Ecosystem carbon response of an Arctic peatland to simulated permafrost thaw.

Permafrost peatlands are biogeochemical hot spots in the Arctic as they store vast amounts of carbon. Permafrost thaw could release part of these long-term immobile carbon stocks as the greenhouse gases (GHGs) carbon dioxide (CO2 ) and methane (CH4 ) to the atmosphere, but how much, at which time-span and as which gaseous carbon species is still highly uncertain. Here we assess the effect of permafrost thaw on GHG dynamics under different moisture and vegetation scenarios in a permafrost peatland. A novel experimental approach using intact plant-soil systems (mesocosms) allowed us to simulate permafrost thaw under near-natural conditions. We monitored GHG flux dynamics via high-resolution flow-through gas measurements, combined with detailed monitoring of soil GHG concentration dynamics, yielding insights into GHG production and consumption potential of individual soil layers. Thawing the upper 10-15 cm of permafrost under dry conditions increased CO2 emissions to the atmosphere (without vegetation: 0.74 ± 0.49 vs. 0.84 ± 0.60 g CO2 -C m-2  day-1 ; with vegetation: 1.20 ± 0.50 vs. 1.32 ± 0.60 g CO2 -C m-2  day-1 , mean ± SD, pre- and post-thaw, respectively). Radiocarbon dating (14 C) of respired CO2 , supported by an independent curve-fitting approach, showed a clear contribution (9%-27%) of old carbon to this enhanced post-thaw CO2 flux. Elevated concentrations of CO2 , CH4 , and dissolved organic carbon at depth indicated not just pulse emissions during the thawing process, but sustained decomposition and GHG production from thawed permafrost. Oxidation of CH4 in the peat column, however, prevented CH4 release to the atmosphere. Importantly, we show here that, under dry conditions, peatlands strengthen the permafrost-carbon feedback by adding to the atmospheric CO2 burden post-thaw. However, as long as the water table remains low, our results reveal a strong CH4 sink capacity in these types of Arctic ecosystems pre- and post-thaw, with the potential to compensate part of the permafrost CO2 losses over longer timescales.

Pectin and Mucin Enhance the Bioadhesion of Drug Loaded Nanofibrillated Cellulose Films.

PURPOSE: Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications. METHODS: Nanofibrillar cellulose and anionic type nanofibrillar cellulose were used as film forming materials with known mucoadhesive components mucin, pectin and chitosan as functional bioadhesion enhancers. Different polymer combinations were investigated to study the adhesiveness, solid state characteristics, film morphology, swelling, mechanical properties, drug release with the model compound metronidazole and in vitro cytotoxicity using TR146 cells to model buccal epithelium. RESULTS: SEM revealed lamellar structures within the films, which had a thickness ranging 40-240 µm depending on the film polymer composition. All bioadhesive components were non-toxic and showed high adhesiveness. Rapid drug release was observed, as 60-80% of the total amount of metronidazole was released in 30 min depending on the film formulation. CONCLUSIONS: The liquid molding used was a straightforward and simple method to produce drug releasing highly mucoadhesive films, which could be utilized in treating local oral diseases, such as periodontitis. All materials used were natural biodegradable polymers from renewable sources, which are generally regarded as safe.

Many human pharmaceuticals are weak inhibitors of the cytochrome P450 system in rainbow trout (Oncorhynchus mykiss) liver S9 fractions.

Introduction: Pharmaceutical residues are widely detected in aquatic environment and can be taken up by nontarget species such as fish. The cytochromes P450 (CYP) represent an important detoxification mechanism in fish, like in humans. In the present study, we assessed the correlation of the substrate selectivities of rainbow trout CYP1A and CYP3A homologues with those of human, through determination of the half-maximal inhibitory concentrations (IC50) of a total sixteen human pharmaceuticals toward CYP1A-like ethoxyresorufin O-deethylase (EROD) and CYP3A-like 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions (RT-S9). Methods: The inhibitory impacts (IC50) of atomoxetine, atorvastatin, azelastine, bimatoprost, clomethiazole, clozapine, desloratadine, disulfiram, esomeprazole, felbinac, flecainide, orphenadrine, prazosin, quetiapine, sulpiride, and zolmitriptan toward the EROD and BFCOD activities in RT-S9 were determined using the IC50 shift assay, capable of identifying time-dependent inhibitors (TDI). Additionally, the nonspecific binding of the test pharmaceuticals to RT-S9 was assessed using equilibrium dialysis. Results: Most test pharmaceuticals were moderate to weak inhibitors of both EROD and BFCOD activity in RT-S9, even if most are noninhibitors of human CYP1A or CYP3A. Only bimatoprost, clomethiazole, felbinac, sulpiride, and zolmitriptan did not inhibit either activity in RT-S9. EROD inhibition was generally stronger than that of BFCOD and some substances (atomoxetine, flecainide, and prazosin) inhibited selectively only EROD activity. The strongest EROD inhibition was detected with azelastine and esomeprazole (unbound IC50 of 3.8 ± 0.5 µM and 3.0 ± 0.8 µM, respectively). None of the test substances were TDIs of BFCOD, but esomeprazole was a TDI of EROD. Apart from clomethiazole and disulfiram, the nonspecific binding of the test pharmaceuticals to the RT-S9 was extensive (unbound fractions <0.5) and correlated well (R 2 = 0.7135) with their water-octanol distribution coefficients. Discussion: The results indicate that the P450 interactions in RT-S9 cannot be explicitly predicted based on human data, but the in vitro data reported herein can shed light on the substrate selectivity of rainbow trout CYP1A1 and CYP3A27 in comparison to their human homologues. The IC50 concentrations are however many orders of magnitude higher than average environmental concentrations of pharmaceuticals. The time-dependent EROD inhibition by esomeprazole could warrant further research to evaluate its possible interlinkages with hepatotoxic impacts on fish.

Tracking Chlamydia - Host interactions and antichlamydial activity in Caenorhabditis elegans.

The fading efficacy of antibiotics is a growing global health concern due to its life-threatening consequences and increased healthcare costs. Non-genetic mechanisms of antimicrobial resistance, such as those employed by Chlamydia pneumoniae and Chlamydia trachomatis, complicate treatment as these bacteria can enter a non-replicative, persistent state under stress, evading antibiotics and linking to inflammatory conditions. Understanding chlamydial persistence at the molecular level is challenging, and new models for studying Chlamydia-host interactions in vivo are urgently needed. Caenorhabditis elegans offers an alternative given its immune system and numerous orthologues of human genes. This study established C. elegans as an in vivo model for chlamydial infection. Both Chlamydia species reduced the worm's lifespan, their DNA being detectable at three- and six-days post-infection. Azithromycin at its MIC (25 nM) failed to prevent the infection-induced lifespan reduction, indicating a persister phenotype. In contrast, the methanolic extract of Schisandra chinensis berries showed anti-chlamydial activity both in vitro (in THP-1 macrophages) and in vivo, significantly extending the lifespan of infected C. elegans and reducing the bacterial load. Moreover, S. chinensis increased the transcriptional activity of SKN-1 in the worms, but was unable to impact the bacterial load or lifespan in a sek-1 defective C. elegans strain. In summary, this study validated C. elegans as a chlamydial infection model and showcased S. chinensis berries' in vivo anti-chlamydial potential, possibly through SEK/SKN-1 signaling modulation.

Real-Time Label-Free Targeting Assessment and in Vitro Characterization of Curcumin-Loaded Poly-lactic-co-glycolic Acid Nanoparticles for Oral Colon Targeting.

The exploitation of curcumin for oral disease treatment is limited by its low solubility, poor bioavailability, and low stability. Surface-functionalized poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) have shown promising results to ameliorate selective delivery of drugs to the gastro-intestinal tract. In this study, curcumin-loaded PLGA NPs (C-PLGA NPs) of about 200 nm were surface-coated with chitosan (CS) for gastro-intestinal mucosa adhesion, wheat germ agglutinin (WGA) for colon targeting or GE11 peptide for tumor colon targeting. Spectrometric and zeta potential analyses confirmed the successful functionalization of the C-PLGA NPs. Real-time label-free assessment of the cell membrane-NP interactions and NP cell uptake were performed by quartz crystal microbalance coupled with supported lipid bilayers and by surface plasmon resonance coupled with living cells. The study showed that CS-coated C-PLGA NPs interact with cells by the electrostatic mechanism, while both WGA- and GE11-coated C-PLGA NPs interact and are taken up by cells by specific active mechanisms. In vitro cell uptake studies corroborated the real-time label-free assessment by yielding a curcumin cell uptake of 7.3 ± 0.3, 13.5 ± 1.0, 27.3 ± 4.9, and 26.0 ± 1.3 µg per 104 HT-29 cells for noncoated, CS-, WGA-, and GE11-coated C-PLGA NPs, respectively. Finally, preliminary in vivo studies showed that the WGA-coated C-PLGA NPs efficiently accumulate in the colon after oral administration to healthy Balb/c mice. In summary, the WGA- and GE11-coated C-PLGA NPs displayed high potential for application as active targeted carriers for anticancer drug delivery to the colon.

Nanofibrillar cellulose hydrogels and reconstructed hydrogels as matrices for controlled drug release.

Concentrated 3% and 6.5% anionic nanofibrillar cellulose (ANFC) hydrogels were introduced as matrix reservoirs for controlled delivery applications of small molecules and proteins. A further aim was to study how the freeze-drying and subsequent rehydration of ANFC hydrogel affects the rheological properties and drug release of selected model compounds from the reconstructed hydrogels. It was demonstrated that the 3% and 6.5% ANFC hydrogels can be freeze-dried with suitable excipients into highly porous aerogel structures and redispersed back into the hydrogel form without significant change in the rheological properties. Freeze-drying did not affect the drug release properties from redispersed ANFC hydrogels, indicating that these systems could be stored in the dry form and only redispersed when needed. For large molecules, the diffusion coefficients were significantly smaller when higher ANFC fiber content was used, indicating that the amount of ANFC fibers in the hydrogel can be used to control the release rate. The release of small molecules was controlled with the ANFC fiber content only to a moderate extent. The results indicate that ANFC hydrogel can be used for controlled delivery of several types of molecules and that the hydrogel can be successfully freeze-dried and redispersed.