Current State of SLC and ABC Transporters in the Skin and Their Relation to Sweat Metabolites and Skin Diseases

With a relatively large surface area (2 m2) and 15% of total body mass, the skin forms the largest organ of the human body. The main functions of the skin include regulation of body temperature by insulation or sweating, regulation of the nervous system, regulation of water content, and protection against external injury. To perform these critical functions, the skin encodes genes for transporters responsible for the cellular trafficking of essential nutrients and metabolites to maintain cellular hemostasis. However, the knowledge on the expression, regulation, and function of these transporters is very limited and needs more work to elucidate how these transporters play a role both in disease progression and in healing. Furthermore, SLC and ABC transporters are understudied, and even less studied in skin. There are sparse reports on relation between transporters in skin and sweat metabolites. This mini review focuses on the current state of SLC and ABC transporters in the skin and their relation to sweat metabolites and skin diseases

Molecular Networks and Macromolecular Molar Mass Distributions for Preliminary Characterization of Danish Craft Beers

Beer is one of the most widely consumed beverages containing up to 200,000 unique small molecules and a largely uncharacterized macromolecular and particulate space. The chemical profiling of beer is difficult due to its complex nature. To address this issue, we have used various state-of-the-art methods to determine the physicochemical characteristics of beer. Specifically, we have successfully generated an LC-MS-based molecular network with minimal sample preparation to profile indoles in beer and confirmed their presence using 1H-NMR. In addition, we have identified different macromolecular signatures in beer of different colors by utilizing AF4-MALS. These preliminary findings lay the foundation for further research on the physicochemical nature of beer

Coupling engineering of Saccharomyces cerevisiae with medium optimization for the production of ergothioneine

Ergothioneine (ERG) is a naturally occurring, exogenous antioxidant that is nonetheless abundant in the human body. It has been shown both to reduce oxidative damage and to be involved in several diseases in vivo1,2. Therefore, ergothioneine is poised to take a place in the dietary supplement industry. Here we describe the engineering of the yeast Saccharomyces cerevisiae and subsequent medium optimization to produce ergothioneine by fermentation. After integrating combinations of biosynthetic pathways from different organisms, we screened yeast strains for their production of ERG. Next, the highest producing strain was engineered with ergothioneine transporters, and its amino acid metabolism was altered by knock-out of Tor1 or Yih1. The bottleneck for ergothioneine production was determined by integration of a second copy of the pathway enzymes. We also optimized the media composition for production of ergothioneine using yeast S. cerevisiae. Following these manipulations, we obtained a titer of 630 mg/l in fed-batch cultivation in bioreactors. This work shows that with further engineering of the strain, current chemical synthesis of ergothioneine could be replaced with a sustainable alternative. 1. Cheah, I. K. & Halliwell, B. Ergothioneine; antioxidant potential, physiological function and role in disease. Biochim. Biophys. Acta - Mol. Basis Dis. 1822, 784–793 (2012). 2. Halliwell, B., Cheah, I. K. & Tang, R. M. Y. Ergothioneine - a diet-derived antioxidant with therapeutic potential. FEBS Lett. (2018). doi:10.1002/1873-3468.1312

Halogenation as a tool to tune antimicrobial activity of peptoids

Abstract Antimicrobial peptides have attracted considerable interest as potential new class of antibiotics against multi-drug resistant bacteria. However, their therapeutic potential is limited, in part due to susceptibility towards enzymatic degradation and low bioavailability. Peptoids (oligomers of N -substituted glycines) demonstrate proteolytic stability and better bioavailability than corresponding peptides while in many cases retaining antibacterial activity. In this study, we synthesized a library of 36 peptoids containing fluorine, chlorine, bromine and iodine atoms, which vary by length and level of halogen substitution in position 4 of the phenyl rings. As we observed a clear correlation between halogenation of an inactive model peptoid and its increased antimicrobial activity, we designed chlorinated and brominated analogues of a known peptoid and its shorter counterpart. Short brominated analogues displayed up to 32-fold increase of the activity against S. aureus and 16- to 64-fold against E. coli and P. aeruginosa alongside reduced cytotoxicity. The biological effect of halogens seems to be linked to the relative hydrophobicity and self-assembly properties of the compounds. By small angle X-ray scattering (SAXS) we have demontrated how the self-assembled structures are dependent on the size of the halogen, degree of substitution and length of the peptoid, and correlated these features to their activity

ETHICAL ISSUES IN NANOMEDICINE

The scientists are moving ahead with their research in nanomedicine but the laws and ethics pertaining to the humanity are lagging behind. It is expected that the time has come to address the social and ethical issues concerning nanomedicine in order to be prepared for the upcoming adverse events. It has also been fully understood that the toxicological analyses in the animals is not fully representative of humans and the potentials risks associated is still untapped. This short review would briefly address the ethical issues related to nanomedicine to hold a short discussion based on science to assess the safety and efficacy of the nanomedicine

ETHICAL ISSUES IN NANOMEDICINE

The scientists are moving ahead with their research in nanomedicine but the laws and ethics pertaining to the humanity are lagging behind. It is expected that the time has come to address the social and ethical issues concerning nanomedicine in order to be prepared for the upcoming adverse events. It has also been fully understood that the toxicological analyses in the animals is not fully representative of humans and the potentials risks associated is still untapped. This short review would briefly address the ethical issues related to nanomedicine to hold a short discussion based on science to assess the safety and efficacy of the nanomedicine