Probiotics for the Management of Oral Mucositis: An Interpretive Review of Current Evidence

Mucositis is one of the major side effects of anti-cancer therapies. Mucositis may lead to other abnormalities such as depression, infection, and pain, especially in young patients. Although there is no specific treatment for mucositis, several pharmacological and non-pharmacological options are available to prevent its complications. Probiotics have been recently considered as a preferable protocol to lessen the complications of chemotherapy, including mucositis. Probiotics could affect mucositis by anti-inflammatory and anti-bacterial mechanisms as well as augmenting the overall immune system function. These effects may be mediated through anti microbiota activities, regulating cytokine productions, phagocytosis, stimulating IgA releasement, protection of the epithelial shield, and regulation of immune responses. We have reviewed available literature pertaining to the effects of probiotics on oral mucositis in animal and human studies. While animal studies have reported protective effects of probiotics on oral mucositis, the evidence from human studies is not convincing

Palm oil: features and applications

Palm fruits are the source of two distinct but related vegetable oils, namely palm oil and palm kernel oil. Palm oil has many food and industrial applications. Ever-increasing demands for palm oil have substantially impacted its industry, creating some environmental concerns. Both types of oil are high in saturated fatty acids with potential cardiovascular risks. Several attempts have been made to reduce undesirable health and environmental impacts. However, additional research and development activities are needed to meet the concerns of the medical professionals and environmental activists

Anti-Atherosclerotic Properties of Wild Rice in Low-Density Lipoprotein Receptor Knockout Mice: The Gut Microbiome, Cytokines, and Metabolomics Study

Background and aim: We previously reported the anti-atherogenic properties of wild rice in low-density lipoprotein receptor knockout (LDL-r-KO) mice. The present study aimed to discover the mechanism of action for such effects. Materials: Fecal and plasma samples from the wild rice treated and control mice were used. Fecal bacterial population was estimated while using 16S rDNA technology. The plasma samples were used to estimate the levels of 35 inflammatory markers and metabolomics, while using Meso Scale multiplex assay and liquid chromatography-mass spectrometry (LC-MS/MS) techniques. Results: Many bacteria, particularly Anaeroplasma sp., Acetatifactor sp., and Prophyromonadaceae sp., were found in higher quantities in the feces of wild rice fed mice as compared to the controls. Cytokine profiles were significantly different between the plasma of treated and control mice. Among them, an increase in the level of IL-10 and erythropoietin (EPO) could explain the anti-atherogenic properties of wild rice. Among many metabolites tested in plasma of these animals, surprisingly, we found an approximately 60% increase in the levels of glucose in the wild rice fed mice as compared to that in the control mice. Conclusion: Additional studies warrant further investigation of the interplay among gut microbiome, inflammatory status, and macronutrient metabolism

Regional antioxidant status in the gastrointestinal tract and the possible role of reactive oxygen-derived substances in peptic ulcer disease

1. Enzymatic and non-enzymatic antioxidant profiles in the various segments of the gastrointestinal tract of male and female rats have been investigated and found to exhibit significant differences (P<0.05). In both sexes, the levels of basal glutathione in the gastric and colonic mucosa are comparable, but lower than those in the proximal and distal segments of the small intestine. The activities of glutathione reductase in various portions of gastrointestinal tract were similar. Glutathione peroxidase showed higher activity in the gastric mucosa than that in other parts of the gastrointestinal tract. No significant differences were found in the activity of superoxide dismutase among the various segments examined. 2. Enzymatic and non-enzymatic antioxidant profiles in the gastric and duodenal mucosa of rabbit, quail, cat, pig and rat have been investigated and found to exhibit significant differences (P<0.05). The levels of basal glutathione were highest in the rat gastric and duodenal mucosa when compared with those in other species. In the duodenal mucosa of all species investigated, the activity of glutathione reductase was higher than that in the corresponding gastric mucosa. The activity of glutathione peroxidase was higher in the gastric mucosa than that in other species examined. Superoxide dismutase showed higher activity in quail duodenal mucosa than in any of the other species studied. 3. The effects of 8% and undiluted ethanol administered by gavage on lesion formation and antioxidant components of the gastric and duodenal mucosa of male and female rats have been examined. Undiluted ethanol produced macroscopic lesions in the body of the stomach in association with decreases in the activity of glutathione reductase and in the level of basal glutathione and an increase in the activity of glutathione peroxidase. Eight percent ethanol produced a small but significant increase (12%) in the level of basal glutathione in rat gastric mucosa when compared with controls. 4. The effects of chronic intermittent stress on the appearance and antioxidant components of the gastric and duodenal mucosa of rats have been examined. No differences in the antioxidant profiles or evidence of macroscopic lesion formation were found.Medicine, Faculty ofAnesthesiology, Pharmacology and Therapeutics, Department ofGraduat

Effects of a "tall oil" -derived phytosterol mixture on the development of atherosclerotic lesions in apo E-deficient mice

Background: The effects of a phytosterol mixture (FCP-3PI) on the plasma cholesterol concentrations and development of atherogenic lesions have been evaluated in apo E-knockout (apo E-KO) mice using a number of biochemical and histological methods. In addition, the systemic effects and the tolerance to FCP-3PI have also been tested in this animal model. FCP-3PI, which is composed of S-sitosterol (69%), campesterol (15%) and sitostanol (16%), was extracted from "tall oil" soap, a by-product of the pulp and paper industry. The degree of purity of the final product was approximately 95% as assessed by gas chromatography. Objectives:The objectives of this thesis were: 1) to determine the effects of dietary supplementation with FCP-3PI on plasma lipid concentrations in apo E-KO mice; 2) to evaluate the cholesterol-lowering properties of FCP-3PI in wild-type normolipidemic mice; 3) to evaluate the effects of FCP-3PI on the quality and extent of atherosclerotic lesions in apo E-KO mice; 4) to compare and contrast cholesterol-lowering and anti-atherogenic effects of FCP-3PI to those of probucol, a well-known lipid lowering agent with antioxidant properties; 5) to test systemic effects of FCP-3PI following its parenteral administration in apo E-KO mice; and finally, to investigate the tolerance of apo E-KO mice to FCP-3PI and its safety when administered over the long-term. Results: Atherosclerosis progression experiments revealed that addition of 2% (w/w) FCP-3PI to a typical "Western" diet resulted in a significant reduction in average total plasma cholesterol concentrations in the treated animals compared to controls. This was accompanied by a significant (p<0.0001) reduction in the average lesion area in the treated animals. This reduced lesion area in the aortic sinuses was accompanied by a substantial reduction in all lesional components, reflecting a delay in the progression of atheromatous changes. The lesion size was strongly correlated with the average plasma total cholesterol concentrations (r=0.69). Cholesterol lowering effects of FCP-3PI were tested in a number of male CD1 mice in the presence or absence of additional dietary cholesterol. FCP-3PI did not significantly reduce plasma total cholesterol in these normolipidemic mice. The lack of cholesterol-lowering effects of FCP-3PI may be due to limited cholesterol absorption in normolipidemic mice. The next experiment was carried out to investigate possible mechanisms of FCP-3PI effects on cholesterol metabolism and atherosclerotic lesion development, and then to compare FCP-3PI effects to those of probucol in apo E-deficient mice. The cholesterol-lowering and anti-atherogenic activities of FCP- 3PI were accompanied by significant alterations in several other features which may be directly/indirectly involved in atherogenesis. Thus, FCP-3PI treatment caused a significant increase in the activity of hepatic HMG-CoA reductase and to a lesser extent in the activity of hepatic cholesterol 7 -hydroxylase. These changes were associated with a significant decrease in hepatic cholesterol content and a 50% increase in fecal cholesterol excretion compared to controls. Hepatic lipase activity was also significantly reduced by FCP-3PI treatment. In addition, FCP-3PI caused a 20% decrease in plasma fibrinogen concentrations. Unlike FCP-3PI, probucol caused a marked decrease in plasma total, VLDL-, LDL-, and HDL-cholesterol concentrations which was associated with a significant increase in atherosclerotic lesion size in the aortic roots of the mice. Probucol also caused a significant increase in plasma fibrinogen concentration compared to controls. These changes were associated with a significant increase in plasma antioxidant enzyme activities. In addition, probucol, unlike FCP-3PI, reduced hepatic LDL receptor binding to two-thirds of that in controls. The activity of both hepatic HMG-CoA reductase and cholesterol 7 hydroxylase was increased in the probucol-treated animals compared to controls. The atherosclerosis regression study revealed no evidence for regression of pre-established atherosclerotic lesions in the aortic roots of the mice fed regular mouse chow supplemented with 2% (w/w) FCP-3PI for 25 weeks. Intraperitoneal injection of FCP-3PI into apo E-KO mice resulted in a significant reduction in the activity of hepatic HMG-CoA reductase, a nonsignificant reduction in plasma total cholesterol concentration and a significant increase in the activity of plasma antioxidant enzymes as compared to controls. Finally, parallel to the first experiment, tolerance of orally administered FCP-3PI was evaluated in apo E-deficient mice. Histological examination revealed no abnormality in tissues examined except for a certain degree of testicular atrophy. FCP-3PI treatment prevented the development of cutaneous xanthomatosis. Urinalysis and hematological data were comparable between the control and FCP-3PI-treated animals except for a significant decrease in platelet count in the treated group. The erythrocytes of the treated mice showed a decreased susceptibility to hypotonic lysis in vitro. Conclusions: We have demonstrated that FCP-3PI has cholesterollowering and anti-atherogenic effects in apo E-KO mice. Moreover, we have demonstrated, for the first time, the effectiveness of FCP-3PI in preventing cutaneous xanthomatosis and retarding the development of atherosclerotic lesions in this animal model. Our data suggest that these effects of FCP-3PI may be mediated through a decrease in plasma VLDL-cholesterol, an increase in fecal cholesterol excretion (most likely due to decreasing cholesterol reabsorption and increasing biliary cholesterol excretion), a decrease in hepatic lipase activity and decrease in plasma fibrinogen concentrations. The lack of toxicity and its abundance in nature along with its low cost make potential use of FCP-3PI in prevention and treatment of human hypercholesterolemia attractive.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat

RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling

Bones as an alive organ consist of about 70% mineral and 30% organic component. About 200 million people are suffering from osteopenia and osteoporosis around the world. There are multiple ways of protecting bone from endogenous and exogenous risk factors. Planned physical activity is another useful way for protecting bone health. It has been investigated that arranged exercise would effectively regulate bone metabolism. Until now, a number of systems have discovered how exercise could help bone health. Previous studies reported different mechanisms of the effect of exercise on bone health by modulation of bone remodeling. However, the regulation of RANKL/RANK/OPG pathway in exercise and physical performance as one of the most important remodeling systems is not considered comprehensive in previous evidence. Therefore, the aim of this review is to clarify exercise influence on bone modeling and remodeling, with a concentration on its role in regulating RANKL/RANK/OPG pathway

Melatonin Modulation of Sirtuin-1 Attenuates Liver Injury in a Hypercholesterolemic Mouse Model

Hypercholesterolemia increases and exacerbates stress signals leading also to liver damage (LD) and failure. Sirtuin1 (SIRT1) is involved in lifespan extension and it plays an essential role in hepatic lipid metabolism. However, its involvement in liver hypercholesterolemic damage is not yet completely defined. This in vivo study evaluated the role of SIRT1 in the hypercholesterolemic-related LD and, then, investigated how oral supplementation of melatonin, pleiotropic indoleamine, may be protective. Control mice and apolipoprotein E-deficient mice (ApoE(-/-)) of 6 and 15 weeks of age were treated or not treated with melatonin at the dose of 10mg/kg/day for 9 weeks. In this study, we evaluated serum biochemical markers, liver SIRT1 expression, and oxidative stress markers. We observed that hypercholesterolemia increased significantly serum cholesterol and triglycerides, reduced significantly liver SIRT1, and, in turn, induced hepatic oxidative stress in untreated ApoE(-/-) mice with respect to control mice. Interestingly, melatonin treatment improved serum biochemical markers and hepatic morphological impairment and inhibited oxidative stress through its antioxidant properties and also by SIRT1 upregulation. In summary, melatonin oral supplementation may represent a new protective approach to block hypercholesterolemic liver alterations involving also a SIRT1-dependent mechanism