Potential role of exosome in post-stroke reorganization and/or neurodegeneration

Currently, stroke is a common and devastating condition, which is sometimes associated with permanent cerebral damages. Although in early time after stroke, the related treatments are mainly focused on the restoration of cerebral blood flow (CBF), at the same time, some changes are commencing that continue for a long time and need to be specially noticed. Previous studies have proposed several molecular mechanisms in these post-stroke events. Exosomes are a type of vesicle, which are formed and secreted by most cells as a mean to transfer cellular constituents such as proteins, DNA and/or RNA to distant cells. Therefore, they are considered as a novel mechanism of cellular communication. Herein, we reviewed the current knowledge on cascades, which are activated after stroke and consequently lead to the reorganization and/or continuance of tissue damage and development of other disorders such as Neurodegenerative diseases (ND). Thereafter, we summarized the latest proofs about the possible participation of exosomes in transferring some components such as proteins and micro-RNAs (miRs), from the affected areas to other parts of the brain and eventually cause the above-mentioned post-stroke events

chronic sleep deprevation and ventricular arrhythmias: effect of symphatic nervous system

Introduction: We assessed the effect of chronic sleep deprivation on incidence of ischemia/reperfusion-induced ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) and the role of the sympathetic nervous system in this respect. Material and methods: Rats were randomly divided into four groups; 1) ischemia/reperfusion group (IR): 30 minutes ischemia followed by 60 minutes reperfusion was induced, 2) control group (CON): rats has been placed in large multiple platforms for 72h prior to ischemia and reperfusion, 3) Chronic sleep deprivation group( SD): 72h sleep deprivation was induced by using small  multiple platform prior to ischemia and reperfusion, 4) Sympathectomy group (SYM): chemical sympathectomy was done 24h before to chronic sleep deprivation and then underwent ischemia and reperfusion. The heart isolated and perfused by langendorff apparatus. After thoracotomy and aorta cannulation, the hearts perfused in the langendorff apparatus using krebs-Henseleit buffer. Hearts were allowed to recovery for 15 min. After recovery period, 15 minutes was considered as baseline prior to 30 minutes ischemia followed by 60 minutes reperfusion.Tow thin stainless stell electrodes fixed on the ventricular apex and right atrium for recording the lead II of electrocardiogram (ECG).Results: There were no significant differences between heart rates between groups, and ventricular tachycardia significantly increased in chronic sleep deprivation group As compared with IR group in ischemia period. Sympathectomy significantly reduced ventricular tachycardia incidence when compared with SD. There is no difference in incidence of ventricular tachycardia between control group and IR group. The incidence of ventricular fibrillation during early reperfusion was significantly augmented (P<0.05) in sleep deprivation group as compared with IR group and Sympathectomy significantly could reverse ventricular fibrillation incidence to IR group level as compared with SD group (P<0.05).Conclusion: Induction of 72 h sleep deprivation prior to ischemia and reperfusion increased the probability of ventricular tachycardia and ventricular fibrillation occurrence during ischemia and reperfusion and chemical sympathectomy could eliminate this effect

Animal protein intake is directly associated with serum level of pentraxin 3 in hemodialysis patients

Inflammation plays an important role in Cardiovascular disease (CVD) pathogenesis as the main cause of mortality in hemodialysis (HD) patients. Despite the relevance of nutrition and dietary intakes for inflammation status, the role of dietary protein sources remains unclear. The aim of this study was to evaluate the association between the different types of dietary protein and pentraxin 3 (PTX3) levels in HD patients. In this multi-center cross-sectional study, 227 adult patients undergoing HD for a minimum 90 days were recruited. A validated 168-item food frequency questionnaire was used to assess dietary intakes. Also, 5 ml blood samples were collected from each patient to measure the concentration of serum PTX3. Overall, 227 patients, including 63 women and 164 men, with a mean age of 58 years, participated in this study. There was a greater intake of animal protein per kilogram dry weight among patients with higher levels of PTX3 (0.46 vs. 0.54 g/kg; P = 0.035). In contrast, consumption of total protein and plant protein per kilogram dry weight was not different across PTX3 levels. Moreover, the chance of increased PTX3 concentration was directly associated with a one-unit increase in animal protein intake per kilogram dry weight, after adjusting for confounders. We did not observe any association between one-unit increases in plant protein intake per kilogram dry weight and chance of increased PTX3. In conclusion, animal protein intake was directly associated with circulating PTX3

An Investigation into the Effects of Chemical, Pharmaceutical, and Herbal Compounds on Neuroglobin: A Literature Review

Neuroglobin (Ngb) is an oxygen-binding globin protein that is mainly expressed in the neurons of the central and peripheral nervous system. However, moderate levels of Ngb have also been detected in non-neural tissues. Ngb and Ngb modulating factors have been increasingly studied over the last decade due to their neuroprotective role in neurological disorders and hypoxia. Studies have shown that a number of chemicals, pharmaceuticals, and herbal compounds can modulate the expression of Ngb at different dose levels, indicating a protective role against neurodegenerative diseases. Iron chelators, hormones, antidiabetic drugs, anticoagulants, antidepressants, plant derivatives and short-chain fatty acids are among these compounds. Therefore, this study aimed to review the literature focused on the possible effects and mechanisms of chemical, pharmaceutical, and herbal compounds on Ngbs

Behavioral and Molecular Effects of Thapsigargin-Induced Brain ER- Stress: Encompassing Inflammation, MAPK, and Insulin Signaling Pathway

Accumulation of misfolded proteins, known as endoplasmic reticulum (ER) stress, is known to participate in Alzheimer’s disease (AD). AD is also correlated with impaired central insulin signaling. However, few studies have probed the relationship between memory, central ER stress, inflammation, hippocampal mitogen-activated protein kinase (MAPK) activity and insulin resistance. The present study aimed to investigate the causative role and underlying mechanisms of brain ER stress in memory impairment and develop a reliable animal model for ER-mediated memory loss. Thapsigargin (TG), a known ER stress activator, was centrally administered. The cognitive function of animals was evaluated by the Morris Water Maze (MWM). To verify the induction of central ER stress, we investigated the mRNA expression of UPR markers in the hippocampus. In addition, the activation of ER stress markers, including Bip, CHOP, and some related apoptosis and pro-inflammatory proteins, such as caspase-3, Bax, Bcl-2, TNF-α, MAPK, and insulin signaling markers, were assessed by Western-blots. The results demonstrated that TG impairs spatial cognition and hippocampal insulin signaling. Meanwhile, molecular results showed a concurrent increment of hippocampal UPR markers, apoptosis, P38 activity, and TNF-α. This study introduced TG-induced ER stress as a pharmacological model for memory impairment in rats and revealed some underlying mechanisms

Trimester-Specific Reference Ranges for Thyroid Hormones in Iranian Pregnant Women

Background. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester-specific reference intervals for a specific population. There is no normative data documented for thyroid hormones on healthy pregnant women in Iran. The present survey was conducted to determine trimester-specific reference ranges for serum TSH, thyroxine (TT4), and triiodothyronine (TT3). Methods. The serum of 215 cases was analyzed for measurement of thyroid function tests by immunoassay method of which 152 iodine-sufficient pregnant women without thyroid autoantibodies and history of thyroid disorder or goiter were selected for final analysis. Reference intervals were defined as 5th and 95th percentiles. Results. Reference intervals in the first, second, and third trimesters were as follows: TSH (0.2-3.9, 0.5-4.1, and 0.6-4.1 mIU/l), .6 ng/dl), respectively. No correlation was found between TSH and TT4 or TT3. Significant correlation was found between TT4 and TT3 in all trimesters ( = 0.35, < 0.001). Conclusion. The reference intervals of thyroid function tests in pregnant women differ among trimesters. Applying trimester-specific reference ranges of thyroid hormones is warranted in order to avoid misclassification of thyroid dysfunction during pregnancy

Association between sun exposure, Vitamin D intake, serum Vitamin D level, and immunoglobulin G level in patients with neuromyelitis optica spectrum disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory disorder in which immunoglobulin G (IgG) autoantibodies possibly play a pathogenic role against the aquaporin-4 water channel protein. Vitamin D may modulate B-cell function and decrease the IgG synthesis and may play a role in NMOSD as a crucial factor. The aim of this study was to investigate the relation between Vitamin D intakes from food, Vitamin D intake from sunlight exposure, blood Vitamin D levels, and IgG-neuromyelitis optica (NMO) level in serum of patients with NMOSD and NMO. Method: In this cross-sectional study, food Frequency Questionnaires (FFQ) and Sun Exposure Questionnaire (SEQ) were completed to evaluate of vitamin D intakes from food and sun light exposure. Moreover, serum levels of 25(OH) vitamin D3 and IgG-NMO were assessed in patients with NMOSD and NMO. Results: We assessed IgG-NMO levels in 29 patients with NMOSD that nine patients (n = 31%) were positive and for the rest it was negative. Sunlight exposure scale (P = 0.01) and 25(OH) D3 (P = 0.04) in IgG-NMO-negative patients were significantly more than patients with positive IgG-NMO. Age, gender, and latitude were not confounder variables. A positive significant correlation was observed between the sun exposure scale and serum levels of 25(OH) D3 in all participants (r = 0.747, P ≤ 0.001). Conclusions: Physiological variation in Vitamin D may apply a significant effect on IgG-NMO synthesis in patients with NMO. Vitamin D may have significant role in pathogenesis of NMOSD and NMO

Endoplasmic reticulum stress as an underlying factor in leading causes of blindness and potential therapeutic effects of 4-phenylbutyric acid: from bench to bedside

Mounting evidence has emerged showing that endoplasmic reticulum (ER) stress participates in triggering cell injuries in ocular tissues, manifested as disorders such as cataracts, age-related macular degeneration, glaucoma, and diabetic retinopathy. ER stress is a condition in which the ER is perturbed by the accumulation of unfolded and misfolded proteins. In a dynamic signaling cascade, the unfolded protein response (UPR) is triggered by three ER-transmembrane stress sensors to restore homeostasis and cell survival, however, if it fails, the cell will undergo a sustained ER stress condition which deteriorates cell function and promote cell death. Sustained ER stress is shown to contribute in a wide range of diseases including ophthalmologic disorders. Targeting ER stress by inhibitor agents might have promising therapeutic implications in treating eye disorders. The current review summarizes the results of the latest studies in support of the potential therapeutic utility of 4-phenylbutyric acid (4-PBA), an FDA approved ER stress inhibitor, in disorders leading to permanent vision loss. The therapeutic potential of 4-PBA in ophthalmic diseases is strongly supported by many experimental studies. Safety and efficacy studies of intravitreal injection of 4-PBA and other ER stress by inhibitors, are lacking.</p

Therapeutic effects of saffron and its components on neurodegenerative diseases

Due to an increase in the number of older people in recent years, neurodegenerative diseases as the most important age-related neurological disorders are considered as a great threat to human health. The treatment strategies for these disorders are symptomatic and there is no known definitive treatment; however, recently, several studies have investigated the effectiveness of some herbs and their components in limiting the progression and treatment of neurodegenerative disorders. In this study, we searched Medline (via PubMed), Scopus, Science Direct, and Google Scholar databases. The keywords used in the search were: saffron [title/abstract] or (saffron compound [title/abstract]) and (neurological disorders [title/abstract]), publication date range (2010–2023), and language (English). After applying inclusion and exclusion criteria, 30 articles remained. Of the 30 articles included in the study, six studies on the treatment of neurodegenerative disorders by saffron and its components were in the clinical trial phase, and 24 studies were in the preclinical phase. Saffron and its compounds can play an important role in inhibiting neuroinflammation and excitotoxic pathways, modulating autophagy and apoptosis, attenuating oxidative damage, and activating defensive antioxidant enzymes, resulting in neuroprotection against neurodegenerative diseases. Therefore, this study aimed to review the studies on the effects of saffron and its compounds on the treatment of neurodegenerative diseases