Metabolomics has emerged as an indispensable tool for exploring complex biological questions, providing the ability to investigate a substantial portion of the metabolome. However, the vast complexity and structural diversity intrinsic to metabolites imposes a great challenge for data analysis and interpretation. Liquid chromatography mass spectrometry (LC-MS) stands out as a versatile technique offering extensive metabolite coverage. In this mini-review, we address some of the hurdles posed by the complex nature of LC-MS data, providing a brief overview of computational tools designed to help tackling these challenges. Our focus centers on two major steps that are essential to most metabolomics investigations: the translation of raw data into quantifiable features, and the extraction of structural insights from mass spectra to facilitate metabolite identification. By exploring current computational solutions, we aim at providing a critical overview of the capabilities and constraints of mass spectrometry-based metabolomics, while introduce some of the most recent trends in data processing and analysis within the field.

The hepatitis E virus is a serious health concern worldwide, with 20 million cases each year. Growing numbers of autochthonous HEV infections in industrialized nations are brought on via the zoonotic transmission of HEV genotypes 3 and 4. Pigs and wild boars are the main animal reservoirs of HEV and play the primary role in HEV transmission. Consumption of raw or undercooked pork meat and close contact with infected animals are the most common causes of hepatitis E infection in industrialized countries. However, during the past few years, mounting data describing HEV distribution has led experts to believe that additional animals, particularly domestic ruminant species (cow, goat, sheep, deer, buffalo, and yak), may also play a role in the spreading of HEV. Up to now, there have not been enough studies focused on HEV infections associated with animal milk and the impact that they could have on the epidemiology of HEV. This critical analysis discusses the role of domestic ruminants in zoonotic HEV transmissions. More specifically, we focus on concerns related to milk safety, the role of mixed farming in cross-species HEV infections, and what potential consequences these may have on public health.

To maintain the continuous genetic variation and increase the genetic gain, appreciable germplasm diversity and its comprehensive characterization is necessary to further utilize gene sources for pre-breeding. The diversity of pepper forms, cultivation traditions and diverse fruit usages are typical for Balkan countries. Considering this rich diversity, 21 pepper accessions from the Balkan region were evaluated for morphological, biochemical, and insect resistance traits during 2018 and 2019 at Maritsa Vegetable Crops Research Institute, Plovdiv, Bulgaria. Among the studied accessions, the highest productivity was observed in pumpkin shape K1115 and kapia type K1081 accessions, with 0.74 kg and 0.70 kg per plant, respectively. Concerning fruit quality, the highest total polyphenols and ferric reducing antioxidant power (FRAP) were observed in pumpkin shape K712 (203.44 mg GAE/100 g FW) and K1103A (11.49 µmol Fe2+/g FW) accessions, respectively. Concerning insect resistance, 38% of studied accessions showed no infestation of green peach aphid. The kapia type K697 accession was seen as the most reliable resistance source, as it was not infested by aphids and had the least thrips (20% on plants) and cotton bollworm (6.67% on plants and 8.34% on fruit) damage. Based on examined traits, accessions were identified for enhanced fruit quality and promising insect resistance and have been included in further pre-breeding efforts.

AbstractThe revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.

Aging presents an increasingly significant challenge globally, driven by the growing proportion of individuals aged 60 and older. Currently, there is substantial research interest in pro-longevity interventions that target pivotal signaling pathways, aiming not only to extend lifespan but also to enhance healthspan. One particularly promising approach involves inducing a hormetic response through the utilization of natural compounds defined as hormetins. Various studies have introduced the flavonoid icariin as beneficial for age-related diseases such as cardiovascular and neurodegenerative conditions. To validate its potential pro-longevity properties, we employed Caenorhabditis elegans as an experimental platform. The accumulated results suggest that icariin extends the lifespan of C. elegans through modulation of the DAF-2, corresponding to the insulin/IGF-1 signaling pathway in humans. Additionally, we identified increased resistance to heat and oxidative stress, modulation of lipid metabolism, improved late-life healthspan, and an extended lifespan upon icariin treatment. Consequently, a model mechanism of action was provided for icariin that involves the modulation of various players within the stress-response network. Collectively, the obtained data reveal that icariin is a potential hormetic agent with geroprotective properties that merits future developments.

Plants are increasingly used for the production of high-quality biological molecules for use as pharmaceuticals and biomaterials in industry. Plants have proved that they can produce life-saving therapeutic proteins (Elelyso™-Gaucher's disease treatment, ZMapp™-anti-Ebola monoclonal antibodies, seasonal flu vaccine, Covifenz™-SARS-CoV-2 virus-like particle vaccine); however, some of these therapeutic proteins are difficult to bring to market, which leads to serious difficulties for the manufacturing companies. The closure of one of the leading companies in the sector (the Canadian biotech company Medicago Inc., producer of Covifenz) as a result of the withdrawal of investments from the parent company has led to the serious question: What is hindering the exploitation of plant-made biologics to improve health outcomes? Exploring the vast potential of plants as biological factories, this review provides an updated perspective on plant-derived biologics (PDB). A key focus is placed on the advancements in plant-based expression systems and highlighting cutting-edge technologies that streamline the production of complex protein-based biologics. The versatility of plant-derived biologics across diverse fields, such as human and animal health, industry, and agriculture, is emphasized. This review also meticulously examines regulatory considerations specific to plant-derived biologics, shedding light on the disparities faced compared to biologics produced in other systems.

Obesity prevalence is becoming a serious global health and economic issue and is a major risk factor for concomitant diseases that worsen the quality and duration of life. Therefore, the urgency of the development of novel therapies is of a particular importance. A previous study of ours revealed that the natural pterocarpan, maackiain (MACK), significantly inhibits adipogenic differentiation in human adipocytes through a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent mechanism. Considering the observed anti-adipogenic potential of MACK, we aimed to further elucidate the molecular mechanisms that drive its biological activity in a Caenorhabditis elegans obesity model. Therefore, in the current study, the anti-obesogenic effect of MACK (25, 50, and 100 μM) was compared to orlistat (ORST, 12 μM) as a reference drug. Additionally, the hybrid combination between the ORST (12 μM) and MACK (100 μM) was assessed for suspected synergistic interaction. Mechanistically, the observed anti-obesogenic effect of MACK was mediated through the upregulation of the key metabolic regulators, namely, the nuclear hormone receptor 49 (nhr-49) that is a functional homologue of the mammalian PPARs and the AMP-activated protein kinase (aak-2/AMPK) in C. elegans. Collectively, our investigation indicates that MACK has the potential to limit lipid accumulation and control obesity that deserves future developments.

Rutin, a flavonoid rich in buckwheat, is important for human health and plant resistance to external stresses. The hydrolysis of rutin to quercetin underlies the bitter taste of Tartary buckwheat. In order to identify rutin hydrolysis genes, a 200 genotypes mini-core Tartary buckwheat germplasm resource was re-sequenced with 30-fold coverage depth. By combining the content of the intermediate metabolites of rutin metabolism with genome resequencing data, metabolite genome-wide association analyses (GWAS) eventually identified a glycosyl hydrolase gene FtGH1, which could hydrolyse rutin to quercetin. This function was validated both in Tartary buckwheat overexpression hairy roots and in vitro enzyme activity assays. Mutation of the two key active sites, which were determined by molecular docking and experimentally verified via overexpression in hairy roots and transient expression in tobacco leaves, exhibited abnormal subcellular localization, suggesting functional changes. Sequence analysis revealed that mutation of the FtGH1 promoter in accessions of two haplotypes might be necessary for enzymatic activity. Co-expression analysis and GWAS revealed that FtbHLH165 not only repressed FtGH1 expression, but also increased seed length. This work reveals a potential mechanism behind rutin metabolism, which should provide both theoretical support in the study of flavonoid metabolism and in the molecular breeding of Tartary buckwheat.

Marrubium species have been used since ancient times as food additives and curative treatments. Their phytochemical composition and various pharmacological activities were the focus of a number of scientific investigations but no comprehensive metabolome profiling to identify the numerous primary and secondary metabolites has been performed so far. This study aimed to generate a comprehensive picture of the total metabolite content of two Marrubium species—M. peregrinum and M. friwaldskyanum—to provide detailed information about the main primary and secondary metabolites. In addition, the elemental composition was also evaluated. For this purpose, non-targeted metabolomic analyses were conducted using GC-MS, UPLC-MS/MS and ICP-MS approaches. Nearly 500 compounds and 12 elements were detected and described. The results showed a strong presence of phenolic acids, flavonoids and their glucosides, which are generally of great interest due to their various pharmacological activities. Furthermore, tissue-specific analyses for M. friwaldskyanum stem, leaves and flowers were carried out in order to outline the sources of potentially important bioactive molecules. The results generated from this study depict the Marrubium metabolome and reveal its dual scientific importance—from one side, providing information about the metabolites that is fundamental and vital for the survival of these species, and from the other side, defining the large diversity of secondary substances that are a potential source of phytotherapeutic agents.

SummaryThe recently describedcanal-1tomato mutant, which has a variegated leaf phenotype, has been shown to affect canalization of yield. The corresponding protein is orthologous to AtSCO2 - SNOWY COTYLEDON2, which has suggested roles in thylakoid biogenesis. Here we characterize thecanal-1mutant through a multi-omics approach, by comparing mutant to wild-type tissues. While whitecanal-1leaves are devoid of chlorophyll, green leaves of the mutant appear wild-type-like, despite an impaired protein function. Transcriptomic data suggest that green mutant leaves compensate for this impaired protein function by upregulation of transcription of photosystem assembly and photosystem component genes, thereby allowing adequate photosystem establishment, which is reflected in their wild-type-like proteome. Whitecanal-1leaves, however, likely fail to reach a certain threshold enabling this overcompensation, and plastids get trapped in an undeveloped state, while additionally suffering from high light stress, indicated by the overexpression of ELIP homolog genes. The metabolic profile of white and to a lesser degree also green tissues revealed upregulation of amino acid levels, that was at least partially mediated by transcriptional and proteomic upregulation. These combined changes are indicative of a stress response and suggest that white tissues behave as carbon sinks. In summary, our work demonstrates the relevance of the SCO2 protein in both photosystem assembly and as a consequence in the canalization of yield.Significance statementThe variegatedcanalized-1tomato mutant was recently described and the underlying geneSCO2suggested to be a yield canalization gene. Through a multi-omics approach we show that mutants require a transcriptional upregulation of photosystem components and assembly components, likely as overcompensation for partially impaired SCO2 function, to produce a wild type-like proteome and functional photosynthetic tissue Our data, furthermore, suggest that variation of green to white leaf area from plant to plant leads to the yield variation.