Integrative molecular medicine最新文献

Background: Rosemary is abundant with phytochemicals and has recently been approved as an antioxidant food preservative in the European Union. The safety of rosemary is well established, however, the benefits on gastrointestinal health are less known. Our overall hypothesis is that the phytochemicals in rosemary including carnosol have the potential to promote gastrointestinal health by activation of the antioxidant sestrin-2 when consumed in our diet.

Methods: Colon cells HCT116 and SW480 were treated with carnosol and evaluated by MTT, immunofluorescence, ELISA, and Western blot analysis to understand the modulation of the PERK/Nrf2/Sestrin-2 pathway.

Results: Carnosol was found to modulate PERK and increase the concentration of nuclear Nrf2. Furthermore, a downstream marker of Nrf2 expression, Sestrin-2 was shown to be upregulated.

Conclusion: Based on these observations carnosol modulates the PERK and Nrf2 pathways along with increased expression of sestrin-2, a known stress inducible antioxidant.

Formidable anti-vaccine movements have been growing as a menace to disrupt beneficial vaccine programs. Although the vaccination-associated adverse effects commonly perceived by vaccine resisters usually represent over-reactions to rare manifestations, converging evidence shows that vaccination-associated health threats could be pervasive when systemic inflammation is considered as a side effect that oozes over time. An anti-vaccine movement thus may not be so unfounded even though the myriad cascades triggered by systemic inflammation have not been brought to a clear focus during any anti-vaccine campaign. Since both pro- and anti-vaccine groups are acting on the same primal impulse - "keep people healthy," reconciliation between the two warring factions should be achievable on a palatable trend that fosters the development of noninvasive vaccines which tend to induce local and transient inflammation along the interface with diminished potential to percolate through internal organs.

The molecular mechanisms involved in human uterine quiescence during gestation and the induction of labor at term or preterm are not completely known. Preterm delivery is associated with major morbidity and mortality and current efforts to prevent delivery until term are largely ineffective. Identification and semi-quantification of proteomic changes in uterine smooth muscle during pregnancy will allow for targeted research into how quiescence is maintained and what changes are associated with induction of labor. Examining preterm labor in this context will provide potential therapeutic targets for the management of preterm labor. We have recently performed two dimensional liquid chromatography coupled with tandem mass spectrometry on myometrial proteins isolated from pregnant patients in labor, pregnant patients not in labor, and pregnant patients in labor preterm. Using a conservative false discovery rate of 1% we have identified 2132 protein groups using this method and semi-quantitative spectral counting shows 201 proteins that have disparate levels of expression in preterm laboring samples. To our knowledge this is the first large scale proteomic study examining human uterine smooth muscle and this initial work has provided a target list for future experiments that can address how changing protein levels are involved in the induction of labor at term and preterm.

Background: The goals of the study were (1) to determine the impact of inorganic mercury exposure on glucose homeostasis; and (2) to evaluate the effectiveness of two community-based interventions in promoting dietary changes among American Indian college students to reduce risk factors for Type-2 Diabetes including fasting glucose, insulin, and mercury levels, weight, and body mass index.

Methods: To accomplish goal one, the National Health and Nutrition Examination Survey (NHANES) dataset was analyzed using a previously published method to determine if there is a relationship between inorganic blood mercury and fasting glucose. To accomplish goal two, ten college students were recruited and randomly assigned to a group receiving the online macroepigenetics nutrition course and the support group for eliminating corn sweeteners. Participants in both groups were assessed for diet patterns, weight, body mass index (BMI), fasting glucose, insulin, and mercury levels. The interventions were implemented over a 10-week period.

Results: Analysis of the NHANES data (n=16,232) determined a direct relationship between inorganic mercury in blood and fasting glucose levels (p<0.001). The participants who took the online macroepigenetics nutrition intervention course significantly improved their diets (p<0.01), and fasting blood glucose levels (p<0.01) while having lower levels of inorganic mercury in their blood compared to the subjects in the group who eliminated corn sweeteners from their diet and participated in the support group. The trend in lower blood inorganic mercury was strong with p=0.052. The participants in the support group who eliminated corn sweeteners from their diet achieved significant weight loss (p<0.01) and reduced their body mass index (p<0.01).

Conclusion: Total blood mercury levels may be influenced by dietary intake of highly processed foods and lower inorganic mercury levels are associated with lower fasting glucose levels. Alternative community-based interventions emphasizing the role food ingredients and toxic substances play in gene modulation and the development of diseases can result in significant dietary improvements and reductions in risk factors associated with type-2 diabetes. A healthier diet can be promoted among community members using a novel online nutrition course. Consumption of corn sweeteners may be a risk factor in the development of obesity.

Ftibamzone (FBZ) is known to be effective against herpes simplex virus that causes genital herpes but poor solubility of FBZ has reduced its therapeutic efficacy. We investigated water-soluble complexes of various nanoparticles with FBZ to improve its solubility as well as increase its absorption. Using phase-solubility technique, we measured formation constant (K_1:1 and K_1:2) values at room temperature in pH 7 buffer. Solubility was determined by dissolving FBZ or FBZ-entrapped nanoparticles in phosphate buffers and pH adjusted to different pH range (2-12). The solutions were then equilibrated for 24 hours and then filtered and analyzed using HPCL. Nanoparticles were formulated using nanoprecipitation technique and cellular uptake of nanoparticle was determined by confocal microscope. No significant FBZ solubility was observed from pH 2 to 10 however we did notice a rapid increase in solubility from pH of 10 to 12 with FBZ solubility of 950 μg/ml. Our log D against pH profile revealed that FBZ is characteristic of an acid drug since unionized group was dominant at low pH. FBZ interaction with methyl-β-cyclodextrin (mβCD) complexation/nanoparticles showed a greater solubility of FBZ compared with FBZ alone while complexation constants were determined to be K_1:1 and K_1:2 were 7.06×10^-3 and 8.98×10^-8 mM^-1 respectively. Only FBZ-chitosan nanoparticles were toxic against MDCK cells. Study demonstrates that FBZ-PLGA nanoparticles could significantly enhance the solubility and absorption of FBZ compared with FBZ alone and has the potential to be used as an effective delivery system for the treatment of genital herpes.