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Background: In-utero xenotransplantation of stem cells in abnormal fetuses effectively treats several genetic illnesses. Objective: The current research aimed to evaluate structural and morphological alterations in the liver of rabbit fetuses following xenotransplantation of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs), using a stereological technique. Methods: All hWJ-MSCs were isolated from the human umbilical cord, and their authenticity was established by flowcytometry and differentiation. At gestational day 14, the rabbits were anesthetized, and hWJ-MSCs were injected into the uteri of 24 fetuses. Twenty-two fetuses were born successfully. Ten rabbit liver specimens were prepared from injected fetuses including; eight rabbits on day three following birth and two rabbits on the 21st post-natal day. The non-injected fetuses were considered positive controls. The livers of the control and hWJ-MSCs-treated rabbits were fixed, processed, stained, and examined through stereological approaches. Results: In the hWJ-MSCs-treated group, the mean liver weight and volume increased by 42% and 78% compared to the control group. The total volume of the hepatocytes increased by 63%, and that of sinusoids by three folds in the treated rabbits. The total volume of the central veins increased by 70%. The total number corresponding to hepatocytes in the experimental group increased by 112% compared to the rabbits in the control. The total volume of the hepatocyte nuclei in the experimental group increased by 117% compared to the rabbits in the control. Conclusion: After xenotransplantation of human MSCs, host tissue microenvironments (here, the rabbit liver) were altered and these included quantitative factors corresponding to the liver tissue and hepatocyte morphometric indices. [ABSTRACT FROM AUTHOR]

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Background and Objectives: Trimethyltin (TMT) is an organotin which causes selective degeneration in hippocampus and leads to the appearance of depression in humans and rodents. The present study investigated the effect of Gallic acid (GA) on depression symptoms, oxidative stress markers and inflammatory cytokines functions in rats' hippocampus after TMT intoxication. Materials and Methods: In this experimental study, 50 adult Wistar rats were randomly devided into 5 groups: Control, TMT+Saline, TMT+GA50, TMT+GA100, and TMT+GA200. 48 h after TMT intoxication, GA-treated groups received 50, 100 and 200 mg/kg of GA, and TMT+saline group received saline for 14 days. After evaluation of depression symptoms, the hippocampal levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), malondealdehyde (MDA), Tumor necrosis factor (TNF-α) and interleukin-1β (IL- 1β) were measured by ELISA technique. Differences between the groups were analyzed by ANOVA with Tukey's post hoc test. Results: The results indicated an increase in the immobility time in the TMT+Saline group compared with the controls and a significant decrease in immobility time in the groups treated with high doses of GA (p˂0.001). GA treatment increased the function of antioxidant enzymes (SOD, CAT and GPX) and decreased MDA, TNF-α and IL-1β in comparison with the TMT+Saline group (p˂0.05). Conclusion: Administration of GA led to amelioration of depression symptoms caused by TMT intoxication through adjustment of inflammatory factors and reduction of oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Utreoplacental Insufficiency (UPI) causes impaired fetal brain development and induces oxidative stress, which ultimately leads to intrauterine growth restriction. Due to the antioxidant properties of Hesperidin (HES), the study aimed to outcome this compound on cognitive impairment and serum level of catalase, antioxidant capacity of total and malondialdehyde following uterine-placental insufficiency in rats. Materials and Methods: Thirty pregnant Wistar rats were randomly divided into 5 groups: control group, UPI+NS (Utreoplacental insufficiency+normal saline), UPI+HES25 (Utreoplacental insufficiency+Hesperidin 25 mg/kg), and UPI+HES50 (Utreoplacental insufficiency+Hesperidin 50mg/kg), UPI+HES100 (Utreoplacental insufficiency+ Hesperidin 100mg/kg). UPI was induced by obstruction of the anterior uterine arteries on day 18 of gestation. Hesperidin or normal saline gavage was performed from day 12 to 18 of gestation. Evaluation of working memory, avoidant learning and anxiety-like behaviors and then evaluation of serum levels of catalase, total antioxidant capacity and malondialdehyde content were performed in one-month-old pups. Results: There was a significant decrease in working and avoidance memory, catalase levels, total antioxidants capacity with increased levels of anxiety and malondialdehyde in the UPI+ NS group compared to the control group (P

Objective Adiponectin has a crucial role in the function, proliferation and viability of β-cell via action of two receptors: AdipoR1 and AdipoR2. Nevertheless, age related change of Adiponectin system genes in pancreas is unclear or controversial. This study sought to investigate the effects of aging process on serum Adiponectin levels, Adiponectin and its receptor expression in the rat pancreas. Materials And Methods In this experimental study, insulin resistance markers including serum insulin and glucose concentrations, homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT), glucose induced insulin secretion (GIIS), serum Adiponectin levels, pancreatic expression of Adiponectin and its receptors were studied in male Sprague-Dawley rats at the age of 2, 5, 10, 18, 52 and 72 weeks of age. Results We found that aging triggered signs of insulin resistance characteristics in rats at 72 age weeks including marked insulin reduction, hyperglycemia and increased HOMA-IR. Circulating Adiponectin as well as pancreatic expression of Adiponectin and AdipoR1 was gradually decreased with age, while the opposite expression pattern of AdipoR2 was observed in the old rats. Conclusion Because Adiponectin and Adiponectin signaling have crucial role in β-cell function and viability, we concluded that reduction of Adiponectin signaling may be involved in aging induced β-cell dysfunction. As a result, manipulation of Adiponectin signaling may be a beneficial approach for improvement of β-cell function in the old people.

Acrylamide (AA) is a toxic and carcinogenic compound produced in cooking process. The purpose of this study is to evaluate the effect of N-acetylcysteine (NAC) on extracellular signal-regulated kinase (ERK) gene expression level and ovarian histopathological changes in AA-treated rats. Thirty-six female adult Wistar rats were randomly divided into 6 groups including control, positive control (+VE Con), negative control (-VE Con), experimental 1 (Exp1), experimental 2 (Exp2) and experimental 3 (Exp3). Twenty eight days after the treatment, ERK gene expression level was measured by real-time PCR method and ovarian histopathological changes were evaluated. The ERK gene expression level was significantly decreased in the +VE Con, Exp1 and Exp2 groups as compared to the control group (p=0.05), but not in the -VE Con and Exp3 groups (p=0.05). Histologically, the +VE Con group showed a significant decrease in the number of primary, secondary and Graafian follicles as well as corpus luteum as compared to the control group (p=0.05), but not in the negative, Exp2 and Exp3 groups (p=0.05). In the Exp1 group, the number of primary and secondary follicles as well as corpus luteum significantly decreased (p=0.05), however, the numbers of Graafian follicle and the corpus luteum were significantly increased as compared to the +VE Con group (p=0.05). The AA was supposed to increase the apoptosis and folliculogenesis degradation in the rat ovarian tissue by decreasing ERK gene expression. Administration of NAC ameliorated the deleterious effects of AA in a dose-dependent manner and improve folliculogenesis by reducing apoptosis level. Thus, the NAC supplement could be helpful in ameliorating animal fertility. [ABSTRACT FROM AUTHOR]

Introduction: The cerebellum has been considered a key structure for the processes involved in sensorimotor integration ultimately leading to motor planning and execution of coordinated movement. Thus, motor deficits and behavioral changes can be associated with cerebellar degeneration. Materials and Methods: Here, the chemical neurotoxin pyridine-2, 3-dicarboxylic acid (quinolinic acid, QA) used to create partially cerebellar Stereotaxicaly administration of QA (0.2 mmol) in the right cerebellar hemisphere (folia VI) caused noticeable motor disturbance in all treated animals. Forty-eight hours after causing lesion, rat bone marrow-derived mesenchymal stem cells (MSCs) were transplanted into damaged cerebellar hemisphere. We investigated the role of MSC transplantation in forms of motor and non-motor learning that involves the cerebellum and its neuroprotective effects in Purkinje cells loss. Results: CM-Dil labeling showed that the transplanted MSCs survived and migrated in the cerebellum 6 weeks after transplantation. The MSC-transplanted group showed markedly improved functional performance on the rotating rod test (p⩽0.0001) and beam walking test (p⩽0.0001) during 6 weeks compared with the controls. For non-motor learning, we used passive avoidance learning test in 3 weeks after transplantation. The results showed that MSC transplantation prevented the development of memory deficit caused by cerebellar degeneration (p⩽0.001). Stereological analysis in 6 weeks after transplantation showed that QA significantly decreases Purkinje cells in vehicle-treated rats and MSC transplantation is neuroprotective and decreases Purkinje cell loss in MSC-treated rats (p⩽0.0001). Conclusion: The results indicate that transplantation of MSCs can significantly reduce the behavioral and neuroanatomical abnormalities of these animals during 6 weeks after engraftment. According to results of this assay, cell therapy by means of bone marrow-derived adult stem cells promises for treatment of cerebellar diseases. [ABSTRACT FROM AUTHOR]

Objective: Cerebral ischemia/reperfusion (I/R) has been known as a major cause of inability and mortality worldwide. Ellagic acid (EA) has many pharmacological effects including antioxidant, antithrombotic and neurorestoration activities. The aim of this study was evaluation of the effects of EA on motor and cognitive behaviors, hippocampal local field potential (LFP), brain oxidative stress in male rats with cerebral 2-vessel occlusion ischemia/reperfusion (2VO I/R)., Materials and Methods: Forty-eight male Wistar rats (250-300 g) were assigned into six groups. 1) The Sham: rats were treated with DMSO10%/normal saline as solvent of EA 3 times daily for 1 week; 2) I/R+Veh; I/R rats received vehicle; 3-5) EA-treated groups: I/R rats received 50, 75, or 100 mg/kg EA; and 6) Cont+EA100: intact rats received EA. The cerebral 2VO I/R was made by the bilateral common carotid arteries closing for 20 min followed by reperfusion. The behavioral tests and hippocampal LFP recording were performed after treatment with EA. The oxidative stress parameters were assayed by special ELISA kits., Results: Cerebral 2VO I/R significantly decreased motor coordination, memory and hippocampal LFP and significantly increased oxidative stress. Treatment with EA improved all I/R complications., Conclusion: The current findings showed that treatment of I/R rats with EA could reverse cognitive and motor functions, and improve the LFP and oxidative stress markers. So, effects of EA on cognitive and motor function may at least in part, be due to its antioxidative actions., Competing Interests: The authors have declared that there is no conflict of interest.

Objectives: Cerebral ischemia/reperfusion (I/R) causes brain inflammation that ultimately causes long time brain function disturbances. We aimed to evaluate the effect of ellagic acid (EA) on anxiety, depression, locomotion behaviors, blood-brain barrier (BBB) permeability, brain edema, and inflammation in male rats with cerebral I/R., Materials and Methods: Sixty male Wistar rats (250-300 g) divided into 6 groups randomly with 10 in each: 1) Sham+Veh; rats submitted to the surgery without any I/R and received vehicle (10% DMSO in normal saline 5 ml/kg, gavages). 2) I/R+Veh; 3-5) I/R+EA; I/R rats received 50, 75 and 100 EA mg/kg, by gavages 3 times daily for one week. The cerebral I/R injury was induced by clamping the bilateral common carotid arteries for 20 minutes followed by reperfusion. Behaviors were tested one week after treatment, and brain tissue cytokines were measured by special ELISA kits., Results: Cerebral I/R disrupted BBB function ( P <0.001), increased brain water content ( P <0.01), anxiety-like ( P <0.001), depression-like ( P <0.001) behaviors and cytokines in the brain tissue ( P <0.001), while decreased locomotion and exploratory behaviors significantly ( P <0.01 and P <0.001, respectively). Administration of EA (100 mg/kg but not other doses) could improve post-ischemic complications such as clinical signs ( P <0.01), BBB function ( P <0.001), brain edema ( P <0.01), brain tissue cytokines ( P <0.001), locomotion and exploratory behaviors significantly ( P <0.05 and P <0.001, respectively)., Conclusion: The results suggest that EA could be a potential therapeutic agent against cerebral I/R, possibly through its intertwined anti-inflammatory effects. Further research is required to investigate the involved mechanisms in details.

Two main characteristics of all types of stem cells are their potency for differentiation and self renewal capacity. There is a lot of interest to find the conditions and factors, which govern these behaviours of stem cells. It is very well documented that retinoic acid (RA) reduces growth rate by induction of cell differentiation in certain conditions and cell lines. On the other hand, hyaluronic acid (HA) is known for its growth induction on cultured cells. A natural source of HA, rabbit vitreous humour (VH), was previously shown to promote wound repair in model animals. In search for its possible mechanisms, VH extract was tested on the cultured mesenchymal stem cells and NTERA2 as human embryonal carcinoma cells in the presence of RA. Changes in some cellular and molecular markers (A2B5, Oct4, Sox2) showed that VH and possibly HA interfere with differentiating effects of RA. Therefore, this reagent may affect cell proliferation and tissue regeneration by inhibition of cell differentiation.

For proper treatment, recycling, or disposal of the pulp and paper mill secondary sludge qualitative and quantitative determination of its characteristics are necessary. Chemical extraction, quantitative characterization, and spectroscopic experiments have been performed to determine the molecular composition and chemical functionality of a pulp and paper mill secondary sludge. In order to extract the low-molecular-weight substances, soxhlet extraction with polar and non-polar solvents was performed where most of the target substances (17±1.3%.) were extracted after 2 hours. Over time, this extraction followed a first-order kinetics. Fiber analyses have shown 12±3% lignin, 28±3% cellulose, and 12±4% hemicelluloses content. The ash content was about 17±0.5%. In this work, 7 and 16% intra- and extracellular polymeric substances, respectively, were extracted from the secondary sludge. EPS and mixture of intra- and extracellular biopolymers have shown similar chemical functionalities. These analyses confirmed that the paper secondary sludge consisted mainly of wood fiber, i.e. lignocellulosic substances, along with proteins and polysaccharides originated from microorganisms.