5 research outputs found

    Can Carbomer be effectively replaced with natural polymers?

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    Polyacrylic acid polymers have a special position within the rheology modifiers category as versatile, stable and inexpensive materials. However, they are synthetic and must be replaced if the product is to be marketed as natural. The aim of this study was to select an effective replacement for Carbomer in an o/w emulsion, using combinations of natural polymers of polysaccharide type. Rheology (both flow and oscillatory) and texture analysis (immersion and de-immersion of a cylinder probe) were employed to determine complete rheological profiles of individual hydrogels, their selected combinations and corresponding emulsions. Sensory tests were than performed on the most successful prototypes and the Carbomer-containing benchmark. This study has shown that Carbomer could not be replaced by a single natural polymer, and that the combination of thickening and gelling materials was necessary for obtaining an optimal alternative

    Site-selective Chlorination of Pyrrolic Heterocycles by Flavin Dependent Enzyme PrnC

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    Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. Whilst there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation has been lacking. Here we describe the first in vitro functional and structural characterization of PrnC, a flavin-dependent halogenase that can act on free-standing pyrroles. Computational modelling and site mutagenesis studies identified three key residues in the catalytic pocket. Moderate resolution map using single-particle cryogenic electron microscopy (CryoEM) reveals PrnC to be a dimer. This native PrnC can halogenate a library of structurally diverse pyrrolic heterocycles in a site-selective manner and was applied in the chemoenzymatic synthesis of a chlorinated analog of the agrochemical fungicide, Fludioxonil

    Sphingosine 1-Phosphate Receptor 2 Induces Otoprotective Responses to Cisplatin Treatment

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    Ototoxicity is a major adverse effect of platinum-based chemotherapeutics and currently, there remains a lack of United States Food and Drug Administration-approved therapies to prevent or treat this problem. In our study, we examined the role of the sphingosine 1-phosphate receptor 2 (S1P2) in attenuating cisplatin-induced ototoxicity in several different animal models and cell lines. We found that ototoxicity in S1P2 knockout mice is dependent on reactive oxygen species (ROS) production and that S1P2 receptor activation with a specific agonist, CYM-5478, significantly attenuates cisplatin-induced defects, including hair cell degeneration in zebrafish and prolonged auditory brainstem response latency in rats. We also evaluated the cytoprotective effect of CYM-5478 across different cell lines and showed that CYM-5478 protects neural-derived cell lines but not breast cancer cells against cisplatin toxicity. We show that this selective protection of CYM-5478 is due to its differential effects on key regulators of apoptosis between neural cells and breast cancer cells. Overall, our study suggests that targeting the S1P2 receptor represents a promising therapeutic approach for the treatment of cisplatin-induced ototoxicity in cancer patients

    Multimodal prerehabilitation for elderly patients with sarcopenia in colorectal surgery

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    Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia
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