Effect of hydro-alcoholic extract of Nigella sativa on cisplatin-induced memory impairment and brain oxidative stress status in male rats.

Objective: Studies have shown the complications of chemotherapy on learning and memory. Empirical evidence suggests that Nigella sativa (NS) has neuroprotective activities. Therefore, the aim of our study was to investigate the effects of NS on cisplatin-induced memory impairment. Materials and Methods: This study was conducted on 40 male rats grouped as: control (saline: 2 ml/kg, intraperitoneally (IP), once weekly/2 weeks), cisplatin (Cis, 2 mg/kg, IP, once weekly/2 weeks), NS (200 mg/kg, IP, once weekly/2 weeks), Cis +NS 200 (2 mg/kg Cis + 200 mg/kg NS, IP, once weekly/2 weeks), and Cis +NS 400 (2 mg/kg Cis + 400 mg/kg NS, IP, once weekly/2 weeks). Morris water maze (MWM) test was used to assess spatial learning and memory. In addition, superoxide dismutase (SOD) activity, and thiol and malondialdehyde (MDA) levels were evaluated in the brain. Results: Cis significantly enhanced the traveled distance and time spent in the target quadrant in the MWM test. Additionally, MDA levels increased in the Cis group, while thiol and SOD decreased in this group. As a result of treatment with NS, behavioral results were reversed in the groups receiving NS compared to the Cis group. Also, NS reduced MDA level but improved SOD and thiol levels in brain tissue samples. Conclusion: NS could improve memory impairment and oxidative stress in animals receiving Cis. Therefore, NS could be used as a potential food supplement to prevent neurotoxicity in patients undergoing chemotherapy.

Combination of curcumin with autologous transplantation of adult neural stem/progenitor cells leads to more efficient repair of damaged cerebral tissue of rat.

NEW FINDINGS: What is the central question of this study? Can the neuroprotective agent curcumin affect restorative action of neural stem/progenitor cells in the injured rat brain? What is the main finding and its importance? In the presence of curcumin, transplantation of neural stem/progenitor cells in the context of PuraMatrix reduced lesion size and reactive inflammatory responses, and boosted survival rate of grafted neurons. In addition it improved the neurological status of injured animals. This could be beneficial in designing new therapeutic approaches for brain injury based on this combination therapy. ABSTRACT: Traumatic brain injury (TBI) is catastrophic neurological damage associated with substantial morbidity and mortality. To date, there is no specific treatment for restoring lost brain tissue. In light of the complex pathology of brain injury, the present study evaluated the effects of combination therapy using autologous neural stem/progenitor cells (NS/PCs), PuraMatrix (PM) and curcumin in an animal model of brain injury. After stereotactic biopsy of subventricular zone tissue and culture of NS/PCs, 36 male Wistar rats (150-200 g) were randomly divided into six groups receiving dimethyl sulfoxide (DMSO),  curcumin (100 mg kg-1 in DMSO), PM + curcumin (100 mg kg-1 in DMSO), NS/PCs + curcumin (100 mg kg-1 in DMSO), NS/PCs + PM + curcumin (100 mg kg-1 in DMSO) and NS/PCs + PM + curcumin (1 µm) following acute brain injury. The animals were evaluated in term of neurological status for 4 weeks, then decapitated. Nissl and TUNEL staining and immunohistochemistry for bromodeoxyuridine, glial fibrillary acidic protein, doublecortin, Map2, Olig2, Iba1 and CD68 were performed. We found that combination therapy by NS/PCs + PM + curcumin reduced the lesion size, astrogliosis, macrophage and microglial reaction as well as the number of apoptotic cells. Moreover, the transplanted cells were able to survive and differentiate after 4 weeks. Besides these findings, transplantation of NS/PCs in the context of PM and curcumin improved the neurological status of injured animals. In conclusion, our data suggest that this combination therapy can be beneficial in developing future therapeutic approaches for brain injury.

"Exercise during hemodialysis and health promoting behaviors: a clinical trial".

BACKGROUND: Health promoting behaviors are among the determinants of health. Hemodialysis causes significant changes in the lives of patients and affects their health promoting behaviors. Accordingly, this study aimed at investigating the effect of exercise during hemodialysis on health promotion behaviors in patients undergoing hemodialysis. METHODS: This study was a two-stage (before and after) clinical trial. The sample of the study consisted of 60 hemodialysis patients in two hospitals in Isfahan who were selected randomly and divided into two groups of control and intervention using random allocation method. A 8-week exercise program by stationary bicycles (Mini-bike) was designed for the intervention group, while the control group underwent a 10-min limbering exercise for 8 weeks. Data were collected using demographic questionnaire and the Health Promoting Lifestyle Profile II (HPLP-II) questionnaire before and after the intervention and were analyzed using SPSS21 software. RESULTS: Based on the independent t-test results, no significant difference was observed between the mean score of health promoting behaviors and its areas before the intervention (P > 0.05). However, the results of this test showed that the mean score of health promoting behaviors and its areas, except for the areas of responsibility (P = 0.052) and spirituality (P = 0.211), was significantly different between the two groups after the intervention (p < 0.05). CONCLUSIONS: The results of this study showed that exercise with stationary bicycle during hemodialysis could promote health promoting behaviors. Thus, this exercise is recommended to be considered as part of the therapeutic protocol of these patients in hemodialysis departments. TRIAL REGISTRATION: The clinical trial was found to be in accordance to the ethical principles and the national norms and standards for conducting medical research in Iran. IRCT registration number: IRCT20150116020675N3 . Registration date: 2019-01-18, 1397/10/28 Approval ID: IR.MUI. RESEARCH: REC.1397.014 Approval Date: 2018-07-01 Evaluated by: Vice-Chancellor in Research Affairs -Medical University of Isfahan.

Improvement of memory and learning by intracerebroventricular microinjection of T3 in rat model of ischemic brain stroke mediated by upregulation of BDNF and GDNF in CA1 hippocampal region.

BACKGROUND: Ischemic stroke is a common leading cause of death and disability with lack of effective therapies. In this study, T3 was intra-ventricularly injected to evaluate gene expression and protein concentration of and brain-derived neurotrophic factor (BDNF) and Glial cell-derived neurotrophic factor (GDNF) in hippocampal CA1 region in rat model of brain ischemia/reperfusion (I/R). METHODS: In this study, transient middle cerebral artery occlusion (tMCAo) was used as model of ischemic brain stroke. Rats were randomly divided in four groups of Co, Sh, tMCAo and tMCAo + T3. Then, a single dose of intra-ventricular T3 was administered via a Hamilton syringe. Passive avoidance test was used as behavioral investigations. After 21 days, the animals were sacrificed and their brains were used for molecular and histopathological studies. RESULTS: T3 significantly improved the learning and memory compared with tMCAo group according to Morris water maze findings (P < 0.05). Step-through latency (STL) significantly decreased in tMCAo group (P < 0.05). There were significant increase in the STL of T3 group compared with tMCAo group (P < 0.05).A significant reduction in BDNF mRNAs and protein levels were observed in the tMCAo compared with Co and Sh group (P < 0.05). A significant increase of BDNF and GDNF mRNAs and proteins was recorded in tMCAo + T3 group compared with Co, Sh and tMCAO groups (P < 0.05). CONCLUSIONS: The results of current study demonstrated that T3 had therapeutic effects on cerebral ischemic stroke by increasing the neurotrophic factors (BDNF, GDNF) in CA1 region of hippocampus. The effects of intracerebroventricular microinjection of T3on memory and learning in rat model of ischemic brain stroke.

Preparing neural stem/progenitor cells in PuraMatrix hydrogel for transplantation after brain injury in rats: A comparative methodological study.

Cultivation of neural stem/progenitor cells (NS/PCs) in PuraMatrix (PM) hydrogel is an option for stem cell transplantation. The efficacy of a novel method for placing adult rat NS/PCs in PM (injection method) was compared to encapsulation and surface plating approaches. In addition, the efficacy of injection method for transplantation of autologous NS/PCs was studied in a rat model of brain injury. NS/PCs were obtained from the subventricular zone (SVZ) and cultivated without (control) or with scaffold (three-dimensional cultures; 3D). The effect of different approaches on survival, proliferation, and differentiation of NS/PCs were investigated. In in vivo study, brain injury was induced 45 days after NS/PCs were harvested from the SVZ and phosphate buffered saline, PM, NS/PCs, or PM+NS/PCs were injected into the brain lesion. There was an increase in cell viability and proliferation after injection and surface plating of NS/PCs compared to encapsulation and neural differentiation markers were expressed seven days after culturing the cells. Using injection method, transplantation of NS/PCs cultured in PM resulted in significant reduction of lesion volume, improvement of neurological deficits, and enhancement of surviving cells. In addition, the transplanted cells could differentiate in to neurons, astrocytes, or oligodendrocytes. Our results indicate that the injection and surface plating methods enhanced cell survival and proliferation of NS/PCs and suggest the injection method as a promising approach for transplantation of NS/PCs in brain injury.

Curcumin as a double-edged sword for stem cells: dose, time and cell type-specific responses to curcumin.

BACKGROUND: The beneficial effects of curcumin which includes its antioxidant, anti-inflammatory and cancer chemo-preventive properties have been identified. Little information is available regarding the optimal dose and treatment periods of curcumin on the proliferation rate of different sources of stem cells. METHODS: In this study, the effect of various concentrations of curcumin on the survival and proliferation of two types of outstanding stem cells which includes bone marrow stem cells (BMSCs) and adult rat neural stem/progenitor cells (NS/PCs) at different time points was investigated. BMSCs were isolated from bilateral femora and tibias of adult Wistar rats. NS/PCs were obtained from subventricular zone of adult Wistar rat brain. The curcumin (0.1, 0.5, 1, 5 and 10 µM/L) was added into a culture medium for 48 or 72 h. Fluorescent density of 5-bromo-2'-deoxyuridine (Brdu)-positive cells was considered as proliferation index. In addition, cell viability was assessed by MTT assay. RESULTS: Treatment of BMSCs with curcumin after 48 h, increased cell survival and proliferation in a dose-dependent manner. However, it had no effect on NSCs proliferation except a toxic effect in the concentration of 10 µM of curcumin. After a 72 h treatment period, BMSCs and NS/PCs survived and proliferated with low doses of curcumin. However, high doses of curcumin administered for 72 h showed toxic effects on both stem cells. CONCLUSIONS: These findings suggest that curcumin survival and proliferative effects depend on its concentration, treatment period and the type of stem cells. Appropriate application of these results may be helpful in the outcome of combination therapy of stem cells and curcumin.

Regulation of connexin 43 and microRNA expression via ß2-adrenoceptor signaling in 1321N1 astrocytoma cells.

Connexin 43 (Cx43) is the main gap junction protein in astrocytes and exerts the same effects on growth inhibition in astrocytoma and glioma as microRNA-146a (miR-146a) in glioma. ß2-adrenergic receptor (AR) signaling modulates Cx43 expression in myocytes via components downstream of protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). However, it remains to be elucidated how expression of Cx43 is modulated in astrocytes. In the present study, 1321N1 astrocytoma cells were treated with ß2-AR signaling agents in order to evaluate the expression of Cx43 and miRNAs. RNA and protein were extracted from the cells for use in reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The results revealed that clenbuterol increased miR-146a level and upregulated Cx43 expression via cAMP/PKA at the mRNA and protein level. Pre-inhibition of adenyl cyclase decreased expression of Cx43 and miR-146a. PKA activation and overexpression of miR-146a in A-1321N1 cells increased the expression of Cx43. ß2-AR stimulation and 6Bnz, a PKA activator, suppressed oncomiRs miR-155 and miR-27a, while 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate, an Epac activator, increased their levels. The current findings demonstrated that ß2-AR signaling has growth inhibitory effects via modulation of the cAMP/PKA pathway in A-1321N1 cells through increasing the expression level of Cx43 and miR-146a as well as decreasing miR-155 and miR-27a levels. Thus, stimulation of the ß2-AR and PKA signaling pathway may be a useful approach for astrocytoma therapy.

Testosterone enhances functional recovery after stroke through promotion of antioxidant defenses, BDNF levels and neurogenesis in male rats.

It is reported that circulating testosterone levels decrease after cerebral ischemia. The aim of this study was to evaluate the effects of testosterone on oxidative stress, brain-derived neurotrophic factor (BDNF) levels, neurogenesis, histological damage and sensorimotor recovery in a castrated male rat model of focal cerebral ischemia. Animals were divided into four groups. For all animals, castrations were conducted 7 days before transient middle cerebral artery occlusion (MCAO) was done and cerebral ischemia was induced. The first group served as sham. Second was MCAO group and received vehicle only, third was MCAO group that was post-treated with testosterone and the fourth was MCAO group post-treated with testosterone and flutamide. Treatment only with testosterone significantly weakened oxidative stress and increased BDNF levels and sensorimotor recovery during a 10 days period. Rats receiving testosterone demonstrated a significant reduction in infarct volume and a significant increase in neurogenesis on 10th day after focal cerebral ischemia. Our results for the first time showed a potential advantageous effect of testosterone after cerebral ischemia in male rats, which was probably mediated by promoting antioxidant defenses, BDNF levels and neurogenesis.

A new and safe method for stereotactically harvesting neural stem/progenitor cells from the adult rat subventricular zone.

BACKGROUND: Adult neural stem/progenitor cells (NS/PCs) are one of the outstanding cell sources for therapeutic purposes in the central nervous system diseases. Autologous transplantation of NS/PCs still is a matter of controversy due to the safety issue as well as efficiency of harvesting these cells from the live mammalian brain subventricular zone (SVZ). NEW METHOD: In this new and safe method, a 16-guage semi-automatic biopsy needle was used stereotactically to remove a piece of SVZ. Then, the proliferation and differentiation capacity of obtained cells were assessed. In addition, the safety of the biopsy procedure was analyzed employing the Morris water maze, modified neurologic severity score, passive avoidance and open field tests. RESULTS: Despite being very small in size, the SVZ specimen could generate a large number of progeny with the ability to differentiate into neuronal and glial cells. The biopsy procedure introduced in this study did not have any impact on the behavioral and neurological processes. COMPARISON WITH EXISTING METHOD(S): existing SVZ biopsy methods were uncontrollable techniques which harvested brain tissue by aspiration using a syringe not a semi-automatic biopsy needle. Also, previous methods were not evaluated in terms of behavior and cognition. CONCLUSIONS: This study revealed a considerable safety and efficacy for the stereotactical removal of the adult rat SVZ to harvest NS/PCs for autologous transplantation.

Autoimmune pancreatitis mimicking carcinoma of the head of the pancreas: a case report.

INTRODUCTION: We report on a case of autoimmune pancreatitis presenting as pancreatic head cancer, which is extremely rare in Iran. Currently, on the PubMed database, no such cases exist. CASE PRESENTATION: A 70-year-old Iranian man presented with recurrent abdominal pain, jaundice and elevated bilirubin and alkaline phosphatase levels. An abdominal computed tomography scan revealed a heterogeneous presence in the pancreatic head as well as dilated intra- and extrahepatic bile ducts. A common bile duct stent had been inserted. Our patient was subsequently diagnosed with pancreatic head cancer.Due to his continued recurrent abdominal pain, our patient returned to the hospital. His levels of bilirubin, alkaline phosphatase and tumor markers were all normal but his immunoglobulin G4 and antinuclear antibodies were extremely high. A biopsy of the pancreatic head heterogeneity by endoscopic ultrasonography was performed.Pathologic samples showed fibrosis associated with lymphoplasmacytic infiltration and no evidence of malignancy. A diagnosis of autoimmune pancreatitis was confirmed, the bile duct stent removed, and an appropriate treatment plan was undertaken. CONCLUSION: Autoimmune pancreatitis should be considered in suspected cases of pancreatic cancer. In these instances, a biopsy of the pancreas will help to differentiate between the two and prevent complications due to disease progression as well as unnecessary surgery.

Renal function and risk factors of moderate to severe chronic kidney disease in Golestan Province, northeast of Iran.

INTRODUCTION: The incidence of end-stage renal disease is increasing worldwide. Earlier studies reported high prevalence rates of obesity and hypertension, two major risk factors of chronic kidney disease (CKD), in Golestan Province, Iran. We aimed to investigate prevalence of moderate to severe CKD and its risk factors in the region. METHODS: Questionnaire data and blood samples were collected from 3591 participants (≥18 years old) from the general population. Based on serum creatinine levels, glomerular filtration rate (GFR) was estimated. RESULTS: High body mass index (BMI) was common: 35.0% of participants were overweight (BMI 25-29.9) and 24.5% were obese (BMI ≥30). Prevalence of CKD stages 3 to 5 (CKD-S3-5), i.e., GFR <60 mL/min/1.73 m(2), was 4.6%. The odds ratio (OR) and 95% confidence interval (95% CI) for the risk of CKD-S3-5 associated with every year increase in age was 1.13 (1.11-1.15). Men were at lower risk of CKD-S3-5 than women (OR = 0.28; 95% CI 0.18-0.45). Obesity (OR = 1.78; 95% CI 1.04-3.05) and self-reported diabetes (OR = 1.70; 95% CI 1.00-2.86), hypertension (OR = 3.16; 95% CI 2.02-4.95), ischemic heart disease (OR = 2.73; 95% CI 1.55-4.81), and myocardial infarction (OR = 2.69; 95% CI 1.14-6.32) were associated with increased risk of CKD-S3-5 in the models adjusted for age and sex. The association persisted for self-reported hypertension even after adjustments for BMI and history of diabetes (OR = 2.85; 95% CI 1.77-4.59). CONCLUSION: A considerable proportion of inhabitants in Golestan have CKD-S3-5. Screening of individuals with major risk factors of CKD, in order to early detection and treatment of impaired renal function, may be plausible. Further studies on optimal risk prediction of future end-stage renal disease and effectiveness of any screening program are warranted.

Renal involvement in patients with hepatitis C virus infection.

INTRODUCTION: Hepatitis C virus (HCV) infection is a hepatotropic virus causing a variety of extrahepatic immunological manifestations and is a risk factor of a variety of extrahepatic diseases, such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN), which is the most common glomerulonephritis. The aim of this study was to evaluate renal involvement in HCV-infected patients. MATERIALS AND METHODS: A total of 300 randomly-selected HCV antibody-positive outpatients at the HCV clinic of Shariati hospital were enrolled. Serum creatinine was measured and glomerular filtration rate was estimated accordingly. Urine proteinuria was measured in 24-hour urine samples. RESULTS: The patients were 249 men (83.2%) and 51 women (16.8%) with a mean age of 37.8 +/- 11.7 years (range, 18 to 70 years). Proteinuria was found in 12 HCV antibody-positive adults (4%), 1 of whom underwent biopsy. He was a 55- year-old man with a 4-month history of facial and lower extremities edema and 3-g proteinuria with a normal kidney function (glomerular filtration rate, 85 mL/min) and normocomplementemia. Kidney biopsy specimens showed MPGN. The frequency of low glomerular filtration rate was 0.7% (2 patients) in the HCV antibody-positive adults. There was no significant relationship between HCV seropositivity and low glomerular filtration rate. CONCLUSIONS: Our observations showed renal involvement in HCV antibody-positive patients. Among immune complex glomerular kidney diseases, MPGN without cryoglobulins is thought to be the most common in these patients.

Frequency, risk factors, and outcome of acute kidney injury following bone marrow transplantation at Dr Shariati Hospital in Tehran.

INTRODUCTION: Bone marrow transplantation (BMT) is a major modality for malignant and hematologic disorders. This procedure is associated with a high morbidity and mortality such as acute kidney injury (AKI). Many factors, such as therapeutic agents, irradiation, and graft versus host disease (GVHD) can cause AKI. Bone marrow transplantation conditioning therapy in Iran is based on drugs such as busulfan and cyclophosphamide and without irradiation therapy. The aim of this study was to evaluate the frequency, risk factors, and mortality of AKI among patients who underwent BMT. MATERIALS AND METHODS: Acute kidney injury was defined as doubling serum creatinine from baseline at any time during the first 180 days posttransplant. The risk of AKI in relation to non-total-body-irradiation-based conditioning regimen, type of graft (allograft and autograft), comorbidities, GVHD, drug toxicity, and veno-occlusive disease were examined in 375 patients with BMT. RESULTS: One hundred and forty-two patients (37.6%) developed AKI at a median of 18 days after transplant. A higher frequency of AKI was observed in patients who received cyclosporine A (40%), patients with allograft BMT (42.1%), and those who developed gastrointestinal GVHD (47.3%) .The remainder AKI cases were associated with amphotericin B, veno-occlusive disease, and hemolytic-uremic syndrome. CONCLUSIONS: The frequency of AKI in our patients with BMT remained high. Cyclosporine A and amphotericin B and the presence of GVHD and veno-occlusive disease increased the risk of AKI within the first 180 days after BMT.

Ulcerative colitis and irritable bowel syndrome: relationships with quality of life.

OBJECTIVES: Quality of life is reduced in inflammatory bowel disease. Irritable bowel syndrome (IBS)-like symptoms seem to be common in inflammatory bowel disease patients during the remission phase. We aimed to (i) assess the prevalence of IBS-like symptoms in ulcerative colitis (UC) patients during the remission phase and (ii) evaluate the impact of IBS symptoms on health-related quality of life (HRQOL) of UC patients in remission compared with the HRQOL of those in the active phase. METHODS: Ninety-five patients with UC (45 patients in the active phase and 50 in remission for at least 12 months) and 100 selected controls (recruited from among those who visited the orthopedic minor trauma outpatient clinic during 2004-2005) completed questionnaires to evaluate IBS-like symptoms according to ROME II criteria: the influence of these symptoms on the HRQOL of UC patients in remission was compared with that on the HRQOL of those in the active phase. Chi square and nonparametric tests were used. RESULTS: The prevalence of IBS-like symptoms in UC patients in remission and controls were 46 and 13%, respectively (P<0.001). HRQOL seemed to be significantly reduced in both active UC patients and UC patients in remission with IBS, compared with UC patients in remission without IBS and with controls (P<0.001). In active UC patients, the mean scores for most elements (as measured by SF36) were considerably lower than for UC patients in remission (P<0.05). CONCLUSION: The prevalence of IBS-like symptoms in UC patients in remission is about three times higher than in controls, and these patients have impaired HRQOL comparable with that of UC patients in the active phase.