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"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: The effect of ischemia/reperfusion (I/R) injury on kidney has been under investigation for many years. But the changes in liver function and oxidative stress status in renal I/R injury is not well known. Recent studies suggest a crosstalk between liver and kidneys. The aim of the present study was to assess liver changes after induction of various degrees of renal I/R injury."n"nMethods: This is an experimental study conducted on 20 male rats that were obtained from animal house of Physiology Department. Twenty male rats were subjected to either sham operation or ischemia (30, 45 and 60 min) followed by 60 min reperfusion periods. Blood samples were drawn post-operatively and plasma creatinine, BUN, ALT and AST were measured. Hepatic glutathione (GSH) and FRAP (ferric reducing antioxidant power) levels and the concentration of IL-10 and tumor necrosis factor (TNF) -alpha were evaluated."n"nResults: Both 45 and 60 min ischemia followed by 1h reperfusion periods resulted in significant increases in plasma creatinine (11.1±1.7mg/dl and 1.24±0.07mg/dl vs 0.55±0.15mg/dl, p

Background: The effect of ischemia/reperfusion (I/R) injury on kidney has been under investigation for many years. But the changes in liver function and oxidative stress status in renal I/R injury is not well known. Recent studies suggest a crosstalk between liver and kidneys. The aim of the present study was to assess liver changes after induction of various degrees of renal I/R injury. Methods: This is an experimental study conducted on 20 male rats that were obtained from animal house of Physiology Department. Twenty male rats were subjected to either sham operation or ischemia (30, 45 and 60 min) followed by 60 min reperfusion periods. Blood samples were drawn post-operatively and plasma creatinine, BUN, ALT and AST were measured. Hepatic glutathione (GSH) and FRAP (ferric reducing antioxidant power) levels and the concentration of IL-10 and tumor necrosis factor (TNF) -alpha were evaluated. Results: Both 45 and 60 min ischemia followed by 1h reperfusion periods resulted in significant increases in plasma creatinine (11.1±1.7mg/dl and 1.24±0.07mg/dl vs 0.55±0.15mg/dl, p<0.05) and BUN (34±3.85mg/dl and 35.0±2.81mg/dl vs 23.75±1.1mg/dl, p<0.05). These rats showed a significant decrease in liver GSH as well as significant increase in TNF-α & IL-10 concentrations. Conclusion: Renal ischemia causes changes in liver function and oxidative stress status. A minimum of 45 min ischemia is needed to study the effects of renal injury on liver as a remote affected organ. [ABSTRACT FROM AUTHOR]

Recent studies have documented that remote organs are affected by ischemic injury to the kidney. Here we studied whether the liver also suffers damage during induction of renal ischemia-reperfusion in rats and compared this to bilateral nephrectomy. Hepatic levels of tumor necrosis factor-alpha increased significantly after 6 and 24 h of renal ischemia or nephrectomy. Malondialdehyde, an index of lipid peroxidation, increased while total glutathione was decreased in the liver in both the renal ischemia and nephrectomy groups, suggesting activation of oxidative stress. Expression of liver spermine-spermidine acetyl transferase, an enzyme upregulated in early phases of hepatic injury was significantly increased 6 h after either kidney ischemia or nephrectomy. Apoptosis was increased in hepatocytes 24 h after nephrectomy. We also found histological evidence of hepatocyte injury following both ischemia and bilateral nephrectomy. Infusion of reduced glutathione, before the induction of renal ischemia, significantly improved liver architecture and was associated with a reduction in hepatic malondialdehyde and serum alanine transaminase levels. Our study shows that acute kidney ischemia or renal failure activates oxidative stress and promotes inflammation, apoptosis, and tissue damage in hepatocytes. [ABSTRACT FROM AUTHOR]

Background: Physical activity and proper nutrition during pregnancy are crucial for maternal and fetal health. However, many pregnant women fail to meet recommended guidelines. This study aimed to assess the effectiveness of an educational intervention based on the Health Belief Model (HBM) in improving these behaviors., Methods: A pre-post with control quasi-experimental study was conducted among 200 pregnant women (100 experimental and 100 control) in Shiraz, Iran. The intervention group attended eight weekly 50-minute educational sessions based on the HBM. Physical activity and nutritional performance were assessed using validated questionnaires at baseline and three months post-intervention. Data were analyzed using paired and independent t -tests, with effect sizes and 95% confidence intervals reported., Results: The intervention significantly improved physical activity (mean score: 29.25 ± 4.42 vs. 12.28 ± 4.36, p  < 0.001) and nutritional performance across all food groups ( p  < 0.001) in the experimental group compared to the control group. Key constructs of the HBM, including perceived sensitivity, severity, benefits, self-efficacy, and cues to action, showed significant increases with notable effect sizes and 95% confidence intervals, while perceived barriers significantly decreased ( p  < 0.001)., Conclusions: The educational intervention based on the HBM effectively improved physical activity and nutritional performance among pregnant women. Integrating such programs into routine prenatal care is recommended, with emphasis on personalized counseling, regular follow-ups, and spousal involvement to sustain behavioral changes and promote maternal and fetal health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Khani Jeihooni, Razmjouie, Jormand, Sedghi Jahromi, Afzali Harsini, Kamyab and Ghaleh Golab.)

Background: Colorectal cancer (CRC), the third most prevalent and lethal disease, accounted for approximately 1.9 million new cases and claimed nearly 861,000 lives in 2018. It is imperative to develop a minimally invasive diagnostic technique for early identification of CRC. This would facilitate the selection of patient populations most suitable for clinical trials, monitoring disease progression, assessing treatment effectiveness, and enhancing overall patient care. Utilizing blood as a biomarker source is advantageous due to its minimal discomfort for patients, enabling better integration into clinical and follow-up trials. Recent findings indicate that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are detectable in the blood of cancer patients, proving crucial in diagnosing various malignancies., Methods: In this case-control study, we collected plasma samples from 30 patients diagnosed with colorectal cancer (CRC) and 30 healthy volunteers. Following RNA extraction, we measured the expression levels of specific biomolecules, including miR-410, miR-211, miR-139, miR-197, lncRNA UICLM, lncRNA FEZF1-AS1, miR-129, lncRNA CCAT1, lncRNA BBOX1-AS1, and lncRNA LINC00698, using real-time quantitative polymerase chain reaction (RT-qPCR). The obtained data underwent analysis using the Mann-Whitney test for non-parametric data and the T-test for parametric data., Results: The level of miR-410, miR-211, miR-139, miR-197, lncRNA UICLM, lncRNA FEZF1-AS1 were significantly higher in patients with CRC than healthy controls (p < .05). Meanwhile, the level of miR-129, lncRNA CCAT1, lncRNA BBOX1-AS1, and lncRNA LINC00698 were higher in healthy controls than in CRC patients (p < .05)., Conclusion: MicroRNA (miRNA) and long noncoding RNAs (lncRNAs) have recently emerged as detectable entities in the blood of cancer patients, playing crucial roles in diagnosing various malignancies. However, their specific relevance in the diagnosis of colorectal cancer (CRC) remains underexplored. This study aimed to investigate miRNA and lncRNA profiles in the plasma fraction of human blood to discern significant differences in content and expression levels between CRC patients and healthy individuals. Our cohort comprised 30 CRC patients and 30 healthy controls, with no statistically significant differences (p < 0.05) in age or gender observed between the two groups. Noteworthy is the uniqueness of our study, as we identified a panel of three significant microRNAs and one significant lncRNA, providing a more reliable prediction compared to existing molecular markers in diagnosing CRC. The four genes examined, including miR-211, miR-129, miR-197, and lncRNA UICLM, demonstrated impeccable results in terms of sensitivity and specificity, suggesting their potential candidacy for inclusion in diagnostic panels. Further validation in a larger statistical population is recommended to confirm the robustness of these genes as promising markers for colorectal cancer diagnosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: Breast cancer is the most common type of cancer in women. The construction of a competing gene network is an important step in the identification of the role of hub genes in breast cancers. In the current research, we used a number of bioinformatics tools to construct this network in breast cancer and investigated the combined effect of garlic and ginger on mice model of breast cancer., Materials and Methods: We chose female mice weighing 18-20 g that were divided into 7 groups including; the cancer group receiving normal saline, different doses of ginger extract (100 and 500 mg/kg), different doses of garlic (50 and 100 mg/kg), tamoxifen (10 mg/ kg) and simultaneous garlic (100 mg/kg) and ginger (500 mg/kg) for 3 weeks intraperitoneal. Then we anesthetized the mice, isolated the tumor, and determined its size. Glutathione reductase and peroxidase levels and HER2, PTEN, and Cullin3 genes expression were measured., Results: We identified 20 hub genes for breast cancer. In animal phase we found that tumor size in all mice receiving garlic and ginger showed a significant decrease compared to the control. Glutathione reductase showed a significant increase in all groups, especially in ginger 500 and combined groups. Glutathione peroxidase increased almost in all groups, especially in ginger 500. Expression of HER2 decreased in all treated groups. Expression of PTEN increased just in the combined group., Conclusion: Taken together, we introduce a number of novel promising diagnostic biomarkers for breast cancer. The use of garlic and ginger in the treatment of cancer can be useful. This action is probably through the antioxidant mechanism, and regulation of the expression of cancer related genes such as PTEN.

GBM, or glioblastoma multiforme, is a brain tumor that poses a great threat to both children and adults, being the primary cause of death related to brain tumors. GBM is often associated with epilepsy, which can be debilitating. Seizures and the development of epilepsy are the primary symptoms that have a severe impact on the quality of life for GBM patients. It is increasingly apparent that the nervous system plays an essential role in the tumor microenvironment for all cancer types, including GBM. In recent years, there has been a growing understanding of how neurotransmitters control the progression of gliomas. Evidence suggests that neurotransmitters and neuromodulators found in the tumor microenvironment play crucial roles in the excitability, proliferation, quiescence, and differentiation of neurons, glial cells, and neural stem cells. The involvement of neurotransmitters appears to play a significant role in various stages of GBM. In this review, the focus is on presenting updated knowledge and emerging ideas regarding the interplay between neurotransmitters and neuromodulators, such as glutamate, GABA, norepinephrine, dopamine, serotonin, adenosine, and their relationship with GBM and the seizures induced by this condition. The review aims to explore the current understanding and provide new insights into the complex interactions between these neurotransmitters and neuromodulators in the context of GBM-related seizures., (© 2023 International Society for Developmental Neuroscience.)

Background: Alterations in DNA methylation play an important role in cancer development and progression. Dietary nutrients and lifestyle behaviors can influence DNA methylation patterns and thereby modulate cancer risk., Introduction: To comprehensively review available evidence on how dietary and lifestyle factors impact DNA methylation and contribute to carcinogenesis through epigenetic mechanisms., Materials and Methods: A literature search was conducted using PubMed to identify relevant studies published between 2005 and 2022 that examined relationships between dietary/lifestyle factors and DNA methylation in cancer. Studies investigating the effects of dietary components (eg, micronutrients, phytochemicals), physical activity, smoking, and obesity on global and gene-specific DNA methylation changes in animal and human cancer models were included. Data on specific dietary/lifestyle exposures, cancer types, DNA methylation targets and underlying mechanisms were extracted., Results: Multiple dietary and lifestyle factors were found to influence DNA methylation patterns through effects on DNA methyltransferase activity, methyl donor availability, and generation of oxidative stress. Altered methylation of specific genes regulating cell proliferation, apoptosis, and inflammation were linked to cancer development and progression., Conclusion: Dietary and lifestyle interventions aimed at modulating DNA methylation have potential for both cancer prevention and treatment through epigenetic mechanisms. Further research is needed to identify actionable targets for nutrition and lifestyle-based epigenetic therapies., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Due to the coronavirus disease 2019 (COVID-19), researchers all over the world have tried to find an appropriate therapeutic approach for the disease. The angiotensin-converting enzyme 2 (ACE2) has been shown as a necessary receptor to cell fusion, which is involved in infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is commonly crucial for all organs and systems. When ACE2 is downregulated via the SARS-CoV-2 spike protein, it results in the angiotensin II (Ang II)/angiotensin type 1 receptor axis overactivation. Ang II has harmful effects, which can be evidenced by dysfunctions in many organs experienced by COVID-19 patients. ACE2 is the SARS-CoV-2 receptor and has an extensive distribution; thus, some COVID-19 cases experience several symptoms and complications. We suggest strategy for the potential protective effect of ACE2 to the viral infection. The current review will provide data to develop new approaches for preventing and controlling the COVID-19 outbreak., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Fereshteh Golab et al.)

Background: Neurostimulation is one of the new therapeutic approaches in patients with drug-resistant epilepsy, and despite its high efficiency, its mechanism of action is still unclear. On the one hand, electrical stimulation in the human brain is immoral; on the other hand, the creation of the epilepsy model in laboratory animals affects the entire brain network. As a result, one of the ways to achieve the neurostimulation mechanism is to use epileptiform activity models In vitro. In vitro models, by accessing the local network from the whole brain, we can understand the mechanisms of action of neurostimulation., Methods: A literature search using scientific databases including PubMed, Google Scholar, and Scopus, using "Neurostimulation" and "epileptiform activity" combined with "high-frequency stimulation", " low-frequency stimulation ", and "brain slices" as keywords were conducted, related concepts to the topic gathered and are used in this paper., Results: Electrical stimulation causes neuronal depolarization and the release of GABAA, which inhibits neuronal firing. Also, electrical stimulation inhibits the nervous tissue downstream of the stimulation site by preventing the passage of nervous activity from the upstream to the downstream of the axon., Conclusion: Neurostimulation techniques consisting of LFS and HFS have a potential role in treating epileptiform activity, with some studies having positive results. Further investigations with larger sample sizes and standardized outcome measures can be conducted to validate the results of previous studies., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)

Introduction: Breast cancer is one of the important factors of cancer-related deaths. Considering the drug resistance, special attention has been paid to natural compounds. This study aimed at evaluating the anti-metastatic activity of fennel in a breast cancer mouse model., Methods: A total of 35 adult female BALB/C mice were used in this study. Breast cancer was induced by subcutaneous injection of 4T1 cells in the right lower flank. The mice received fennel extracts daily via intraperitoneal injection for two weeks. Meanwhile, tumor volume was measured every day using calipers. After two weeks, each animal was anesthetized. The protein expression of HSP 70 & 90 was measured in liver tissue and ovary. The expression of her2 was measured in tumor tissue. The activity of Glutathione peroxidase and reductase as anti-oxidant agents were measured in serum., Results: Tumor size significantly decreased after nine days' treatment of the fennel. The expression of HER2 increased in the tumor tissue and decrease with different dose of fennel. Fennel treatment caused a decrease in the protein expression of HSP 70 & 90 in the liver tissues., Conclusion: Based on our findings, fennel has anti-tumor and anti-metastatic activities against aggressive cancers.

Background and Aims: Alzheimer's disease (AD) is the main cause of dementia and over the 55 million people live with dementia worldwide. We aimed to establish the first database called the Iranian Alzheimer's Disease Registry to create a powerful source for future research in the country. In this report, the design and early results of the Iranian Alzheimer's Disease Registry will be described., Methods: We performed this multicenter investigation and patients' data including age, sex, educational level, disease status, Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS) from 2018 to 2021 were collected, registered, and analyzed by GraphPad Prism software., Results: Totally 200 AD patients were registered in our database. 107 (54%) were women and age of 147 (74%) were over 65. The mean age for men and women was 76.20 ± 8.29 and 76.40 ± 8.83 years, respectively. 132 (66%) were married and 64 (32%) were illiterate. Also, 94 (47%) were in the moderate stage of disease, and 150 (75%) lived at home together with their families. The most frequent neurological comorbidity was psychosis ( n  = 72, 36%), while hypertension was the most common non-neurological comorbidity ( n  = 104, 52%). The GDS score of women in the mild stage (5.23 ± 2.9 vs. 6.9 ± 2.6, p  = 0.005) and moderate stage (5.36 ± 2.4 vs. 8.21 ± 2.06, p  = <0.001) of the disease was significantly greater than men. In univariate analysis, MMSC score was remarkably associated with stroke ( β  = -2.25, p  = 0.03), psychosis ( β  = -2.18, p  = 0.009), diabetes ( β  = 3.6, p = <0.001), and hypercholesteremia ( β  = 1.67, p  = 0.05). Also, the MMSE score showed a notable relationship with stroke ( β  = -2.13, p  = 0.05) and diabetes ( β  = 3.26, p  = <0.001) in multivariate analysis., Conclusion: Iranian Alzheimer's Disease Registry can provide epidemiological and clinical data to use for purposes such as enhancing the current AD management in clinical centers, filling the gaps in preventative care, and establishing effective monitoring and cure for the disease., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Glycogen synthase kinase-3 (GSK-3) is a critical molecule in Alzheimer's disease (AD) that modulates two histopathological hallmarks of AD: Amyloid beta (Aβ) plaques and neurofibrillary tangles composed of aberrant hyper-phosphorylation of tau protein. This study was performed to investigate the protective effect of flavone apigenin through inhibition of GSK-3 and the involvement of this kinase in the inhibition of BACE1 expression and hyperphosphorylation of tau protein in an AD rat model. 15 nM of aggregated amyloid-beta 25-35 was microinjected into the left lateral ventricle of an AD rat. Apigenin (50 mg/kg) was administered orally 45 min before the Aβ injection and continued daily for three weeks. Immunohistochemistry and western blot analysis showed that apigenin significantly reduced the hyperphosphorylation of tau levels in the hippocampus. Real-time PCR analysis revealed significant inhibition of the mRNA level of β secretase (BACE1) and GSK-3β, but Apigenin had no effect on the level of GSK-3α. The results demonstrate that apigenin has a protective effect against amyloid-beta 25-35 by decreasing the expression of GSK-3β with the consequence of lowering the hyperphosphorylation of tau protein and suppressing BACE1 expression., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Obesity is among the most severe challenges of our era, with significant health consequences and a high economic burden for health systems. Therefore, many countries have developed political agendas to cope with this ever-rising challenge. Along with chemical medications developed to manage obesity, researchers have focused on some natural ingredients and herbal extracts that are effective in reducing weight. The current study investigated the association between Foeniculum vulgar (fennel) extracts and body weight, lipid profile, and leptin., Methods: In total, 35 adult male BALB/c mice were investigated in sham, fennel 50 mg/kg, fennel 100 mg/kg, and fennel 200 mg/kg (n=7) groups. The mice were administered fennel extracts for fourteen days while weighted at the intervention's beginning and end. Then, their weight, lipid profile, serum leptin, and expression of leptin protein in the hypothalamus were measured., Results: After providing the intervention, leptin receptor protein expression was increased in all groups, while serum leptin didn't change significantly. Moreover, a significant decrease was observed in the cholesterol dose of 100 mg/kg/day, triglycerides in 100 and 200 mg/kg/day, and LDL in 50 and 100 mg/kg/day. Serum HDL was increased significantly in a dose of 100 mg/kg/day., Conclusion: Fennel extract can decrease the lipid profile by changing the expression of the leptin receptor., Highlights: Obesity contributes to many health problems and dyslipidemia.Leptin is known for its hunger-blocking can regulate food intake and affects the levels of lipid. circulation.Fennel is a plant with strong antioxidant activities [18] that can influence (increase) satiety and (reduce) food intake.Fennel contains phytosterols that are known to reduce cholesterol solubilization that in turn decreases its absorption.Fennel extract can improve the lipid profile by influencing the leptin receptor expression., Plain Language Summary: Obesity is one of the most serious challenges of our era, with significant health consequences. Researchers have focused on some natural ingredients and herbal extracts. The current study aimed to investigate the association between Foeniculum vulgar (fennel) extracts and body weight, lipid profile, and leptin. After treatment of fennel, leptin receptor protein expression was increased in all groups, while serum leptin didn't change significantly. A significant decrease was observed in the cholesterol, triglycerides and LDL in some doses of fennel. Serum HDL was increased significantly in a dose of 100 mg/kg/day. So fennel extract can decrease the lipid profile by changing the expression of the leptin receptor., Competing Interests: Conflict of interest The authors declared no conflicts of interest., (Copyright© 2021 Iranian Neuroscience Society.)

Background: In vitro obtaining oocytes can be an appropriate alternative for patients with gonadal insufficiency or cancer survivors. The purpose of the current research was isolating stem cells from ovarian cortical tissue as well as evaluating the effectiveness of follicle stimulating hormone (FSH), basic fibroblast growth factor (bFGF), and neurotrophin 3 (NT3) in differentiating to oocyte-like cells., Methods: A human ovary was dissected and cortical tissue pieces were cultured for cell isolation. Isolated cells were divided into 8 groups (3 cases in each group) of control, FSH, NT3, bFGF, FSH+NT3, FSH+bFGF, NT3+bFGF, and FSH+NT3+ bFGF. Pluripotency specific gene (OCT4-A and Nanog), initial germ cells (c-KIT and VASA) and PF growth initiators (GDF-9 and Lhx-8) were evaluated by qRTPCR. Experiments were performed in triplicate and there were 3 samples in each group. The results were analyzed using one-way ANOVA and p-value less than 0.05 was considered statistically significant., Results: Flow cytometry results showed that cells isolated from the ovarian cortex expressed markers of pluripotency. The results showed that the expression of Nanog, OCT4, GDF-9 and VASA was significantly increased in FSH+NT3 group, while treatment with bFGF caused significant expression of c-KIT and Lhx-8 (p<0.05). Also, according to the results, isolated cells treated with NT3 significantly increased c-KIT expression., Conclusion: According to our results, the ovarian cortex cells could be differentiated into primordial follicles if treated with the proper combination of FSH, bFGF, and NT3. These findings provided a new perspective for the future of in vitro gamete proudest., Competing Interests: Conflict of Interest There is no conflict of interest., (Copyright© 2021, Avicenna Research Institute.)

Purpose: Coenzyme Q10 (CoQ10), having potent antioxidant and anti-inflammatory pharmacological properties, has recently been shown to be a safe and promising agent in maintaining remission of ulcerative colitis (UC). This trial was, therefore, designed to determine CoQ10 efficacy on inflammation and antioxidant status, antimicrobial peptides, and microRNA-146a expression in UC patients., Methods: In this randomized double-blind controlled trial, 88 mild-to-moderate UC patients were randomly allocated to receive CoQ10 (200 mg/day) or placebo (rice flour) for 2 months. At the baseline and at an 8-week follow-up, serum levels of Nrf2, cathelicidin LL-37, β-defensin 2, IL-10, IL-17, NF-κB p65 activity in peripheral blood mononuclear cells (PBMCs), simple clinical colitis activity index questionnaire (SCCAIQ), and quality of life (IBDQ-32 score), as well as an expression rate of microRNA-146a were measured., Results: A significant reduction was detected in the serum IL-17 level, activity of NF-κB p65 in PBMCs, and also SCCAI score in the CoQ10 group compared to the placebo group, whereas IL-10 serum concentrations and IBDQ-32 score of the CoQ10 group considerably increased versus the control group; the changes of these variables were also significantly different within and between groups at the end of the study. Furthermore, CoQ10 remarkably increased serum levels of cathelicidin LL-37. A significant change in serum cathelicidin LL-37 levels was also observed between the two groups. No statistical difference, however, was seen between the two groups in terms of the serum levels of Nrf2 and β-defensin 2 and the relative expression of microRNA-146a., Conclusions: Our results indicate that CoQ10 supplementation, along with drug therapy, appears to be an efficient reducer of inflammation in patients with mild-to-moderate UC at a remission phase., Trial Registration: The research has also been registered at the Iranian Registry of Clinical Trials (IRCT): IRCT20090822002365N17., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Maternal diabetes during pregnancy affects the development of hippocampus in the offspring. Brain-derived neurotrophic factor (BDNF) has received increasing attention for its role in regulating the survival and differentiation of neuronal cells in developing and adult brain. In the current study, we evaluated the effects of maternal diabetes and insulin treatment on expression and distribution pattern of BDNF in the hippocampus of neonatal rats at the first two postnatal weeks. We found no differences in hippocampal expression of BDNF between diabetics with normal control or insulin treated neonatal rats at postnatal day (P0) (P > 0.05 each). Nevertheless, there was a marked BDNF downregulation in both sides' hippocampi of male/female diabetic group in two-week-old offspring (P ≤ 0.05 each). Furthermore, the numerical density of BDNF + cells was significantly reduced in the right/left dentate gyrus (DG) of male and female newborns born to diabetic animals at all studied postnatal days (P ≤ 0.05 each). In addition, a lower number of reactive cells have shown in the all hippocampal subareas in the diabetic pups at P14 (P ≤ 0.05 each). Our results have demonstrated that the insulin-treatment improves some of the negative impacts of diabetes on the expression of hippocampal BDNF in the newborns. We conclude that diabetes in pregnancy bilaterally disrupts the expression of BDNF in the hippocampus of the both male and female newborns at early postnatal days. In addition, good glycemic control by insulin in the most cases is sufficient to prevent the alterations in expression of BDNF protein in developing hippocampus., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Alopecia universalis (AU) congenital, known as generalized atrichia, is a severe form of autosomal recessive alopecia that results in complete hair loss of scalp and body. Mutations in the human hairless gene (HR) are associated with the phenotype of the disease. A consanguineous couple who had a child with the generalized atrichia sign referred to us for genetic counseling. According to the patient's symptoms and after thorough examination and history taking, the HR gene was the candidate gene to be assessed and analyzed. For this purpose targeted primers were designed for all exons of the HR gene followed by running PCR for exons amplification. Finally, the PCR products were sequenced. Whole-gene sequence analysis revealed a nonsense homozygous mutation in exon 6 that, according to the ACMG guide, is a pathogenic variant. Sequence analysis of the exon in parents reveals that they are heterozygout for the non-sense mutation, as well., Competing Interests: Conflict of interest There is no conflict of interest., (Copyright © 2021 Heidary et al. Published by Tehran University of Medical Sciences.)

This research investigated the effect of co-supplementation of selenium with zinc on weight control and the inflammatory and oxidative status in relation to obesity. Male Wistar rats ( N  = 32) were randomly divided into four groups after induction of obesity model: 1) "Zn" was supplemented with zinc sulfate (15 mg/kg BW), 2) "Se" supplemented with selenium as sodium selenate (0.5 mg/kg BW), 3) "Zn + Se" which received Zn (15 mg/kg BW) + Se (0.5 mg/kg BW), and 4) "HFD" as the control group. The intervention was done for eight weeks. At the end of treatment, serum and tissue level of Zn, Se, SOD, GSH-Px, MDA, leptin, TNF-α, and IL-6 was evaluated. Weight and food intake were significantly reduced in the Se group( p  < .001), while in the Zn group, weight gain due to obesity was prevented compared to the control group ( p  = .48). There was a significant and stronger increase in SOD, GSH-Px levels and a remarkable decrease in MDA, leptin, TNF-α, and IL-6 in the group receiving the combination of two supplements than either alone( p  < .001). Leptin had a positive correlation with inflammatory factors and lipid peroxidation marker and showed an inverse relationship with Zn and Se levels and anti-oxidative enzymes( p  < .05). The analysis showed the mediating role of leptin in the effects of zinc. Co-supplementation of selenium and zinc may have a synergistic effect in reduction of oxidative and inflammatory markers. Regarding the effect of zinc on inflammatory factors and lipid peroxidation, leptin can play a mediating role., Competing Interests: The authors declare no conflict of interest. There is not any financial or personal relationships that might bias the work., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Temporal lobe epilepsy leads to a disturbance in the function and dynamic of the mitochondria. The mitoKATP channel is an important factor in controlling mitochondrial function. In this study, the protective role of mitoKATP was studied in temporal lobe epilepsy through the regulation of mitochondrial dynamic proteins. After induction of epilepsy, 5-HD (the inhibitor of mitoKATP) was administered daily for either 24 or 72 h. The results revealed an imbalance in dynamic proteins after epilepsy, specifically in the first 72 h. The disturbance in the mitochondrial dynamic worsened after blocking mitoKATP. In conclusion, mitoKATP has an important role in balancing mitochondrial dynamic proteins in epilepsy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Breast cancer is described as a serious disease and one of the important factors of cancer-related deaths. Considering the drug resistance, special attention has been paid to natural compounds. This study aimed at evaluating the anti-metastatic activity of fennel in a breast cancer mouse model. Methods: A total of 28 adult female BALB/C mice were used in this study. Breast cancer was induced by subcutaneous injection of 4T1 cells in the right lower flank. The mice received fennel extracts daily via intraperitoneal injection for two weeks. Meanwhile, tumor volume was measured every day using calipers. After two weeks, each animal was anesthetized. The expression levels of ki-67 and dysadherin as tumor markers, as well as E-cadherin as a tumor suppressor, were measured in tumor tissue and ovary. Also the expression of her2 was measured in ovary. Results: Tumor size significantly decreased after nine days treatment of the fennel. Fennel treatment caused an increase in the ratio of the expression of E-cadherin to Ki-67 and dysadherin in the tumor tissues. On the other hand, the expression of Ki-67 and HER2 decreased in the ovary. Conclusion: Based on our findings, fennel has anti-tumor and anti-metastatic activities against aggressive cancers.

Introduction: Hepcidin is the main modulator of systemic iron metabolism, and its role in the brain has been clarified recently. Studies have shown that hepcidin plays an important role in neuronal iron load and inflammation. This issue is of significance because neuronal iron load and inflammation are pathophysiological processes that are highly linked to neurodegeneration. Moreover, the activity of hepcidin has recently been manipulated to recover the neuronal impairment caused by brain inflammation in animal models., Methods: Streptozotocin (STZ) was used to induce type 1 diabetes. Male Wistar rats (n = 40) with a weight range of 200-250 g were divided into control, diabetic, diabetic + insulin, and diabetic + dalteparin groups. Dalteparin (100 mg/kg IP) and insulin (100 mg/kg SC) were administered for 8 weeks. At the end of the experiment, Y-maze and passive avoidance tasks were carried out. The animals were perfused randomly and their hippocampal tissue was isolated for the analysis of markers such as lipid peroxidation like Malondialdehyde (MDA), hepcidin expression, iron, and ferritin. Blood samples were taken for the measurement of serum inflammatory cytokine Interleukin (IL)-6., Results: The findings indicated that treatment with dalteparin reduced IL-6, MDA, ferritin, and hepcidin expression in diabetic rats compared to treatment with insulin (P<0.05). Moreover, treatment with dalteparin did not decrease the iron level or prevented its decline., Conclusion: Treatment with dalteparin improved the cognitive dysfunctions and symptoms of Alzheimer disease in STZ-induced diabetic rats by appropriately modulating and reducing oxidative stress and neuroinflammation. This may enhance the existing knowledge of therapeutics to reduce cognitive impairment in diabetes and is suggested to be a potential therapeutic agent in diabetes., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2020 Iranian Neuroscience Society.)

Background: previous studies have suggested that methamphetamine (METH) abuse may affect orexin regulation. However, the data regarding the relationship between the current level of orexin and the vulnerability to METH abuse are minimal. Here, we have investigated the correlation between the gene expression level of the orexin-1 receptor (OX1R) in the rat prefrontal cortex (PFC) and blood lymphocytes and susceptibility to METH dependence and its impact on novelty-seeking behavior., Methods: male Wistar rats were first examined for novelty-seeking behavior by the novel object recognition test, and the expression level of OX1R in their blood lymphocytes was evaluated by real-time PCR. Then, the susceptibility to METH abuse was investigated by voluntary METH oral consumption test. According to the amounts of METH consumption, the animals were divided into two groups of METH preferring and non-preferring. Half of the rats in each group were sacrificed, and the level of OX1R in their blood lymphocytes and PFC tissue was measured. The other half were sacrificed for the same reason after two weeks of drug abstinence., Results: The indexes of novelty-seeking behavior were significantly higher in the METH- preferring group compared to the non-preferring animals. Furthermore, the expression level of OX1R in the blood lymphocytes and PFC in the preferring group was considerably higher than the non-preferring group., Conclusion: Up-regulation of the mRNA expression level of OX1R in the lymphocytes and PFC may predict vulnerability to the METH consumption and novelty-seeking, which may serve as a potential biomarker for METH abuse., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Noscapine is an antitumor alkaloid derived from Papaver somniferum plants. Our previous study has demonstrated that exposure of noscapine on primary murine fetal cortical neurons exposed to oxygen-glucose deprivation/reperfusion (OGD/R) has neuroprotective effects. In current study, the effects of noscapine on cardiomyocytes (H9c2 cells) damage caused by 120 minutes (min) of OGD/R were evaluated and we determined whether the addition of BD1047, sigma-one receptor antagonist, prevents the protective effects of noscapine in H9c2 cells through the production of nitric oxide (NO) and apoptosis. To initiate OGD, H9c2 cells was transferred to glucose-free DMEM, and placed in a humidified incubation chamber. Cell viability was assessed with noscapine (1-5 μM) in the presence or absence of BD1047, 24 hours (h) after OGD/R. Cell viability, NO production and apoptosis ratio were evaluated by the MTT assay, the Griess method and the quantitative real-time PCR. Noscapine considerably improved the survival of H9c2 cells compared to OGD/R. Also, noscapine was extremely capable of reducing the concentrations of NO and Bax/Bcl-2 ratio expression. While the BD1047 administration alone diminished cell viability and increased the Bax/Bcl-2 ratio and NO levels. The addition of noscapine in the presence of BD1047 did not increase the cell viability relative to noscapine alone. Noscapine exerted cardioprotective effects exposed to OGD/R-induced injury in H9c2 cells, at least partly via attenuation of NO production and Bax/Bcl-2 ratio, which indicates that the sigma-one receptor activation is involved in the protection by noscapine of H9c2 cells injured by OGD/R.

Background: Multiple sclerosis (MS) is a devastating autoimmune disorder characterized by oligodendrocytes (OLGs) loss and demyelination. In this study, we have examined the effects of metformin (MET) on the oligodendrogenesis, redox signaling, apoptosis, and glial responses during a self-repairing period (1-week) in the animal model of MS., Methods: For induction of demyelination, C57BL/6 J mice were fed a 0.2% cuprizone (CPZ) for 5 weeks. Thereafter, CPZ was removed for 1-week and molecular and behavioral changes were monitored in the presence or absence of MET (50 mg/kg body weight/day)., Results: MET remarkably increased the localization of precursor OLGs (NG2 + /O4 + cells) and subsequently the renewal of mature OLGs (MOG + cells) in the corpus callosum via AMPK/mammalian target of rapamycin (mTOR) pathway. Moreover, we observed a significant elevation in the antioxidant responses, especially in mature OLGs (MOG + /nuclear factor erythroid 2-related factor 2 (Nrf2 + ) cells) after MET intervention. MET also reduced brain apoptosis markers and lessened motor dysfunction in the open-field test. While MET was unable to decrease active astrogliosis (GFAP mRNA), it reduced microgliosis by down-regulation of Mac-3 mRNA a marker of pro-inflammatory microglia/macrophages. Molecular modeling studies, likewise, confirmed that MET exerts its effects via direct interaction with AMPK., Conclusions: Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs. These findings facilitate the development of new therapeutic strategies based on AMPK activation for MS in the near future.

Misfolded proteins are the main common feature of neurodegenerative diseases, thereby, normal proteostasis is an important mechanism to regulate the neural survival and the central nervous system functionality. The ubiquitin-proteasome system (UPS) is a non-lysosomal proteolytic pathway involved in numerous normal functions of the nervous system, modulation of neurotransmitter release, synaptic plasticity, and recycling of membrane receptors or degradation of damaged and regulatory intracellular proteins. Aberrant accumulation of intracellular ubiquitin-positive inclusions has been implicated to a variety of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Myeloma (MM). Genetic mutation in deubiquitinating enzyme could disrupt UPS and results in destructive effects on neuron survival. To date, various agents were characterized with proteasome-inhibitory potential. Proteins of the ubiquitin-proteasome system, and in particular, E3 ubiquitin ligases, may be promising molecular targets for neurodegenerative drug discovery. Phytochemicals, specifically polyphenols (PPs), were reported to act as proteasome-inhibitors or may modulate the proteasome activity. PPs modify the UPS by means of accumulation of ubiquitinated proteins, suppression of neuronal apoptosis, reduction of neurotoxicity, and improvement of synaptic plasticity and transmission. This is the first comprehensive review on the effect of PPs on UPS. Here, we review the recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders. This review attempts to summarize the latest reports on the neuroprotective properties involved in the proper functioning of natural polyphenolic compounds with implication for targeting ubiquitin-proteasome pathway in the neurodegenerative diseases. We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. Future studies should focus on molecular mechanisms by which PPs can interfere this complex regulatory system at specific stages of the disease development and progression., (Copyright © 2020 Momtaz, Memariani, El-Senduny, Sanadgol, Golab, Katebi, Abdolghaffari, Farzaei and Abdollahi.)

Background & Aims: Curcumin is a biologically active phytochemical ingredient found in turmeric and has antioxidant pharmacologic actions that may benefit patients with polycystic ovarian syndrome (PCOS). The aim in this trial was to evaluate the efficacy of curcumin supplementation on oxidative stress enzymes, sirtuin-1 (SIRT1) and Peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) gene expression in PCOS patients., Methods: Seventy-two patients with PCOS were recruited for this randomized, double-blinded, clinical trial. Thirty-six patients received curcumin, 1500 mg (three times per day), and 36 patients received placebo for 3 months. Gene expression of SIRT1, PGC1α and serum activity of glutathione peroxidase (Gpx) and superoxide dismutase (SOD) enzymes were evaluated at the beginning of trial and at 3-month follow-up., Results: Sixty-seven patients with PCOS completed the trial. Curcumin supplementation significantly increased gene expression of PGC1α (p = 0.011) and activity of the Gpx enzyme (p = 0.045). Curcumin also non-significantly increased gene expression of SIRT1 and activity of the SOD enzyme., Conclusions: Curcumin seems to be an efficient reducer of oxidative stress related complications in patients with PCOS. Further studies on curcumin should strengthen our findings., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: The dynorphin (DYN)/kappa opioid receptor (KOR) system plays an important role in the development of addiction, and dysregulation of this system could lead to abnormal activity in the reward pathway. It has been reported that the expression state of the neurotransmitters and their receptors in the brain is reflected in peripheral blood lymphocytes (PBLs)., Methods: We have evaluated the PBLs and plasma samples of four groups: 1) subjects with severe opioid use disorder (SOD), 2) methadone-maintenance treated (MMT) individuals, 3) long-term abstinent subjects having former SOD, and 4) healthy control subjects (n = 20 in each group). The mRNA expression level of preprodynorphin (pPDYN) and KOR in PBLs has been evaluated by real-time PCR. Peptide expression of PDYN in PBLs has been studied by western blot, and DYN concentration in plasma has been measured by ELISA., Results: The relative expression level of the pPDYN mRNA and PDYN peptide in PBLs were significantly up-regulated in SOD, MMT, and abstinent groups compared to control subjects. No significant difference was found in the plasma DYN concentration between study groups. The expression level of the KOR mRNA in PBLs was significantly decreased in all three study groups compared to the control subjects., Conclusion: the expression changes in the DYN/KOR system after chronic exposure to opioids, including methadone, seems to be stable and does not return to normal levels even after 12 months abstinence. These long-time and permanent changes in PBLs may serve as a biomarker and footprint of SOD development in the periphery., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Oligodendrocytes (OLGs) damage and myelin distraction is considered as a critical step in many neurological disorders especially multiple sclerosis (MS). Cuprizone (cup) animal model of MS targets OLGs degeneration and frequently used to the mechanistic understanding of de- and remyelination. The aim of this study was exploring the effects of metformin on the OLGs regeneration, myelin repair and profile of neurotrophic factors in the mice brain after cup-induced acute demyelination., Methods: Mice (C57BL/6 J) were fed with chow containing 0.2% cup for 5 weeks to induce specific OLGs degeneration and acute demyelination. Next, the cup was withdrawn to allow one-week recovery (spontaneous remyelination). At the end of this period, mature OLGs markers, myelin-associated neurite outgrowth inhibitor protein A (NogoA), premature specific OLGs transcription factor (Olig2), anti-apoptosis marker (survivin), neurotrophic factors, and AMPK activation were monitored in the presence or absence of metformin (50 mg/kg body weight/day) in the corpus callosum (CC)., Results: Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG + cells, MBP + cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2 + precursor cells., Conclusions: This study for the first time reveals that metformin-induced AMPK, a master regulator of energy homeostasis, activation following toxic demyelination could potentially accelerate regeneration and supports spontaneous demyelination. These findings suggest the development of new therapeutic strategies based on AMPK activation for MS in the near future. Graphical abstract An overview of the possible molecular mechanisms of action of metformin-mediated remyelinationa.

Aims: Gamma amino butyric acid (GABA) imbalance plays a critical role in most neurological disorders including epilepsy. This study assessed the involvement of mild exercise on GABA imbalance following by seizure induction in rats., Main Methods: Seizure was induced by pentylentetrazole (PTZ) injection. Animals were divided into sham, seizure, exercise (EX), co-seizure-induced exercise (Co-SI EX) and Pre-SI EX groups. In the Co-SI EX group, doing exercise and seizure induction was carried out during four weeks. Animals in the Pre-SI EX group exercised in week 1 to week 8 and seizures were induced in week 5 to week 8. Seizure properties, neural viability and expressions of glutamic acid decarboxylase 65 (GAD65) and GABA A receptor α1 in the hippocampus were assessed., Key Findings: Seizure severity reduced and latency increased in the Co-SI EX and Pre-SI EX groups compared to seizure group. The mean number of dark neurons decreased in all exercise groups compared to seizure group in both CA1 and CA3 areas. The gene level of GAD65 and GABA A receptor α1 was highly expressed in the Co-SI EX group in the hippocampal area. Distribution of GAD65 in the both CA1 and CA3 areas increased in the EX and Co-SI EX groups. GABA A receptor α1 was up-regulated in the CA3 area of Co-SI EX group and down-regulated in the CA1 and CA3 areas of Pre-SI EX group., Significance: These findings suggest that exercise develop anti-epileptic as well as neuroprotective effects by modulating of GABA disinhibition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q 10 (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25-30 g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5 mg/kg). The experimental groups were exposed to EMF at a frequency of 50 Hz and intensity of 5.9 mT for 7 hr daily over 1 week or treated with CoQ10 (10 mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ10., (© 2019 Wiley Periodicals, Inc.)

Introduction: One of the serious complications of stroke is memory impairment, which is considered as one of the complications of reperfusion of tissue. The present study was designed to compare the effect of administration of Trolox, carnosic acid and Human Chorionic Gonadotropin (HCG) immediately after reperfusion of the stroke tissue on the memory and hippocampal histology., Method: Ischemia-Reperfusion Model (IRI) was created by bilateral occlusion of the common carotid artery for 15 minutes and the first dose was administered immediately after reperfusion. 10 days after ischemia, passive avoidance memory test and apoptotic protein levels were evaluated., Results: Cerebral Ischemia perfusion reduced the time of latency in entering the dark box in the ischemic group. Administration of Trolox and HCG increased this latency time, while treatment with carnosic acid had no effect. Also, IRI significantly reduced the number of healthy cells in the hippocampus. Administration of Trolox, carnosic acid and HCG increased the number of healthy cells and decreased the expression of Caspase-3 and Bax, but significantly increased the expression of Bcl-2 compared to the ischemic group., Conclusion: Findings indicate the beneficial effects of HCG and Trolox on the improvement of memory and the number of healthy cells in the hippocampal region. It is worth noting that the amount of apoptosis in the hippocampus was significantly reduced by Trolox, HCG and Carnosic acid., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The resistance of temporal lobe epilepsy to classic drugs is thought to be due to disruption in the excitation/inhibition of this pathway. Two chloride transporters, NKCC1 and KCC2, are expressed differently for the excitatory state of Gamma-Amino Butyric Acid (GABA). The present study explored the effect of bumetanide as a selective NKCC1 inhibitor either alone or in combination with the phenobarbital in the pilocarpine model of epilepsy., Methods: An animal model of Status Epilepticus (SE) was induced with pilocarpine in Wistar male rats followed by phenobarbital and or bumetanide or saline administration for 45 days after the induction of SE by Intraperitoneal (IP) injection. The rats were monitored, their behavior was recorded, and after 24 hours they were sacrificed to study the expression of NKCC1 and KCC2 using real time PCR., Results: The data showed that the effects of a combination of bumetanide with phenobarbital on frequency rate and duration of seizure attack were more than those of the phenobarbital alone. In addition, in the bumetanide and combined treatment groups, NKCC1 expression decreased significantly, compared with untreated epileptic animals. A delayed decrement in NKCC1/KCC2 expression ratio after bumetanide application was also observed., Conclusion: The combination of bumetanide with phenobarbital increases the inhibition of SE and maximizes the potential of GABA signaling pathway, and can be considered as an effective therapeutic strategy in patients with epilepsy., Competing Interests: Conflict of interest There is no conflict of interest.

Cuprizone (Cup) is a copper chelating agent frequently used to study factors that affect oligodendrocytes (OLGs) death and acute demyelination. Triptolide (TP), a nuclear factor-kappaB (NF-κB) blocker, is a major bioactive component of Tripterygium wilfordii Hook f. (TWHf) with various therapeutic activities. In this study, we examined the effects of TP on neuroglia activation, inflammation, apoptosis, demyelination, and behavioral deficits in the Cup-induced toxic model of multiple sclerosis (MS). C57BL/6 J mice were fed with chow containing 0.2% Cup for 6 weeks to induce detectable neuroinflammation and myelin loss. TP was administered intraperitoneally at different doses (125, 250 or 500 μg/kg/day) during the last week of the Cup challenge. Although TP substantially decreased Cup-induced NF-κB extra activation, TNF-α and IL-1 over expression, and gliosis in a dose-dependent manner, only low dose of TP (TP-125) was able to raise the number of OLGs precursor cells (NG-2 + /O4 + ), reduce Bax/Bcl-2 ratio and improve behavioral deficits. In addition, TP-125 decreased NF-κB activation on GFAP + astrocytes more than MAC-3 + microglial and MOG + oligodendrocytes which suggested the possibility of specific dampening of NF-κB signaling in reactive astrocytes. Behavioral assessments by open-field and rota-rod tests showed that only TP-125 notably improved motor function and motor coordination compared to the Cup group. These findings highlight the pivotal role of NF-κB signaling in the oligodendrogenesis and lesion reduction in demyelination diseases such as MS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB). We have shown that this reduced expression pattern is mediated by the transcriptional co-repressor CtBP (C-terminal binding protein). Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway. Our findings have been shown that metformin has anticonvulsant and antiepileptic properties, and suggesting that antiglycolytic compounds such as metformin may represent a new class of drugs for treating epilepsy.

Multiple Sclerosis (MS), is a disease that degenerates myelin in central nervous system (CNS). Reactive oxygen species (ROSs) are toxic metabolites, and accumulating data indicate that ROSs-mediated apoptosis of oligodendrocytes (OLGs) plays a major role in the pathogenesis of MS under oxidative stress conditions. In this study, we investigated the role of endogenous antioxidant alpha-lipoic acid (ALA) as ROSs scavenger in the OLGs loss and myelin degeneration during cuprizone (cup)-induced demyelination in the experimental model of MS. Our results have shown that ALA treatment significantly increased population of mature OLGs (MOG + cells), as well as decreased oxidative stress (ROSs, COX-2 and PGE2) and apoptosis mediators (caspase-3 and Bax/Bcl2 ratio) in corpus callosum (CC). Surprisingly, ALA significantly stimulates population of NG2 chondroitin sulfate proteoglycan positive glia (NG2 + cells or polydendrocytes), from week 4 afterward. Accordingly ALA could prevents apoptosis, delays demyelination and recruits OLGs survival and regeneration mechanisms in CC. We conclude that ALA has protective effects against toxic demyelination via reduction of redox signaling, and alleviation of polydendrocytes vulnerability to excitotoxic challenge.

Context: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions., Objective: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated., Material and Methods: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p.) from the first day of cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin oligodendrocyte glycoprotein (MOG + )/caspase-3 + cells), gliosis (H&E staining, glial fibrillary acidic protein (GFAP + ) and macrophage-3 (Mac-3 + ) cells) and inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal cell-derived factor 1 α (SDF-1α) or CXCL12] during cup intoxication were examined., Results: High dose of EA (EA-80) increased mature oligodendrocytes population (MOG + cells, p < 0.001), and decreased apoptosis (p < 0.05) compared with the cup mice. Treatment with both EA doses did not show any considerable effects on the expression of CXCL12, but significantly down-regulated the expression of IL-17 and up-regulated the expression of IL-11 in mRNA levels compared with the cup mice. Only treatment with EA-80 significantly decreased the population of active macrophage (MAC-3 + cells, p < 0.001) but not reactive astrocytes (GFAP + cells) compared with the cup mice., Discussion and Conclusion: In this model, EA-80 effectively reduces lesions via reduction of neuroinflammation and toxic effects of cup on mature OLGs. EA is a suitable therapeutic agent for moderate brain damage in neurodegenerative diseases such as multiple sclerosis.

Introduction: The 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug and a major source of substance abuse, which ultimately leads to sensations of well-being, elation and euphoria, moderate derealization/depersonalization, and cognitive disruptions, as well as intense sensory awareness. The mechanisms involved in memory impairment induced by MDMA are not completely understood., Methods: The current study used 40 Sprague-Dawley rats, weighted 200 to 250 g. Experiments were performed in four groups, each containing 10 rats. The first group of rats was used as the control, treated with dimethyl sulfoxide (DMSO). The second group was treated with MDMA. The third group was treated with MDMA and CGS (the adenosine A 2A receptor agonist, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine) (CGS 21680) and the fourth group was treated with MDMA and SCH (the A 2A receptor antagonist [7-(2-phenylethyl)-5-amino-2-(2-furyl-) pyrazolo-[4, 3-e]-1, 2, 4 triazolo [1,5-] pyrimidine]) (SCH 58261). The drugs in all groups were administrated intraperitoneally (i.p.) once a day for 7 days. In 5 rats of each group, following perfusion, samples were taken from hippocampi to investigate apoptosis. Accordingly, the samples were stained using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay kit, and studied by light microscopy. In other rats, fresh tissue was also removed to study the expression of bax and bcl-2 by Western blotting technique., Results: It was observed that the coadministration of MDMA with CGS reduced bax expression and prevented apoptosis of hippocampal cells. The coadministration of MDMA and SCH increased bax expression, and also increased the frequency of hippocampal cell apoptosis., Conclusion: The results of the current study showed that administration of CGS with MDMA decreased the common side effects associated with MDMA., Competing Interests: Conflict of Interest The authors declared no conflicts of interest.

Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p) from the first day of the Cup diet. Microglia activation (microgliosis) and expression of microglia related chemokines during Cup challenge were examined. Results shows that EA significantly decreased the number of activated microglia cells (Iba-1+ cells) and also restricted proliferation of these cell population (Iba-1+/Ki67+ cells) in dose dependent manner. Consequently, concentration of microglial pro-inflammatory chemokines including monocyte chemoattractant protein-1/Chemokine (C-C motif) ligand 2 (MCP-1/CCL2), and macrophage inflammatory protein 1-alpha/Chemokine (C-C motif) ligand 3 (MIP-1-α/CCL3) dramatically reduced in CC after EA treatment. According to this results, we conclude that EA is a suitable therapeutic agent for moderation brain damages in neuro-inflammatory diseases.

Liver ischemia/reperfusion (IR) injury is a complex phenomenon that may cause local as well as remote organ injuries. Reactive oxygen species (ROS) along with many pro- and anti- inflammatory cytokines are implicated in the development of organ injury. The renal functional, histological, oxidative stress and inflammatory indices were studied during a short and a longer period of liver IR. Rats were subjected to either sham operation or 90 min partial liver ischemia followed by 4 or 24 h of reperfusion. Serum ALT, AST, ALK and LDH levels, BUN and creatinine, renal MDA level, SOD and catalase activities were evaluated as well as serum IL-6 and IL-10 concentrations along with renal histological evaluation. Ninety minutes liver ischemia /4 h reperfusion caused an increase in BUN and renal MDA levels and a decrease in SOD and catalase activities. It also caused an increase in serum IL-6 and IL-10 levels. 24 h liver reperfusion resulted in a reduction in BUN levels and lower oxidative damages demonstrated by a decrease in renal MDA levels and an increase in renal SOD and catalase activities comparing to 4 h reperfusion group. Evaluations indicated improvement in histology such as less cytoplasmic vacuolation and lower tubular debris. Serum inflammatory indices (IL-6 and IL-10 levels) were also reduced. This study showed that liver IR damage causes renal injury including functional, inflammatory and oxidative status changes. The remote kidney damage was then improved by continuing reperfusion from 4 to 24 h.