Evidence that endothelial lipase remodels high density lipoproteins without mediating the dissociation of apolipoprotein A-I

Endothelial lipase (EL) is a triglyceride lipase gene family member that has high phospholipase and low triglyceride lipase activity. The aim of this study was to determine whether the phospholipase activity of EL is sufficient to remodel HDLs into small particles and mediate the dissociation of apolipoprotein A-I (apoA-I). Spherical, reconstituted HDLs (rHDLs) containing apoA-I only [(A-I)rHDLs], apoA-II only [(A-II)rHDLs], or both apoA-I and apoA-II [(A-I/A-II) rHDLs] were prepared. The rHDLs, which contained only cholesteryl esters in their core and POPC on the surface, were incubated with EL. As the rHDLs did not contain triacylglycerol, only the POPC was hydrolyzed. Hydrolysis was greater in the (A-I/A-II)rHDLs than in the (A-I)rHDLs. The (A-II)rHDL phospholipids were not hydrolyzed by EL. EL remodeled the (A-I)rHDLs and (A-I/A-II)rHDLs, but not the (A-II)rHDLs, into smaller particles. The reduction in particle size was related to the amount of phospholipid hydrolysis, with the diameter of the (A-I/A-II)rHDLs decreasing more than that of the (A-I)rHDLs. These changes did not affect the conformation of apoA-I, and neither apoA-I nor apoA-II dissociated from the rHDLs. Comparable results were obtained when human plasma HDLs were incubated with EL. These results establish that the phospholipase activity of EL remodels plasma HDLs and rHDLs into smaller particles without mediating the dissociation of apolipoproteins.     

How statin drugs affect exosomes?

Statins reduce serum cholesterol and isoprenoids by the inhibition of cholesterol synthesis in the mevalonate pathway. Exosomes are extracellular vesicles (30–200 nm) released by all cells that regulate cell-to-cell communication in health and disease by transferring functional proteins, metabolites and nucleic acids to recipient cells. There are many reports that show an effect of statins on exosomes, from their production and release to their content and performance. In this review, we have summarized existing data on the impact of statins on the biosynthesis, secretion, content, uptake and function of exosomes.     

Recommended Practice Regarding Selection of Sensitivity Analysis Methods Applied to Microbial Food Safety Process Risk Models

A guideline is presented for selection of sensitivity analysis methods applied to microbial food safety process risk (MFSPR) models. The guideline provides useful boundaries and principles for selecting sensitivity analysis methods for MSFPR models. Although the guideline is predicated on a specific branch of risk assessment models related to food-borne diseases, the principles and recommendations provided are typically generally applicable to other types of risk models. Applicable situations include: prioritizing potential critical control points; identifying key sources of variability and uncertainty; and refinement, verification, and validation of a model. Based on the objective of the analysis, characteristics of the model under study, amount of detail expected from sensitivity analysis, and characteristics of the sensitivity analysis method, recommendations for selection of sensitivity analysis methods are provided. A decision framework for method selection is introduced. The decision framework can substantially facilitate the process of selecting a sensitivity analysis method.     

Transforming growth factor-β signaling: Tumorigenesis and targeting for cancer therapy

Transforming growth factor (TGF)-β is a multitasking cytokine such that its aberrant expression is related to cancer progression and metastasis. TGF-β is produced by a variety of cells within the tumor microenvironment (TME), and it is responsible for regulation of the activity of cells within this milieu. TGF-β is a main inducer of epithelial–mesenchymal transition (EMT), immune evasion, and metastasis during cancer progression. TGF-β exerts most of its functions by acting on TβRI and TβRII receptors in canonical (Smad-dependent) or noncanonical (Smad-independent) pathways. Members of mitogen-activated protein kinase, phosphatidylinositol 3-kinase/protein kinase B, and nuclear factor κβ are involved in the non-Smad TGF-β pathway. TGF-β acts by complex signaling, and deletion in one of the effectors in this pathway may influence the outcome in a diverse way by taking even an antitumor role. The stage and the type of tumor (contextual cues from cancer cells and/or the TME) and the concentration of TGF-β are other important factors determining the fate of cancer (progression or repression). There are a number of ways for targeting TGF-β signaling in cancer, among them the special focus is on TβRII suppression.     

Dissatisfaction with Veterinary Services Is Associated with Leopard (Panthera pardus) Predation on Domestic Animals

Human-carnivore conflicts challenge biodiversity conservation and local livelihoods, but the role of diseases of domestic animals in their predation by carnivores is poorly understood. We conducted a human-leopard (Panthera pardus) conflict study throughout all 34 villages around Golestan National Park, Iran in order to find the most important conflict determinants and to use them in predicting the probabilities of conflict and killing of cattle, sheep and goats, and dogs. We found that the more villagers were dissatisfied with veterinary services, the more likely they were to lose livestock and dogs to leopard predation. Dissatisfaction occurred when vaccination crews failed to visit villages at all or, in most cases, arrived too late to prevent diseases from spreading. We suggest that increased morbidity of livestock makes them particularly vulnerable to leopard attacks. Moreover, conflicts and dog killing were higher in villages located closer to the boundaries of the protected area than in distant villages. Therefore, we appeal for improved enforcement and coordination of veterinary services in our study area, and propose several priority research topics such as veterinarian studies, role of wild prey in diseases of domestic animals, and further analysis of potential conflict predictors.     

The promise of stem cell markers in the diagnosis and therapy of epithelial dysplasia and oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer. Epithelial dysplasia is often initiated in the cells and cell nuclei adjacent to the epithelial cell membrane. Reduced cell–cell adhesions enable cancer cells to detach from the tumor and disseminate to other organs. The mutations in epithelial dysplasia markers such as E‐cadherin and epithelial cell adhesion molecules (CD326) can lead to proliferation, growth and survival of the tumor cells and persistence of numerous malignancies that play a key role in epithelial dysplasia of OSCC. Accordingly, these genes can be considered prognostic markers or potential therapeutic targets for the tailored management of patients with OSCC. The gene expression profile of OSCC stem cells indicates a differential pattern that facilitates establishing a cell signature. Owing to the highly tumorigenic behavior of cancer stem cells and the role of these cells in tumor differentiation, treatment resistance, relapse, and metastasis, we reviewed the role of stem cell markers in epithelial dysplasia and OSCC.     

Harnessing an Integrative In Silico Approach to Engage Highly Immunogenic Peptides in an Antigen Design Against Epsilon Toxin (ETX) of Clostridium perfringens

International Journal of Peptide Research and Therapeutics - Epsilon toxin (ETX) is one of four lethal toxins of Clostridium perfringens produced by types B and D of the pathogen. This pore-forming...