Evaluation of Verbascum flower extracts as a natural source of pigments with potential health benefits.

Crocins are bioactive glucosylated apocarotenoids that confer a yellow pigmentation. In addition to their coloring ability, crocins offer potential health benefits because of their antioxidant and anti-inflammatory properties. These compounds are present in the flowers and fruits of a few plant species, including saffron, gardenia, Buddleja and Verbascum species. Saffron extracts have been used for the formulation of functional foods. However, there is no evidence of the use of the other plants producing crocins in the food industry. This study evaluated the effect of the addition of ground dry flowers of two Verbascum species, with antioxidant activity, as well as dry fruit powder, from a recently engineered tomato plant producing fruits that accumulate high levels of crocins, as functional ingredients during the processing of rice, wheat cous-cous and maize noodles, providing a yellow pigmentation. Correlation analyses revealed that the increased antioxidant activity in the three food matrices was due to the presence of crocins, which showed no toxicity. Furthermore, in vitro digestion showed that crocins were more bioaccessible from rice than from cous-cous or maize noodles, inferring the importance of the food matrix in bio accessibility. The obtained results showed the commercial potential of Verbascum's flowers, as a source of crocins, natural pigments with antioxidant activities.

Exploring the viral landscape of saffron through metatranscriptomic analysis.

Saffron (Crocus sativus L.), a historically significant crop valued for its nutraceutical properties, has been poorly explored from a phytosanitary perspective. This study conducted a thorough examination of viruses affecting saffron samples from Spanish cultivars, using high-throughput sequencing alongside a systematic survey of transcriptomic datasets from Crocus sativus at the Sequence Read Archive. Our analysis unveiled a broad diversity and abundance, identifying 17 viruses across the 52 analyzed libraries, some of which were highly prevalent. This includes known saffron-infecting viruses and previously unreported ones. In addition, we discovered 7 novel viruses from the Alphaflexiviridae, Betaflexiviridae, Potyviridae, Solemoviridae, and Geminiviridae families, with some present in libraries from various locations. These findings indicate that the saffron-associated virome is more complex than previously reported, emphasizing the potential of phytosanitary analysis to enhance saffron productivity.

Neuroprotective properties of exosomes and chitosan nanoparticles of Tomafran, a bioengineered tomato enriched in crocins.

Saffron has many pharmacological properties in addition to being a frequently used food seasoning. Crocin and picrocrocin which accumulate in saffron stigma, are responsible for these pharmacological properties. These natural products have health-promoting effects for the prevention and treatment of numerous diseases, including age-related cognitive and memory disfunction. Currently, crocin and picrocrocin are obtained from saffron, considered as the spice with the highest price in the market. To develop an efficient and low-cost approach to producing these compounds with high bioactivity, biosynthetic genes isolated from saffron can be exploited in the metabolic engineering of heterologous hosts and the production of crocins in productive crop plants. Recently, we engineered tomato fruit producing crocins (Tomafran). In this study, we demonstrated that crocin-rich extract, encapsulated in chitosan or in exosomes may function as a neuroprotective strategy. Crocins contained in the Tomafran extracts and much lower doses in chitosan nanoparticles or exosomes were enough to rescue the neuroblastoma cell line SH-SY5Y after damage caused by okadaic acid. Our results confirm the neuroprotective effect of Tomafran and its exosomes that may be useful for the delay or prevention of neurodegenerative disorders such as Alzheimer's disease.

Population Pharmacokinetics of Vancomycin and Meropenem in Pediatric Extracorporeal Membrane Oxygenation Support.

Objective: Describe primary pharmacokinetic/pharmacodynamic (PK/PD) parameters of vancomycin and meropenem in pediatric patients undergoing ECMO and analyze utilized dosing to reach PK/PD target. Design: Prospective, multicentric, population PK analysis. Setting: Two hospitals with pediatric intensive care unit. Patients: Pediatric patients (1 month - 15 years old) receiving vancomycin and meropenem for empiric or definitive infection treatment while ECMO support. Measurements and Main Results: Four serum concentration were obtained for patients receiving vancomycin (n = 9) and three for meropenem (n = 9). The PK/PD target for vancomycin was a ratio of the area under the curve to the minimal inhibitory concentration (AUC/MIC) of >400, and for meropenem was 4 times above MIC for 50% of the dosing interval (fT50% > 4xMIC). Pharmacokinetic modeling was performed using PMetrics 1.5.0. We included nine patients, with 11 PK profiles for each antimicrobial. The median age of patients was 4 years old (2 months - 13 years) and 45% were male. Creatinine clearance (CL) was 183 (30-550) ml/min/1.73 m2. The median dose was 13.6 (range 10-15) mg/kg every 6-12 h and 40 mg/kg every 8-12 h for vancomycin and meropenem, respectively. Two compartment models were fitted. Weight was included as a covariate on volume of the central compartment (Vc) for meropenem. Weight was included as a covariate on both Vc and clearance (CL) and serum creatinine was also included as a covariate on CL for vancomycin. The pharmacokinetic parameters CL and Vc were 0.139 ± 0.102 L/h/kg and 0.289 ± 0.295 L/kg for meropenem and 0.060 ± 0.055 L/h/kg and 0.419 ± 0.280 L/kg for vancomycin, respectively. Across each dosing interval 91% of patients achieved the PK/PD targets for adequate exposure for meropenem and 63.6% for vancomycin. Conclusion: Pharmacokinetic/pharmacodynamic objectives for vancomycin were achieved partially with conventional doses and higher dosing with extended infusion were needed in the case of meropenem.

YK-4-279 Attenuates Progression of Pre-Existing Pigmented Lesions to Nodular Melanoma in a Mouse Model.

More options are needed for the effective treatment of melanoma. In a previous study, we discovered the small molecule drug YK-4-279 almost completely inhibited tumor progression in the BrafCA;Tyr-CreERT2;Ptenflox/flox transgenic mouse model. YK-4-279 had no effect on tumor initiation but blocked progression of invasive melanoma. Our current study was designed as a treatment model, where YK-4-279 was administered during pigmented lesion formation. The study design included the use of three groups: (1) a control group that received only DMSO without a drug (MOCK), (2) mice following our prior studies with YK-4-279 administered at the time of tumor induction (YK-4-279), and (3) mice treated during tumor initiation (YK-4-279 delay). While the MOCK mice had progression of tumors, both YK-4-279 and YK-4-279 delay groups had a significant block or delay of progression. The majority of mice in the YK-4-279 groups had a block of progression, while the YK-4-279 delay group had either a partial block (60% in male mice or 29% in females) or a delay in disease progression in females (28 days in controls to 50 days in YK-4-279 delay group). Here, we demonstrate that YK-4-279 has a significant impact on blocking or delaying tumor progression in a pre-clinical treatment model of melanoma.

Inhabited subsurface wet smectites in the hyperarid core of the Atacama Desert as an analog for the search for life on Mars.

The modern Martian surface is unlikely to be habitable due to its extreme aridity among other environmental factors. This is the reason why the hyperarid core of the Atacama Desert has been studied as an analog for the habitability of Mars for more than 50 years. Here we report a layer enriched in smectites located just 30 cm below the surface of the hyperarid core of the Atacama. We discovered the clay-rich layer to be wet (a phenomenon never observed before in this region), keeping a high and constant relative humidity of 78% (aw 0.780), and completely isolated from the changing and extremely dry subaerial conditions characteristic of the Atacama. The smectite-rich layer is inhabited by at least 30 halophilic species of metabolically active bacteria and archaea, unveiling a previously unreported habitat for microbial life under the surface of the driest place on Earth. The discovery of a diverse microbial community in smectite-rich subsurface layers in the hyperarid core of the Atacama, and the collection of biosignatures we have identified within the clays, suggest that similar shallow clay deposits on Mars may contain biosignatures easily reachable by current rovers and landers.

Author Correction: Aeolian transport of viable microbial life across the Atacama Desert, Chile: Implications for Mars.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Aeolian transport of viable microbial life across the Atacama Desert, Chile: Implications for Mars.

Here we inspect whether microbial life may disperse using dust transported by wind in the Atacama Desert in northern Chile, a well-known Mars analog model. By setting a simple experiment across the hyperarid core of the Atacama we found that a number of viable bacteria and fungi are in fact able to traverse the driest and most UV irradiated desert on Earth unscathed using wind-transported dust, particularly in the later afternoon hours. This finding suggests that microbial life on Mars, extant or past, may have similarly benefited from aeolian transport to move across the planet and find suitable habitats to thrive and evolve.

Gloeocapsopsis AAB1, an extremely desiccation-tolerant cyanobacterium isolated from the Atacama Desert.

The comprehensive study of microorganisms that evolved in the Atacama Desert, the driest and oldest on earth, may help to understand the key role of water for life. In this context, we previously characterized the microenvironment that allows colonization of the underside of quartzes in the Coastal Range of this desert by hypolithic microorganisms (Azua-Bustos et al. Microb Ecol 58:568-581, 2011). Now, we describe the biodiversity composition of these biofilms and the isolation from it of a new cyanobacterial strain. Based on morphologic and phylogenetic analyses, this isolate (AAB1) was classified as a new member of the Gloeocapsopsis genus. Physiological, morphological and molecular responses by isolate AAB1 show that this strain is extremely tolerant to desiccation. Our results also indicate that the isolate biosynthesizes sucrose and trehalose in response to this stressful condition. We identified two candidate genes involved in sucrose synthesis, namely sucrose 6-phosphate synthase and sucrose 6-phosphate phosphatase. Thus, the Gloeocapsopsis isolate AAB1 may represent a suitable model for understanding tolerance to low water availability.

Extreme environments as potential drivers of convergent evolution by exaptation: the Atacama Desert Coastal Range case.

We have recently discovered a variety of unrelated phototrophic microorganisms (two microalgae and one cyanobacteria) in specialized terrestrial habitats at The Coastal Range of the Atacama Desert. Interestingly, morphological and molecular evidence suggest that these three species are all recent colonists that came from aquatic habitats. The first case is Cyanidiales inhabiting coastal caves. Cyanidiales are microalgae that are commonly found in warm acid springs, but have also been recently discovered as cave flora in Italy. The case is Dunaliella biofilms colonizing spider webs in coastal caves; Dunaliella are microalgae typically found in hypersaline habitats. The third case is Chroococcidiopsis, a genus of Cyanobacteria commonly found in deserts around the world that has also been described in warm springs. Thus, we show that the traits found in the closest ancestors of the aforementioned species (which inhabited other unrelated extreme environments) seem to be now useful for the described species in their current subaerial habitats and may likely correspond to cases of exaptations. Altogether, the Coastal Range of the Atacama Desert may be considered as a place where key steps on the colonization of land by phototrophic organisms seem to be being repeated by convergent evolution of extant microalgae and Cyanobacteria.