Specific Metabolites Research Articles

Health-Promoting Effects, Phytochemical Constituents and Molecular Genetic Profile of the Purple Carrot 'Purple Sun' (Daucus carota L.).

The purple carrot cultivar 'Purple Sun' (Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid (1), phenolic acid derivatives (2 and 6), hydroxycinnamic acid derivatives (9, 10, 12-14, 16, 17, 19, 22, and 23), anthocyanins (3-5, 7, 8, 11, and 18), flavanonols (15 and 21), flavonols (20 and 24), oxylipins (25, 26, and 28), and the sesquiterpene 11-acetyloxytorilolone (27); compound 26, corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (-) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus. The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, 'Purple Sun' is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations.

Unveiling physiological responses and modulated accumulation patterns of specialized metabolites in Mentha rotundifolia acclimated to sub-tropical environment.

The online version contains supplementary material available at 10.1007/s12298-024-01489-8.

Multi‐Stimuli‐Responsive Network of Multicatalytic Reactions using a Single Palladium/Platinum Catalyst

AbstractGiven her unrivalled proficiency in the synthesis of all molecules of life, nature has been an endless source of inspiration for developing new strategies in organic chemistry and catalysis. However, one feature that remains thus far beyond chemists’ grasp is her unique ability to adapt the productivity of metabolic processes in response to triggers that indicate the temporary need for specific metabolites. To demonstrate the remarkable potential of such stimuli‐responsive systems, we present a metabolism‐inspired network of multicatalytic processes capable of selectively synthesising a range of products from simple starting materials. Specifically, the network is built of four classes of distinct catalytic reactions—cross‐couplings, substitutions, additions, and reductions, involving three organic starting materials—terminal alkyne, aryl iodide, and hydrosilane. All starting materials are either introduced sequentially or added to the system at the same time, with no continuous influx of reagents or efflux of products. All processes in the system are catalysed by a multifunctional heteronuclear PdII/PtII complex, whose performance can be controlled by specific additives and external stimuli. The reaction network exhibits a substantial degree of orthogonality between different pathways, enabling the controllable synthesis of ten distinct products with high efficiency and selectivity through simultaneous triggering and suppression mechanisms.

Multi-Stimuli-Responsive Network of Multicatalytic Reactions using a Single Palladium/Platinum Catalyst.

Given her unrivalled proficiency in the synthesis of all molecules of life, nature has been an endless source of inspiration for developing new strategies in organic chemistry and catalysis. However, one feature that remains thus far beyond chemists' grasp is her unique ability to adapt the productivity of metabolic processes in response to triggers that indicate the temporary need for specific metabolites. To demonstrate the remarkable potential of such stimuli-responsive systems, we present a metabolism-inspired network of multicatalytic processes capable of selectively synthesising a range of products from simple starting materials. Specifically, the network is built of four classes of distinct catalytic reactions-cross-couplings, substitutions, additions, and reductions, involving three organic starting materials-terminal alkyne, aryl iodide, and hydrosilane. All starting materials are either introduced sequentially or added to the system at the same time, with no continuous influx of reagents or efflux of products. All processes in the system are catalysed by a multifunctional heteronuclear PdII/PtII complex, whose performance can be controlled by specific additives and external stimuli. The reaction network exhibits a substantial degree of orthogonality between different pathways, enabling the controllable synthesis of ten distinct products with high efficiency and selectivity through simultaneous triggering and suppression mechanisms.

The arginine and nitric oxide metabolic pathway regulate the gut colonization and expansion of Ruminococcous gnavus

Ruminococcus gnavus is a mucolytic commensal bacterium whose increased gut colonization has been associated with chronic inflammatory and metabolic diseases in humans. Whether R.gnavus metabolites can modulate host intestinal physiology remains largely understudied. We performed untargeted metabolomic and bulk RNA-seq analyses using R.gnavus monocolonization in germ-free mice. Based on transcriptome-metabolome correlations, we tested the impact of specific arginine metabolites on intestinal epithelial production of nitric oxide (NO) and examined the effect of NO on the growth of various strains of R.gnavus invitro and in nitric oxide synthase 2 (Nos2)-deficient mice. R.gnavus produces specific arginine, tryptophan, and tyrosine metabolites, some of which are regulated by the environmental richness of sialic acid and mucin. R.gnavus colonization promotes expression of amino acid transporters and enzymes involved in metabolic flux of arginine and associated metabolites into NO. R.gnavus induced elevated levels of NOS2, while Nos2 ablation resulted in R.gnavus expansion invivo. The growth of various R.gnavus strains can be inhibited by NO. Specific R.gnavus metabolites modulate intestinal epithelial cell NOS2 abundance and reduce epithelial barrier function at higher concentrations. Intestinal colonization and interaction with R.gnavus are partially regulated by an arginine-NO metabolic pathway, whereby a balanced control by the gut epithelium may restrain R.gnavus growth in healthy individuals. Disruption in this arginine metabolic regulation will contribute to the expansion and blooming of R.gnavus.

Whole-Genome Sequencing of Three Lactiplantibacillus plantarum Strains Reveals Potential Metabolites for Boosting Host Immunity Safely.

In response to the growing demand for immune-related products, this study evaluated the safety and immune-modulating potential of three newly discovered Lactiplantibacillus plantarum strains (GKM3, GKK1, and GKD7) through toxicity tests and whole-genome sequencing. Safety evaluations, including the analysis of antimicrobial resistance genes, virulence factors, plasmids, and prophages, classified these strains as safe for human consumption. Acute oral toxicity tests further supported their safety. To evaluate their immune-modulating potential, dendritic cells were exposed to these strains, and the secretion of key cytokines (IFN-β and IL-12) was measured. Among the strains, GKK1 exhibited the highest enhancement of IFN-β and IL-12 production, suggesting its potential as an immune-stimulating probiotic. Bioinformatics analysis revealed potential metabolic pathways and secondary metabolites, including predicted bacteriocins, associated with immune modulation. The presence of a nitrate reductase region in the GKK1 strain indicated its ability to produce nitric oxide, a critical molecule involved in immune regulation and host defense. The presence of glucorhamnanrelated gene clusters in GKK1 also suggested immune-enhancing effects. Nitrate reductase expression was confirmed using qPCR, with the highest levels detected in GKK1. Moreover, this study is the first to show an anti-inflammatory effect of plantaricin A, linked to its presence in strain GKM3 and its potential therapeutic applications due to sequence similarity to known antiinflammatory peptides. Overall, these three L. plantarum strains demonstrated a safe profile and GKK1 showed potential as an immunity-enhancing probiotic. However, additional investigation is required to confirm the involvement of specific metabolic pathways, secondary metabolites, and bacteriocins in immune responses.

Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis

ObjectiveThe specific breast milk-derived metabolites that mediate host–microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation.DesignWe enrolled 250 mother–infant pairs and collected...

Exploring the potential of omics technologies in medicinal plant research: A review in Colombia

This review presents advances in the implementation of high-throughput sequencing and its application to the knowledge of medicinal plants. We conducted a bibliographic search of papers published in PubMed, Science Direct, Google Scholar, Scopus, and Web of Science databases and analyzed the obtained data using VOSviewer (version 1.6.19). Given that medicinal plants are a source of specialized metabolites with immense therapeutic values and important pharmacological properties, plant researchers around the world have turned their attention toward them and have begun to examine them widely. Recent advances in sequencing technologies have reduced cost and time demands and accelerated medicinal plant research. Such research leverages full genome sequencing, as well as RNA (ribonucleic acid) sequencing and the analysis of the transcriptome, to identify molecular markers of species and functional genes that control key biological traits, as well as to understand the biosynthetic pathways of bioactive metabolites and regulatory mechanisms of environmental responses. As such, the omics (e.g., transcriptomics, metabolomics, proteomics, and genomics, among others) have been widely applied within the study of medicinal plants, although their usage in Colombia is still few and, in some areas, scarce.

Gut microbiota metabolically mediate intestinal helminth infection in Zebrafish.

Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome, and that changes in the gut microbiome are associated with variation in a class of endogenously-produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlights specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.

Differentiated response of Hypericum perforatum to foliar application of selected metabolic modulators: Elicitation potential of chitosan, selenium, and salicylic acid mediated by redox imbalance

Plants plastically alter their metabolism in response to environmental stimuli, which induces changes in the accumulation of specialized metabolites. This ability can be utilized to manipulate plant phytochemistry in a desired direction. However, the abundance of secondary metabolites in the different plant species, especially medicinal, is enormous; therefore, it is difficult to establish a clear direction for the effects of metabolic modulators on phytochemical composition, especially given the possibility of using different types thereof. In order to gain insight into these changes, we investigated the effects of foliar-applied chitosan (ChL, 100 mg/L), selenium (Se, 10 mg/L), salicylic acid (SA, 150 mg/L), or an equal volume mixture thereof on Hypericum perforatum L. metabolism. Selenium and SA proved to be the more effective than ChL in enhancing the accumulation of phenolic compounds. The greatest increase was found in the concentration of neochlorogenic acid after Se-spraying. The treatment with the elicitors generally increased the concentration of identified flavonoids, but not the level of naphthodianthrone or phloroglucinol metabolites. The most pronounced response was observed on day 10 following the application of the compounds, and is likely the consequence of elevated levels of O2−˙, free proline, and modulated activity of enzymatic antioxidants.

Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients.

Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells. This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis. We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance. These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.

Relationships between tryptophan-related gut metabolites, brain activity, and autism symptomatology.

Gut microbial metabolites have been theorized to play a causative role in the pathophysiology of autism spectrum disorder (ASD). This hypothesis is based on results from mechanistic preclinical studies and several correlational studies showing differences in gut microbial composition between ASD subjects and neurotypical (NT) controls. However, alterations in how the human brain interacts with the gut microbiome in ASD have not been examined. In this cross-sectional, case-control observational study, fecal metabolomics, task-based functional magnetic resonance imaging (fMRI), and behavioral assessments were obtained from 43 ASD and 41 NT children aged 8-17. The fMRI tasks were based on socio-emotional and sensory paradigms that commonly show strong evoked brain differences in ASD participants. General linear models and mediational modeling were applied to examine the links between tryptophan metabolism and evoked brain activity and behavior. Results indicated that fecal levels of specific tryptophan-related metabolites were associated with: 1) brain activity atypicalities in regions previously implicated in ASD (i.e., insula and cingulate); and 2) ASD severity and symptomatology (i.e., ADOS scores, disgust propensity, and sensory sensitivities). Importantly, activity in the mid-insula and mid-cingulate significantly mediated relationships between the microbial tryptophan metabolites, indolelactate and tryptophan betaine, and ASD severity and disgust sensitivity. To our knowledge, this is the first study to elucidate how interactions between gut metabolites and brain activity may impact autism symptomatology, particularly in functional brain pathways associated with vagal and interoceptive/emotion processing.

Prophage induction can facilitate the in vitro dispersal of multicellular Streptomyces structures.

Streptomyces are renowned for their prolific production of specialized metabolites with applications in medicine and agriculture. These multicellular bacteria present a sophisticated developmental cycle and play a key role in soil ecology. Little is known about the impact of Streptomyces phage on bacterial physiology. In this study, we investigated the conditions governing the expression and production of "Samy", a prophage found in Streptomyces ambofaciens ATCC 23877. This siphoprophage is produced simultaneously with the activation of other mobile genetic elements. Remarkably, the presence and production of Samy increases bacterial dispersal under in vitro stress conditions. Altogether, this study unveiled a new property of a bacteriophage infection in the context of multicellular aggregate dynamics.

Insights into the biodegradation of fipronil through soil microcosm-omics analyses of Pseudomonas sp. FIP_ A4

Fipronil, a phenylpyrazole insecticide, is used to kill insects resistant to conventional insecticides. Though its regular and widespread use has substantially reduced agricultural losses, it has also caused its accumulation in various environmental niches. The biodegradation is an effective natural process that helps in reducing the amount of residual insecticides. This study deals with an in-depth investigation of fipronil degradation kinetics and pathways in Pseudomonas sp. FIP_A4 using multi-omics approaches. Soil-microcosm results revealed ∼87% degradation within 40 days. The whole genome of strain FIP_A4 comprises 4.09 Mbp with 64.6% GC content. Cytochrome P450 monooxygenase and enoyl-CoA hydratase-related protein, having 30% identity with dehalogenase detected in the genome, can mediate the initial degradation process. Proteome analysis revealed differential enzyme expression of dioxygenases, decarboxylase, and hydratase responsible for subsequent degradation. Metabolome analysis displayed fipronil metabolites in the presence of the bacterium, supporting the proposed degradation pathway. Molecular docking and dynamic simulation of each identified enzyme in complex with the specific metabolite disclosed adequate binding and high stability in the enzyme-metabolite complex. This study provides in-depth insight into genes and their encoded enzymes involved in the fipronil degradation and formation of different metabolites during pollutant degradation. The outcome of this study can contribute immensely to developing efficient technologies for the bioremediation of fipronil-contaminated soils.

The acetyltransferase SCO0988 controls positively specialized metabolism and morphological differentiation in the model strains Streptomyces coelicolor and Streptomyces lividans.

Streptomycetes are well-known antibiotic producers possessing in their genomes numerous silent biosynthetic pathways that might direct the biosynthesis of novel bio-active specialized metabolites. It is thus of great interest to find ways to enhance the expression of these pathways to discover most needed novel antibiotics. In this study, we demonstrated that the over-expression of acetyltransferase SCO0988 up-regulated the production of specialized metabolites and accelerated sporulation of the weak antibiotic producer, Streptomyces lividans and that the deletion of this gene had opposite effects in the strong antibiotic producer, Streptomyces coelicolor. The comparative analysis of the acetylome of a S. lividans strain over-expressing sco0988 with that of the original strain revealed that SCO0988 acetylates a broad range of proteins of various pathways including BldKB/SCO5113, the extracellular solute-binding protein of an ABC-transporter involved in the up-take of a signal oligopeptide of the quorum sensing pathway. The up-take of this oligopeptide triggers the "bald cascade" that regulates positively specialized metabolism, aerial mycelium formation and sporulation in S. coelicolor. Interestingly, BldKB/SCO5113 was over-acetylated on four Lysine residues, including Lys425, upon SCO0988 over-expression. The bald phenotype of a bldKB mutant could be complemented by native bldKB but not by variant of bldKB in which the Lys425 was replaced by arginine, an amino acid that could not be acetylated or by glutamine, an amino acid that is expected to mimic acetylated lysine. Our study demonstrated that Lys425 was a critical residue for BldKB function but was inconclusive concerning the impact of acetylation of Lys425 on BldKB function.

Characterization of Meat Metabolites and Lipids in Shanghai Local Pig Breeds Revealed by LC-MS-Based Method.

The meat of local livestock breeds often has unique qualities and flavors. In this study, three Shanghai native pig breeds (MSZ, SWT, and SHB) exhibited better meat quality traits than globalized commercial pig breeds (DLY). Subsequently, metabolomic and lipidomic differences in the longissimus dorsi (L) and gluteus (T) muscles of the Shanghai native pig breeds and DLY pig breed were compared using liquid chromatography-mass spectrometry (LC-MS). The results demonstrated that the metabolites mainly consisted of (28.16%) lipids and lipid-like molecules, and (25.87%) organic acids and their derivatives were the two most dominant groups. Hundreds of differential expression metabolites were identified in every compared group, respectively. One-way ANOVA was applied to test the significance between multiple groups. Among the 20 most abundant differential metabolites, L-carnitine was significantly different in the muscles of the four pig breeds (p-value = 7.322 × 10-11). It was significantly higher in the L and T muscles of the two indigenous black pig breeds (MSZ and SWT) than in the DLY pigs (p-value < 0.001). Similarly, lipidomic analysis revealed the PA (18:0/18:2) was significantly more abundant in the muscle of these two black breeds than that in the DLY breed (p-value < 0.001). These specific metabolites and lipids might influence the meat quality and taste properties and lead to customer preferences. Therefore, this study provided insights into the characterization of meat metabolites and lipids in Shanghai native pig breeds.

Sperm-borne miR-34c-5p and miR-191-3p as markers for sperm motility and embryo developmental competence.

Sperm-borne microRNAs play a pivotal role in influencing essential cellular processes during fertilization, impacting the quality of embryo development. Dysregulated microRNA profiles have been associated with compromised embryonic development and increased incidences of pregnancy loss. This study aimed to investigate the potential associations between the abundance of miR-34c-5p and miR-191-3p in human spermatozoa with sperm quality, as well as with embryo quality and metabolic performance during in vitro development. Thirteen couples who underwent a total of 13 cycles participated in this study. The sperm quality was assessed using conventional methods following World Health Organization guidelines. Quantitative polymerase chain reaction was employed to measure microRNA abundance in spermatozoa. Embryos were categorized as good, lagging, or bad based on morphokinetic evaluation. Evaluation of embryo metabolic performance involved tracking changes in specific metabolites within the cultured media using nuclear magnetic resonance spectroscopy. Statistical analysis was conducted to explore the correlation between microRNA abundance in human spermatozoa and all other collected data. Our findings revealed a negative correlation between the abundance of miR-34c-5p (but not miR-191-3p) and total sperm motility, potentially mediated by the modulation of key signaling pathways. Additionally, higher levels of miR-34c-5p in spermatozoa were strongly associated with the consumption or release of key metabolites by developing embryos, particularly those linked with lipid and glucose metabolism, suggesting enhanced metabolic performance, while miR-191-3p was mostly associated with glucose consumption. Concurrently, only miR-34c-5p content in spermatozoa correlated with higher embryo quality. This study provides evidence suggesting that the abundance of miR-34c-5p in spermatozoa is correlated not only with total sperm motility but also with markers of embryo developmental competence, highlighting the potential significance of this sperm microRNA content as a biomarker in assisted reproduction.

Common metabolism and transcription responses of low-cadmium-accumulative wheat (Triticum aestivum L.) cultivars sprayed with nano-selenium

Cadmium (Cd) contamination in soils threatens food security, while cultivating low-Cd-accumulative varieties, coupled with agro-nanotechnology, offers a potential solution to reduce Cd accumulation in crops. Herein, foliar application of selenium nanoparticles (SeNPs) was performed on seedlings of two low-Cd-accumulative wheat (Triticum aestivum L.) varieties grown in soil spiked with Cd at 3 mg/kg. Results showed that foliar application of SeNPs at 0.16 mg/plant (SeNPs-M) significantly decreased the Cd content in leaves of XN-979 and JM-22 by 46.4 and 40.8 %, and alleviated oxidative damage. The wheat leaves treated with SeNPs-M underwent significant metabolic and transcriptional reprogramming. On one hand, four specialized antioxidant metabolites such as L-Tyrosine, beta-N-acetylglucosamine, D-arabitol, and monolaurin in response to SeNPs in JM-22 and XN-979 is the one reason for the decrease of Cd in wheat leaves. Moreover, alleviation of stress-related kinases, hormones, and transcription factors through oxidative post-translational modification, subsequently regulates the expression of defense genes via Se-enhanced glutathione peroxidase. These findings indicate that combining low-Cd-accumulative cultivars with SeNPs spraying is an effective strategy to reduce Cd content in wheat and promote sustainable agricultural development.

Comparison of nanovesicles derived from Panax notoginseng at different size: physical properties, composition, and bioactivity.

Plant-derived nanovesicles have emerged as potential agents for combating tumors. In this study, we investigated the inhibitory effects of Panax notoginseng-derived nanovesicles (PnNVs) on the proliferation and migration of squamous cell carcinoma. Additionally, we explored the relationship between plant tuber size and the physical properties, composition and bioactivity of these nanovesicles. We isolated PnNVs from Panax notoginseng tubers of varying sizes: small-sized (s_PnNVs), medium-sized (m_PnNVs) and large-sized (l_PnNVs), and evaluated for size, potential, and morphology. Cellular uptake efficiency was assessed using confocal microscopy and flow cytometry. The ability of different PnNVs to inhibit oral squamous cell carcinoma cells was evaluated using plate cloning, CCK8 assay, and scratch healing assay. Off-target metabolomics was used to compare metabolic compounds of different PnNVs. Our findings revealed that s_PnNVs exhibited lower potential but had the highest cellular uptake efficiency, whereas m_PnNVs were characterized by the smallest size and lowest cellular uptake efficiency. Notably, m_PnNVs demonstrated the most effective inhibition of squamous cell carcinoma growth and migration. Compositional analyses showed that PnNVs were rich in proteins and contained lower levels of RNA, with l_PnNVs having the highest protein content. Furthermore, untargeted metabolomics analysis revealed a significant increase in the expression of specific antitumour-related metabolites in m_PnNVs compared to s_PnNVs and l_PnNVs. Overall, our results underscore the influence of plant tuber size on the bioactivity of the nanovesicles from which they are derived, emphasizing its importance for experimental design and study reproducibility.

Causal associations among gut microbiota, 1400 plasma metabolites, and asthma: a two-sample Mendelian randomization study.

Emerging evidence indicates a correlation between imbalances in intestinal microbiota and changes in plasma metabolites in the progression of asthma. However, the causal link between these factors remains unclear. A two-sample Mendelian randomization (MR) study was employed to evaluate the potential causal connection between gut microbiota, plasma metabolites, and asthma susceptibility. Gut microbiota data from expansive genome-wide genotype studies and 16S fecal microbiome datasets were examined by the MiBioGen Alliance. Asthma data were procured from the FinnGen biobank analysis, while comprehensive Genome-Wide Association Studies (GWAS) summary statistics for plasma metabolites were derived from the NHGRI-EBI GWAS Catalog. Fluctuations in intestinal flora and plasma metabolites in asthma patients were evaluated using the weighted mode method. Additionally, pleiotropic and heterogeneity analyses were performed to ascertain the reliability of the findings. Upon examining the gut microbiota through MR with the IVW method, alongside tests for heterogeneity and pleiotropy, findings reveal a negative association between the abundance of the Christensenellaceae R.7 group and asthma risk. In contrast, the Bifidobacterium and Prevotella 7 genera exhibit a positive association with asthma risk, indicating they may be potential risk factors (p < 0.05). Furthermore, MR analysis of 1,400 metabolites employing Weighted median, IVW, and Weighted mode methods resulted in p-values below 0.05. Subsequent tests for pleiotropy and heterogeneity showed that the levels of 3,5-dichloro-2,6-dihydroxybenzoic acid have a negative correlation with asthma, whereas the phenylalanine to phosphate ratio has a positive correlation, suggesting their potential as risk factors for asthma (p < 0.05). The current Mendelian randomization study provides evidence supporting a potential causal link between specific gut microbiota taxa, plasma metabolites, and asthma. These findings offer novel perspectives for future research and the development of treatment and prevention strategies for asthma.