Consumption of PY compared with LF with main meals showed no significant effects on weight loss. However, it may have positive effects on lipid profiles and insulin sensitivity during a weight-loss program. This trial was registered at http://www.irct.ir/ as IRCT201402177754N8.
Considerable evidence shows that the tumor microenvironment is an active participant in preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia is a prominent characteristic of the solid tumor microenvironment. The transcription factor hypoxia-inducible factor-1α (HIF-1α) is an important mediator of hypoxic response of tumor cells that modulates the expression of specific genes involved in tumor immunosuppression. Using a 4T1 breast cancer model, we show that in vivo administration of PX-478, an inhibitor of oxygen-sensitive HIF-1α, led to reduced expression of Foxp3 and VEGF transcript and/or protein, molecules that are directly controlled by HIF-1. When combined with dendritic cell (DC)-based vaccination, HIF-1α inhibition resulted in an augmented cytotoxic T lymphocyte effector function, improved proliferation status of T cells, increased production of inflammatory cytokine IFN-γ, as well as reduced regulatory function of T cells in association with slower tumor growth. Taken together, our findings indicate that the use of HIF-1α inhibition provides an immune adjuvant activity, thereby improves the efficacy of tumor antigen-based DC vaccine.
Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.
Background:Based on different studies it was shown that exercise training is an important factor in preconception and prenatal care.Objective:The aim of this study was to determine whether regular preconception exercise training with or without exercise training during pregnancy decreases detrimental effects of maternal high fat diet on female offspring bone health.Materials and Methods:Twenty-four C57BL/6 female mice were fed high-fat diet (35%) and were randomly divided into four groups: trained in preconception period and exercised during pregnancy (TE); trained in preconception periods but unexercised during pregnancy (TC); untrained in preconception periods but exercised during pregnancy (CE); untrained and unexercised (CC). Trained mice were subjected to a protocol of moderate endurance exercise training over a period of 4 weeks before pregnancy. TE and CE Dams groups had access to wheels throughout pregnancy until delivery. Analyses were performed on the female offspring that did not have access to running wheels or exercise training during any portion of their lives. The relative expression levels of β-catenin, Peroxisome proliferator-activated receptor ƴ (PPARƴ), osteoprotegerin (OPG), and Receptor activator of nuclear factor NF-kB ligand (RANKL) were determined by Quantitative RT-PCR (qPCR).Results:Exercise during pregnancy in isolation had no effect on any measure genes but exercise both before and during pregnancy affected all genes. Exercise only before pregnancy increased β-catenin and OPG and decreased PPARƴ, RANKL, and RANKL/OPG ratio (p<0.001). Conclusion: This study demonstrated that maternal exercise training before and during pregnancy may modulate the risk of bone disorders in offspring of mothers fed a high-fat diet.
Background: Contrary to the reports about the useful effects of atorvastatin on blood lipids and insulin sensitivity by up-regulation of peroxisome proliferative-activated receptor gamma (PPAR-γ) expression, to our knowledge, there is inconclusive results about vitamin E. Also, there is no study to assess co-administration of vitamin E and atorvastatin on PPAR-γ mRNA expression, insulin sensitivity and lipid profile in diabetic patients. We compared this effect in hyperlipidemic subjects with type 2 diabetes mellitus (T2DM). Methods: At the present randomized clinical trial (RCT), 30 T2DM women with hyperlipidemia were categorized into the treated group with 20 mg atorvastatin plus 400 IU vitamin E supplement (n = 15) or atorvastatin plus placebo (n = 15) per day for 12 weeks. Anthropometric and biochemical measures were done at the baseline and after the 12-week intervention. PPAR-γ mRNA expression was measured in the peripheral blood mononuclear cells (PBMCs) of all patients. Results: After adjusting for the baseline measures, vitamin E resulted in significant improvements in insulin sensitivity in terms of HOMA-IR (-1.01±0.52 vs. -2.56 ± 0.54, P = 0.04) and serum insulin (-0.55±0.35 vs. -6.5 ± 1.3, P < 0.001), compared with the atorvastatin plus placebo. Adjusted for the baseline variables, compared with the atorvastatin plus placebo, vitamin E supplementation could up-regulate PPAR-γ mRNA expression (OR=5.4, 95% CI=0.8-36.9, P=0.04) in PBMC of T2DM women. Conclusions: Vitamin E supplementation along with atorvastatin may improve insulin sensitivity through up-regulation of PPAR-γ gene. More RCTs are needed to reach conclusive results. Trial registration: The present study is registered under ClinicalTrials.gov Identifier no. IRCT20170918036256N1.
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