Ascorbic Acid Supplementation Improves Adolescent Stress-induced Cognitive Impairment Through Restoration of Behavioral, Biochemical and Electrophysiological Alterations in Male Rats.

The present research study aimed to investigate the role of Ascorbic acid (AA) on synaptic plasticity, learning, and memory impairment induced by unpredicted chronic mild stress (CUMS) in adolescent male rats. Adolescent male rats were divided into: 1) vehicle, 2) CUMS, 3-5) CUMS plus various doses of AA by oral gavage (CUMS-10/100/400 mg/kg), and 6) AA400 mg/kg by oral gavage. In Morris Water Maze, the time latency decreased, while the time spent in the target quadrant increased in CUMS group treated with AA at the dose of 400 mg/kg. In passive avoidance, the latency of entering into the dark chamber decreased in CUMS group treated with AA (400 mg/kg). In biochemical test results, nitrite and MDA significantly decreased, while thiol content, SOD, and catalase activity in CUMS group that received AA400mg/kg was increased. IL-10, BDNF and Ki67 increased, while TNF-a and AChE activity were decreased in CUMS group treated with AA simultaneously. The results of our study showed that chronic stress during adolescence could cause learning and memory disorders as well as synaptic plasticity. In addition, we showed that AA can prevent this problem by reducing oxidative stress, inflammation, increasing the amount of BDNF, and neurogenesis.

Oral administration of bacterial probiotics improves Helicobacter pylori-induced memory impairment in rats: Insights from behavioral and biochemical investigations.

There are numerous evidence supporting the association between Helicobacter pylori (H. pylori) infection and the occurrence of cognitive deficits in humans. In this regard, treatment of H. pylori infection has been suggested as an effective strategy to decelerate the neurodegenerative processes of memory deficits in AD patients. Numerous studies support the beneficial effects of probiotics on various pathological conditions, particularly cognitive deficits, however, this concern has not been addressed in relation to the memory impairment induced by H. pylori infection. In the present study, we aimed to reveal whether oral administration of two bacterial probiotics (including Lactobacillus rhamnosus and Lactobacillus plantarum), could ameliorate H. pylori-induced memory deficits at behavioral level in rats. Besides, cellular mechanisms were investigated by biochemical methods to find out how probiotic effects are mediated in hippocampal circuitry. Male Wistar rats were infected by H. pylori for 3 consecutive days, then probiotic treatment was done for the next 3 days and after a drug-free period (12 days), animals were assessed by Morris Water Maze and Novel Object Recognition tests. Finally, rats were euthanized by CO2 and hippocampal tissues were excised for biochemical measurements. Results indicated that H. pylori infection markedly impairs memory function in rats which is associated with alterations of oxidative, inflammatory, neurotrophic, and cholinergic markers. Interestingly, treatment with either of the probiotics alone or in combination, significantly improved the H. pylori-induced memory deficits and this was associated with restoration of balance in biochemical factors within the hippocampal neurons.

Feeding metformin during pregnancy and lactation periods improved learning and memory impairment in the rat offspring exposed to febrile seizure: Role of oxidative stress and inflammatory response.

BACKGROUND: Many clinical evidences have reported the higher risk of seizure in young children and infants after exposure to hyperthermia, which more likely can cause brain damage and affect cognitive function, so, many researches were focused on prevention or treatment of febrile seizure (FS) with minimal adverse effects. Considering the potential effects of oxidative stress as a prominent trigger in FS, and demonstrating the anti-oxidant effects of metformin, the present study aimed to investigate the protective effect of metformin administration in prenatal and lactation periods in rat pups exposed to hyperthermia by which induced seizure. METHOD AND MATERIALS: Pregnant rats were divided into six groups: (1) vehicle: pregnant rats received normal saline during pregnancy and lactation; (2) FS: pregnant rats received normal saline during pregnancy and lactation; (3-5) FS-Met50/100/150 mg/kg: pregnant rats received different doses of metformin including 50, 100 and 150 mg/kg during pregnancy and lactation; (6) Met150 mg/kg: pregnant rats received Met150 mg/kg during pregnancy and lactation. The male pups born to mothers received in all FS groups exposed to hyperthermia. All experimental groups were allowed to grow up, and after the lactation period, they were subjected for behavioural tests and biochemical analysis. RESULTS: According to the present findings, the prenatal and lactation exposure to the highest dose of metformin demonstrated significant difference with FS group in both behavioural and biochemical test analyses. Although the remaining doses of metformin were also effective, the much better results were reported with the highest dose of metformin (150 mg/kg). Interestingly, the highest dose of metformin administered alone demonstrated better result than vehicle in probe trial test. CONCLUSION: Considering the present research and related study in relation to metformin in ameliorating the epilepsy symptoms, there are numerous evidences on positive effect of metformin on seizure. Although the exact mechanism is unclear, the anti-oxidant effect of metformin is strongly supported.

Omega-3 fatty acids prevent nicotine withdrawal-induced impairment of learning and memory via affecting oxidative status, inflammatory response, cholinergic activity, BDNF and amyloid-B in rat hippocampal tissues.

In the present study, the main objective was to reveal whether treatment by Omega-3 fatty acids could prevent the adverse effects of adolescent nicotine withdrawal on spatial and avoidance memory in male rats. For this purpose, Morris water maze and passive avoidance tests were performed on male Wistar rats and the hippocampal levels of oxidative stress markers, inflammatory indices, brain-derived neurotrophic factor, nitrite, amyloid-B and acetylcholinesterase (AChE) were measured. Moreover, density of dark neurons were assessed in CA1 and CA3 regions. Results showed that adolescent nicotine exposure followed by a period of drug cessation exacerbates the behavioral indices of learning and memory through affecting a variety of biochemical markers within the hippocampal tissues. These changes lead to elevation of oxidative and inflammatory markers, reduction of neurotrophic capacity and increased AChE activity in hippocampal tissues. In addition, it was observed that co-administration of nicotine with Omega-3 fatty acids significantly prevents nicotine withdrawal-induced adverse effects through restoration of the mentioned biochemical disturbances. Therefore, we suggest administration of Omega-3 fatty acids as a safe, inexpensive and effective therapeutic strategy for prevention of memory dysfunctions associated with nicotine abstinence during adolescence.

Vitamin B12 reversed anxiety and depression induced by adolescent nicotine withdrawal through alteration the inflammatory, oxidative and serotoninergic profiles in male rats.

BACKGROUND: The present study aims to assess the effect of vitamin B12 (Vit B12) on depression-like behavior caused by nicotine (Nic) withdrawal, which is more likely due to the anxiogenic effect of Nic in adolescent male rats, through assessing behavioral and biochemical analysis. METHODS: Adolescent male rats were divided into vehicle (received normal saline), and experimental groups that received Nic (2 mg/kg, intraperitoneally (i.p.)) for three consecutive weeks and after that, the group that received normal saline was divided into two groups, one of which returned to a regular diet, and the second one received Vit B12 (1.5 mg/kg). The Nic group was divided into five groups, one of which received bupropion (Bup, 20 mg/kg), three of which received different doses of Vit B12 (0.5, 1, and 1.5 mg/kg), and the last one returned to a normal diet without treatment, which was considered as the withdrawal period. RESULTS: Behavioral analysis showed that Nic withdrawal induced anxiety and depression. Vit B12 and Bup reduced anxiety and depression induced by Nic withdrawal. The biochemical analysis demonstrated the more activity of oxidative stress factors and pro-inflammatory cytokines in which Nic was administered, whereas both Vit B12 and Bup reversed the results and improved the activity of both antioxidant and anti-inflammatory parameters. Furthermore, both serum and cortical Vit B12 levels dramatically decreased in nicotine group, whereas treatment with both Vit B12 and Bup as desirable treatments corrected Vit B12 levels. CONCLUSION: According to the present findings, the results revealed that Vit B12 is comparable with Bup in attenuation of Nic withdrawal symptoms. In addition, both Bup and Vit B12 improved the decreased serum and cortical levels of Vit B12, which caused by nicotine. Administration of Vit B12 in normal animals demonstrated better results in reducing antioxidant and anti-inflammatory parameters, which explores new hope to introduce Vit B12 as a novel antioxidant and anti-inflammatory agent to treat not only withdrawal, but also other diseases related to the prominent role of oxidative stress or inflammatory pathways, such as Alzheimer's disease.

A step forward to overcome the cytotoxicity of graphene oxide through decoration with tragacanth gum polysaccharide.

Hybridization of nanomaterials (NMs) with natural polymers is one of the best techniques to promote their exciting properties. In this way, the main objective of this work was to investigate the efficiency of decoration of the graphene oxide (GO) nano-sheets with tragacanth gum (TG) polysaccharide. To aim this, different approaches were used (with and without ultrasonic treatment) and various tests (XRD, FTIR, Raman, UV-Vis, DLS, Zeta potential, contact angle, AFM, FE-SEM, TEM, and MTT assay) were conducted. Test results indicated that the nano-hybrids were successfully synthesized. Furthermore, our findings represented that, the TG hybridized GO (TG-GO) appreciably enhanced the biocompatibility of GO. Moreover, it was demonstrated that the ultrasonic treatment of TG solution put a remarkable impact on the microstructure, wettability, and also surface charge characteristic of fabricated nano-hybrids and consequently improved the biocompatibility against L929-fibroblast cells.

COVID-19: Why does disease severity vary among individuals?

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the current pandemic, coronavirus disease 2019 (COVID-19). While all people are susceptible to the SARS-CoV-2 infection, the nature and severity of the disease vary significantly among individuals and populations. Importantly, reported disease burdens and case fatality rates differ considerably from country to country. There are, however, still uncertainties about the severity of the disease among individuals or the reason behind a more severe disease in some cases. There is a strong possibility that the severity of this disease depends on a complicated interaction between the host, virus, and environment, which leads to different clinical outcomes. The objective of this article is to point out the essential influential factors related to the host, virus, and environment affecting the clinical outcome of COVID-19.

Advanced sequence optimization for the high efficient yield of human group A rotavirus VP6 recombinant protein in Escherichia coli and its use as immunogen.

Rotavirus is the important etiological agents of infectious diarrhea among children under 5 years old. Rotaviruses are divided into 10 serogroups (A-J) and each group is based on genetic properties of major structural protein VP6. We designed a novel VP6 sequence optimization to increase the expression level of this protein. Numerous factors such as codon adaptation index, codon pair bias, and guanine-cytosine content were adapted based on Escherichiacoli codon usage. In addition, the ribosome binding site (RBS) of pET-15b was redesigned by the RBS calculator and the secondary structure of VP6 messenger RNA was optimized in the whole length of the coding sequence. Various factors including isopropyl beta- d-thiogalactoside (IPTG) concentration, temperature, and induction time were analyzed for the optimization of the best expression in E. coli by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting. The recombinant VP6 (rVP6) protein was purified by the Ni-sepharose and then the hyperimmune sera were generated against rVP6 in rabbits. Among three different temperatures, IPTG concentrations, and postinductions, the level of rVP6 was higher at 37°C, 1 mM of IPTG, and 8 h, respectively. Also, the high expression level of rVP6 was obtained in the insoluble aggregate form (43.8 g/L). After purification, the yield of rVP6 was 10.83 g/L. The rVP6 specific antiserum was confirmed by both immunofluorescent and western blotting. The versatile sequence optimization was the reason to produce a high level of rVP6 compared to other reports and can potentially apply to produce cheaper commercial kits to diagnose serological tests and new rotavirus vaccines.