

OBJECTIVE: Bone marrow (BM) is one of the major hematopoietic organs in postnatal life that consists of a heterogeneous population of stem cells which have been previously described. Recently, a rare population of stem cells that are called very small embryonic-like (VSEL) stem cells has been found in the BM. These cells express several developmental markers of pluri- potent stem cells and can be mobilized into peripheral blood (PB) in response to tissue injury. In this study we have attempted to investigate the ability of these cells to migrate toward an injured spinal cord after transplantation through the tail vein in a rat model. MATERIALS AND METHODS: In this experimental study, VSELs were isolated from total BM cells using a fluorescent activated cell sorting (FACS) system and sca1 and stage specific embryonic antigen (SSEA-1) antibodies. After isolation, VSELs were cultured for 7 days on C2C12 as the feeder layer. Then, VSELs were labeled with 1,1´-dioctadecyl-3,3,3´,3´- tetramethylindocarbocyanine perchlorate (DiI) and transplanted into the rat spinal cord injury (SCI) model via the tail vein. Finally, we sought to determine the presence of VSELs in the lesion site. RESULTS: We isolated a high number of VSELs from the BM. After cultivation, the VSELs colonies were positive for SSEA-1, Oct4 and Sca1. At one month after transplantation, real-time polymerase chain reaction analysis confirmed a significantly increased expres- sion level of Oct4 and SSEA-1 positive cells at the injury site. CONCLUSION: VSELs have the capability to migrate and localize in an injured spinal cord after transplantation.

Chronic Aerobic Exercise Decreases Lectin-Like Low Density Lipoprotein (LOX-1) Receptor Expression in Heart of Diabetic Rat.

BACKGROUND: Overexpression of lectin-like low density lipoprotein (LOX-1) receptor plays an important role in hyperglycemia-induced vascular complications such as atherosclerosis. Based on the beneficial effects of exercise on preventing cardiovascular complications of diabetes, we aimed to examine the protective effects of aerobic exercise on expression of LOX-1 receptor and production of free radicals in the heart of diabetic rats. METHODS: Four groups of rats were used: (n = 5 per group): sedentary normal, trained normal, sedentary diabetes and trained diabetes. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg). The exercise protocol was consisted of swimming 30 min/day, 5 days/week for eight weeks. Plasma glucose was evaluated at initiation, weeks 4 and 8 of experiment. At the end of experiment, rats were sacrificed and the heart was removed for determination of nitrate, malondialdehyde, and LOX-1 gene expression. RESULTS: In normal non-diabetic rats, the blood glucose level was <150 mg/dl; however, the induction of diabetes resulted in levels more than >400 mg/dl. Gene expression of LOX-1 was increased in the heart of diabetic rats. Exercise reduced the gene expression of this protein in diabetic states without reducing the blood glucose. Finally, swimming exercise decreased the malondialdehyde and nitrate levels in heart tissue both in control and diabetic rats. CONCLUSION: Swimming exercise reduces heart expression of the LOX-1 receptor in accompany with reduction of free radicals production. Since these parameters are important in generation of diabetic complications, swimming exercise is a good candidate for reducing these complications.

The effect of rosemary extract on spatial memory, learning and antioxidant enzymes activities in the hippocampus of middle-aged rats.

BACKGROUND: The Rosemary extract (RE) possesses various antioxidant, cytoprotective and cognition- improving bioactivities. In this study, we postulated which doses of RE have a more effect on the hippocampus of middle-aged rats. METHODS: In this experimental study, thirty-two middle-aged male Wistar rats were fed by different doses (50,100 and 200 mg/kg/day) of RE (containing 40% carnosic acid) or distilled water for 12 weeks. The effects of different RE doses on learning and spatial memory scores, hippocampal neuronal survival, antioxidant enzymes and lipid peroxidation amount were evaluated by one and two way analysis of variance (ANOVA). RESULTS: It seemed that RE (100mg/kg) could recover the spatial memory retrieval score (p< 0.05). The amount of activity of SOD, GPx and CAT enzymes in the hippocampus of animals of the RE (100mg/kg) group showed a significant increase compared to the normal group (p< 0.01), (p< 0.01) and (p< 0.05), respectively. Also, the amount of activity of GPx in the RE (50 mg/kg) group of animals showed a significant increase compared to the normal group (p< 0.05). No significant difference was found between the groups in the MDA level. CONCLUSION: The results revealed that rosemary extract (40% carnosic acid) may improve the memory score and oxidative stress activity in middle aged rats in a dose dependent manner, especially in 100mg/kg.

Potential preventive role of Iranian Achillea wilhelmsii C. Koch essential oils in acetaminophen-induced hepatotoxicity.

BACKGROUND: The essential oil of Achillea wilhelmsii C. Koch (100 & 200 mg/kg b.w, i.p) was evaluated against acetaminophen induced hepatic injuries in rats. For this purpose, the activities of cytochrome P450 (CYP450), glutathione s-transferase (GST) and markers of liver injuries (ALT, AST, ALP) together with level of GSH measured analytically in time intervals (2, 4, 8, 16 & 24 h) after treatments confirmed by histophatological consideration in rat livers. RESULTS: Administration of acetaminophen (500 mg/kg bw, i.p) significantly increased the activity of CYP450 concomitant with increasing the release of ALT and AST. Whereas, GSH level and GST activity were decreased significantly after acetaminophen treatment. Treatment of rats with Achillea wilhelmsii essential oils significantly modulate these parameters to normal values. Also, histophatological analysis of liver biopsies was consistent with the biochemical findings. CONCLUSION: The data led us to conclude the curative potential of Achillea wilhelmsii essential oils against APAP induced hepatic injuries.