The gastrointestinal microbiota affects brain function, including memory and learning. In this study we investigated the effects of probiotics on memory and oxidative stress biomarkers in an experimental model of Alzheimer's disease. Sixty rats were randomly divided into 5 groups: control; control-probiotics, which received probiotics for 8 weeks; sham operation, which received an intrahippocampal injection of phosphate-buffered saline; Alzheimer, which received an intrahippocampal injection of β-amyloid (Aβ1-42); and Alzheimer-probiotics, which in addition to being injected with Aβ1-42, received 2 g (1 × 10 CFU/g) of probiotics (Lactobacillus acidophilus, L. fermentum, Bifidobacterium lactis, and B. longum) for 8 weeks. Memory and learning were measured using the Morris water maze, and oxidative stress biomarkers in the hippocampus were measured using ELISA kits. Morris water maze results indicated that compared with the Alzheimer group, the Alzheimer-probiotics group had significantly improved spatial memory, including shorter escape latency and travelled distance and greater time spent in the target quadrant. There was also improvement in oxidative stress biomarkers such as increased malondialdehyde levels and superoxide dismutase activity following the β-amyloid injection. Overall, it seems that probiotics play a role in improving memory deficit and inhibiting the pathological mechanisms of Alzheimer's disease by modifying microbiota.

Preconditioning of mesenchymal stem cells (MSCs) with melatonin (MT) has shown promising results in animal models of myocardial infarction, renal ischemia and cerebral ischemia. Here, we use this strategy in the liver fibrosis induced by CCl4. There were five groups: normal, CCl4, CCl4 + vehicle, CCl4 + BMMSCs and CCl4 + MT-bone marrow (BM)-derived MSCs (MT-BMMSCs). CCl4 was injected twice weekly for 8 weeks and treatment either with cells or vehicle was performed at the beginning of week 5 with a single dose. BMMSCs were preconditioned with MT for 24 h before injection. MT-BMMSCs had a high ability of homing into the injured liver (P ≤ 0.05 vs. BMMSCs). The CCl4 + MT-BMMSCs group showed higher percentage of glycogen storage but lower percentage of collagen and lipid accumulation (P ≤ 0.05 vs. CCl4 + BMMSCs). The CCl4 + MT-BMMSCs group showed lower expressions of transforming growth factor-β1 (TGF-β1) and Bax and lower content of sera alanine aminotransferase (ALT) but higher expressions of matrix metalloproteinases (MMPs) and Bcl2 compared with the BMMSCs group (P ≤ 0.05). The results showed the better therapeutic outcomes of MT preconditioning by probably improving cell homing and also better maintenance of the balance between matrix degrading and accumulating factors.

Melatonin is known for being beneficial in targeting liver diseases. This study aimed to investigate whether melatonin post-treatment is capable of rat carbon tetrachloride (CCl)-induced liver fibrosis reduction. Thirty-two male Sprague-Dawley rats were divided into 4 groups: normal; fibrosis with CCl injection (1 mL/kg) twice weekly for 8 weeks; phosphate-buffered saline (PBS); and melatonin (20 mg/kg) for a further 4 weeks on cessation of CCl. At the beginning of week 13, liver tissue samples were used for hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), Masson's trichrome (MT), and Oil Red O staining, quantitative real-time PCR (qRT-PCR) analysis of the matrix metalloproteinase-9 (MMP-9), MMP-13, transforming growth factor-β1 (TGF-β1), Bcl-2, and Bax genes as well as immunofluorescence (IF) of the first 3, and sera for measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and hydroxyproline. Chronic administration of CCl followed by considerable increase in tissue disruption, macro- and micro-vesicles, collagen, lipid droplets (LDs), AST, ALT, hydroxyproline, TGF-β1, and Bax, and decrease in glycogen depository, albumin, Bcl-2, MMP-9, and MMP-13; however, the pattern was reverse when it comes to melatonin treatment (for all p < 0.05). Our results reveal the beneficial aspects of melatonin in treatment of liver fibrosis probably via inhibition of TGF-β1expression.

There is a positive relation between decreases of triiodothyronine (T3) amounts and severity of stroke. The aim of this study was to evaluate the effect of exogenous T3 application on levels of neurogenesis markers in the subventricular zone. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. There were 4 experimental groups: sham, ischemic, vehicle, and treatment. Rats were injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. Animals were sacrificed at day 7 after ischemia. There were high levels of brain-derived neurotrophic factor, nestin, and Sox2 expressions in gene and protein levels in the T3 treatment group (P ≤ .05 vs ischemic group). Treatment group showed high levels of sera T3 and thyroxine (T4) but low levels of thyrotropin (TSH), tumor necrosis factor-α, and interleukin-6 (P ≤ .05 vs ischemic group) at day 4 after ischemia induction. Findings of this study revealed the effectiveness of exogenous T3 application in the improvement of neurogenesis possibly via regulation of proinflammatory cytokines.

Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.