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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.)

Normal aging in mammals is accompanied by a decline in learning and memory. Dopamine plays a vital role in regulating cognitive functions, but it declines with age: During non-pathological aging, dopamine levels, receptors, and transporters decrease. Regarding the role of the dopaminergic system's changes in old age, we examined the effect of age and applied dopamine on working memory, synaptic transmission, and long-term potentiation (LTP) induction and maintenance in young adult and mature adult mice. We employed the Y-maze spontaneous alteration test to evaluate working memory. Maturation had no observed effect on working memory performance. Interestingly, working memory performance increased following intracerebroventricular administration of dopamine only in mature adult mice. We employed evoked field potential recording (in vitro) to assess the effects of age and maturation on the long-term potentiation (LTP) induction and maintenance. There was no difference in LTP induction and maintenance between young and mature adult mice before dopamine application. However, the application of dopamine on mature adult murine slices increased LTP magnitude compared to slices from young adults. According to the obtained results, it may be concluded that hippocampal neural excitability increased in mature adult subjects, and application of dopamine abolished the difference in neural excitability among young mature and adult mature groups; which was accompanied with increment of working memory and synaptic potentiation in mature adult animals., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: The mechanisms behind seizure suppression by deep brain stimulation (DBS) are not fully revealed, and the most optimal stimulus regimens and anatomical targets are yet to be determined. We investigated the modulatory effect of low-frequency DBS (L-DBS) in the ventral tegmental area (VTA) on neuronal activity in downstream and upstream brain areas in chemically kindled mice by assessing c-Fos immunoreactivity., Materials and Methods: In this experimental study, 4-6 weeks old BL/6 male mice underwent stereotaxic implantation of a unilateral stimulating electrode in the VTA followed by pentylenetetrazole (PTZ) administration every other day until they showed stage 4 or 5 seizures following 3 consecutive PTZ injections. Animals were divided into control, sham-implanted, kindled, kindled-implanted, L-DBS, and kindled+L-DBS groups. In the L-DBS and kindled+L-DBS groups, four trains of L-DBS were delivered 5 min after the last PTZ injection. 48 hours after the last L-DBS, mice were transcardially perfused, and the brain was processed to evaluate c-Fos expression by immunohistochemistry., Results: L-DBS in the VTA significantly decreased the c-Fos expressing cell numbers in several brain areas including the hippocampus, entorhinal cortex, VTA, substantia nigra pars compacta, and dorsal raphe nucleus but not in the amygdala and CA3 area of the ventral hippocampus compared to the sham group., Conclusion: These data suggest that the possible anticonvulsant mechanism of DBS in VTA can be through restoring the seizure-induced cellular hyperactivity to normal.

A patient with epilepsy was shown to have neurobiological, psychological, cognitive, and social issues as a result of recurring seizures, which is regarded as a chronic brain disease. However, despite numerous drug treatments, approximately, 30%-40% of all patients are resistant to antiepileptic drugs. Therefore, newer therapeutic modalities are introduced into clinical practice which involve neurostimulation and direct stimulation of the brain. Hence, we review published literature on vagus nerve stimulation, trigeminal nerve stimulation, applying responsive stimulation systems, and deep brain stimulation (DBS) in animals and epileptic patient with an emphasis on drug-resistant epilepsy., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2023 Iranian Neuroscience Society.)

Low frequency deep brain electrical stimulation (LFS) is a potential therapeutic strategy to control seizures in epilepsy patients. Given the functional connection of the olfactory bulb with the hippocampal formation, in this study the effect of applying LFS in the olfactory bulb on seizure severity, and learning and memory was investigated in hippocampal kindling. In male Wistar rats (250-300 g), a tripolar electrode was inserted in the CA1 region of the right hippocampus to apply kindling stimulations and record the afterdischarges (ADs). Two bipolar electrodes were also inserted bilaterally into the olfactory bulbs for applying LFS. In the kindled group, the animals received daily kindling stimulations to produce stage 5 seizures for three consecutive days. In one group of subjects, LFS was administered 2-3 min after the last kindling stimulation. Within this group, subjects were divided into two subgroups: one subgroup received two and the other subgroup received four packages of LFS protocol. Obtained data showed that bilateral LFS application to the left and right olfactory bulb reduced seizure severity. Among the protocols, applying four packages of LFS had a greater anticonvulsant effect compared to applying two packages LFS. Applying LFS in the olfactory bulb of kindled subject restored performance on measures that test short- and long-term memory - the Y maze and Morris water maze test - and applying four packages of LFS was more effective than two. These results indicated that applying LFS to the olfactory bulb had anticonvulsant effects and ameliorated the seizure-induced impairment of working and spatial memory. These effects appear to be depended on the number of applied LFS and were greater by increasing the number of LFS., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Nitric oxide (NO) deficiency is associated with obesity. Nitrate could act as a substrate for production of NO and is a novel therapeutic agent in obesity. This study aims at determining effects of long-term nitrate administration on obesity indices in normal adult female rats., Methods: Female Wistar rats were divided into four groups (n = 10/each): i.e. control group received tap water and three treatment groups received water containing 50, 100 and 150 mg/L sodium nitrate for 6 months. Body weight (g) was measured monthly; naso-anal length (cm) and obesity indices including body mass index (BMI), Lee index, abdominal and thoracic circumferences were determined every two months. Both white adipose tissue (WAT) and brown adipose tissue (BAT) were weighted and then adiposity index was calculated. In addition, level of NOx (nitrate + nitrite) in serum and adipose tissues were measured at the end of the study., Results: Compared to controls, body weights and naso-anal length were significantly (P < 0.001) lower in all nitrate-treated rats. Compared to controls, nitrate-treated rats had also lower adiposity indices, BMI, Lee index, abdominal and thoracic circumferences (13%, 17% and 22% for BMI and 5%, 6% and 8% for lee index at dose 50, 100, and 150 mg/L, respectively). In addition, nitrate administration increased NOx levels in serum and adipose tissues., Conclusions: Long-term nitrate administration has favorable effects on adiposity. It increases brown and decreases white adipose tissues in normal female rats; these observations could potentially help in management of obesity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: A common mood disorder, depression has long been considered a leading cause of disability worldwide. Chronic stress is involved in the development of various psychiatric diseases including major depressive disorder. Stress can induce depressive-like symptoms and initiate neurodegenerative processes in the brain. The neurodegenerative theory of depression holds impaired axonal transport as a negative factor in neural survival. Axonal transport is a critical mechanism for normal neuronal function, playing crucial roles in axon growth, neurotransmitter secretion, normal mitochondrial function and neural survival., Methods and Materials: To investigate the effects of stress-induced depression, in the present study, we evaluated behavior by forced swimming test (FST), corticosterone plasma level by ELISA assay, hippocampal mRNA expression of three genes (NGF, kinesin and dynein) via real-time PCR and hippocamp count by Nissl staining in male Wistar rats., Results: Our data demonstrated a significant decrease in the expression of NGF, kinesin and dynein genes in CUMS groups compared to the control group (non-stressed) (p < 0.05). CUMS also caused an elevation in immobility time and corticosterone plasma level in the stressed group compared to the controls (p < 0.01 and p < 0.05, respectively)., Conclusion: The results suggested that the possibility of stress-induced depressive behavior associated with hippocampal neurodegeneration process is correlated with a low expression of kinesin and dynein, the two most important proteins in axonal transport., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Reduced bioavailability of nitric oxide (NO) is associated with pathogenesis of type 2 diabetes. Nitrite can act as a substrate for generation of systemic NO. The aim of this study was to examine the effects of nitrite administration on glucose-stimulated insulin secretion (GSIS) and islet insulin content in obese type 2 diabetic rats., Methods: Male rats were divided into 4 groups: Control, control + nitrite, diabetes, and diabetes + nitrite. Sodium nitrite (50 mg/L in drinking water) was administered for 8 weeks. Diabetes was induced using high-fat diet and low-dose of streptozotocine. Serum levels of fasting glucose, insulin, and lipid profile were measured and the insulin resistance/sensitivity indices were calculated every 2 weeks. Glycated hemoglobin (HbA 1C ) was measured every month. At the end of the study, tissue levels of glucose transporter 4 (GLUT4) protein and serum interleukin-1 beta (IL-1β) were measured as well as glucose and insulin tolerance test were done. GSIS from isolated pancreatic islets and islet insulin content were also determined., Results: Nitrite administration significantly increased insulin secretion in both control and diabetic rats in presence of 16.7 mM glucose. Nitrite also significantly increased islet insulin content by 27% and 39% in both control and diabetic rats, respectively. Nitrite decreased elevated serum IL-1β in diabetic rats (4.0 ± 0.2 vs. 2.9 ± 0.2 pg/mL, P = 0.001). In diabetic rats, nitrite also significantly increased tissue levels of GLUT4 by 22% and 26% in soleus muscle and epididymal adipose tissue, respectively. In addition, nitrite significantly improved glucose and insulin tolerance, insulin sensitivity, lipid profile, and decreased fasting glucose and insulin, but had no effect on HbA 1C ., Conclusions: Long-term nitrite administration increased both insulin secretion and insulin content in obese type 2 diabetic rats. In addition, nitrite therapy had favorable effects on glucose tolerance, insulin resistance, inflammation, and dyslipidemia in type 2 diabetic rats., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Random-pattern skin flaps are commonly used to repair skin tissue defects in surgical tissue reconstruction. However, flap necrosis in the distal area due to ischemia injury is still challenging for its applications in plastic surgery. The complications of diabetes will further increase the risk of infection and necrosis. Methods: This study induced type 2 diabetes mellitus (T2DM) rats with a high-fat diet and STZ. The survival rate of the skin flap was observed by adding inorganic sodium nitrate to drinking water. Histology and immunohistochemistry were used to detect the damage to the skin flap. The nitrate content was measured by total nitric oxide and nitrate/nitrite parameter assay. Dihydroethidium and malondialdehyde (MDA) assays were used to value oxidative stress. Rat colon feces were collected for 16s rRNA gene sequence. Results: Our studies showed that nitrate administration leads to anti-obesity and anti-diabetic effects. Nitrate directly increased the survival area of skin flaps in diabetic rats and mean blood vessel density by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. The 16s rRNA sequence revealed that nitrate may regulate the homeostasis of the gut microbiota and re-store energy metabolism. Conclusion: Dietary nitrate has been shown to maintain the homeostasis of oxidative stress and gut microbiota to promote flap survival in rats with T2DM. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in reproductive-aged women, is associated with metabolic disturbances. The present study aimed to examine changes in body weight (BW) and glucose and insulin tolerance in a prenatally-androgenized (PNA) rat model of PCOS compared to control with increasing age. Pregnant rats in the experimental group were subcutaneously injected with 5 mg of free testosterone on the 20th day of pregnancy, while the control group received the solvent. Female offspring of both groups, PNA rats (rat model of PCOS) and control, were examined in terms of changes in BW, glucose and insulin tolerance at 3, 6, 12 and 20 months of age. BW at birth (6.53 ± 0.89 vs. 5.60 ± 1.18 g; P = 0.038), 15 (25 ± 1.15 vs. 22.36 ± 3.98 g; P = 0.019) and 30 (59.37 ± 10.19 vs.49.9 ± 9.39 g; P = 0.022) days of age was significantly increased in the rat model of PCOS compared to control, but no significant differences were observed in BW of the rat model of PCOS compared to control at 60 (P = 0.155) and 75 (P = 0.932) days or at 3 (P = 0.239), 6 (P = 0.782), 12 (P = 0.755) and 20 (P = 0.092) months of age. Rat model of PCOS showed impaired glucose tolerance (IGT) at 3 months of age (P = 0.020) and insulin resistance (IR) with increasing age (3-20 months of age) compared to control. Increased BW before puberty, IGT at 3 months of age and IR with increasing age were observed in our rat model of PCOS. This rat model may contribute to a better understanding of underlying mechanisms of changes in BW, IGT and IR in future studies., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Mean-field models have been developed to replicate key features of epileptic seizure dynamics. However, the precise mechanisms and the role of the brain area responsible for seizure onset and propagation remain incompletely understood. In this study, we employ computational methods within The Virtual Brain framework and the Epileptor model to explore how the location and connectivity of an Epileptogenic Zone (EZ) in a mouse brain are related to focal seizures (seizures that start in one brain area and may or may not remain localized), with a specific focus on the hippocampal region known for its association with epileptic seizures. We then devise computational strategies to confine seizures (prevent widespread propagation), simulating medical-like treatments such as tissue resection and the application of an anti-seizure drugs or neurostimulation to suppress hyperexcitability. Through selectively removing (blocking) specific connections informed by the structural connectome and graph network measurements or by locally reducing outgoing connection weights of EZ areas, we demonstrate that seizures can be kept constrained around the EZ region. We successfully identified the minimal connections necessary to prevent widespread seizures, with a particular focus on minimizing surgical or medical intervention while simultaneously preserving the original structural connectivity and maximizing brain functionality. [ABSTRACT FROM AUTHOR]

Sodium nitrite and quercetin are frequently employed as protective agents on glucose levels, levels of thyroid hormones, and lipid profile. The present study aimed to see the quercetin effect on some biochemical parameters in adult rats treated with sodium nitrite. A total of twenty-one laboratory animals (Wistar albino rats) were used in this experiment, separated into three groups of seven animals each. During the trial, Group I was given water only to drink and Group II received sodium nitrite directly by oral feeding needle. The study used 80 mg.kg-1/body weight (BW) of sodium nitrite, while Group IIIreceived drinking water containing sodium nitrite orally in doses of up to 80 mg.kg-1 BW and quercetin with a (50 mg/kg). After blood was drawn and serum extracted, the parameters determined were thyroid hormones, lipids, Homeostasis Model Evaluation for Insulin Resistance (HOMA-IR) and glucose level. The study observed that compared to the controls, the insulin (HOMA-IR) and sugar levels and lipid profile of the sodium-nitrite treated group were much higher. The sodium nitrite-treated group also had a substantial drop in thyroid hormone concentrations and a rise in Thyroid Stimulated Hormone (TSH), whereas the quercetin alleviated the harmful effects of sodium nitrate by lowering blood sugar, insulin, HOMA-IR, and improved the lipid profile. There was an improvement in glucose, insulin resistance, lipidemia, and TSH hormone levels, which increased as a result of exposure to nitrite. Thus, the present study demonstrated how quercetin protected against sodium nitrite-induced toxicity by improving several biochemical parameters in adult rats. [ABSTRACT FROM AUTHOR]

Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABAA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABAA receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABAA receptor subunit genes. OS was calculated using the Kaplan–Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABAA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABAA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABAA receptors as a therapeutic target in glioma. [ABSTRACT FROM AUTHOR]

The organ of Corti of mammals has an organized structure in which row of inner and outer hair cells (HCs) are enclosed within the numerous cells on the basilar membrane. Given the prevalence of sensorineural hearing loss due to aging and acoustic insult, it is highly desirable to develop a protocol that produces cochlear sensory cells and their associated spiral sensory neurons as a tool to advance understanding of inner ear development. The replacement of damaged auditory neurons holds promise for significantly improving clinical outcomes in deaf patients. Cell therapy is one of the treatment options for deafness. The progress in cell therapy and reprogramming techniques has opened avenues to stimulate either endogenous or transplanted stem cells, aiming to replace and repair damaged inner ear HCs and restore auditory function. In fact, current research focuses on generating functional HCs. Various approaches are being explored to regenerate auditory HCs and facilitate neural connections. Here is an overview of existing experimental culture setups for the HCs and auditory neurons regeneration and their potential treatment for hearing disorders [ABSTRACT FROM AUTHOR]

Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3−) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional l-arginine–NO synthase (l-NOS) pathway, whereas endogenous NO production by l-arginine is inhibited under hypoxia–ischemia or disease conditions. In contrast, exogenous NO3−/NO2−/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3−/NO2−/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3−/NO2−/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria. [ABSTRACT FROM AUTHOR]

Neuropsychiatric disorders have a high incidence worldwide. Kinesins, a family of microtubule-based molecular motor proteins, play essential roles in intracellular and axonal transport. Variants of kinesins have been found to be related to many diseases, including neurodevelopmental/neurodegenerative disorders. Kinesin-12 (also known as Kif15) was previously found to affect the frequency of both directional microtubule transports. However, whether Kif15 deficiency impacts mood in mice is yet to be investigated. In this study, we used the CRISPR/Cas9 method to obtain Kif15−/− mice. In behavioral tests, Kif15−/− female mice exhibited prominent depressive characteristics. Further studies showed that the expression of BDNF was significantly decreased in the frontal cortex, corpus callosum, and hippocampus of Kif15−/− mice, along with the upregulation of Interleukin-6 and Interleukin-1β in the corpus callosum. In addition, the expression patterns of AnkG were notably changed in the developing brain of Kif15−/− mice. Based on our previous studies, we suggested that this appearance of altered AnkG was due to the maladjustment of the microtubule patterns induced by Kif15 deficiency. The distribution of PSD95 in neurites notably decreased after cultured neurons treated with the Kif15 inhibitor, but total PSD95 protein level was not impacted, which revealed that Kif15 may contribute to PSD95 transportation. This study suggested that Kif15 may serve as a potential target for future depression studies. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possible effects of chronic nitrate supplementation on the metabolites of energy metabolism during high-intensity, high-volume intermittent training (HIHVT). In this placebo-controlled double-blind study, 17 participants exercised 3 times a week on a cycle ergometer. Sodium nitrate or sodium chloride as the placebo was supplemented daily at 8.5 mg/kg body weight for 10 days. The training exercise consisted of a warm-up, a 45-min interval period, and a post-exercise period. Oxygen uptake, respiratory exchange ratio, and various parameters were measured in the venous blood and plasma. During training, the oxygen uptake and respiratory exchange ratio did not differ between the nitrate and the placebo group. Venous plasma concentrations of nitrate and nitrite were significantly increased in the nitrate group (p < 0.001 and p = 0.007, respectively). Triglyceride concentrations were significantly lower in the nitrate group than in the placebo group (p = 0.010). The concentration of free fatty acids in the plasma did not change upon nitrate supplementation and no significant differences were observed in the contribution of fat to energy metabolism during exercise. An increase in plasma ammonia concentration was observed in the nitrate group during and after exercise (p = 0.048). Metabolites of energy-rich phosphates did not differ between the nitrate and chloride groups, suggesting no improvement in efficiency through the supplemented nitrate. It was concluded that nitrate supplementation did not reduce oxygen uptake and adenosine triphosphate resynthesis by hydrolysis or through creatine kinase activity during high-intensity, high-volume intermittent exercise. Although, lipid metabolism as well as amino acid metabolism might be affected by nitrate supplementation during HIHVT. [ABSTRACT FROM AUTHOR]

Objective(s): Nitrite, a nitric oxide (NO) donor, increases insulin secretion from pancreatic islets and has positive metabolic effects in type 2 diabetes (T2D). Here, we test the hypothesis of whether nitrite-induced insulin secretion is due to blunting of diabetes-induced oxidative stress in the islets. Materials and Methods: T2D was created in male rats using a combination of streptozotocin at 25 mg/kg and a high-fat diet. Wistar rats were assigned to 3 groups (n=6 in each group), including control, T2D, and T2D+nitrite; the latter group consumed drinking water containing sodium nitrite (50 mg/l) for eight weeks. At the end of the study, mRNA levels of NADPH oxidase (Nox1, 2, 3, and 4), superoxide dismutase (SOD1, 2, and 3), glutathione peroxides (GPX1 and 7), glutathione reductase (GR), catalase, thioredoxin (TXN1 and 2), and thioredoxin reductase (TXNRD1) were measured in the isolated pancreatic islets. Results: In the islets of diabetic rats, mRNA expressions of Nox1, 2, and 4 were higher, whereas expressions of SOD1, 2, catalase, GPX1, 7, GR, and TXN1 were lower than controls. Nitrite significantly (all P-values<0.05) decreased gene expression of Nox1 (0.39-fold) and Nox4 (0.23-fold) and increased gene expression of SOD1 (2.2-fold), SOD2 (2.8-fold), catalase (2.7-fold), GPX1 (2.2- fold), GPX7 (6.0-fold), GR (3.0-fold), TXN1 (2.1-fold), and TXNRD1 (2.3-fold) in diabetic rats. Conclusion: Nitrite decreased oxidative stress in isolated pancreatic islets of rats with T2D by suppressing oxidants and augmenting anti-oxidants. These findings favor the notion that nitriteinduced insulin secretion is partially due to decreased oxidative stress. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Decreased nitric oxide (NO) bioavailability is involved in the pathophysiology of T2D and its complications. L‐citrulline (Cit), a precursor of NO production, has been suggested as a novel therapeutic agent for T2D. Available data from human and animal studies indicate that Cit supplementation in T2D increases circulating levels of Cit and L‐arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia. The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β‐oxidation, and decreased glyceroneogenesis in the adipose tissue. Thus, Cit has antihyperglycemic, antidyslipidemic, and antioxidant effects and has the potential to be used as a new therapeutic agent in the management of T2D. This review summarizes available literature from human and animal studies to explore the effects of Cit on metabolic parameters in T2D. It also discusses the possible mechanisms underlying Cit‐induced improved metabolic parameters in T2D. [ABSTRACT FROM AUTHOR]

Background & Aims: Type 2 diabetes is the most common endocrine disease occurs due to glucose intolerance due to imbalance between reserves and insulin demand. Diabetes can also cause damage and cell death or apoptosis (1, 2).Recent research shows the vital role of p53 in the development of diabetes. The aim of this study was to study changes in p53 gene expression in liver tissue and insulin resistance index after HIIT and Zataria multiflora (Thyme) extract in obese type 2 diabetic rats. Methods: The statistical population of the study consisted of male Wistar rats from Royan Institute. All rats were fed a high-fat diet (45 to 60% fat) for 5 months or 20 weeks. after the Rats became obese and reached an average weight of about 407 ± 50 g, to create a type 2 diabetic model, 25mg/kg STZ was injected intraperitoneally. Rats with fasting glucose between 150 to 400 mg/dl was considered as a criterion for diabetes and all rats were diabetic divided into 4 groups control, HIIT, Thyme, HIIT-Thyme. HIIT protocol, performed for five sessions per week with 2-minute alternation of 2 and 8 intervals with 80 to 90% VO2max and a one-minute rest cycle with 50 to 56% vo2max. Running time increased from 16 minutes in the first week to 34 minutes in the eighth week. Thyme extract was given by gavage at a dose of 200 mg / kg 5 days a week for eight week. At the end of the training period and 48 hours after the last training session, the experimental training groups and after 12 hours of fasting, the rats were anesthetized and sacrificed by ether anesthetic. Blood samples were collected from the heart. Glucose was measured using an auto-analyzer. Insulin measured by a special kit of Pars Azmoun Company. The insulin resistance index was calculated using the formula and the expression of liver tissue P53 genes expression was also measured by RT-PCR. Statistical analyze performed with one-way ANOVA and two-factor analysis of variance test for comparison between groups and determination of the effect size and post-hoc method. Results: According to the results, these findings were observed: The mean weight in the experimental groups of exercise, thyme and HIIT-Thyme groups increased slightly compared to control group. The mean concentration of glucose in the exercise group was significantly lower than the control group (P = 0.001) and also in the HIIT-Thyme group, there was no significant difference (P = 0.99) compared to the thyme group. Moreover, in the Thyme-HIIT group there was a significant decrease (P = 0.001) compared to the control group. Also, HIIT led to a significant reduction in glucose and insulin resistance index (P<0.05). The mean insulin concentration in the HIIT group was significantly higher than the control group (P = 0.005) group and in the HIIT-Thyme group was not significantly different compared to the thyme group (P = 0.218); however, the Thyme group had a significant increase compared to the control group. The mean insulin resistance index in the HIIT group (2.04) and ThymeHIIT was significantly lower than the control group but Thyme group was not significantly different from the control group (P = 0.994).HIIT reduced P53 gene expression in hepatocytes compared with controls (P <0.009). HIIT and consumption of Thyme extract also significantly reduced P53 gene expression in hepatocytes compared with the control group (P <0.05). Conclusion: The P53 gene, which is a tumor suppressor gene, is mutated and inactive in a wide range of cancers, this gene has been given the title of "protector of the genome", now new research shows that this gene has profound effects on metabolism and other Its activation can lead to obesity and type 2 diabetes, and for this reason another name was given to this gene "protector against obesity" (11). While the role of this gene is well known during decades of cancer research, little information is available about its role in metabolism. Previous studies have shown that the role of P53 in metabolism and its function is important for tumor suppression (12), this gene also has effects on heart disease, obesity and type 2 diabetes (13).P53 gene regulates glucose transporters. Maintaining proper function of glucose transporters is crucial in glucose homeostasis and suppression of diabetes (11). P53 regulates the function of glucose transporters by influencing their transcription and transport. For example, p53 activated by genotoxic stress can directly bind to GLUT1 and GLUT4 promoters and repress their transcription. P53 also suppresses GLUT3 expression, but this occurs through an indirect mechanism by inhibiting IkB kinase or IKK (11). P53 gene negatively regulates glycolysis. It affects glucose levels by directly regulating degradation (glycolysis) and synthesis (gluconeogenesis). Following DNA damage, p53 can reprogram the cell's energy production strategies from glycolysis to mitochondrial respiration (or oxidative phosphorylation) in order to suppress tumor progression (11). The first p53 target gene identified to inhibit glycolysis is TIGAR (TP53-induced glycolysis and apoptosis regulator) (30). TIGAR overexpression reduces the level of fructose 2, 6-bisphosphate (Fru-2, 6-P2), which activates the glycolysis promoter PFK1 (6-phosphofructo-1-kinase). P53 also regulates the stability of phosphoglycerate mutase (PGM), another enzyme important for the completion of glycolysis through the conversion of 3-phosphoglycerate (3-PG) to 2- phosphoglycerate (2-PG). It has been shown that the pentose phosphate pathway (PPP), an alternative mechanism for glucose consumption for energy production, is partially blocked by p53 through a direct interaction between p53 and its rate-limiting enzyme, glucose 6-phosphate dehydrogenase (G6PD). 30). P53 also negatively regulates pyruvate dehydrogenase kinase-2 (PDK2) through both transcriptional and post-translational mechanisms to activate the PDH complex that converts pyruvate to acetyl-CoA to shift the balance from glycolysis to mitochondrial respiration (28, 31). The results of the present study show a significant decrease in the expression of the P53 gene in the liver tissue in the intense interval training group, and also the decrease in the expression of this gene in the interaction group of interval training - thyme can indicate the effect of interval training on the decrease in the expression of the P53 gene in the liver tissue. According to the mentioned regulatory pathways, but in the thyme group alone, no significant decrease in the expression of this gene was observed, which can be inferred that when using thyme extract to use its medicinal, antioxidant and anti-inflammatory properties, performing periodic exercises its effectiveness can be improved by further reducing the expression of the P53 gene. Suppression of hepatic glucose production by reducing the expression of the P53 gene can effectively improve diabetes and be used to treat it, in a way, it can be said that targeting components in the gluconeogenic pathway can improve hyperglycemia (10, 11). HIIT with thyme extract in diabetic rats led to improved glycemic profile and changes in glucose and insulin levels, as well as positive and appropriate changes in the expression of P53 gen expression in hepatic tissue. [ABSTRACT FROM AUTHOR]

Many short-term studies with dietary nitrate supplementation in humans and animal models reported positive effects on the cardiovascular system, exercise efficiency, and immune function. However, there has been long-standing concern related to cancer and adverse hormonal effects. We studied the long-term effects of different potassium nitrate (KNO3) concentrations on laboratory mice longevity and structural changes in their organs. Four groups of male mice were treated with 0 mg (0%), 45 mg (1%), 90 mg (2%), and 140 mg (3%) KNO3 in the drinking water. The groups were monitored for agility and health status daily. The lifespan of mice and organ pathological changes were analyzed. We found no detrimental effects of life-long supplementation of KNO3 on the survival of mice in treatment groups. Nitrate supplementation was associated with a lower level of pathological changes (p = 0.002). We conclude that KNO3 supplementation had no carcinogenic effect on mice and possibly prevented the organs from aging. [ABSTRACT FROM AUTHOR]

Nitrate, a nitric oxide (NO) donor, has antiobesity effect in female rats. This study hypothesized that the antiobesity effect of nitrate in female rats is due to the browning of white adipose tissue (WAT). Female Wistar rats (aged 8 months) were divided into two groups (n = 10/group): the control group received tap water and the nitrate group received water containing 100 mg/L of sodium nitrate for 9 months. At months 0, 3, 6, and 9, obesity indices were measured. At month 9, gonadal adipose tissue was used to measure messenger RNA (mRNA) and protein levels of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), PPAR‐γ coactivator 1‐α (PGC1‐α), uncoupling protein 1 (UCP1), and adipocyte density and area. After the 9‐month intervention, nitrate‐treated rats had lower body weight, body mass index, thoracic circumference, and abdominal circumference by 6.4% (p =.012), 9.1% (p =.029), 6.0% (p =.056), and 5.7% (p =.098), respectively. In addition, nitrate‐treated rats had higher PPAR‐γ (mRNA: 1.78‐fold, p =.016 and protein: 19%, p =.076), PGC1‐α (mRNA: 1.69‐fold, p =.012 and protein: 68%, p =.001), and UCP1 (mRNA: 2.50‐fold, p =.001 and protein: 81%, p =.001) in gonadal adipose tissue. Nitrate also reduced adipocyte area by 35% (p =.054) and increased adipocyte density by 31% (p =.086). In conclusion, antiobesity effect of nitrate in female rats is associated with increased browning of gonadal adipose tissue as indicated by higher expression of PPAR‐γ, PGC1‐α, and UCP1 and reduced adipocyte area and increased adipocyte density. Significance statement: In this study, the effect of nitrate on obesity indices as well as the expression of the genes involved in the browning of white adipose tissue (WAT), including peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), PPAR‐γ coactivator 1‐α (PGC1‐α), and uncoupling protein 1 (UCP1) were measured in female rats. Results indicate that after a 9‐month intervention, nitrate‐treated rats had lower body weight, body mass index, thoracic, and abdominal circumference. In addition, chronic nitrate administration at a low dose increased mRNA and protein levels of PPAR‐γ, PGC1‐α, and UCP1, decreased adipocyte area, and increased adipocyte density in the gonadal adipose tissue. These findings indicate that the antiobesity effect of nitrate is associated with the browning of WAT. [ABSTRACT FROM AUTHOR]

Sulfur-doped graphitic carbon nitride (S-g-C3N4) is introduced as a novel mercury ion recognition element in order to fabricate Hg2+-selective potentiometric sensor. S-g-C3N4 was synthesized via heating the mixture of urea and thiourea. The obtained material was characterized utilizing different techniques. The S-g-C3N4 material was then applied to a carbon paste electrode (CPE) in order to construct a potentiometric sensor. It was found that, the electrode, impregnated with S-g-C3N4, exhibited significant sensitivity for mercury ion concentration change. However, the graphitic materials obtained via pyrolysis of pure urea or pure thiourea were not sensitive to mercury ion. Moreover, it was shown that, chemical exfoliation of bulk S-g-C3N4 into the nanosheets (nano-S-g-C3N4) led to significantly better potentiometric response for mercury ion, regarding the Nernstian slope of the related potentiometric electrode. The electrode containing 80% graphite powder, 1% NaTPB, 5% nano-S-g-C3N4 and 14% n-eicosane provided a stable potential response to Hg2+ and exhibited a Nernstian slope of 30.17 (± 0.61) mVdecade−1, over a wide linear concentration range of 1 × 10–7–1 × 10–2 mol L−1. The detection limit of the electrode was estimated to be 6.5 × 10–8 mol L−1. The electrode provided fast response time of 50 s and long-term stability (more than 5 months). The most important interfering ions such as Cu2+, Pb2+, Ni2+and Cd2+ showed no significant effect on the potential response of the S-g-C3N4-modified CPE, highlighting the selective performance of this sensor. This sensor was applied for mercury ion content estimation in some types of water samples. [ABSTRACT FROM AUTHOR]

Background and Objective: Nitrate, as nitric oxide (NO) donor, has been suggested as a nutrition-based treatment for decreasing the risk of menopause-related obesity. This study aimed to specify the effects of chronic inorganic nitrate administration on uncoupling protein-1 (UCP-1), peroxisome proliferator-activated-receptor-947; (PPAR-947;) coactivator-1945; (PGC-1945;), and PPAR-947; expression in gonadal adipose tissue (GAT) of ovariectomized (OVX) rats., Methods: Female rats were assigned to 3 groups: Control, OVX, and OVX+nitrate (n=7/group), which consumed water containing inorganic nitrate (100 mg/L) for 9 months. At month 9, GAT was used for the measurement of NO metabolites (NOx), mRNA levels of NO synthases (endothelial (eNOS), inducible (iNOS), neuronal (nNOS)), and mRNA and protein levels of UCP-1, PGC-1945;, and PPAR-947;., Results: OVX rats had lower NOx concentration (45%) and eNOS (38%) and nNOS (30%) expression in GAT that was restored to normal values following nitrate administration. OVX rats had significantly lower mRNA and protein levels of UCP-1 (83% and 30%), PGC-1945; (65% and 39%), and PPAR-947; (66% and 34.5%) in GAT. Chronic inorganic nitrate administration in OVXrats increased mRNA and protein levels of UCP-1 (128% and 34%), PGC-1945; (115% and 43%), and PPAR-947; (236% and 38%), respectively., Conclusion: In OVX rats, chronic nitrate administration increased gene and protein levels of UCP-1, PGC-1945;, and PPAR-947; in GAT, indicating the anti-obesity effects of nitrate are partially mediated by the white adipose tissue (WAT) browning. Moreover, the stimulatory effect of inorganic nitrate on the WAT browning in OVX rats was associated with blunting the OVXinduced NO deficiency in GAT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Exercise and antioxidants consumption are known as protective effect against the risk of diabetes. Therefore, the current study aimed to investigate the effects of eight weeks of high-intensity interval training (HIIT) and thyme honey on the expression of Nkx2.5 and Tbx5 genes in the heart tissue of male type 2 diabetic rats. Material & Methods: This experimental study was performed on 36 male diabetic rats which were randomly divided into four groups of control (n=8), HIIT (n=10), thyme honey (n=8), and HIIT+thyme honey (n=10). The HIIT training intervention was conducted in eight weeks (five sessions per week) and included 2 to 8 intervals with 2 min running at 80%-90% VO2max and 1 min at 50%-56% VO2max. Additionally, the supplement groups consumed 3 g/kg of thyme honey, 5 days/week. Both Nkx2.5 and Tbx5 gene expression in heart tissue were measured using real-time RTPCR. To evaluate the differences among the groups, ANOVA and LSD post hoc tests were used at the significance level of P≤0.05. (Ethic code: IR.SSRC.REC.1399.080) Findings: The results revealed that the expression of the Nkx2.5 gene was significantly increased only in the HIIT group, compared to the control group (P=0.03); however, it was not observed in other intervention groups (P>0.05). The expression of the Tbx5 gene was significantly increased in both HIIT (P=0.02) and HIIT+thyme honey (P=0.02) groups, compared to the control group. Discussion & Conclusion: The HIIT is associated with increased expression of the Nkx2.5 and Tbx5 genes in the heart tissue of diabetic rats; however, it can not be said exactly that thyme honey has similar effects in diabetic rats. [ABSTRACT FROM AUTHOR]

Introduction: Chronic stress, which has been prevalent in human life, induce structural changes in the hippocampus. Depression and impairment of memory are serious comorbidities of chronic stress. In this study, we evaluated the impact of an Iranian honey pretreatment on memory deficit, depression and the hippocampal neuronal loss in the chronic unpredictable mild stress (CUMS) model. Methods: Adult male Wistar rats were divided into the control groups that received water or honey (0.2 or 2g/kg) and CUMS groups that subjected different, randomly and unpredictable mild stressors for 4 weeks. Ten days before starting the CUMS procedures, the animals received honey (0.2 or 2g/kg, daily, orally), which was continued until sacrificing. Morris water maze and sucrose performance tests were used to evaluate the spatial learning and memory and depressive-like behavior in the animals respectively. Hippocampus and whole brain samples were collected for further biochemical and histological analysis. Results: Honey reversed the depression-like behavior and ameliorated the spatial memory deficit induced by CUMS. Also, honey decreased cell death in the hippocampus and reduced the malondialdehyde level in treated animals. Conclusion: These results revealed that honey diminished learning and memory deficits and depression in chronic stress conditions. [ABSTRACT FROM AUTHOR]

Diabetic mellitus is a chronic metabolic disorder that is associated with several complications including testicular dysfunction. This research investigated the protective action of the ethyl acetate extract from Shorea roxburghii (SRE) on diabetes induced testicular damage in rats. Diabetic rats were orally administered with SRE at doses of 100 and 400 mg/kg for 4 weeks. SRE improved the body weight gain, testes weight, testes index and increased serum concentration of testosterone. Furthermore, SRE increased the testicular antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase. In addition, SRE ameliorated testicular inflammatory mediators such as myeloperoxidase, tumor necrosis factor alpha, interleukin 6, p38 MAPK and nuclear factor kappa B activation and decreased testicular cell apoptosis in the treated diabetic rats. SRE also raised sperm parameters after treatment of diabetic rats. Conclusively, our results suggested that SRE ameliorated diabetes induced testicular damage by inhibiting oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Is aortic dysfunction, a significant contributor to cardiovascular disease in metabolic syndrome, expressed uniformly across both the thoracic and abdominal aorta?What is the main finding and its importance?Our study shows that, in the setting of metabolic syndrome, functional and structural deficits in the aorta are differentially expressed along its length, with the abdominal portion displaying more extensive vascular abnormalities. It is, therefore, likely that early interventional strategies targeting the abdominal aorta might alleviate cardiovascular pathologies driven by the metabolic syndrome. The extent of vascular dysfunction associated with metabolic syndrome might vary along the length of the aorta. In this study, we investigated regional functional and structural changes in the thoracic and abdominal aorta of a rat model of metabolic syndrome, namely, high‐fat diet (HFD) streptozotocin‐induced diabetes mellitus (HFD‐D). Four‐week‐old male Wistar albino rats were fed with either HFD or control diet (CD) for 10 weeks. At week 6, 40 mg/kg streptozotocin and its vehicle were injected i.p. into HFD and CD groups, respectively. At the end of the feeding period, rats were euthanised and aortic segments collected for assessment of vascular functional responses and histomorphometry. Tail‐cuff systolic blood pressures (154 ± 6 vs. 110 ± 4 mmHg) and areas under the curve for oral glucose and i.p. insulin tolerance tests were greater in HFD‐D versus CD rats. Abdominal aortic vasoconstriction in response to noradrenaline and KCl was greater in HFD‐D compared with CD rats. Thoracic vasoconstrictor responses to noradrenaline, but not KCl, were greater in the HFD‐D group. Abdominal, but not thoracic, endothelium‐dependent vasorelaxation in response to acetylcholine was blunted in HFD‐D relative to CD rats; however, nitric oxide‐dependent vasorelaxation in HFD‐D rats was impaired in both thoracic and abdominal segments. The abdominal aorta of HFD‐D rats showed deranged interlamellar spacing and increased lipid plaque deposition. In conclusion, vascular dysfunction in metabolic syndrome is expressed differentially along the length of the aorta, with the abdominal aorta exhibiting increased susceptibility to vasoconstrictors and greater deficits in endothelium‐dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Purpose: To critically examine the research on novel supplements and strategies designed to enhance carbohydrate delivery and/or availability. Methods: Narrative review. Results: Available data would suggest that there are varying levels of effectiveness based on the supplement/supplementation strategy in question and mechanism of action. Novel carbohydrate supplements including multiple transportable carbohydrate (MTC), modified carbohydrate (MC), and hydrogels (HGEL) have been generally effective at modifying gastric emptying and/or intestinal absorption. Moreover, these effects often correlate with altered fuel utilization patterns and/or glycogen storage. Nevertheless, performance effects differ widely based on supplement and study design. MTC consistently enhances performance, but the magnitude of the effect is yet to be fully elucidated. MC and HGEL seem unlikely to be beneficial when compared to supplementation strategies that align with current sport nutrition recommendations. Combining carbohydrate with other ergogenic substances may, in some cases, result in additive or synergistic effects on metabolism and/or performance; however, data are often lacking and results vary based on the quantity, timing, and inter-individual responses to different treatments. Altering dietary carbohydrate intake likely influences absorption, oxidation, and and/or storage of acutely ingested carbohydrate, but how this affects the ergogenicity of carbohydrate is still mostly unknown. Conclusions: In conclusion, novel carbohydrate supplements and strategies alter carbohydrate delivery through various mechanisms. However, more research is needed to determine if/when interventions are ergogenic based on different contexts, populations, and applications. [ABSTRACT FROM AUTHOR]

Introduction: Mood disorders such as depression and anxiety disorders have been affecting a relatively high proportion of the world's population. Neuroplasticity hypothesis of depression proposes that lack of brain-derived neurotrophic factor (BDNF) can cause structural changes in the brain. The extract of Ginkgo biloba (Gb) leaves can restore much of the damage in the nervous system. We examined the antidepressant role of Gb extract (EGb 761) on BDNF expression modulation in the hippocampus of rats subjected to repeated restraint stress (RRS). Methods: Adult male rats were randomly divided into 10 groups: control, controlvehicle treated, stress, stress-vehicle treated, as well as three control and three experimental groups pretreated with EGb (15, 30, 60mg/kg, IP daily) for 21 days. They underwent restraint stress on a daily basis, 6 hours for 21 consecutive days. Weight changes, locomotor activity and forced swim test (FST) were employed to assess depressive-like symptoms. The serum corticosterone level was also measured by ELISA. Hippocampal BDNF DNA methylation and protein expression were assayed by methylation sensitive restriction enzymes (Real Time PCR) and Western-blotting respectively in all groups. Results: Pre-treatment with 30 and 60 mg/kg/day of Gb extract significantly attenuated depressive-like effects in the body weight, FST and serum corticosterone level in RSS rats compared to control groups. Further, it inhibited chronic stress-induced alterations in the hippocampal BDNF DNA methylation and protein expression. Conclusion: These findings suggest that Gb can induce an antidepressant role through its modulation effect on the hippocampal BDNF expression. [ABSTRACT FROM AUTHOR]

2-(N-pipyridino methyl)-1-cyano cyclohexanol was synthesized, characterized and used as an ionophore in construction of polyvinyl chloride (PVC) potentiometric sensor for Hg2+ determination. The best result was obtained with membrane composition of PVC (29%), sodium tetraphenylborate as ionic additive (1%), 2-(N-pipyridino methyl)-1-cyano cyclohexanol (12%) and dibutylphthalate (58%). The designed electrode showed an acceptable Nernstian slope (29.1 mV/decade) for Hg2+ over a wide concentration range from 5 × 10–7 to 1 × 10–2 M with a detection limit of 2.5 × 10–7 M. The potential response was independent from pH in the range of 6.0–9.0 and the sensor response time was relatively short (~25 s). The sensor performance was invariable for at least 6 weeks. Electrode selectivity was evaluated by matched potential method. Finally, the proposed sensor was used as an indicator electrode in potentiometric titration of Hg2+ with ethylenediaminetetraacetic acid and in direct determination of mercury(II) in aqueous samples with admissible accuracy and high reproducibility. [ABSTRACT FROM AUTHOR]

Mitogen-activated protein kinase (MAPK) signal transduction pathways may be involved in the destruction of pancreatic islet β cells induced by inflammatory cytokines. The present study aimed to investigate the role of different MAPK signal transduction pathways in the interleukin-1β (IL-1β)-induced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 mouse pancreatic cells. Min6 cells were stimulated with different concentrations of glucose (0.0, 5.5, 11.1 and 22.2 mmol/l), or different concentrations of IL-1β (0.00, 0.25 and 2.50 ng/ml) in combination with high glucose (22.2 mmol/l) and the culture supernatant was collected. The concentration of insulin was measured by enzyme-linked immunosorbent assay and the activation of different MAPK pathways was assessed by measuring the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-jun N-terminal kinase (JNK) via western blotting. The production of reactive oxygen species (ROS) was determined via flow cytometry, and cell viability was detected by Cell Counting Kit-8 assay. Reverse transcription-quantitative PCR was used to detect the insulin 1 gene. The results revealed that glucose activated ERK1/2 phosphorylation, but inhibited JNK and p38 phosphorylation in a concentration-dependent manner. Furthermore, IL-1β inhibited glucose-stimulated insulin secretion in a dose-dependent manner. Western blotting revealed that IL-1β inhibited the activation of ERK1/2 phosphorylation and attenuated the inhibition of p38 phosphorylation induced by glucose stimulation. JNK was neither activated nor inhibited by IL-1β. These results suggest that MAPK signal transduction pathways participated in the IL-1β-induced GSIS inhibition in Min6 cells, with the ERK1/2, JNK and p38 signaling pathways playing different roles. [ABSTRACT FROM AUTHOR]

Background and Aim. Rutin is a flavonol with neuroprotective activity. The aim of the present study is to investigate the role of the glutamatergic system in the antidepressant-like effect of rutin in a mouse model of maternal separation (MS) stress focusing on histological changes in the CA3 area of the hippocampus. Methods. Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups (n = 8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes. Results. Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration. Conclusion. Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin. [ABSTRACT FROM AUTHOR]

The antidiabetic properties of Tiliacora triandra ethanol extract in diabetic rats induced with high‐fat diet (HFD)/streptozotocin (STZ) was investigated. Rats were fed with HFD for 4 weeks to induced insulin resistance, and thereafter administered with 35 mg/kg of STZ to induce diabetes. Diabetic rats received 100 and 400 mg/kg of T. triandra daily for 30 days. The body weight, blood glucose level, food and fluid intake were monitored. Furthermore, biochemical and histological assessment was performed to evaluate the hypoglycemic effect of the extract in the treated rats. T. triandra significantly decreased the blood glucose level, increased the body weight and insulin secretion. Furthermore, T. triandra attenuated hyperlipidemia, improved liver and kidney functions of treated diabetic rats. Thus, T. triandra could effectively attenuate diabetes and it complications. Practical applications: Tiliacora triandra is a common vegetable consumed in Thailand and Laos. It is traditionally employed in the treatment of fever, cancer, malaria, and diabetes. The extract from the aerial part was investigated for its antidiabetic properties. The results obtained provides important pharmacological information that supports the use of T. triandra in management of diabetes. [ABSTRACT FROM AUTHOR]

Background: Obesity is characterized by excessive body fat, insulin resistance and dyslipidemia, which increases the chances of developing chronic diseases like type 2 diabetes, cardiovascular diseases, hypertension, nonalcoholic fatty liver diseases, some types of cancers and neurodegenerative diseases. Kukoamine B (Kuk B) is a spermine alkaloid obtained from Lycium chinense, and it has been shown to possess antidiabetic, antioxidant and anti-inflammatory properties. In this study, we evaluated the therapeutic effect of Kuk B on high-fat diet/high-fructose (HFDFr)-induced insulin resistance and obesity in experimental rats. Materials and Methods: Rats were fed with either normal rat diet or HFDFr for 10 consecutive weeks. The groups that were fed with HFDFr received Kuk B (25 and 50 mg/kg) from the beginning of the 6th week to the 10th week. After treatment, the effect of Kuk B on body weight, food, water intake, insulin, blood glucose, serum biochemical parameters, hepatic oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and proinflammatory cytokine (interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α)) levels was determined. Histopathological analysis of the liver tissues was also performed. Results: HFDFr-fed rats showed a significant increase in body weight, fasting blood glucose, insulin, lipid accumulation and liver function enzymes. In addition, HFDFr diet increased hepatic MDA, TNF-α, IL-1β and IL-6 and decreased hepatic SOD, CAT and GSH-Px activities. On the other hand, Kuk B significantly attenuated body weight, insulin resistance, lipid accumulation, oxidative stress and inflammation. Conclusion: These results indicated that Kuk B showed protective effect against HFDFr-induced metabolic disorders by downregulating lipid accumulation, oxidative stress and inflammatory factors. [ABSTRACT FROM AUTHOR]

More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague–Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-MS (NMS) group. Nissl staining analysis indicated a significant reduction in the number of neurons at the prefrontal cortex and hippocampus, including the CA1, CA2, CA3, and DG regions of SD rats in the MS group. Immunohistochemistry results showed that the percentages of synaptophysin-positive area in the prefrontal cortex and hippocampus (including the CA1, CA2, CA3, and DG regions) slice of the MS group significantly decreased compared with those of the NMS group. Western blot analysis was used to assess synaptic-plasticity protein markers, including postsynaptic density 95, synaptophysin, and growth-associated binding protein 43 protein expression in the cortex and hippocampus. Results showed that the expression levels of these three proteins in the MS group were significantly lower than those in the NMS group. LC–MS/MS analysis revealed no significant differences in the peak areas of sex hormones and their metabolites, including estradiol, testosterone, androstenedione, estrone, estriol, and 5β-dihydrotestosterone. Through the application of nontargeted metabolomics to the overall analysis of differential metabolites, pathway-enrichment results showed the importance of arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In summary, the MS model caused adult SD rats to be susceptible to depression, which may regulate synaptic plasticity through arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and phenylalanine, tyrosine, and tryptophan biosyntheses. [ABSTRACT FROM AUTHOR]

Polyvinylpyridine (PVPy) is a linearly structured polymer-containing aromatic heterocyclic compound. PVPy is easily prepared via radical polymerization of vinylpyridine using an initiator of azobisisobutyronitrile in which different haloalkanes can be used for the quaternization of pyridine units. The pyridine moieties of the polymer backbone can lead to an enhanced electrical conductivity in this polymeric material. For this reason, this vinyl polymer has been extensively applied in electrode organization for electrochemical applications. Thus, we aimed to review the uses of PVPy in the electrode structure and/or its application for the modification of electrochemical electrodes in systems such as sensors for monitoring and determining humidity and various chemicals. [ABSTRACT FROM AUTHOR]

Enzymatic polymerization of 2,6-diaminopyridine (DAP) compound in the presence of HRP (Horse radish peroxidase) and H2O2 (hydrogen peroxide) with Poly(DAP-en) with the structures of two different types of polymers obtained by the oxidative polymerization of Poly(DAP-ox) using H2O2 in an aqueous basic environment was illuminated by 1H-NMR, 13C-NMR, FT-IR, UV-Vis spectral methods. GPC (gel permeation chromatography), TGA (thermal gravimetric analysis), DSC (differential scanning calorimetry), CV (cyclic voltammetry), fluorescence analysis and conductivity measurements to characterize the compounds and their electronic structure were examined. SEM analyzes were performed for the morphological properties of the compounds. As a result of the analysis, it was observed that the polymer obtained by enzymatic polymerization was better than the polymer obtained by oxidative method. It was observed that the results of the fluorescence measurements were better than Poly(DAP-en) in Poly(DAP-ox) emitting blue and green light. According to TGA analysis, the first decay temperatures for Poly (DAP-en) and Poly (DAP-ox) were calculated as 342 °C and 181 °C, respectively. The higher value of glass transition temperature for poly (DAP-en) confirms that the average molar mass is higher than 8650 Da for Poly (DAP-en) according to GPC analysis. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a gas that serves as a ubiquitous signaling molecule participating in physiological activities of various organ systems. Nitric oxide is produced in the endocrine pancreas and contributes to synthesis and secretion of insulin. The potential role of NO in insulin secretion is disputable – both stimulatory and inhibitory effects have been reported. Available data indicate that effects of NO critically depend on its concentration. Different isoforms of NO synthase (NOS) control this and have the potential to decrease or increase insulin secretion. In this review, the role of NO in insulin secretion as well as the possible reasons for discrepant findings are discussed. A better understanding of the role of NO system in the regulation of insulin secretion may facilitate the development of new therapeutic strategies in the management of diabetes. [ABSTRACT FROM AUTHOR]

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New Findings: What is the central question of this study?Can low‐dose inorganic nitrate supplementation prevent testicular structural and functional alterations in streptozotocin‐induced type 1 diabetic male rats?What is the main finding and it's important?Treatment with a low dose of inorganic nitrate for 2 months had protective effects on the male reproductive system in diabetic rats including improved body weight loss, sperm and testis parameters, spermatogenesis index and testicular histology as well as increased serum testosterone levels. These favourable effects may be associated with increased serum insulin and decreased serum glucose, and with modulation of apoptosis in testis. Inorganic nitrate supplementation is a possible therapeutic agent in diabetes. The aim of this study was to evaluate the effect of nitrate on the reproductive system in streptozotocin‐induced diabetic male rats. Fifty male Wistar rats were allocated randomly to five groups: control (C), control plus nitrate (CN), diabetic (D), diabetic plus insulin (DI) and diabetic plus nitrate (DN). Sodium nitrate was administered for 2 months in the drinking water (100 mg l−1) of the CN and DN groups. Insulin was injected at 2–4 U daily in the DI group. Serum glucose level and body weight were measured at the beginning of the study and at regular intervals. At the end of the study, serum levels of glucose, insulin, nitrogen oxides (NOx), luteinizing hormone (LH), follicle‐stimulating hormone (FSH) and testosterone were assessed as well as sperm parameters, testis morphometry and histology, and testicular miR‐34b and p53 mRNA expression. Nitrate treatment in diabetic rats significantly improved sperm parameters, epididymal weight, spermatogenesis and testicular histology as well as decreasing serum glucose and testicular p53 gene and miR‐34b expression, although it had no effect on serum LH and FSH levels. In diabetic rats, serum insulin and NOx, body weight, testicular and epididymal weight, sperm count and motility, testis morphology, spermatogenesis indices, Johnsen's score, and testosterone were significantly lower than in controls. Nitrate administration increased serum insulin, NOx and testosterone levels in the DN group. Consuming water supplemented with sodium nitrate could improve diabetes‐induced testicular functional and structural disorders; these favourable effects may be related to increased serum insulin and decreased serum glucose, as well as modulation of apoptosis in testis. [ABSTRACT FROM AUTHOR]

This study attempted to elucidate the possible mechanism of magnesium sulfate (MgSO4) administration on reducing insulin resistance in type 2 diabetic rats. Fifty Wistar rats were divided into five groups: NDC was fed the normal diet, CD received high‐fat diet with 35 mg/kg of streptozotocin, CD‐Mg animals received MgSO4 via drinking water, CD‐Ins1, and CD‐Ins2 animals treated with low or high dose of insulin. Body weight and blood glucose levels were measured weekly. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test, and metabolic cage assessment were performed monthly. After 12 weeks, the hyperinsulinemic‐euglycemic clamp was performed for all animals and blood sample was taken to measure glycated hemoglobin (HbA1c), plasma insulin, glucagon, calcium, and magnesium levels. Liver and gastrocnemius muscle were isolated to measure glucagon receptor (GR), Glucose 6 phosphatase (G6Pase), Phosphoenolpyruvate carboxykinase (Pepck) and Glucose transporter 4 (Glut4) genes expression and GLUT4 protein translocation into the cell membrane. Consuming of high‐fat diet generated insulin‐resistant rats. Magnesium or insulin therapy altered insulin resistance, blood glucose, IPGTT, gluconeogenesis pathway, GR, body weight, the percentage of body fat, and HbA1C in diabetic rats. Administrations of MgSO4 or insulin in Type 2 diabetes mellitus animals increase GLUT4 gene and protein expression. Mg could improve glucose tolerance via stimulation of Glut4 gene expression and translocation and also suppression of the gluconeogenesis pathway and GR gene expression. Mg also increased glucose infusion rate and displayed beneficial effects in the treatment of glucose metabolism and improved insulin resistance. [ABSTRACT FROM AUTHOR]

Methyl-β-cyclodextrin (MβCD) is a cyclic oligosaccharide, commonly used as a pharmacological agent to deplete membrane cholesterol. In this study, we examined the effect of MβCD on adipose-derived mesenchymal stromal cells (ASCs) isolated form healthy horses (ASCCTRL) and from horses suffering from metabolic syndrome (ASCEMS). We investigated the changes in the mRNA levels of the glucose transporter 4 (GLUT4) and found that MβCD application may lead to a significant improvement in glucose transport in ASCEMS. We also showed that MβCD treatment affected GLUT4 upregulation in an insulin-independent manner via an NO-dependent signaling pathway. Furthermore, the analysis of superoxide dismutase activity (SOD) and reactive oxygen species (ROS) levels showed that MβCD treatment was associated with an increased antioxidant capacity in ASCEMS. Moreover, we indicated that methyl-β-cyclodextrin treatment did not cause a dysfunction of the endoplasmic reticulum and lysosomes. Thereby, we propose the possibility of improving the functionality of ASCEMS by increasing their metabolic stability. [ABSTRACT FROM AUTHOR]

Background: Depressive symptoms are one of the main clinical features of the cerebral small-vessel disease (CSVD). However, the pathogenesis of depressive symptoms of CSVD has not been fully studied, and a lack of effective diagnostic methodseffective diagnostic methods exists. Recently, the emerging body of evidence regarding exosomes has rendered them potentially key players in the neuropsychiatric disease theragnostic. This study's aim was to investigate serumexosome proteomic expression in CSVD patients with depressive symptoms and to screen and analyze potential biomarkers for clinical diagnosis., Methods: Serum samples were collected from 36 CSVD patients, including 18 cerebral small-vessel disease (CSVD+D) patients with depressive clinical manifestations and 18 cerebral small-vessel disease patients that did not present depression-related clinical manifestations (CSVD-D). This investigation employed tandem mass tag (TMT) combined with mass spectrometry for sample detection and quantitative analysis of proteins. The differential proteins with significant dysregulated expression levels in patient plasma exosomes were screened and analyzed through bioinformatics techniques., Results: This investigation focused on a global collection of 659 quantifiable proteins. Compared to the CSVD-D group, 7 up-regulated and 30 down-regulated proteins were identified in the CSVD+D group (P < 0.05). Gene ontology (GO) enrichment analyses revealed proteomic expression profile dysregulations within serum exosomes in patients with depression, such as desmosomes and keratins, rendering them as potential biomarkers. Kyoto encyclopedia of genes and genomes (KEGG) database investigations revealed the differentially expressed proteins to be highly aggregated within the estrogen signaling pathway., Conclusion: This investigation pioneered TMT proteomic evaluation of serum exosomes within CSVD patients suffering from depression and reveals the shifts in proteomic expression profiles by serum exosomes within such patients. This study identified several important molecular / signal pathway abnormalities related to depression. These results provide a possible means to further clarify the pathogenesis of depressive symptoms of cerebrovascular disease and its diagnosis and treatment in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)