Protective Effect of Baclofen on Ovarian Cystogenesis and Morphine-Induced Lipid Profile Change in Female Rats.

Introduction: Morphine induces ovarian cysts that cause obesity and disrupt sex hormone secretion. Baclofen, a gamma-aminobutyric acid receptor agonist, can help regulate sex hormones and reduce harmful blood lipids by protecting against morphine-induced gamma-aminobutyric acid inhibition. We investigated the prophylactic effect of baclofen in rats receiving morphine by comparing with the untreated groups. Materials and Methods: Forty eight female Wistar rats were randomly divided into several groups, including control (saline 1 mL/kg, i.p.), morphine (5 mg/kg, i.p.), baclofen (10, 20, and 30 mg/kg, i.p.), and baclofen (10, 20, and 30 mg/kg) before morphine (5 mg/kg). Twenty four hours after the treatment, blood and serum samples were taken to check the levels of gonadotropins (LH & FSH) and lipid profile. The ovaries and uterus were also studied, and a proinflammatory nitric oxide (NO) diagnostic test was completed. The results were analyzed using analysis of variance (α = 0.05). Results: In comparison with the control group, the levels of LH and not FSH decreased in the morphine group and the number of ovarian cysts was more in the morphine group. These problems were not observed in the group of baclofen alone and baclofen + morphine. However, the triglyceride level increased slightly in the baclofen 30 mg/kg + morphine group. But the LDL level somewhat decreased. The proinflammatory NO system did not show significant activation in the ovary and uterus, except for the baclofen 10 mg/kg + baclofen group. Conclusion: Morphine can cause ovarian cysts by lowering LH but baclofen prophylaxis can protect reproductive properties by adapting major metabolic changes.

GHz repetition rate, sub-100-fs Ho:CALGO laser at 2.1†µm with watt-level average power.

We report on a GHz fundamental repetition rate Kerr-lens mode-locked Ho:CALGO laser emitting at 2.1 µm. The laser employs a ring cavity to increase the fundamental repetition rate to 1.179 GHz and can be made to oscillate in both directions stably with nearly identical performance: for the counterclockwise oscillation, it generates 93-fs pulses at 1.68 W of average power, whereas 92 fs and 1.69 W were measured for the clockwise operation. Our current results represent the highest average power from a 2-µm GHz oscillator and, to our knowledge, the first sub-100-fs pulse duration from a Ho-based oscillator.

Lived experiences of neurofibromatosis type 1 patients: Social life, stigma, and intervention strategies.

Neurofibromatosis type 1 (NF1) is a neurogenetic disorder associated with visual-spatial problems, executive dysfunction, and language deficits, making patients experience social isolation, stigma, anxiety, and depression. Here, we explored NF1 patients' lived experiences by conducting semi-structured, in-depth interviews with 21 NF1 patients and 16 care providers. The thematic analysis uncovered dimensions of NF1 patients' social lives at different ecological levels, including their relationships with family, friends, teachers, coworkers, providers, and society. Positive dimensions of NF1 patients' social life (e.g. familial support and sacrifice, responsibility, and self-sufficiency, supportive friends, and professors) counter negative dimensions (e.g. the vulnerability in sexual relationships, social interactions, discriminatory professors, misconceptions about abilities, appearance bias, internalized and social stigma, violence, and low self-esteem). Adaptive strategies used or suggested by NF1 patients at personal (e.g. supportive network, positive reframing, acceptance of their bodies) and social levels (e.g. psychological support, group therapy, public awareness, and governmental support) were identified.

Epilepsy and associated factors in elderly people of Amirkola, North of Iran (The Amirkola Health and Ageing Project).

Background: Knowledge about the associated factors with epilepsy in the elderly in Iran is limited. Therefore, this study aimed to determine the prevalence of epilepsy and associated factors in Amirkola elderly patients. Methods: This cross-sectional study is a part of a comprehensive and cohort research of "The Amirkola Health and Ageing Project". The Mini-mental State Examination was used for cognitive impairment, Geriatric Depression Scale for psychiatric diseases and the Physical Activity Scale for Elderly questionnaire for physical activity. Results: The prevalence of epilepsy was 35 from 1482 participants (24/1000). The significant association between Parkinson's Disease (OR=6.25, 95%CI=1.35-28.4, P=0.001), falls (OR= 3.81, 95%CI=1.62-8.97, P=0.001), depression (P=0.001), hyperphosphatemia (P=0.039) and hypokalemia (P= 0.031) concluded with epilepsy. Past history of stroke (6 % versus 2%, OR= 2.8, 95%CI, 0.97-8.27, P=0.07), increased serum level of triglyceride (OR= 1.96, 95%CI= 0.99-3.88, P=0.06) and low-density lipoprotein (LDL) (P=0. 45) were seen in epileptic patients vs. non-epileptic patients. Conclusion: Parkinson's disease, frequency of falls and depression were the associated factors in epileptic patients and a correlation between past history of stroke, increased serum level of triglyceride and LDL with epilepsy were seen. Associated factors required screening, diagnosis and treatment.

Silver nanoparticles modify the hypothalamic-pituitary-interrenal axis and block cortisol response to an acute stress in zebrafish, Danio rerio.

The present study aimed at assessing the effects of exposure to silver nanoparticle (AgNP) and a subsequent acute stress on the expression of various genes involved in the hypothalamus-pituitary-interrenal (HPI) axis in zebrafish, Danio rerio. The fish were exposed to 0 (Control), 0.1 (LC), 0.4 (MC), and 1.2 (HC) mg Ag/L (as AgNP) over a 2-week period, followed by an acute air exposure stress. The whole body cortisol and the expression of selected genes in the fish brain and kidney were analyzed, before and after the acute stress. The results showed that AgNP increased basal cortisol levels and the expression of corticotropin releasing factor, prohormone convertase 1, pro-opiomelanocortin, and melanocortin 2 receptor; however, it suppressed/inhibited whole body cortisol, brain corticotropin releasing factor responses, pro-opiomelanocortin, and the kidney melanocortin 2 receptor responses to the acute stress. AgNP down-regulated the expression of the steroidogenic acute regulatory protein, but it intensified the gene expression in response to the acute stress. Before the acute stress, LC treatment exhibited an up-regulation in Cytochrome P450-11A-1 expression, but MC and HC treatments induced down-regulation. After the acute stress, the AgNP-exposed fish exhibited decreased Cytochrome P450-11A-1 expressions, compared with the Control. Exposure to AgNP significantly increased Cytochrome P450-11B expression. However, after the acute stress, LC treatment exhibited an up-regulation, but MC and HC treatments exhibited down-regulation in the Cytochrome P450-11B gene expression. In conclusion, AgNP suppressed cortisol response to stress, which appears to be a consequence of alterations in the HPI axis at the transcriptomic levels.

Paeonol Ameliorates Cuprizone-Induced Hippocampal Demyelination and Cognitive Deficits through Inhibition of Oxidative and Inflammatory Events.

Multiple sclerosis (MS) is a chronic and inflammatory disorder of the central nervous system with autoimmune nature that is typified by varying degrees of demyelination and axonal damage. Paeonol is an active ingredient in some medicinal plants with anti-inflammatory and neuroprotective property. This study was conducted to reveal whether paeonol can alleviate hippocampal demyelination and cognitive deficits in cuprizone-induced murine model of demyelination as a model of MS. C57BL/6 mice received oral cuprizone (400 mg/kg) for 6 weeks, and paeonol was administered p.o. at two doses of 25 or 100 mg/kg, starting from the second week post-cuprizone for 5 weeks. After assessment of learning and memory in different tasks, oxidative stress and inflammation were evaluated besides immunohistochemical assessment of hippocampal myelin basic protein (MBP). Paeonol (100 mg/kg) properly ameliorated cognitive deficits in Y maze, novel object discrimination (NOD) test, and Barnes maze with no significant improvement of performance in passive avoidance task. In addition, paeonol treatment at the higher dose was also associated with partial restoration of hippocampal level of oxidative stress and inflammatory markers including MDA, ROS, GSH, SOD, catalase, NF-kB, and TNF. Besides, paeonol improved MMP as an index of mitochondrial integrity and health and reduced MPO as a factor of neutrophil infiltration. Furthermore, paeonol treatment prevented hippocampal MBP immunoreactivity, indicating its prevention of demyelination. In conclusion, the current study showed the preventive effect of paeonol against cuprizone-induced demyelination and cognitive deficits through reversing most oxidative stress- and inflammation-related parameters in addition to its improvement of mitochondrial health.

Synthesis and Antinociceptive Activity of Newly Modified Amine Analogs of Phencyclidine in Mice.

BACKGROUND: Phencyclidine (PCP, I) and its substituted analogs are significant and broadly abused psychotomimetic drugs that affect the central nervous system. They possess many pharmacological properties due to the presence of specific receptors in the brain. AIMS AND OBJECTIVE: Methyl group, despite strong electron-donating and characters of dipole moments, was placed on various positions of phenyl and amine moieties of phencyclidine along with the substitution of benzylamine, piperazine, and aniline derivatives in place of piperidine ring of phencyclidine to create novel compounds of the core with analgesic properties. MATERIALS AND METHODS: For evaluation of the analgesic activities of newly synthesized compounds, they were screened by tests of tail immersion (thermal) and formalin (chemical) pains. The obtained data with the control and PCP groups were also compared. RESULTS: The outcomes indicated that some new compounds have more antinociceptive effects than PCP in tail immersion and formalin tests. In the tail immersion test, the methyl piperazine analog (III) shows more efficacy than others. In the formalin test, none of the compounds are as effective as phencyclidine at the earliest time-point, but compounds IV and V show effectiveness during the second stage of formalin pain. CONCLUSION: It can be concluded that the methyl-piperazine analog of phencyclidine was the best candidate to decrease acute thermal pain, and benzylamine derivatives were suitable candidates to reduce chemical pains.

Fabrication of nano-decorated ZnO-fibrillar chitosan exhibiting a superior performance as a promising replacement for conventional ZnO.

In this research, bioactive nano-hybrids based on the nano-fibrillar chitosan-ZnO (NF-CS-ZnO) were synthesized to diminish the toxicity of ZnO-NPs. The successful formation of nano-hybrids was confirmed by FT-IR, UV-Vis, and FE-SEM analyses, showing a uniform spherical ZnO-NPs with an average diameter of 20-30 nm, homogeneously dispersed on NF-CS. The obtained results demonstrated a remarkable antibacterial activity of NF-CS-ZnO-0.6 nano-hybrid against E. coli and S. aureus and, interestingly, no cytotoxic on normal cells (even at a high concentration of 100 µg/mL). Furthermore, NF-CS hybridization efficiently decreased the up-regulation in Cas3, Cas9, and Il6 of inspected fishes compared to the ZnO-NPs. Histopathological examination revealed hepatocyte necrosis in the fish exposed to ZnO-NPs and hyperemia exposed to NF-CS-ZnO-0.6 nano-hybrid. Finally, NF-CS efficiently improved the bio-safety and bactericidal activity of ZnO-NPs; therefore, NF-CS-ZnO nano-hybrid is prominently recommended as a talented low-toxicity antibacterial agent replacement of conventional ZnO-NPs for use in different applications.

Hesperetin ameliorates electroconvulsive therapy-induced memory impairment through regulation of hippocampal BDNF and oxidative stress in a rat model of depression.

Depression is one of the most common mental health disorders and it is generally characterized by negative mood. Although electroconvulsive therapy (ECT) is an effective treatment for depression, however, it can cause cognitive deficit. Hesperetin, an active ingredient in citrus peels, has antioxidant and neuroprotective properties. In this study, we evaluated the effect of hesperetin on memory impairment induced by ECT in a reserpine-induced depression model in male rat. For this purpose, 105 male rats weighing 230-250 g were randomly divided into control and reserpine-treated groups. The reserpine-treated animals were subdivided into: Reserpine, Hesperetin (10 and 20 mg/kg), ECT and ECT+Hesperetin (10 and 20 mg/kg). After taking the drugs, the effect of hesperetin was evaluated through behavioral NORT, Y Maze, FST, SPT and also via assessment of hippocampal brain-derived neurotrophic factor (BDNF) and oxidative stress biomarkers i.e., MDA, SOD and GSH. As a result, our biochemical studies showed a significant decrease of MDA in groups treated with ECT+Hesperetin as compared to ECT and hesperetin groups (P < 0.001) and a marked increase in SOD, GSH and BDNF in ECT+Hesperetin 20 group as compared to other groups (p < 0.05). Also, the results of behavioral tests revealed that treatment with hesperetin can increase the novel object recognition index and alternation behaviors in Y maze test as compared to the groups treated with hesperetin or ECT (p < 0.05). These results suggest that co-administration of hesperetin with ECT is effective for improvement of cognitive function and can alleviate ECT-induced memory impairment in reserpine-treated rats.

Enhanced radiotherapy efficacy of breast cancer multi cellular tumor spheroids through in-situ fabricated chitosan-zinc oxide bio-nanocomposites as radio-sensitizing agents.

Overwhelming evidence has shown that three-dimensional multicellular tumor spheroids (MCTSs) as a mimic of in-vivo tumor can accurately exhibit cellular responses to treatments. So, we compared the capability of pure zinc oxide nanoparticles (ZnO-NPs) and chitosan-ZnO bio-nanocomposites (CS-ZnO BNCs) for enhancing the radiosensitization of MDA-MB-231 breast cancer cells (BCCs) in the 3D-MCTSs model. ZnO-NPs and CS-ZnO BNCs were synthesized by a facile co-precipitation method. FE-SEM images revealed that the uniform spherical ZnO-NPs with an average diameter of 35 nm were successfully dispersed on chitosan. MDA-MB-231 MCTSs which were formed in a non-adherent culture plate, possessed functional features of in-vivo tumor. The priority of such culture method to conventionally used 2D monolayer (or parental) cell culture is the mimicking of tumor microenvironment. The toxicity of CS-ZnO BNCs and ZnO-NPs against the MDA-M-231 BCCs was evaluated using MTT-colorimetric assay, which demonstrated superior biocompatibility of CS-ZnO BNCs compared to pure ZnO-NPs (even at high concentration of 100 µg/mL). Survival fraction analysis of cells under clinical X-ray irradiation (6 MV) showed that MCTSs had a higher radioresistance compared to parental cells. Besides, the clonogenic potential of irradiated MCTSs was significantly decreased by the addition of CS-ZnO BNCs similar to that of monolayer cells. The sensitivity enhancement ratios (SER) for MCTSs and monolayer cells were calculated 1.5 and 1.63, respectively. Further, tracking of radiobiological properties and apoptosis induction of MCTSs showed that CS-ZnO BNCs not only could lead to the creation of higher radiation-induced complex DNA break and apoptosis death in MCTSs, but also weakened DNA repair mechanisms. It was found that non-toxic concentration of CS-ZnO BNCs has promising potential to enhance radiosensitivity of resistant-MCTSs as a superior in-vitro tumor model. So, CS-ZnO BNCs can be a prominent candidate for overcoming the resistance of BCCs to radiotherapy.

Effects of dietary monoterpene, myrcene, administration on immune- and health-related genes expression in common carp gill following exposure to copper sulfate.

The present study assessed the potential benefits of myrcene administration to suppress negative effects of copper exposure on immune-, antioxidant-, tight junction-, stress- and osmoregulatory-related gene expressions in common carp (Cyprinus carpio) gill. Fish were fed with diets containing 0% (control), 0.5% (M0.5) and 1% (M1) myrcene for 6 weeks, and then, exposed to 0.25 mg/L copper for further two weeks. The fish gill samples were taken for gene expression assays after six and eight weeks. The results showed that there were interaction effects of myrcene levels and copper exposure on superoxide dismutase (sod), catalase (cat), glutathione peroxidase (gpx), glutathione-s-transferase (gst), glutathione reductase (gr), heat shock protein-70 (hsp70), interleukin 1-beta (il1b), interleukin 10 (il10), tumor necrosis factor-alpha (tnfa), occludin (occl), caludin 3 (cld3), caludin 7 (cld7), and Na+-K+-ATPase (nka) genes expressions. Overall, the M0.5 treatment had significantly lower antioxidant genes expression, and higher hsp70, cytokines, tight-junction proteins, and nka genes expression, compared to the control treatment, before copper exposure. Copper exposure significantly down-regulated most of the tested genes (except il10), however, the M0.5 treatment had significantly higher antioxidant (except gpx), hsp70, cld7, and nka gene expression compared to the control treatment. The M1 treatment showed fluctuated antioxidant gene expressions, down-regulated gene expression of the pro-inflammatory cytokines, and occl, and up-regulation of cld3 gene expressions, before copper exposure. After copper exposure, this treatment had significantly higher gr and cat expression compared to the control; moreover, there was a marked up-regulation in il10 gene expression in this treatment, which was the highest value among all treatment combinations. In conclusion, copper exposure significantly down-regulates antioxidant-, inflammatory-, and tight junction-related along with hsp70 and nka genes expression in common carp gills. Pre-treatment with 0.5% myrcene is beneficial to suppress such negative effects, probably due to its antioxidant properties. However, myrcene administration must be done with caution, as higher levels may interfere with antioxidant and immune defenses.

Distributed Fault-Tolerant Control of Multiagent Systems: An Adaptive Learning Approach.

This paper focuses on developing a distributed leader-following fault-tolerant tracking control scheme for a class of high-order nonlinear uncertain multiagent systems. Neural network-based adaptive learning algorithms are developed to learn unknown fault functions, guaranteeing the system stability and cooperative tracking even in the presence of multiple simultaneous process and actuator faults in the distributed agents. The time-varying leader's command is only communicated to a small portion of follower agents through directed links, and each follower agent exchanges local measurement information only with its neighbors through a bidirectional but asymmetric topology. Adaptive fault-tolerant algorithms are developed for two cases, i.e., with full-state measurement and with only limited output measurement, respectively. Under certain assumptions, the closed-loop stability and asymptotic leader-follower tracking properties are rigorously established.

New Amine and Aromatic Substituted Analogues of Phencyclidine: Synthesis and Determination of Acute and Chronic Pain Activities.

BACKGROUND: Phencyclidine (PCP, I) is a synthetic drug with remarkable physiological properties. PCP and its analogues exert many pharmacological activities and interact with some neurotransmitter systems in the central nervous system like particular affinity for PCP sites in NMDA receptors or dopamine uptake blocking or even both. AIM AND OBJECTIVE: The following research, methyl group with electron-donating and dipole moment characters was added in different positions of phenyl ring along with the substitution of benzylamine (with many pharmacological effects) instead of piperidine ring of I to produce new compounds (II-V) of this family with more analgesic activities. MATERIALS AND METHODS: Analgesic activities of these new compounds were measured by tail immersion and formalin tests for acute and chronic pains, respectively. Also, the outcomes were compared with control and PCP (10 mg/kg) groups. RESULTS: The results indicate that compounds III, IV, and V have more acute and chronic antinociceptive effects than PCP and compound II which may be concerned with more antagonizing activities of these new painkillers for the blockage of dopamine reuptake as well as high affinity for NMDA receptors PCP binding site. CONCLUSION: It can be concluded that the benzylamine derivative of phencyclidine with a methyl group on the benzyl position on phenyl ring (V) is a more appropriate candidate to reduce acute and chronic (thermal and chemical) pains compared to other substituted phenyl analogs (II-IV) and PCP.

Expression of immune, antioxidant and stress related genes in different organs of common carp exposed to indoxacarb.

The aim of the present study was to investigate the effects of chronic exposure of common carp (Cyprinus carpio) to indoxacarb on immune, antioxidant and stress gene expression. After 21 days exposure to 0, 0.75, 1.5 and 3 ppm indoxacarb, expression of IL-1ß, IL-8, IL-10, TNF-α, IFN-γ, SOD, CAT, HSP70, IGF-I and IGF-II were assessed in liver, kidney and gills. In general, exposure to low concentration of indoxacarb increased inflammatory cytokine gene expression (IL-1ß, IL-8, IL-10, TNF-α and IFN-γ) and inhibits inflammatory cytokines' expression at higher concentrations. The assessment of antioxidant gene expression (SOD and CAT) in different organs indicate that they were increased by low concentrations of indoxacarb to deal with primary oxidative situation. However, higher concentrations of indoxacarb caused reduction in oxidative gene expression. IGF genes expression in liver significantly increased at a concentration of 0.75 ppm treatment, then it decreased at 1.5 ppm indoxacarb and increased again by increasing in the indoxacarb concentration to 3 ppm. The expression of HSP70 in kidney showed a significant elevation in 0.75 and 1.5 ppm treatments compared with 3 ppm treatment and the control group. The expression of this gene in liver was significantly increased in 1.5 and 3 ppm treatments. The same pattern of expression was also observed in gill. Overall, indoxacarb exposure affects common carp health at transcription levels. Changes in the genes expression generally suggest that indoxacarb exposure led to interference in inflammation, oxidative stress and tissue damage.

Using of keratin substrate for enrichment of HT29 colorectal cancer stem-like cells.

Eradication of cancer stem-like cells (CSLCs) are becoming increasingly an important target for new cancer therapies. The ability to study their behavior in vitro will provide the opportunity for high-throughput testing of more effective treatments. In this study, spheroid-like structures' formation and enrichment of HT29 CSLCs were evaluated on a wool keratin-based substrate as a bio-mimic of natural extracellular matrix (ECM) proteins. The results indicated that culturing on keratin substrate increased spheroid formation ability and radio-/chemoresistance of HT29 cells. Moreover, cell surface expression of CD133 CSLCs' marker and the mRNA level of stemness genes such as Nanog, Oct4, and c-MYC were increased. These data suggest that keratin can potentially be used for spheroid-like structure formation and enrichment of HT29 CSLCs. In addition, it seems that the induction of stemness characteristics on keratin substrate is probably because of the activation of α2 ß1 integrin signaling pathway. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1264-1271, 2019.

Mucosal immune parameters, immune and antioxidant defence related genes expression and growth performance of zebrafish (Danio rerio) fed on Gracilaria gracilis powder.

In the present study zebrafish (Danio rerio) has been used as model organism to establish the effects of dietary supplementation of Gracilaria gracilis powder (GP) on mucosal and innate immune parameters, antioxidant enzymes, and growth. In order to establish these features, zebrafish were fed for eight weeks with experimental diets containing different levels of Red algae, 0.25, 0.5 and 1% of GP; also, a group was fed with control diet. At the end of the experimental period the antioxidant superoxide dismutase and catalase (SOD, CAT) genes expression, interleukin 1 beta (il-1ß), lysozyme (LYZ), tumor necrosis factor alpha (TNF-α) for immune-related genes expression, total immunoglobulin (Ig), total protein, alkaline phosphatase (ALP) activity for innate immune parameters, and growth performance have been established. The GP dietary supplementation showed differences in SOD and CAT expression in zebrafish whole body respect to the control group. Non-signifcant differences were noticed among the different groups in case of TNF-α, LYZ and il-1expression (P > 0.05). The skin mucus total Ig and total protein in the group fed on 1% of GP were significantly higher respect to control group (P < 0.05). 0.25 and 0.5% of GP dietary supplementation significantly enhanced skin mucus ALP activity levels (P < 0.05). No significant differences were recorded for growth performances among groups (P > 0.05). The results obtained in the present study revealed that G. gracilis could be takes in account as fishes diet supplementation for its immune system stimulants effects.

Powder of the White Bottom Mushroom, Agaricus bisporus (Agaricomycetes), Improved Immunomodulatory and Health-Promoting Effects of Lactobacillus casei in Zebrafish (Danio rerio).

This study was conducted to investigate the effects of Lactobacillus casei and Agaricus bisporus administration, alone or in combination, on skin mucus immune parameters and the expression of selected genes related to growth, appetite, mucosal immunity, and antioxidant enzymes in zebrafish (Danio rerio). Zebrafish (n = 600) were randomly stocked in 12 aquariums and assigned to 1 of 4 treatments, which were repeated in triplicate. During a 60-day feeding trial, fish were fed experimental diets: (1) basal diet (control group); (2) basal diet + L. casei (107 colony-forming units/g; Pro group); (3) basal diet + 1% A. bisporus [mushroom powder [MP] group); and (4) basal diet + 1% A. bisporus + L. casei (107 colony-forming units/g) (MP + Pro group). The results demonstrated that oral administration of A. bisporus + L. casei significantly (P < 0.05) upregulated the expression of growth-related genes (gh and igf1). Similar results were observed for expression of mucosal immune-related genes (tnf-alpha, lyz, and il1b) and for antioxidant-related genes (sod, cat) in zebrafish fed A. bisporus + L. casei (P < 0.05). Also, nonspecific skin mucus immune parameters in the MP + Pro group were significantly (P < 0.05) higher than those in the MP, Pro, and control groups. These results also demonstrate the potential of combined administration of A. bisporus and L. casei as a beneficial feed additive in aquaculture.

Trigonelline mitigates lipopolysaccharide-induced learning and memory impairment in the rat due to its anti-oxidative and anti-inflammatory effect.

Brain inflammation is associated with cognitive dysfunction, especially in elderly. Trigonelline is a plant alkaloid and a major component of coffee and fenugreek with anti-diabetic, antioxidant, anti-inflammatory, and neuroprotective effects. In this study, the beneficial effect of trigonelline against lipopolysaccharide (LPS)-induced cognitive decline was assessed in the rat. LPS was injected i.p. at a dose of 500 µg/kg to induce neuroinflammation and trigonelline was administered p.o. at doses of 20, 40, or 80 mg/kg/day 1 h after LPS that continued for one week. Trigonelline-treated LPS-challenged rats showed improved spatial recognition memory in Y maze, discrimination ratio in novel object discrimination test, and retention and recall in passive avoidance paradigm. Additionally, trigonelline lowered hippocampal malondialdehyde (MDA) and acetylcholinesterase (AChE) activity and improved superoxide dismutase (SOD), catalase, and glutathione (GSH). Furthermore, trigonelline depressed hippocampal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), and tumor necrosis factor α (TNF α) in LPS-challenged rats. All of the effects of trigonelline followed a dose-dependent pattern and in some aspects, it acted even better than the routinely-used anti-inflammatory drug dexamethasone. Collectively, trigonelline is capable to diminish LPS-induced cognitive decline via suppression of hippocampal oxidative stress and inflammation and appropriate modulation of NF-κB/TLR4 and AChE activity.

Apple cider vinegar boosted immunomodulatory and health promoting effects of Lactobacillus casei in common carp (Cyprinus carpio).

The present study was performed to investigate the immunomodulatory and health promoting effects of combined or singular administration of apple cider vinegar (ACV) and Lactobacillus casei in common carp (Cyprinus carpio) diet. An 8-week feeding trial was designed with following treatments: Control (basal diet), Pro (contains 107 CFU g-1L. casei), LACV (contains 1% ACV), HACV (contains 2% ACV), Pro + LACV (contains 107 CFU g-1L. casei plus 1% ACV) and Pro + HACV (contains 107 CFU g-1L. casei plus 2% ACV). Evaluation of skin mucus revealed notable increase of total Ig level and lysozyme activity in Pro + LACV and Pro + HACV treatments compared other groups (P < 0.05). Similarly, serum total Ig and lysozyme activity in HACV, Pro + LACV and Pro + HACV fed carps was remarkably higher than other groups (P < 0.05). However, regarding serum alternative complement (ACH50) activity significant difference was observed just between Pro + HACV and control treatment (P < 0.05). The highest expression of immune related (LYZ, TNF-alpha, IL1b, IL8) and antioxidant enzymes genes (GSR, GST) were observed in carps fed Pro + HACV and Pro + LACV. The expression of GH gene expression in Pro, LACV and HACV treatments was significantly higher than those in control group (P < 0.05). The highest expression level of GH and IGF1 was observed in fish fed combined Pro and ACV (P < 0.05). These results indicated that co-administration of ACV boosted immunomodulatory and health promoting effects of L. casei and can be considered as a promising immunostimulants in early stage of common carp culture.

Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer's disease: an exploration of underlying mechanisms.

RATIONALE: Alzheimer's disease (AD) is a neurodegenerative disorder with irreversible loss of intellectual abilities. Current therapies for AD are still insufficient. OBJECTIVE: In this study, the effect of ellagic acid on learning and memory deficits was evaluated in intrahippocampal amyloid beta (Aß25-35)-microinjected rats and its modes of action were also explored. METHODS: AD rat model was induced by bilateral intrahippocampal microinjection of Aß25-35 and ellagic acid was daily administered (10, 50, and 100 mg/kg), and learning, recognition memory, and spatial memory were evaluated in addition to histochemical assessment, oxidative stress, cholinesterases activity, and level of nuclear factor-kappaB (NF-κB), Toll-like receptor 4 (TLR4), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). RESULTS: The amyloid beta-microinjected rats showed a lower discrimination ratio in novel object and alternation score in Y maze tasks and exhibited an impairment of retention and recall capability in passive avoidance paradigm and higher working and reference memory errors in radial arm maze (RAM). In addition, amyloid beta group showed a lower number of Nissl-stained neurons in CA1 area in addition to enhanced oxidative stress, higher activity of cholinesterases, greater level of NF-κB and TLR4, and lower level of nuclear/cytoplasmic ratio for Nrf2 and ellagic acid at a dose of 100 mg/kg significantly prevented most of these abnormal alterations. CONCLUSIONS: Ellagic acid pretreatment of intrahippocampal amyloid beta-microinjected rats could dose-dependently improve learning and memory deficits via neuronal protection and at molecular level through mitigation of oxidative stress and acetylcholinesterase (AChE) activity and modulation of NF-κB/Nrf2/TLR4 signaling pathway.