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Recent researches have proposed that phylogenetic methods can be effective tools for exploiting the untapped potential of medicinal plants. Under the assumption that medicinal properties tend to be phylogenetically clustered, phylogenies can be used to narrow down the relevant species for bioprospecting, increase the discovery rate and reduce the time and costs involved. Nonetheless, some restrictions exist. By integrating ethnobotanical knowledge with phylogenetic methods, it has often been necessary to group plants into macro-categories of therapeutic effects, limiting the potential of the approach. In many studies “hot nodes” corresponding to lineages overrepresented in medicinal taxa were identified. However, as larger phylogenies and databases become available, the possibility of huge lineages being identified by “hot nodes” is also likely to increase, once again posing a prioritization problem. To tackle these issues, we propose a new analysis pipeline, mixing existing and new developed methods. Briefly, our workflow is as follows: 1) using selected databases that integrate traditional medicine data with growing molecular information, species linked to specific diseases or specific biological effects are obtained; 2) different methods to estimate the phylogenetic clustering of taxa are applied using a reference phylogeny; 3); where a phylogenetic signal has emerged, “hot nodes” are repeatedly estimated to assess their robustness; 4) in case of large lineages subtended by stable “hot nodes”, a (relative) probability of being linked to the disease or biological effect of interest is calculated for each taxa; 5) results are summarised and graphically displayed to combine different information. To test our pipeline data related to 10 diseases and 10 biological effects were obtained from two different public databases and were analysed together with a published phylogeny including ~ 30,000 species. Our results show the effectiveness of the approach suggesting that

There are almost 400,000 recognized plant species, each one containing different molecules that may have useful effects on the human body. Considering this diversity, the use of a strategic approach to identify the plants to investigate is crucial to efficiently discover therapeutic compounds. One of these approaches is the phylogenetic one, as closely related plant species tend to share biochemistry and medicinal properties. The aim of this work is to apply different phylogenetic methods to construct a pipeline useful for the selection of plants with high potential for drug research. Thus, a phylogenetic tree containing 32.223 species was downloaded, and lists of medicinal plants correlated with 12 diseases were obtained from the CMAUP medicinal plants database. Five monophyletic subtrees were extracted from the reference phylogenesis, and for all of them, for each plant list, the phylogenetic signal was measured using different methods. In the presence of phylogenetic signals, subsequent analyses were done to determine the exact position of phylogenetic clumping by identifying the hot nodes. The trees containing the species descending from the hot nodes were extracted, and those with more than 14 tips were plotted. From the analysis of the 12 lists, a total of 198 trees were plotted. These trees contain information about the plants identified by the method as having high potential in treating the disease. This work was able to apply a pipeline of different phylogenetic methods that can be used for the selection of potential plants for drug discovery.

The Vigna Savi genus, of the Fabaceae family, includes different important crops, such as Vigna unguiculata (cowpea), Vigna angularis (adzuki bean), and others. They can grow in dry climates and poor soils, and their seeds are abundant both in nutrients and nutraceutical compounds. Variants of these plants are also present in the wild while the majority of the Vigna species were never domesticated. Among the useful compounds of these plants are the Bowman-Birk protease inhibitors (BBI), molecules produced as defensive mechanism against insect attacks. Various nutraceutical effects of these proteins on humans have been demonstrated, including chemopreventive e and anticarcinogenic ones. This study analysed the natural genetic variability of two BBI isoforms in different species of the genus Vigna. In particular, the two isoforms encode for a trypsin-trypsin BBI, characterized by two trypsin-specific domains (BBI-TT) and the second one, a trypsin-chymotrypsin BBI, characterized by one trypsin and one chymotrypsin-specific domain (BBI-TC). For this purpose, the sequences of both genes were first obtained from 12 published genomes. Then DNA was extracted from 44 Vigna species and different primers were used to amplify and then sequence both genes. Ultimately, the BBI-TT were obtained from 34 species, revealing 55 haplotypes corresponding to 40 isoforms and 32 mature proteins. Meanwhile the BBI-TC were obtained from 40 species, revealing 70 haplotypes corresponding to 56 isoforms and 39 mature proteins. A phylogenetic tree of both genes was constructed to study their evolution and to apply an ancestral sequence reconstruction analysis. Furthermore, sites under selective pressure were identified with different algorithm approaches. In conclusion, this work provided insights about the evolution of these genes in Vigna and allowed the detection of several natural forms of BBI. These natural proteins could potentially be used to improve the defences of cultivated plants or f

Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear growth stunting, slowed neurocognitive development, and unresponsiveness to oral vaccines. Prenatal exposure to malnutrition and breast feeding by malnourished mothers replicates EED. Pups are characterized by deprivation of secretory IgA (SIgA) and altered development of the gut immune system and microbiota. Extracellular ATP (eATP) released by microbiota limits T follicular helper (Tfh) cell activity and SIgA generation in Peyer's patches (PPs). Administration of a live biotherapeutic releasing the ATP-degrading enzyme apyrase to malnourished pups restores SIgA levels and ameliorates stunted growth. SIgA is instrumental in improving the growth and intestinal immune competence of mice while they are continuously fed a malnourished diet. The analysis of microbiota composition suggests that amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organisms, irrespective of the actual microbial ecology.

Societal Impact Statement: The legume crop cowpea is grown worldwide, but 90% of the world's total share is produced in Africa. It is a promising species due to its resilience properties, balance of macro and micronutrients and presence of health-promoting bioactive compounds. In African countries, cowpea has a crucial role in guaranteeing food security as a subsistence crop for families and commercial income for small farmers. The discovery of compounds with high nutraceutical value and bioactive properties supports socio-economic policies to improve health and nutrition, especially in low- and middle-income countries. In turn, this encourages biodiversity protection and crop enhancement programmes. Summary: Bowman–Birk protease inhibitors (BBIs) are a restricted group of small proteins in plants mainly involved in defence mechanisms against pests. BBIs are demonstrated to be active components capable of reducing the viabilities of different cancer cell lines. BBI bioactivity is directly linked to the inhibition capacity, but the variability and the efficiency against the physiological targets of different BBI isoforms remain still unexplored. We analysed the natural genetic diversity of two main genes encoding BBI trypsin-trypsin (BBI-TT) and trypsin-chymotrypsin (BBI-TC) in wild and domesticated cowpea samples mainly spread in Sub-Saharan Africa. We analysed DNA sequences and respective amino acidic isoforms/isoproteins to explore signs of natural selection and haplotype relationships. Moreover, we calculated the binding energy between BBIs and their biological targets to identify which are the most efficient inhibitors and their geographical locations. We found a high level of haplotype diversity for both genes, almost exclusively in wild accessions and detected positive and negative selection signals in the amino acid sequences. Furthermore, in the wild diversity pool, some BBI-TT and BBI-TC mature proteins were potentially better interactors with the physiolog

Intestinal epithelial cells represent the first line of defense from invading enteric pathogens. During the course of infection, pro-inflammatory programmed cell death is an effective way to eliminate invading microbes and to create a localized inflammatory environment. On the other hand, pathogens evolved countless strategies to overcome cell death and to keep the host alive ensuring their spread. It was previously shown that Shigella flexneri apyrase interacts with OmpA to contribute to a proper polar exposition of IcsA, which mediates actin-based motility. However, apyrase is also an ATP-diphosphohydrolase whose catalytic activity function has not been elucidated yet. Herein, we demonstrated that apyrase contributes to the manipulation of host cell fate by S. flexneri since it is released within the host cell cytoplasm during infection to degrade intracellular ATP. Thus, apyrase contributes to prevent caspase-1 activation, thereby downregulating the activation of pyroptosis in infected cells. Overall, apyrase is involved in the modulation of host cell survival and dampens the inflammatory response.

Domesticated plants possess only a small fraction of the genetic variability found in their wild relatives, and this variability represents an important resource. One of these plants is Vigna unguiculata (L.) Walp., or cowpea, an important crop which has several features suitable for sustainable agriculture. Bowman-Birk protease inhibitors (BBI) are useful molecules produced by plants, especially Fabaceae and Poaceae, as defensive mechanism against insects attack. Nutraceutical effects of these proteins on humans have been demonstrated, including chemopreventive and anticarcinogenic ones. In this study we analyzed the natural genetic variability of two BBI isoforms of Vigna unguiculata in both wild and domesticated accessions. In particular the two isoforms encode for a trypsin-trypsin BBI, characterized by two trypsin-specific domains (BBI-TT) and the second one, a trypsin-chymotrypsin BBI, characterized by one trypsin and one chymotrypsin-specific domain (BBI-TC). For this purpose, both genes were sequenced from about 450 individuals belonging to 124 wild and 67 domesticated accessions, obtaining 24 haplotypes corresponding to 13 isoforms of BBI-TT and 29 haplotypes corresponding to 20 isoforms of BBI-TC. Most of the haplotypes found belonged exclusively to wild accessions plants. For both genes, haplotypes and isoforms distributions were mapped, and network analyses were performed to understand haplotypes relationships. Furthermore, sites under selective pressure were identified with different algorithm approaches. This work allowed the detection of several natural forms of BBI, found mostly in wild plants, that could potentially be used to improve the defenses of cultivated plants or for pharmaceutical and nutritional purposes.

The current climate change and increasing climate variability represent a serious global challenge that demands urgent responses. Among the multiple actions that should be taken, afforestation and reforestation are the most common strategies. The current paper aims to assess the potential of tree species to be used in urban forestry in the Po Plain ecoregional province (Northern Italy) using DNA barcoding approach for plant traceability and ecophysiological indexes (shade, drought and waterlogging) for plant selection. DNA barcoding markers results showed a 55.5% of success, but the power of discrimination increased to 94.5% when considering only the autochthonous ecoregional species pool. Concerning ecophysiological markers, Fagus sylvatica, Abies alba, Picea abies and Taxus baccata were very shade-tolerant. The best performing trees concerning drought tolerance were oak species (Quercus ilex, Q. pubescens and Q. cerris), pines (Pinus pinea, P. nigra and P. sylvestris) and Fraxinus ornus. Only a few tree species (Salix alba, Alnus glutinosa, Populus nigra and Prunus padus) showed high tolerance to waterlogging. The combination of both approaches makes it possible to select the most suitable species, based on eco-pedological and microclimatic conditions, and to trace their identity along the entire supply chain, from nursery to planting, for urban forestry.

We elucidate grapevine evolution and domestication histories with 3525 cultivated and wild accessions worldwide. In the Pleistocene, harsh climate drove the separation of wild grape ecotypes caused by continuous habitat fragmentation. Then, domestication occurred concurrently about 11,000 years ago in Western Asia and the Caucasus to yield table and wine grapevines. The Western Asia domesticates dispersed into Europe with early farmers, introgressed with ancient wild western ecotypes, and subsequently diversified along human migration trails into muscat and unique western wine grape ancestries by the late Neolithic. Analyses of domestication traits also reveal new insights into selection for berry palatability, hermaphroditism, muscat flavor, and berry skin color. These data demonstrate the role of the grapevines in the early inception of agriculture across Eurasia.

BACKGROUND AND AIMS: Although plastid genes are widely used in phylogenetic studies, signals of positive selection have been scarcely investigated in the grape family. The plastomes from 91 accessions of Vitaceae were examined to understand the extent to which positive selection is present and to identify which genes are involved. Moreover, the changes through time of genes under episodic positive selection were investigated and the hypothesis of an adaptive process following the Cretaceous-Palaeogene (K/Pg) transition about 66 million years ago was tested. METHODS: Different codon-substitution models were used to assess pervasive and episodic positive selection events on 70 candidate plastid genes. Divergence times between lineages were estimated and stochastic character mapping analysis was used to simulate variation over time of the genes found to be under episodic positive selection. KEY RESULTS: A total of 20 plastid genes (29 %) showed positive selection. Among them, 14 genes showed pervasive signatures of positive selection and nine genes showed episodic signatures of positive selection. In particular, four of the nine genes (psbK, rpl20, rpoB, rps11) exhibited a similar pattern showing an increase in the rate of variation close to the K/Pg transition. CONCLUSION: Multiple analyses have shown that the grape family has experienced ancient and recent positive selection events and that the targeted genes are involved in essential functions such as photosynthesis, self-replication and metabolism. Our results are consistent with the idea that the K/Pg transition has favoured an increased rate of change in some genes. Intense environmental perturbations have influenced the rapid diversification of certain lineages, and new mutations arising on some plastid genes may have been fixed by natural selection over the course of many generations.

Legumes are one of the most economically important and biodiverse families in plants recognised as the basis to develop functional foods. Among these, the Vigna genus stands out as a good representative because of its relatively recent African origin as well as its outstanding potential. Africa is a great biodiversity centre in which a great number of species are spread, but only three of them, Vigna unguiculata, Vigna subterranea and Vigna vexillata, were successfully domesticated. This review aims at analysing and valorising these species by considering the perspective of human activity and what effects it exerts. For each species, we revised the origin history and gave a focus on where, when and how many times domestication occurred. We provided a brief summary of bioactive compounds naturally occurring in these species that are fundamental for human wellbeing. The great number of wild lineages is a key point to improve landraces since the domestication process caused a loss of gene diversity. Their genomes hide a precious gene pool yet mostly unexplored, and genes lost during human activity can be recovered from the wild lineages and reintroduced in cultivated forms through modern technologies. Finally, we describe how all this information is game-changing to the design of future crops by domesticating de novo.

Background: Pancreatic cancer incidence is growing, but the prognosis for survival is still poor. Patients with pancreatic cancer often suffer from malnutrition and sarcopenia, two clinical conditions that negatively impact oncological clinical outcomes. The aim of this systematic review was to analyze the impact of different nutritional interventions on clinical outcomes in patients with pancreatic cancer during chemotherapy. Methods: A systematic review of MedLine, EMBASE, and Web of Science was carried out in December 2022, identifying 5704 articles. Titles and abstracts of all records were screened for eligibility based on inclusion criteria, and nine articles were included. Results: All nine articles included were prospective studies, but a meta-analysis could not be performed due to heterogenicity in nutritional intervention. This Systematic Review shows an improvement in Quality of Life, nutritional status, body composition, oral intake, and Karnofsky Performance Status, following nutritional interventions. Conclusions: This Systematic Review in pancreatic cancer patients during chemotherapies does not allow one to draw firm conclusions. However, nutritional support in pancreatic cancer patients is advisable to ameliorate oncological care. Further well-designed prospective studies are needed to identify nutritional support’s real impact and to establish a reliable way to improve nutritional status of pancreatic cancer patients during chemotherapy.