The effect of Zingiber Officinale Extract on Preventing Demyelination of Corpus Callosum in a Rat Model of Multiple Sclerosis

Background: Multiple sclerosis (MS) is the most prevalent neurological disability of young adults. Anti-inflammatory drugs have relative effects on MS. The anti-inflammatory and antioxidative effects of Zingiber officinale (ginger) have been proven in some experimental and clinical investigations. The aim of this study was to evaluate the effects of ginger extract on preventing myelin degradation in a rat model of MS. Methods: Forty nine male Wistar rats were used in this study and divided into four control groups: the normal group, cuprizone-induced group, sham group (cuprizone [CPZ] + sodium carboxymethyl cellulose [NaCMC]), standard control group (fingolimod + cuprizone), including three experimental groups of CPZ, each receiving three different doses of ginger extract: 150, 300, and 600mg/kg /kg/day. Results: Ginger extract of 600 mg/kg prevented corpus callosum from demyelination; however, a significant difference was observed in the fingolimod group (p < 0.05). Difference in the CPZ group was quite significant (p < 0.05). Conclusion: Treatment with ginger inhibited demyelination and alleviated remyelination of corpus callosum in rats. Therefore, it could serve as a therapeutic agent in the MS.

Molecular aspects of pancreatic ß-cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA.

Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic ß-cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic ß-cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and survival of the ß cell via activation or inhibition of several processes and targets, such as receptor-signal transduction, enzyme activity, gene expression, ion channel transport, and apoptosis. Besides oxidative stress, microRNAs and noncoding RNAs have emerged as epigenetic regulators that could affect pancreatic ß-cell dysfunction. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in T2D pathogenesis. Here, we summarized the molecular aspects of pancreatic ß-cell dysfunction. Moreover, we highlighted the roles of oxidative stress, microRNAs, and noncoding RNAs in pancreatic ß-cell dysfunction.

Alterations in lipid peroxidation, lipid profile, insulin sensitivity, and hepatic histopathological changes in diabetic rats following the treatment with Salvadora persica.

We examined the effects of various partitions of Salvadora persica extract on lipid profile (LP), lipid peroxidation, and insulin sensitivity (IS) of diabetic rats. The rats were divided into normal control, diabetic control (DC), standard, sham, and test groups. The test groups were treated with an oral dose of 200, 400, and 600 mg/kg of crude, aqueous, and ethyl acetate partition of S. persica extract. After 21 days of experiment, the fasting blood glucose (FBS), LPs, lipid peroxidation, IS, liver enzymes levels, liver histopathology, and body weight alteration were evaluated. A significant decrease in FBS and lipid profile (except HDL) were observed in rats treated with various dose of extract compared with the DC rats ( P < 0.05). Treating diabetic rats with various extracts of S. persica meaningfully decreased the level of malondialdehyde ( P < 0.05). Animals treated with various dose of aqueous extract showed better results ( P < 0.01). On the basis of used indirect indexes to determine IS, all partitions of extracts showed anti-insulin resistance effects in diabetic rats. On the basis of our statistical analyzing, treating diabetic rats with all of the three extracts of S. persica decreased the elevated levels of alanine phosphatase, aspartate aminotransferase, and alanine transferase. Also, pathological changes in the liver tissue were reduced following treatment with the S. persica. In conclusion, our results give evidence that the S. persica extract, especially aqueous partition, has a healing effect on diabetes and can be considered as an alternative therapy for this disease.

Novel Effects of Rosa damascena Extract on Patients with Neurocognitive Disorder and Depression: A Clinical Trial Study.

BACKGROUND: Dementia as a major cognitive neurological disorder is defined as impairment in one or more cognitive territories compared with the former level of performance. This disorder disrupts patient's independence, and the patient would need others aid in order of doing daily and complex activities. The aim of this study was to evaluate the efficacy of Rosa damascena extract in the improvement of cognitive function in patients with dementia. METHODS: This study is a randomized double-blind, placebo-controlled clinical trial on 40 patients older than 55 years with dementia referred to Specialized Elderly Patients Clinic in 2015-2016. Patients were divided randomly into two groups (control and intervention). The intervention group used donepezil and R. damascena capsules, and in control group, placebo capsule instead of R. damascena added on donepezil. Four test was filled three times at the study initiation, after month one and also after month three: Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination Revised (ACE-R) were used for cognition evaluation, for depression assessment, Geriatric Depression Scale was administered, and checklist of memory and behavioral disorders were filled. RESULTS: The results showed add-on donepezil and R. damascena versus placebo improved cognitive impairment based on MMSE with P = 0.002, ACE-R with total P = 0.001, depression (P = 0.012), behavioral disorders (P < 0.001), and daily activity (P < 0.001). CONCLUSIONS: The R. damascena extract affected cognitive impairment of dementia patients significantly and also have significant effects on improving depression and behavioral problems.

The effects of maternal diabetes and insulin treatment on neurogenesis in the developing hippocampus of male rats.

Diabetes in pregnancy is associated with an increasing risk of congenital malformations and central nervous system disorders (CNS) especially hippocampal neuronal circuitry disruption as a discreet region involved in neurogenesis phenomenon. This study aimed to investigate the effect of maternal diabetes and insulin treatment on the expression and distribution pattern of NeuN and DCX as two important markers of neurogenesis paradigm in developing rat hippocampus. All animals were randomly divided into three groups as follows: Control group, Diabetic (STZ-D), Diabetic treated with insulin (STZ-INS). Diabetes was induced in Wistar female rats by Sterptozotocin intraperitoneal injection (single does). Following confirmation of diabetes, animals were mated with non-diabetic males. Four to six units of protamine-Zinc insulin were delivered subcutaneously (SC) in insulin treated group. At the post-natal day 14 (P14), the brain of male offspring's were removed for further study. In fact Immunofluorescence staining and Real time - PCR assays are used for evaluation of neurogenesis phenomenon. Our results showed a significant higher level of hippocampal DCX expression and an increase in the mean number of DCX positive cells in the DG of diabetic group male offspring (P < 0.05). We also found an insignificant up-regulation in the expression of DCX and the mean number of positive cells in the insulin-treated diabetic group neonates as compared to control group (P > 0.05). Nevertheless the results of immunofluorescence staining for NeuN also indicated that the mean number of NeuN+ cells was significantly lower in dentate gyrus of diabetic group male offspring (P < 0.05). Besides, there were significant down- regulation in the hippocampal mRNA expression of NeuN in diabetic pups compare to control (P < 0.05 each). Our results revealed that diabetes during pregnancy has an adverse effect on the hippocampal neurogenesis in rat neonates. Furthermore, the control of glycemia by insulin is sufficient to prevent the alterations in expression of neurogenesis markers.

Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome.

Diabetes mellitus (DM) is known as one of important common endocrine disorders which could due to deregulation of a variety of cellular and molecular pathways. A large numbers studies indicated that various pathogenesis events including mutation, serin phosphorylation, and increasing/decreasing expression of many genes could contribute to initiation and progression of DM. Insulin resistance is one of important factors which could play critical roles in DM pathogenesis. It has been showed that insulin resistance via targeting a sequence of cellular and molecular pathways (eg, PI3 kinases, PPARγ co-activator-1, microRNAs, serine/threonine kinase Akt, and serin phosphorylation) could induce DM. Among of various factors involved in DM pathogenesis, microRNAs, and exosomes have been emerged as effective factors in initiation and progression of DM. A variety of studies indicated that deregulation of these molecules could change behavior of various types of cells and contribute to progression of DM. Resistin is other main factor which is known as signal molecule involved in insulin resistance. Multiple lines evidence indicated that resistin exerts its effects via affecting on glucose metabolism, inhibition of fatty acid uptake and metabolism with affecting on a variety of targets such as CD36, fatty acid transport protein 1, Acetyl-CoA carboxylase, and AMP-activated protein kinase. Here, we summarized various molecular aspects are associated with DM particularly the molecular pathways involved in insulin resistance and resistin in DM. Moreover, we highlighted exosomes and microRNAs as effective players in initiation and progression of DM.

Childhood Laryngeal Dystonia Following Bilateral Globus Pallidus Abnormality: A Case Study and Review of Literature.

INTRODUCTION: Dystonia is a disorder of movement caused by various etiologies. Laryngeal dystonia is caused by the spasm of laryngeal muscles. It is a disorder caused by vocal fold movement in which excessive adduction or abduction of the vocal folds occurs during speech. The pathophysiology of this type of dystonia is not fully known. Some researchers have suggested that basal ganglia structures and their connections with cortical areas have been involved in the pathogenesis of dystonia. CASE REPORT: In this paper a 7.5-year-old boy suffering from laryngeal dystonia with bilateral lesions in Globus Pallidus is presented. The patient also suffered from swallowing problems, monotone voice, vocal tremor, hypersensitivity of gag reflex, and stuttering. Drug treatment failed to cure him; therefore, he was referred to rehabilitation therapy. CONCLUSION: In conclusion, special attention should be brought upon laryngeal dystonia, especially in patients showing Extra-pyramidal symptoms and/or abnormalities of the basal ganglia. In children, laryngeal dystonia may be potentially fatal. Lack of consideration for this condition during rehabilitation therapy can lead to serious consequences for a child.

Childhood Neurogenic Stuttering Due to Bilateral Congenital Abnormality in Globus Pallidus: A Case Report and Review of the Literature.

Objective The basal ganglia are a group of structures that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex and thalamus. Some speech disorders such as stuttering can resulted from disturbances in the circuits between the basal ganglia and the language motor area of the cerebral cortex. Stuttering consists of blocks, repetitive, prolongation or cessation of speech. We present a 7.5 -year-old male child with bilateral basal ganglia lesion in globus pallidus with unclear reason. The most obvious speech disorders in patient was stuttering, but also problems in swallowing, monotone voice, vocal tremor, hypersensitivity of gag reflex and laryngeal dystonia were seen. He has failed to respond to drug treatment, so he went on rehabilitation therapy when his problem progressed. In this survey, we investigate the possible causes of this type of childhood neurogenic stuttering.

Effect of maternal diabetes on gliogensis in neonatal rat hippocampus.

BACKGROUND: Diabetes in pregnancy is a common metabolic disorder associated with various adverse outcomes in the offspring including impairments in attention and memory and alterations in social behavior. Glial cells are proven to have a critical role in normal function of neurons, and alteration in their activity could contribute to disturbance in the brain function. The aim of this study was to investigate the effect of maternal diabetes on hippocampal mRNA expression and distribution pattern of glial fibrillary acidic protein (GFAP) immunoreactive glial cells in the dentate gyrus (DG) of rat neonate at postnatal day 14 (P14). MATERIALS AND METHODS: Wistar female rats were randomly allocated in control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by injection of streptozotocin from 4 weeks before gestation until parturition. After delivery, the male offspring was euthanized at P14. RESULTS: Our results showed a significant higher level of hippocampal GFAP expression and an increase in the mean number of GFAP positive cells in the DG of diabetic group offspring (P < 0.05). We also found an insignificant up-regulation in the expression of GFAP and the mean number of positive cells in the insulin-treated diabetic group neonates as compared to control group (P > 0.05). CONCLUSION: The present study revealed that diabetes during pregnancy strongly increased the glial cells production in the developing rat hippocampus.

The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects.

BACKGROUND: Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. METHODS: The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. RESULTS: Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. CONCLUSIONS: Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals.

Neuroprotective effects of Rosa damascena extract on learning and memory in a rat model of amyloid-ß-induced Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is an age-related progressive neurodegenerative disease, which is characterized clinically by serious impairment in memory and cognition. Current medications only slow down the dementia progression and the present treatment one-drug one-target paradigm for anti-AD treatment appears to be clinically unsuccessful. Therefore, alternative therapeutic strategies are urgently needed. With respect to multifunctional and multitargeted characteristics of Rosa damascena via its effective flavonoids, we investigated the effects of R. damascena extract on behavioral functions in a rat model of amyloid-ß (A-ß)-induced Alzheimer's disease. MATERIALS AND METHODS: After preparation of the methanolic extract of the R. damascena, HPLC analysis and toxicity studies, median lethal dose (LD50) and dose levels were determined. For evaluation of baseline training behavioral performance, Morris water maze and passive avoidance tests were used. A-ß was injected bilaterally into CA1 area of the hippocampus. Twenty-one days after injection of A-ß, the first probe trial of the behavioral tests were used to confirm learning and memory impairment. To examine the potential effects of the extract on behavioral tasks, the second probe trials were performed after one month administration of R. damasena extract. RESULTS: Results showed that the R. damascena extract significantly improved the spatial and long-term memories in the extract- treated groups in a dose-dependent manner, as in the middle and high doses it had significant effect. CONCLUSION: According to these results, we concluded that R. damascena can reverse behavioral deficits caused by A-ß, and may provide a new potential option for prevention and treatment of the cognitive dysfunction in Alzheimer's disease.

Study of carbon nano-tubes effects on the chondrogenesis of human adipose derived stem cells in alginate scaffold.

BACKGROUND: Osteoarthritis is one of the most common diseases in middle-aged populations in the World and could become the fourth principal cause of disability by the year 2020. One of the critical properties for cartilage tissue engineering (TE) is the ability of scaffolds to closely mimic the extracellular matrix and bond to the host tissue. Therefore, TE has been presented as a technique to introduce the best combination of cells and biomaterial scaffold and to stimulate growth factors to produce a cartilage tissue resembling natural articular cartilage. The aim of study is to improve differentiation of adipose derived stem cells (ADSCs) into chondrocytes in order to provide a safe and modern treatment for patients suffering from cartilage damages. METHODS: After functionalization, dispersions and sterilizing carbon nano-tubes (CNTs), a new type of nanocomposite gel was prepared from water-soluble CNTs and alginate. ADSCs seeded in 1.5% alginate scaffold and cultured in chondrogenic media with and without transforming growth factor-ß1 (TGF-ß1) for 7 and 14 days. The genes expression of sex determining region Y-box 9 (SOX9), types II and X collagens was assessed by real-time polymerase chain reaction and the amount of aggrecan (AGC) and type I collagen was measured by ELISA. RESULTS: Our findings showed that the expression of essential cartilage markers, SOX9, type II collagen and AGC, in differentiated ADSCs at the concentration of 1 µg/ml CNTs in the presence of TGF-ß1 were significantly increased in comparison with the control group (P < 0.001). Meanwhile, type X collagen expression and also type I collagen production were significantly decreased (P < 0.001). CONCLUSIONS: The results showed that utilized three-dimensional scaffold had a brilliant effect in promoting gene expression of chondrogenesis.

Plastination of decalcified bone by a new resin technique.

BACKGROUND: The scope of this study was to preserve whole detailed structure of dissected and decalcified bones, taken from used cadavers, by a new plastination technique. MATERIALS AND METHODS: Specimens we used in this study were sheep femurs and human bones including pelvis, femur, tibia, and fibula. Bones, at first, fixed with 5% formalin and were decalcified with 5% nitric acid, and then were fixed again and washed under the tap water. The resulted flexible bones were dehydrated in -25°C acetone and degreased them in +25°C acetone. Then, the experimental and control specimen were placed in the vacuum chamber for forced impregnation with our new flexible unsaturated polyester resin (UP89 method) and silicon resin (S10 method), respectively. Finally, the strength and flexibility of plastinated decalcified specimens were investigated by tensometer, and the weight diversity was measured by digital balance. RESULTS: Plastinated bones prepared by this technique were found to be dried, non-fragile, durable, odorless, non-greasy, and demonstrating all detailed structures of the bones. Tensile and weight tests results indicated that plastinated decalcified femurs have owned higher flexibility and strength but lesser weight than plastinated undecalcified femurs. The characteristics of both experimental and control groups of plastinated decalcified specimens were found to have no significant difference. CONCLUSIONS: Our synthesized resin found to be much more economical than conventional plastination method. In more details, properties of these new products were the same as, S10 method, from points of strength, flexibility and weight, but, since the money cost for producing them was about one fifth that of S10 method.

Novel effects of Rosa damascena extract on memory and neurogenesis in a rat model of Alzheimer's disease.

The number of older people who are suffering from memory impairment is increasing among populations throughout the world. Alzheimer's disease (AD) affects about 5% of people over 65 years old. The hippocampus, a brain area critical for learning and memory, is especially vulnerable to damage in the early stages of AD. Emerging evidence suggests that loss of neurons and synapses are correlated with dementia in this devastating disease. Therefore, neurogenesis and synaptogenesis in adulthood could serve as a preventive as well as a therapeutic target for AD. This study investigated the effect of Rosa damascena extract on neurogenesis and synaptogenesis in an animal model of AD. Molecular, cellular, and behavioral experiments revealed that this treatment could induce neurogenesis and synaptic plasticity and improve memory in AD. Our study suggests that R. damascena is a promising treatment for mild memory impairments and AD.

Comparison between Chondrogenic Markers of Differentiated Chondrocytes from Adipose Derived Stem Cells and Articular Chondrocytes In Vitro.

OBJECTIVE(S): Osteoarthritis is one of the most common diseases in middle-aged population in the world. Cartilage tissue engineering (TE) has been presented as an effort to introduce the best combination of cells, biomaterial scaffolds and stimulating growth factors to produce a cartilage tissue similar to the natural articular cartilage. In this study, the chondrogenic potential of adipose derived stem cells (ADSCs) was compared with natural articular chondrocytes cultured in alginate scaffold. MATERIALS AND METHODS: Human ADSCs were obtained from subcutaneous adipose tissue and human articular chondrocytes from non-weight bearing areas of knee joints. Cells were seeded in 1.5% alginate and cultured in chondrogenic media for three weeks with and without TGFß3. The genes expression of types II and X collagens was assessed by Real Time PCR and the amount of aggrecan (AGC) and type I collagen measured by ELISA and the content of glycosaminoglycan evaluated by GAG assay. RESULTS: Our findings showed that type II collagen, GAG and AGC were expressed, in differentiated ADSCs. Meanwhile, they produced a lesser amount of types II and X collagens but more AGC, GAG and type I collagen in comparison with natural chondrocytes (NCs). CONCLUSION: Further attempt should be carried out to optimize achieving type II collagen in DCs, as much as, natural articular chondrocytes and decline of the production of type I collagen in order to provide efficient hyaline cartilage after chondrogenic induction, prior to the usage of harvested tissues in clinical trials.

Comparative analysis of the frequency and distribution of stem and progenitor cells in the adult mouse brain.

The neurosphere assay can detect and expand neural stem cells (NSCs) and progenitor cells, but it cannot discriminate between these two populations. Given two assays have purported to overcome this shortfall, we performed a comparative analysis of the distribution and frequency of NSCs and progenitor cells detected in 400 mum coronal segments along the ventricular neuraxis of the adult mouse brain using the neurosphere assay, the neural colony forming cell assay (N-CFCA), and label-retaining cell (LRC) approach. We observed a large variation in the number of progenitor/stem cells detected in serial sections along the neuraxis, with the number of neurosphere-forming cells detected in individual 400 mum sections varying from a minimum of eight to a maximum of 891 depending upon the rostral-caudal coordinate assayed. Moreover, the greatest variability occurred in the rostral portion of the lateral ventricles, thereby explaining the large variation in neurosphere frequency previously reported. Whereas the overall number of neurospheres (3730 +/- 276) or colonies (4275 +/- 124) we detected along the neuraxis did not differ significantly, LRC numbers were significantly reduced (1186 +/- 188, 7 month chase) in comparison to both total colonies and neurospheres. Moreover, approximately two orders of magnitude fewer NSC-derived colonies (50 +/- 10) were detected using the N-CFCA as compared to LRCs. Given only 5% of the LRCs are cycling (BrdU+/Ki-67+) or competent to divide (BrdU+/Mcm-2+), and proliferate upon transfer to culture, it is unclear whether this technique selectively detects endogenous NSCs. Overall, caution should be taken with the interpretation and employment of all these techniques.