Distinct phosphorylation profiles of tau in brains of patients with different tauopathies.

Tauopathies are neurodegenerative diseases that are characterized by pathological accumulation of tau protein. Tau is hyperphosphorylated in the brain of tauopathy patients, and this phosphorylation is proposed to play a role in disease development. However, it has been unclear whether phosphorylation is different among different tauopathies. Here, we investigated the phosphorylation states of tau in several tauopathies, including corticobasal degeneration, Pick's disease, progressive supranuclear palsy (PSP), argyrophilic grain dementia (AGD) and Alzheimer's disease (AD). Analysis of tau phosphorylation profiles using Phos-tag SDS-PAGE revealed distinct phosphorylation of tau in different tauopathies, whereas similar phosphorylation patterns were found within the same tauopathy. For PSP, we found 2 distinct phosphorylation patterns suggesting that PSP may consist of 2 different related diseases. Immunoblotting with anti-phospho-specific antibodies showed different site-specific phosphorylation in the temporal lobes of patients with different tauopathies. AD brains showed increased phosphorylation at Ser202, Thr231 and Ser235, Pick's disease brains showed increased phospho-Ser202, and AGD brains showed increased phospho-Ser396. The cis conformation of the peptide bond between phospho-Thr231 and Pro232 (cis ptau) was increased in AD and AGD. These results indicate that while tau is differently phosphorylated in tauopathies, a similar pathological mechanism may occur in AGD and AD patients. The present data provide useful information regarding tau pathology and diagnosis of tauopathies.

Lipid profile dysregulation in opium users based on Fasa PERSIAN cohort study results.

One of the main health problems in many societies is the increased opium abuse, which was found to be correlated with many problems like cardiovascular disease. This study aimed to evaluate the correlation of opium use with blood lipoproteins as the risk factor of CVD. This was a cross-sectional study conducted on participants of the first phase of the PERSIAN Cohort study who were aged between 35 and 70 years old. Demographic characteristics; history of smoking, alcohol, and opium consumption; medical history; and medications were asked and the related checklists were filled out. The levels of physical activity and fat intake were also registered. As well, lipoprotein profiles were investigated by blood sampling. The linear and logistic regression was used to analyze the relationship between opium and lipid profile and the statistical significant level was considered as < 0.05. Among 9300 participants with a mean age of 48.06 ± 9.44 years old, 49.6% of them were men. About 24.1% of the participants used opium. In the linear regression models, unlike TG (ß = 2.2, p = 0.36), total cholesterol (ß = - 2.5, p = 0.02), LDL (ß = - 2.0, p = 0.04), and HDL (ß = - 1.0, p = 0.04) were significantly lower in people who used opium compared to the others. In the logistic regression models, abnormal level of LDL (OR = 0.78, p = 0.003) and total cholesterol (OR = 0.82, p = 0.008) were less in people who used opium compared to the others. This study showed that there is a correlation between opium usage and lower levels of total cholesterol and LDL; however, the lower level of HDL in normal range was seen in opium users. Considering the current evidences, most of them showed the increased risks of ischemic heart disease, heart attack, hypertension, cerebrovascular disease, and cancer in opium users. Therefore, Healthcare providers and patients should be noticed about the deleterious effects of opium consumption on various vascular events. In addition, it is necessary for managers and policy makers of the health care system to take the necessary measures to raise the level of awareness and health literacy of the general public about the high-risk side effects of opium use and to take necessary and effective strategies to prevent and reduce its use.

The Therapeutic Effect of Shark Liver Oil in a Rat Model of Acetic Acid-Induced Ulcerative Colitis.

Ulcerative colitis (UC) is one of the most well-known types of inflammatory bowel disease that manifests as recurrent inflammation of rectum and colon. The goal of this study is to evaluate the protective effects of shark liver oil (SLO) on acetic acid-induced ulcerative colitis in rats. Eighty induced UC rats were randomly divided into ten equal groups and received the following treatments for seven days: 1 ml of normal saline rectally, 1 ml of gel base (carboxymethyl cellulose) rectally, 10 mg/kg of Asacol rectally, 10 mg/kg of mesalazine orally, 5% gel form of SLO rectally, 10% gel form of SLO rectally, 200 mg of SLO orally, and 400 mg of SLO orally. We examined the oxidative stress indices, histopathological features, and body weight changes, as well as the function of the liver and kidneys at the end of treatment. Administration of 10% rectal and 400 mg oral SLO resulted in a significant weight gain. Also, glutathione peroxidase activity was significantly higher in 5% and 10% SLO-treated groups, and elevated superoxide dismutase activity in rats that received 5% SLO was observed compared to negative control and Asacol groups. While no significant changes were observed in most of the kidney and liver function markers, higher levels of aspartate aminotransferase were detected in the group that received 400 mg SLO orally compared to negative control and Asacol groups. Many histopathological signs of improvement were observed in mesalazine, Asacol, and SLO groups. There were no significant changes detected in the mean rank among different groups. Our data indicate that SLO supplementation could improve the amelioration of acetic acid-induced UC in rats due to its antioxidant effects.

Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle.

Abnormal deposition of misfolded proteins is a neuropathological characteristic shared by many neurodegenerative disorders including Alzheimer's disease (AD). Generation of excessive amounts of aggregated proteins and impairment of degradation systems for misfolded proteins such as autophagy can lead to accumulation of proteins in diseased neurons. Molecules that contribute to both these effects are emerging as critical players in disease pathogenesis. Furthermore, impairment of autophagy under disease conditions can be both a cause and a consequence of abnormal protein accumulation. Specifically, disease-causing proteins can impair autophagy, which further enhances the accumulation of abnormal proteins. In this short review, we focus on the relationship between the microtubule-associated protein tau and autophagy to highlight a feed-forward mechanism in disease pathogenesis.

Effects of Cupressus sempervirens extract on the healing of acetic acid-induced ulcerative colitis in rat / Efeitos do extrato de Cupressus sempervirens na cicatrização de colite ulcerativa induzida por ácido acético em ratos

ABSTRACT Ulcerative colitis is a chronic inflammatory condition of the colon with an unknown etiology. In this study, we aimed to evaluate the therapeutic effects of Cupressus sempervirens extract on the healing of acetic acid-induced ulcerative colitis in rat. Fifty-five male rats divided into five equal treatment groups were used for this study and received the following treatments: Group 1, 250 mg/kg asacol; Group 2, 1 ml gel base (carboxymethyl cellulose); Group 3, 0.5% gel form of C. sempervirens extract; Group 4, 1% gel form of C. sempervirens extract, and; Group 5, considered as negative control and received 1 ml of normal saline. Body weight changes, histopathological and antioxidant changes in the colon tissue were evaluated. Significant weight gain was observed in rats that received 1% gel extract of C. sempervirens. Significant superoxide dismutase activity was also detected in 0.5 and 1% gel extract groups compared to C. sempervirens extract, Asacol and in 1% gel extract groups compared to the gel base group. Furthermore, both gel extract groups had significant lower total antioxidant capacity compared to Asacol group. Several histopathological lesions including inflammation, ulceration, crypt disarray, and goblet cell depletion were detected in the different groups, however, the mean rank of pathological changes showed no significant difference among the five groups. In summary, our results showed that hydroalcoholic extracts of C. sempervirens leaves produces healing effects in acetic acid induced ulcerative colitis.

RESUMO A colite ulcerativa é uma doença inflamatória crônica do cólon com uma etiologia desconhecida. O objetivo deste estudo foi avaliar os efeitos terapêuticos do extrato de Cupressus sempervirens na cicatrização de colite ulcerativa induzida por ácido acético em ratos. Cinquenta e cinco ratos machos divididos em cinco grupos de tratamento iguais foram utilizados para este estudo e receberam os seguintes tratamentos: Grupo 1: 250 mg/kg de asacol; Grupo 2: 1 mL de gel base (carboximetilcelulose); Grupo 3: extrato de C. sempervirens a 0,5% em gel; Grupo 4: extrato de C. sempervirens a 1% em gel e; Grupo 5: considerado controle negativo que recebeu 1 mL de solução salina normal. Alterações no peso corporal, alterações histopatológicas e antioxidantes no tecido do cólon foram avaliadas. Ganho de peso significativo foi observado em ratos que receberam extrato em gel de C. sempervirens a 1%. Atividade significativa de superóxido dismutase também foi detectada em grupos de extrato em gel de 0,5 e 1% em comparação com o extrato de C. sempervirens, Asacol e em grupos de extrato em gel a 1% em comparação com o grupo base de gel. Além disso, ambos os grupos de extrato em gel apresentaram capacidade antioxidante total significativamente menor em comparação ao grupo Asacol. Várias lesões histopatológicas, incluindo inflamação, ulceração, desarranjo da cripta e depleção de células caliciformes foram detectadas nos diferentes grupos; no entanto, a classificação média de alterações patológicas não apresentou diferença significativa entre os cinco grupos. Em resumo, nossos resultados mostraram que extratos hidroalcoólicos de folhas de C. sempervirens produzem efeitos cicatrizantes em colite ulcerativa induzida por ácido acético.

The Preventive Effects of Neural Stem Cells and Mesenchymal Stem Cells Intra-ventricular Injection on Brain Stroke in Rats.

INTRODUCTION: Stroke is one of the most important causes of disability in developed countries and, unfortunately, there is no effective treatment for this major problem of central nervous system (CNS); cell therapy may be helpful to recover this disease. In some conditions such as cardiac surgeries and neurosurgeries, there are some possibilities of happening brain stroke. Inflammation of CNS plays an important role in stroke pathogenesis, in addition, apoptosis and neural death could be the other reasons of poor neurological out come after stroke. In this study, we examined the preventive effects of the neural stem cells (NSCs) and mesenchymal stem cells (MSCs) intra-ventricular injected on stroke in rats. AIM: The aim of this study was to investigate the preventive effects of neural and MSCs for stroke in rats. MATERIALS AND METHODS: The MSCs were isolated by flashing the femurs and tibias of the male rats with appropriate media. The NSCs were isolated from rat embryo ganglion eminence and they cultured NSCs media till the neurospheres formed. Both NSCs and MSCs were labeled with PKH26-GL. One day before stroke, the cells were injected into lateral ventricle stereotactically. RESULTS: During following for 28 days, the neurological scores indicated that there are better recoveries in the groups received stem cells and they had less lesion volume in their brain measured by hematoxylin and eosin staining. Furthermore, the activities of caspase-3 were lower in the stem cell received groups than control group and the florescent microscopy images showed that the stem cells migrated to various zones of the brains. CONCLUSION: Both NSCs and MSCs are capable of protecting the CNS against ischemia and they may be good ways to prevent brain stroke consequences situations.