Targeting the Gut Microbiota and Host Immunity with a Bacilli-Species Probiotic during Antibiotic Exposure in Mice.

Antibiotic therapy is necessary for the treatment of bacterial infections; however, it can also disrupt the balance and function of commensal gut microbes and negatively affect the host. Probiotics have been tested as a means to counteract the negative effects of antibiotic therapy, but many probiotics are also likely destroyed by antibiotics when taken together. Here we aimed to test the efficacy of a non-pathogenic spore-forming Bacillus-species containing a probiotic blend provided during antibiotic therapy on host immune defenses in mice. Mice were exposed to antibiotics and supplemented with or without the probiotic blend and compared to control mice. Fecal and cecal contents were analyzed for gut microbes, and intestinal tissue was tested for the expression of key enzymes involved in vitamin A metabolism, serum amyloid A, and inflammatory markers in the intestine. The probiotic blend protected against antibiotic-induced overgrowth of gram-negative bacteria and gammaproteobacteria in the cecum which correlated with host immune responses. Regional responses in mRNA expression of enzymes involved with vitamin A metabolism occurred between antibiotic groups, and intestinal inflammatory markers were mitigated with the probiotic blend. These data suggest prophylactic supplementation with a spore-forming Bacillus-containing probiotic may protect against antibiotic-induced dysregulation of host immune responses.

Determinants of long-term health-related quality of life in adult patients with mild traumatic brain injury.

PURPOSE: Mild traumatic brain injury (mTBI) usually leads to the appearance of post-concussion symptoms (PCS) which may resolve after a short time. In this study, the mental and physical aspects of quality of life (QoL) were evaluated 6 months after mTBI, and the association of demographic and injury-related factors, post-injury primary executive function and PCS types with the long-term QoL status was investigated. METHODS: 123 eligible mTBI patients of initial sampling participated in follow-up phase of this longitudinal study. The demographic, clinical, and para-clinical data of patients were recorded. Paraclinical data comprised brain lesion volume, type and location determined by CT scan. The executive function and primary PCS were examined during the discharge using the verbal fluency task and a checklist, respectively. QoL was measured via SF-36 questionnaire. The collected data were entered into SPSS 22, and analyzed using appropriate statistical tests. RESULTS: Youngers aged between 18 and 35 years and women had a lower QoL score than others. Primary somatic and cognitive PCS together were associated with poor QoL. There was no significant difference in QoL and executive function scores between the normal and abnormal brain CT groups. However, among people with abnormal CT, those having multifocal lesions including at least an intracranial hemorrhage type such as intra parenchymal hemorrhage or extra-axial bleeding together with other intracranial lesions or skull fracture demonstrated less QoL score in SF-36. A significant correlation was discovered between the scores of the executive function and QoL in mental dimensions of SF-36. CONCLUSIONS: This study emphasizes on the clinical significance of early executive function and PCS examination in mTBI population, as well as optimal management of the victims regardless of the initial brain CT findings, especially in high-risk populations.

Early-Life Gut Microbiome-The Importance of Maternal and Infant Factors in Its Establishment.

The early-life microbiome is gaining appreciation as a major influencer in human development and long-term health. Multiple factors are known to influence the initial colonization, development, and function of the neonatal gut microbiome. In addition, alterations in early-life gut microbial composition is associated with several chronic health conditions such as obesity, asthma, and allergies. In this review, we focus on both maternal and infant factors known to influence early-life gut colonization. Also reviewed is the important role of infant feeding, including evidence-based strategies for maternal and infant supplementation with the goal to protect and/or restore the infant gut microbiome.

DHA supplementation during prenatal ethanol exposure alters the expression of fetal rat liver genes involved in oxidative stress regulation.

Prenatal ethanol (EtOH) exposure is known to induce adverse effects on fetal brain development. Docosahexaenoic acid (DHA) has been shown to alleviate these effects by up-regulating antioxidant mechanisms in the brain. The liver is the first organ to receive enriched blood after placental transport. Therefore, it could be negatively affected by EtOH, but no studies have assessed the effects of DHA on fetal liver. This study examined the effects of maternal DHA intake on DHA status and gene expression of key enzymes of the glutathione antioxidant system in the fetal liver after prenatal EtOH exposure. Pregnant Sprague-Dawley dams were intubated with EtOH for the first 10 days of pregnancy, while being fed a control or DHA-supplemented diet. Fetal livers were collected at gestational day 20, and free fatty acids and phospholipid profile, as well as glutathione reductase (GR) and glutathione peroxidase-1 (GPx1) gene expressions, were assessed. Prenatal EtOH exposure increased fetal liver weight, whereas maternal DHA supplementation decreased fetal liver weight. DHA supplementation increased fetal liver free fatty acid and phospholipid DHA independently of EtOH. GR and GPx1 messenger RNA (mRNA) expressions were significantly increased and decreased, respectively, in the EtOH-exposed group compared with all other groups. Providing DHA normalized GR and GPx1 mRNA expression to control levels. This study shows that maternal DHA supplementation alters the expression of fetal liver genes involved in the glutathione antioxidative system during prenatal EtOH exposure. The fetal liver may play an important role in mitigating the signs and symptoms of fetal alcohol spectrum disorders in affected offspring.

Rolipram potentiates bevacizumab-induced cell death in human glioblastoma stem-like cells.

AIMS: Glioblastoma cancer stem-like cells (GCSCs) promote themselves proliferation by secreting the vascular endothelial growth factor A (VEGFA) in an autocrine manner, positively regulated by phosphodiesterase IV (PDE4). In the current study, we investigated the putative cytotoxic effect of bevacizumab, a VEGFA blocker, alone and in combination with a specific inhibitor of PDE4 called rolipram on GCSCs isolated from human surgical tumor specimen with a focus on PI3K/AKT pathway. MAIN METHODS: CD133+/CD15+ GCSCs were characterized by flow cytometry and expanded in a serum-free primary culture system. The cell survival, apoptosis, and protein expression values were measured using MTT assay, TUNEL staining and western blot, successively. Intracellular cAMP and free secreted VEGFA levels were assessed by cAMP enzyme immunoassay and ELISA, respectively. KEY FINDINGS: Bevacizumab suppressed GCSCs survival with IC50~6.5µg/ml and enhanced the levels of apoptosis, p53 and cleaved-caspase3 along with a decrease in free VEGFA levels and ERKs activation. However, there was no significant modulation of AKT phosphorylation on serine 473, the intracellular PDE4A, VEGFA and cAMP levels. More cytotoxicity in co-treated cells coupled with a more substantial decline in the free VEGFA levels and a greater increase in the quantities of p53 and cleaved-caspase3 compared to those treated with bevacizumab alone. Co-treatment reduced phospho-AKT, endogenous VEGFA and PDE4A values but elevated cAMP levels. SIGNIFICANCE: This study highlighted a booster cytotoxic effect of combined rolipram and bevacizumab treatment on the GCSCs primary culture, suggesting that this approach is warranted in treatment of GBMs overexpressing VEGFA and PDE4A.

The Role of Dietary Cholesterol in Lipoprotein Metabolism and Related Metabolic Abnormalities: A Mini-review.

Cholesterol plays a vital role in cell biology. Dietary cholesterol or "exogenous" cholesterol accounts for approximately one-third of the pooled body cholesterol, and the remaining 70% is synthesized in the body (endogenous cholesterol). Increased dietary cholesterol intake may result in increased serum cholesterol in some individuals, while other subjects may not respond to dietary cholesterol. However, diet-increased serum cholesterol levels do not increase the low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, nor do they decrease the size of LDL particles or HDL cholesterol levels. Elevated levels of LDL cholesterol, reduced HDL cholesterol levels, and small, dense LDL particles are independent risk factors for coronary artery disease. Dietary cholesterol is the primary approach for treatment of conditions such as the Smith-Lemli-Opitz syndrome. Recent studies have highlighted mechanisms for absorption of dietary cholesterol. These studies have help understand how dietary and/or pharmaceutical agents inhibit cholesterol absorption and thereby reduce LDL cholesterol concentrations. In this article, various aspects of cholesterol metabolism, including dietary sources, absorption, and abnormalities in cholesterol metabolism, have been summarized and discussed.

Animal models of atherosclerosis.

In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans' stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research.

Nutritional constituents and health benefits of wild rice (Zizania spp.).

Wild rice (Zizania spp.) seems to have originated in North America and then dispersed into Eastern Asia and other parts of the world. Nutritional analysis shows that wild rice is rich in minerals, vitamins, protein, starch, dietary fiber, and various antioxidant phytochemicals, while it is low in fat. Wild rice has been recognized as a whole grain by the US Food and Drug Administration; in the North American marketplace it is currently sold as and considered to be a health-promoting food. Recent scientific studies have revealed antioxidant and lipid-lowering properties of wild rice, while others have documented cardiovascular benefits associated with the long-term consumption of wild rice in experimental settings. The present review article summarizes various features of wild rice and its cultivation, including its plantation, harvest, nutritional composition, and biological properties. While evidence for the cardiovascular benefits of wild rice consumption is accumulating, additional studies are warranted to determine the clinical benefits of regular consumption of wild rice.