Display omitted
•Photosynthesis and respiration rate are modelled in a HRABP for digestate treatment.•A standard photo-respirometric model calibration protocol is proposed and validated.•The method ...allows for fast and reliable calibration of algae-bacteria growth models.•Commonly used models fitted well experimental photosynthesis and respiration data.•Optimal growth conditions can be identified for different algae strains and seasons.
This study aimed at evaluating the effects of different environmental conditions (irradiance, temperature, pH and dissolved oxygen) on a microalgae-bacteria consortium cultivated in a pilot-scale open pond and fed on the liquid fraction of anaerobic digestate. A standardized photo-respirometry protocol was followed to evaluate the activity of microalgae under different conditions. Two datasets (specific photosynthetic oxygen production rates and respiratory oxygen consumption rates) were obtained for each environmental parameter, throughout the entire range of conditions found in the outdoor cultivation system. Different kinetic models available in literature were fitted to experimental data and the resulting outputs were compared through model selection estimators, in order to select the most appropriate equations. The proposed set of equations constitute a modelling tool for the prediction of algal growth rates in algae-bacteria systems, as a function of environmental conditions.
Recent genome sequencing efforts have led to the rapid accumulation of uncharacterized or “orphaned” secondary metabolic biosynthesis gene clusters (BGCs) in public databases. This increase in ...DNA-sequenced big data has given rise to significant challenges in the applied field of natural product genome mining, including (i) how to prioritize the characterization of orphan BGCs and (ii) how to rapidly connect genes to biosynthesized small molecules. Here, we show that by correlating putative antibiotic resistance genes that encode target-modified proteins with orphan BGCs, we predict the biological function of pathway specific small molecules before they have been revealed in a process we call target-directed genome mining. By querying the pan-genome of 86 Salinispora bacterial genomes for duplicated house-keeping genes colocalized with natural product BGCs, we prioritized an orphan polyketide synthase-nonribosomal peptide synthetase hybrid BGC (tlm) with a putative fatty acid synthase resistance gene. We employed a new synthetic double-stranded DNA-mediated cloning strategy based on transformation-associated recombination to efficiently capture tlm and the related ttm BGCs directly from genomic DNA and to heterologously express them in Streptomyces hosts. We show the production of a group of unusual thiotetronic acid natural products, including the well-known fatty acid synthase inhibitor thiolactomycin that was first described over 30 years ago, yet never at the genetic level in regards to biosynthesis and autoresistance. This finding not only validates the target-directed genome mining strategy for the discovery of antibiotic producing gene clusters without a priori knowledge of the molecule synthesized but also paves the way for the investigation of novel enzymology involved in thiotetronic acid natural product biosynthesis.
Aims
Fructooligosaccharides (FOSs) known for their health properties and β‐(2→6)‐levan‐type FOSs have shown prebiotic and immunomodulatory activities that overcome those of commercial β‐(2→1)‐FOSs, ...but costs do not favour their use. Moreover, FOSs can reach the bloodstream through the diet, and little is known about their direct effect on cells. The aim of this work was to produce high‐content FOSs by Bacillus subtilis natto CCT7712 in a bioreactor using commercial sucrose and to evaluate their antiproliferative effects in OVCAR‐3 cells.
Methods and Results
FOS production reached 173·60 g l−1, 0·2 vvm aeration and uncontrolled pH. Levan‐type FOSs, composed of β‐(2 → 6) links and mainly GF3 (6‐nystose), were identified using RMN spectroscopy, FT‐IR and ESI‐MS. FOSs decreased the viability and proliferation of OVCAR‐3 cells, and the effects were associated with an increased pro‐inflammatory response by the induction of IL‐8 and TNF‐α, and the repression of ER‐β genes. The metabolic profiles showed disruption of cellular homeostasis that can be associated with a decrease in proliferation.
Conclusions
The high production of levan‐type FOSs from B. subtilis natto CCT7712 in a bioreactor was achieved, and they showed antiproliferative potential in OVCAR‐3 cells.
Significance and Impact of the Study
FOS could be a good target for future therapeutic studies and commercial use.
The malignant transformation of a cell produces the accumulation of several cellular adaptions. These changes determine variations in biological processes that are necessary for a cancerous cell to ...survive during stressful conditions. Autophagy is the main nutrient recycling and metabolic adaptor mechanism in eukaryotic cells, represents a continuous source of energy and biomolecules, and is fundamental to preserve the correct cellular homeostasis during unfavorable conditions. In recent decades, several findings demonstrate a close relationship between autophagy, malignant transformation, and cancer progression. The evidence suggests that autophagy in the cancer context has a bipolar role (it may act as a tumor suppressor and as a mechanism of cell survival for established tumors) and demonstrates that the targeting of autophagy may represent novel therapeutic opportunities. Accordingly, the modulation of autophagy has important clinical benefits in patients affected by diverse cancer types. Currently, about 30 clinical trials are actively investigating the efficacy of autophagy modulators to enhance the efficacy of cytotoxic chemotherapy treatments. A deeper understanding of the molecular pathways regulating autophagy in the cancer context will provide new ways to target autophagy for improving the therapeutic benefits. Herein, we describe how autophagy participates during malignant transformation and cancer progression, and we report the ultimate efforts to translate this knowledge into specific therapeutic approaches to treat and cure human cancers.
Metal-based flocculants are commonly used for biomass harvesting in microalgae-based bio-refineries. Besides the high separation efficiency, additional aspects should be considered, related to the ...toxicity of metals for the algal biomass. Partitioning tests for commonly used flocculants (i.e., FeCl3 and Al2(SO4)3) showed that metals were mostly transferred to the solid phase with more than 95% of dosed metal ending up into the biomass, and low metal concentrations in the liquid effluent (lower than 0.4 mg L−1 for both metals), thus allowing for water reuse. Photosynthesis inhibition was tested on microalgae and microalgae-bacteria cultures, using a standardized photo-respirometry protocol in which typical concentrations used during coagulation-flocculation were assessed. Modelling dose-response curves, concentrations corresponding to 50% inhibition (IC50) were obtained, describing short-term effects. The obtained IC50 ranged from 13.7 to 28.3 mg Al L−1 for Al, and from 127.9 to 195.8 mg Fe L−1 for Fe, showing a higher toxicity for the Al-based flocculant. The recovery of photosynthesis inhibition was also quantified, to evaluate the possibility of reusing/recycling the harvested biomass. The results highlighted that the residual photosynthetic activities, evaluated after 1 h and 24 h of exposure to metals were partially recovered, especially for Al, passing from 67.3% to 94.6% activity, respectively, while long-term Fe effects were stronger (passing from 64.9% to 77.6% activity). A non-toxic flocculant (cationic starch) was finally tested, excluding potential effects due to biomass aggregation, as the reduction of photosynthetic activity only reached 3.4%, compared to control. Relevant modifications to the light availability and the optical properties of algal suspensions were assessed, identifying a strong effect of iron which caused an increase of the light absorbance up to approximately 40% at high Fe concentrations. Possible implications of dosing metallic flocculants in MBWWT processes are discussed, and suggestions are given to perform inhibition tests on flocculating chemicals.
Display omitted
•Fe- and Al-based flocculants inhibited algal photosynthesis in the short-term.•Mixed algae-bacteria cultures were more resistant than algal monocultures.•Al inhibition was higher than Fe, but with faster recovery and lower light effects.•Biomass coagulation using cationic starch did not impact algal photosynthesis.•Metallic flocculants were predominantly transferred to the solid phase.
Prevalence of oropharyngeal dysphagia among the elderly is high, but underestimated and underdiagnosed. It may give raise to relevant complications impacting on morbidity, hospital length of stay and ...health care costs. Dysphagia evaluation and management is a multidisciplinary task; it includes a detailed history taking, clinical and instrumental exams, and identification of the risk of aspiration. Long-standing individual abilities and impairments determine the goals of an ad hoc rehabilitation program. Currently there are no standard algorithmic approaches for the management of dysphagia in the elderly. Education of health professionals on early diagnosis and improvement of therapeutic strategies are mainstays to allow maximal recovery potential in this population. This narrative review summarizes the current rehabilitation approaches for dysphagia in the elderly. The aim is to inform the treating health care professionals, whether caring physician, physical medicine doctor, speech/swallowing therapist or nurse, on the state-of-the-art and stimulate discussion in the scientific community.
The treatment of textile effluents by the conventional method based on activated sludge followed by a chlorination step is not usually an effective method to remove azo dyes, and can generate ...products more mutagenic than the untreated dyes. The present work evaluated the efficiency of conventional chlorination to remove the genotoxicity/mutagenicity of the azo dyes Disperse Red 1, Disperse Orange 1, and Disperse Red 13 from aqueous solutions. The comet and micronucleus assays with HepG2 cells and the Salmonella mutagenicity assay were used. The degradation of the dye molecules after the same treatment was also evaluated, using ultraviolet and visible absorption spectrum measurements (UV–vis), high performance liquid chromatography coupled to a diode-array detector (HPLC-DAD), and total organic carbon removal (TOC) analysis. The comet assay showed that the three dyes studied induced damage in the DNA of the HepG2 cells in a dose-dependent manner. After chlorination, these dyes remained genotoxic, although with a lower damage index (DI). The micronucleus test showed that the mutagenic activity of the dyes investigated was completely removed by chlorination, under the conditions tested. The Salmonella assay showed that chlorination reduced the mutagenicity of all three dyes in strain YG1041, but increased the mutagenicity of Disperse Red 1 and Disperse Orange 1 in strain TA98. With respect to chemical analysis, all the solutions showed rapid discoloration and a reduction in the absorbance bands characteristic of the chromophore group of each dye. However, the TOC was not completely removed, showing that chlorination of these dyes is not efficient in mineralizing them. It was concluded that conventional chlorination should be used with caution for the treatment of aqueous samples contaminated with azo dyes.
Textile dyes are discarded into the aquatic ecosystem via industrial effluents and potentially expose humans and local biota to adverse effects. The commercial dye CI Disperse Blue 291 which contains ...the aminoazobenzene 2-(2-bromo-4,6-dinitrophenyl)azo-5(diethylamino)-4-methoxyacetanilide (CAS registry no. 56548-64-2), was tested for genotoxicity and cytotoxicity in the human hepatoma cell line HepG2, using the comet assay, micronucleus (MN) test and a cell viability test. Five different concentrations of the test compound were examined: 200
μg/ml, 400
μg/ml, 600
μg/ml, 800
μg/ml and 1000
μg/ml. An increase in comet tail length and in the frequency of MN was detected with exposure of cells to concentrations of the commercial dye from 400
μg/ml. Furthermore, the dye was found to decrease cell viability. The results of this study demonstrate for the first time the genotoxic and mutagenic effects of the dye CI Disperse Blue 291 in mammalian cells, thus stressing the need to develop non-mutagenic dyes and to invest in improving the treatment of effluents. These measures will help to prevent harmful effects that these compounds can have on humans and aquatic organisms that come in contact with them.
Abstract The drug named defibrotide (DFT) has been studied for many years. It has been shown to possess many activities: profibrinolytic, antithrombotic–thrombolytic, antiischemic (heart, liver, ...kidney, skin, brain), antishock, antiatherosclerotic, antirejection and anti-angiogenic. The previously displayed activities, as antithrombotic, profibrinolytic and anti-inflammatory, suggested its use in vascular disorders, as in the treatment of peripheral obliterative arterial disease and in thrombophlebitis. Some years after, the use of DFT in hepatic veno-occlusive disease has been also proposed. Even if DFT was considered for long time a multi-target drug, now it could be considered on the whole as a drug able to protect endothelium against activation. The present work reviews the more important experimental and clinical studies performed to detect DFT effects.