The use of recombinant tissue plasminogen activator in in acute ischemic stroke is associated with increased level of BDNF

Much concern was directed towards the crucial role of recombinant tissue plasminogen activator (rt-PA) in improving neuroplasticity in patients with acute ischemic stroke. The aim of the work to investigate the effect of treating patients with acute ischemic stroke with rt-PA, on the level of brain derived neurotrophic factor (BDNF) as a marker of neuroplasticity. This study was conducted on 47 patients presenting with acute ischemic stroke (during the first 4.5 h from stroke onset); 26 patients of them eligible for receiving rt-PA (patient group) and 21 patients having contraindications for treatment with rt-PA (control group). Neurological, radiological and laboratory assessment (including BDNF serum level) were done for both groups at stroke onset (before receiving rt-PA) and at day 7. There was a statistically significant increase in BDNF serum level from day 1 to day 7 in rt-PA treated patients in comparison to control group (P-value? 0.001). Serum level of BDNF is significantly higher at the onset of stroke in female patients and non-smokers than males or smokers (P-value?=?0.011, 0.01 respectively). There was no effect of either age, body mass index, hypertension, diabetes, drug abuse, past or family history of stroke, valvular heart diseases, atrial fibrillation, cardiomyopathy, ejection fraction, carotid atherosclerotic changes, lipid profile or uric acid, on BDNF serum level measured at the onset of stroke. Treatment of patients with acute ischemic stroke with rt-PA causes significant improvement in neuroplasticity through increasing BDNF serum level.

     

Rebamipide potentially mitigates methotrexate-induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study

Methotrexate (MTX) is a widely used chemotherapeutic agent; nevertheless, the nephrotoxicity associated with its use has limited its clinical use. Rebamipide (REB) is a gastro-protective agent with diverse promising biological activities. Here, we investigated the renoprotective effects of REB against MTX-induced nephrotoxicity in rats. Male Wistar rats were allocated into four groups: the normal control group, the REB group (100 mg kg⁻¹ day⁻¹, PO, for 12 days), the MTX group (which received a single injection of 20 mg/kg, ip), and the REB + MTX group (which received 100 mg kg⁻¹ day⁻¹ REB for 7 days before and 5 days after being injected with 20 mg/kg MTX). Interestingly, MTX triggered kidney injury, characterized by renal dysfunction along with histopathological alterations. Moreover, increased reactive oxygen species level and inflammatory response were detected in the kidney of MTX-treated rats. However, REB prevented MTX-induced oxidative kidney injury and boosted an antioxidant balance. Mechanistically, REB markedly activated the NRF-2 protein and upregulated the expression of both SIRT-1 and FOXO-3 genes. Additionally, REB administration strongly inhibited the inflammatory response by downregulating both NF-κB-p65 and TLR-4. Finally, the coadministration of REB and MTX activated the mTOR/PI3K/AKT signaling pathway. Simultaneously, REB treatment attenuated the reduction in glomerular size, the widening of the capsular spaces, and the tubular cell damage due to MTX administration. Taken together, these results indicate the potential of REB as adjuvant therapy to prevent nephrotoxicity in patients receiving MTX treatment.     

Situating language in a minimal social context: how seeing a picture of the speaker’s face affects language comprehension

Natural use of language involves at least two individuals. Some studies have focused on the interaction between senders in communicative situations and how the knowledge about the speaker can bias language comprehension. However, the mere effect of a face as a social context on language processing remains unknown. In the present study, we used event-related potentials to investigate the semantic and morphosyntactic processing of speech in the presence of a photographic portrait of the speaker. In Experiment 1, we show that the N400, a component related to semantic comprehension, increased its amplitude when processed within this minimal social context compared to a scrambled face control condition. Hence, the semantic neural processing of speech is sensitive to the concomitant perception of a picture of the speaker’s face, even if irrelevant to the content of the sentences. Moreover, a late posterior negativity effect was found to the presentation of the speaker’s face compared to control stimuli. In contrast, in Experiment 2, we found that morphosyntactic processing, as reflected in left anterior negativity and P600 effects, is not notably affected by the presence of the speaker’s portrait. Overall, the present findings suggest that the mere presence of the speaker’s image seems to trigger a minimal communicative context, increasing processing resources for language comprehension at the semantic level.     

The effect of different storage media on the monomer elution and hardness of CAD/CAM composite blocks

ObjectiveThis study aimed to assess the effect of different storage media on the hardness and monomer elution of CAD/CAM composite blocks.MethodsFive resin-composite blocks (RCB), one polymer-infiltrated ceramic network (PICN) block (Enamic (EN)), one ceramic-filled poly ether ether ketone (PEEK) block (Dentokeep (DK)), and one feldspathic ceramic block. Microhardness was measured using a Vickers indenter tester (FM-700, Future Tech Corp., Japan). In addition 4 conventional resin-composites were investigated for monomer elution using high performance liquid chromatography (HPLC) after storage in different media for 3 months. The data were analysed by three-way ANOVA, two-way ANOVA, one-way ANOVA, Tukey’s post hoc test and the independent t-test (α = 0.05 for all tests).ResultsThe specimens stored in the water had a hardness reduction ranging from 0.9% to 24.4%. In artificial saliva, the specimens had a hardness reduction ranging from 2.8% to 23.2%. The hardness reduction percentage in 75% Ethanol/Water (E/W) ranged between 3.8% and 35.3%. All materials, except GR (resin-composite block) and DK (Polyetheretherketone (PEEK)), showed a variable extent of monomer elution into 75% E/W with significantly higher amounts eluted from conventional composites. GRA and GND (conventional resin-composites) eluted TEGDMA in artificial saliva and GRA eluted TEGDMA in water.SignificanceThe hardness of CAD/CAM composite blocks was affected by different storage media, and they were not as stable as ceramic, with PICN exhibited superior hardness stability to all of the resin-composite blocks in all the storage media and was comparable to ceramic block. The hardness reduction percentage of the CAD/CAM composite blocks was influenced by the filler loading and resin-matrix composition.Minimal or no monomer elution from CAD/CAM blocks was detected.     

Using an UPLC/MS-based untargeted metabolomics approach for assessing the antioxidant capacity and anti-aging potential of selected herbs

Aging is an unavoidable fate that afflicts all life, during this process in mammals reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging. Therefore, the maintenance of antioxidant homeostasis is an important anti-aging strategy for skin. Nature has excellent anti-aging remedies that act externally as well as internally to delay the visual signs of aging. In view of this fact, the present study investigates the in vitro anti-aging activity of five medicinal plants belonging to phenolic rich families namely Rosmarinus officinalis, Lavandula officinalis, Matricaria chamomilla, Camellia sinensis and Pelargonium graveolens. The selected plants are those most frequently used in the preparation of ethnomedicinal recipes for the prevention or treatment of aging. The inhibitory effects of the ethanolic and aqueous extracts of the five selected plants on the activity of tyrosinase, elastase, and collagenase enzymes were investigated. Furthermore, the chemical composition of the plants and the antioxidant capacity of their extracts were assessed. The results showed that R. officinalis had the highest total phenolics content which was correlated with its potent antioxidant and anti-aging activities. To pinpoint the active metabolites in the tested extracts, we evaluated the metabolite variations using ultra-performance liquid chromatography coupled with high resolution electrospray ionization-tandem mass spectrometry (UPLC-HR-ESI-MS/MS). Multivariate data analysis (MVDA) revealed that R. officinalis significantly accumulated metabolites from the aromatic diterpenoid, flavonoid and phenolic acid classes. These results indicate that rosemary can be used for further development of topical preparations with anti-aging properties.

Aging is an unavoidable fate that afflicts all life, during this process in mammals, reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging.     

Low dose γ radiation enhances antidepressant effect of resveratrol: Behavioral and neurochemical studies

The low dose of radiation (LDR) has received growing attention for its beneficial neuroprotective effect. This study was designed to investigate the enhancing effect of LDR on the antidepressant potential of resveratrol against diazepam‐induced depression in mice. Female mice divided into five groups; control, diazepam (2 mg/kg), LDR (0.5Gy) + diazepam, resveratrol (20 mg/kg) + diazepam, LDR + resveratrol+diazepam. Mice received diazepam showed depressive symptoms as evidenced by decreased locomotor activity in the open field and increased immobility time in the forced swimming and tail suspension tests integrated with a marked decline in biogenic amines (serotonin, norepinephrine, and dopamine) in brain tissues. These effects were ameliorated by LDR or resveratrol administration demonstrating an antidepressant activity. Interestingly, LDR triggered the antidepressant effect of resveratrol as it restored the changes in behavioral tests, neurotransmitters, and neuro‐histoarchitecture. In conclusion, these findings suggested that LDR could be considered as a novel adjuvant that augmented the resveratrol antidepressant effect and might serve as a potential therapeutic approach for depression.     

Modulation of JNK-1/ β-catenin signaling by Lactobacillus casei,inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice

Colon cancer is a complex disease that involves numerous genetic alterations that change the normal colonic mucosa into invasive adenocarcinoma. In the current study, the protective effects of inulin (prebiotic), Lactobacillus casei (L. casei, probiotic) and their combination (synbiotic) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male Swiss mice were evaluated. Animals were divided into: Control group, DMH-treated group, DMH plus inulin, DMH plus L. casei and DMH plus inulin plus L. casei-treated groups. Fecal microbiome analysis, biochemical measurements, histopathological examination of the colon tissues, immunostaining and Western blotting analysis of β-catenin, GSK3β and JNK-1 were performed. The prebiotic-, probiotic- and synbiotic-treated groups showed decreased levels of carcinoembryonic antigen and a lower number of aberrant crypt foci compared to the DMH-treated group with the synbiotic group exhibiting a superior effect. Furthermore, all treatments showed a body weight-reducing effect. Administration of inulin, L. casei or their combination increased the expression level of phospho-JNK-1 while they decreased the expression level of β-catenin and phospho-GSK3β. Remarkably, L. casei treatment resulted in enrichment of certain beneficial bacterial genera i.e. Akkermansia and Turicibacter. Therefore, administration of L. casei and inulin as a synbiotic combination protects against colon cancer in mice.

The lactobacillus casei and inulin modulate the expression of JNK-1, GSK3β and β-catenin proteins and enrich the beneficial bacteria to protect from colon cancer in mice.