Betanin improves motor function and alleviates experimental Parkinsonism via downregulation of TLR4/MyD88/NF-κB pathway: Molecular docking and biological investigations.

Parkinson's disease (PD) is a progressive neuroinflammatory and degenerative disease. In this study, we investigated the neuroprotective action of betanin in the rotenone-induced Parkinson-like mice model. Twenty-eight adult male Swiss albino mice were divided into four groups: Vehicle, Rotenone, Rotenone + Betanin 50 mg/kg, and Rotenone + Betanin 100 mg/kg. Parkinsonism was induced by subcutaneous injection of 9 doses of rotenone (1 mg/kg/48 h) plus betanin at 50 and 100 mg/kg/48 h in rotenone + betanin groups for twenty days. Motor dysfunction was assessed after the end of the therapeutic period using the pole, rotarod, open-field, grid, and cylinder tests. Malondialdehyde, reduced glutathione (GSH), Toll-like receptor 4 (TLR4), myeloid differentiation primary response-88 (MyD88), nuclear factor kappa- B (NF-κB), neuronal degeneration in the striatum were evaluated. In addition, we assessed the immunohistochemical densities of tyrosine hydroxylase (TH) in Str and in substantia nigra compacta (SNpc). Our results showed that rotenone remarkably decreased (results of tests), increased decreased TH density with a significant increase in MDA, TLR4, MyD88, NF-κB, and a decrease in GSH (p < 0.05). Treatment with betanin significantly results of tests), increased TH density. Furthermore, betanin significantly downregulated malondialdehyde and improved GSH. Additionally, the expression of TLR4, MyD88, and NF-κB was significantly alleviated. Betanin's powerful antioxidative and anti-inflammatory properties can be related to its neuroprotective potential as well as its ability to delay or prevent neurodegeneration in PD.

Topiramate affords neuroprotection in diabetic neuropathy model via downregulating spinal GFAP/inflammatory burden and improving neurofilament production.

The current study aimed to test the neuroprotective action of topiramate in mouse peripheral diabetic neuropathy (DN) and explored some mechanisms underlying this action. Mice were assigned as vehicle group, DN group, DN + topiramate 10-mg/kg and DN + topiramate 30-mg/kg. Mice were tested for allodynia and hyperalgesia and then spinal cord and sciatic nerves specimens were examined microscopically and neurofilament heavy chain (NEFH) immunostaining was performed. Results indicated that DN mice had lower the hotplate latency time (0.46-fold of latency to licking) and lower von-Frey test pain threshold (0.6-fold of filament size) while treatment with topiramate increased these values significantly. Sciatic nerves from DN control mice showed axonal degeneration while spinal cords showed elevated GFAP (5.6-fold) and inflammatory cytokines (∼3- to 4-fold) but lower plasticity as indicated by GAP-43 (0.25-fold). Topiramate produced neuroprotection and suppressed spinal cord GFAP/inflammation but enhanced GAP-43. This study reinforces topiramate as neuroprotection and explained some mechanisms included in alleviating neuropathy.

Biobanking for Genomic and Personalized Health Research: Participant Perceptions and Preferences.

Introduction: Biospecimens and associated data are invaluable tools in Genomics and Personalized Health (GAPH) research and can aid in the discovery of disease etiology and the development of therapeutics. Objective: To examine the experiences of patients invited to a particular GAPH study, Spectrometry in TIA Rapid Assessment (SpecTRA), and to explore broader biospecimen and data sharing preferences among a larger group of patients who had opted into a Permission to Contact for research program. Methods: An electronic survey was e-mailed to 515 participants. The survey was completed by 38% of participants, an unspecified number of whom were also SpecTRA participants. Results: Of those respondents who recalled participating in SpecTRA, 96% strongly agreed, agreed, or were neutral when asked if they received enough information to make an informed decision. Seventy-two percent agreed and 20% were neutral when asked if their study questions were addressed. Ninety-six percent of all respondents felt that SpecTRA's aim to develop a proteomic test for stroke was a worthwhile investment for health care, 98% said they were willing to provide a sample and/or information to facilitate the project's goals, and 96% to health research in general. Fifty-three percent of all participants suggested they would be comfortable sharing health information collected during SpecTRA with for-profit organizations, 87% with nonprofit organizations, and 38% said it matters to them where in the world their sample/information would be sent. Conclusions: Our results suggest that while there is room for improvement in providing adequate information to enable participants' understanding of the purpose of GAPH studies such as SpecTRA, patients are supportive of GAPH in general. Results also suggest that willingness to participate would likely be impacted by factors such as the study's commercial and national affiliations. This study indicates that further work is required to guide improvements on how the GAPH research community describes studies to potential participants, and to enable participation options that incorporate variable participant preferences.

The stem cell mobilizer StemEnhance reduces fibrosis and enhances proliferation in Thioacetamide induced-liver cirrhosis in the adult male albino rat

StemEnhance (SE) is a haematopoietic stem cell mobilizer deduced from natural planet products. Preclinical studies showed that SE advances cardiovascular muscle recovery and relieves the symptoms and signs of diabetes. However, the efficacy of SE in improving liver cirrhosis has not been investigated. This study was done to assess the helpful effects of SE in a Thioacetamide (TAA)-induced rodent model of liver cirrhosis. Thirty adult male albino rats, 16¡­18 weeks old and 210¡­240 gm weight, were used in this study. They were divided equally into three groups: 1. normal control group: received saline intraperitoneal injection (i.p.) twice weekly for 12 weeks and served as a control; 2. cirrhosis group: liver cirrhosis was induced by (i.p.) injection of TAA (200 mg/kg body weight) twice a week for 8 weeks and left untreated; 3. cirrhosis/SE group: liver cirrhosis was induced the same way and then treated daily orally with SE at a dose of 300 mg/kg body weight dissolved in distilled water for 4 weeks. All the studied groups were sacrificed 12 weeks after beginning experiments. SE was found to alleviate hepatic fibrosis, improve histopathological changes and enhance hepatocyte proliferation. In addition, TNF-¥á mRNA expression was down-regulated in TAA-induced cirrhotic livers after SE administration. We conclude that SE has a beneficial role in relieving liver fibrosis and improving liver function in the rat model of liver cirrhosis

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Effects of Ginko biloba leaf extract on the neurogenesis of the hippocampal dentate gyrus in the elderly mice.

Aging is associated with reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. We assessed the effect of Ginkgo biloba (Gb) on hippocampal neurogenesis in elderly male mice using immunohistochemistry. We used anti-caspase-3 as a marker of apoptosis, anti-GFAP as a marker of neural stem cells, anti-Ki-67 as a specific marker for cellular proliferation and anti-doublecortin (DCX) to detect newly born neurons in the hippocampal dentate gyrus (DG) of aged male mice. The 24-month-old male mice were divided into two groups: a control group treated with distilled water and a group fed with Gb at a dose of 100 mg/kg once daily for 28 days. A sharp decrease in apoptotic cells in Gb-treated compared to nontreated mice was observed by anti-csapase-3 immunostaining. A large number of GFAP+ve cells was found in the subgranular zone of the DG of Gb-treated mice, suggesting an increase in the pool of neural stem cells by Gb treatment. There was also an increase in Ki-67 immunoreactive cells, indicating increased cell proliferation in the DG in the Gb-treated compared to nontreated group. A significant increase in newborn DCX+ve neurons with well-developed tertiary dendrites was also found in the Gb-treated compared to nontreated group. Using Western blot analysis, the expression of DCX protein in the Gb group was also significantly increased compared to the control. The results support a beneficial role of Gb on hippocampal neurogenesis in the context of brain aging.

Glycosyltransferase encoding gene EXTL3 is differentially expressed in the developing and adult mouse cerebral cortex.

Exostosin tumor-like 3 (EXTL3) is a glycosyltransferase involved in heparan sulfate (HS) biosynthesis. HS proteoglycans are critically involved in different steps during brain development. The present in situ hybridization in mice revealed wide EXTL3 expression at different grades in the central and peripheral nervous system components including the neural retina and neural crest-derived structures at embryonic days (E) 11.5, E12.5, E14.5, and E16.5. In the neopallial cortex, an intense EXTL3 expression was observed in the neuroepithelial cells lining the ventricular zone at E11.5 and E12.5. The signal decreased at E14.5 and was further downregulated at E16.5 in the ventricular zone. The pioneer neurons of the preplate at E12.5 differentially expressed the gene. Heavily stained among weakly or negatively stained neurons were observed. At E14.5, the cortical plate cells were moderately and homogeneously stained. In contrast, at E16.5, an upregulated and differential expression pattern was detected. The labeling pattern at E16.5 subdivided the cortical plate cells into a large number of heavily, a moderate number of less intensely, and some negatively stained cell populations. Interestingly, the distinct expression pattern displayed by the three main cell types of the adult cerebral cortex was similar to that of the late corticogenesis stage (E16.5). In the adult, the strongest expression was observed in the pyramidal neurons. The granule-type neurons showed less intense staining while the glia cells were devoid of signals. Our data revealed that EXTL3 expression is developmentally regulated in the mouse nervous system and suggested that it differentially contributes to brain development and corticogenesis.

Alpha1,4-N-acetylglucosaminyltransferase encoding gene EXTL3 expression pattern in mouse adult and developing tissues with special attention to the pancreas.

EXTL3 encodes alpha1,4-N-acetylglucosaminyltransferases I and II enzymes, which are involved in chain initiation and elongation of heparan sulfate (HS) biosynthesis. HS proteoglycans are critically involved in a variety of biological phenomena at various levels of complexity in adult and embryonic lives. Dedicated functions of HS proteoglycans are due to variable HS chains that interact with different cellular proteins, and can be regulated by their synthesizing enzymes. EXTL3 protein is also a putative receptor for Reg protein, a growth signal mediator for the beta-cells of the pancreas. The present Northern blot analysis revealed two EXTL3 transcripts (6.2 and 3.4 kb), which were differentially expressed in different mouse adult tissues. The strongest expression was in the adult brain and pancreas. In the adult pancreas, a comparable intensity of both signals was detected. In the embryonic pancreas, the longer transcript was predominant, and showed a biphasic expression pattern with a peak at E11.5, whereas the shorter one showed a steady level of expression throughout the whole period of pancreatic development. By in situ hybridization, the acini of adults and embryos were strong positive for EXTL3 mRNA. Mature islets of Langerhans gave a weak signal, whereas the developing islets showed moderately positive reaction albeit less intense than the acini. In situ hybridization revealed a wide and differential expression pattern of EXTL3 mRNA in embryonic tissues. At the early stages, intense reaction was found in the developing neurons of the brain and spinal cord and in the epithelia of the developing GIT, pancreas, liver and kidney of embryos. Our data suggested that EXTL3 expression is developmentally regulated, and may contribute to the regulated production of HS in different adult and embryonic tissues.