PubMed
The Impact of Temperature on the Leaves of <em>Ceratonia siliqua</em> L.: Anatomical Aspect, Secondary Metabolite Analysis, and Antimicrobial Activity of the Extracts
Plants (Basel). 2025 Feb 11;14(4):557. doi: 10.3390/plants14040557.ABSTRACTCeratonia siliqua L. (Fabaceae) is an evergreen sclerophyllous species that successfully overcomes the challenges of the Mediterranean climate. Commonly, biosynthesis of secondary metabolites is a major reaction of the plants thriving in the Mediterranean formations against temperature stress. Due to concerns about the climate crisis, we studied the impact of 6-day low (5 °C) and high (40 °C) temperature stress on young carob seedlings. In stressed plants, mainly the heat-treated, the leaves appear xeromorphic. Parameters of the physiology of the plants such as chlorophyll-a and -b, total phenolic content, and oxidative stress were measured and presented via Principal Component Analysis. Chlorophyll-a and -b contents are inferior in cold-stressed leaves while heat-stressed leaves accumulate more phenolics and experience higher oxidative stress as compared to their cold-stressed counterparts. The phytochemical profile of different extracts obtained from stressed carob leaves was identified so as to gain insight into metabolites produced under stress. Moreover, LC-HRMS/MS metabolomic workflow was utilized for the discovery of biomarkers, over- or under-regulated in stressed conditions. The antimicrobial activity of carob leaf extract fractions was assessed against six human pathogen strains and three phytopathogen bacterial strains. MeOH-H2O and dichloromethane (DCM) extracts presented notable activity against Candida albicans and Saccharomyces cerevisiae, while DCM extracts inhibited the growth of Erwinia amylovora. We may conclude that carob tree exposure to temperature stress does not have a significant influence on secondary metabolic pathways.PMID:40006816 | DOI:10.3390/plants14040557
Proteome and Metabolome Analyses of Albino Bracts in Davidia involucrata
Plants (Basel). 2025 Feb 11;14(4):549. doi: 10.3390/plants14040549.ABSTRACTAlthough the mechanisms underlying albino phenotypes have been examined in model plants and major crops, our knowledge of bract albinism is still in its infancy. Davidia involucrata, a relic plant called dove tree, is best known for the intriguing trait with a pair of white bracts covering the capitula. Here, comparative physiological, cytological, proteomic, and metabolomic analyses were performed to dissect the albinism mechanism of D. involucrata bracts. The bracts exhibited low chlorophyll and carotenoid contents, reduced photosynthetic efficiency, and impaired chloroplast structure. The severe deficiency of photosynthetic pigments and the substantial decrease in cuticle thickness made the bracts light-sensitive. In total, 1134 differentially expressed proteins (DEPs) were obtained between bracts and leaves. Pathway enrichment analysis of DEPs revealed that photosynthetic pigment biosynthesis and photosynthesis were suppressed, whereas protein processing in endoplasmic reticulum, flavonoid biosynthesis, and the ubiquitin-proteasome system (UPS) were activated in bracts. Strikingly, DEPs implicated in chloroplast development, including PPR and AARS proteins, were mainly down-regulated in bracts. We further investigated albinism-induced metabolic changes and detected 412 differentially abundant metabolites (DAMs). Among them, enhanced flavonoids accumulation can plausibly explain the role of bracts in pollinator attraction. Amino acids and their derivatives in bracts showed remarkably increased abundance, which might be causally linked to enhanced UPS function. Our work could lay foundations for understanding albinism mechanisms and adaptive significance of plant bracts and facilitate future utilization of D. involucrata resources.PMID:40006808 | DOI:10.3390/plants14040549
Integrated Analysis of Metabolites and Biological Endpoints Bring New Insights into Sulfamethoxazole Stress Tolerance in Ryegrass
Plants (Basel). 2025 Feb 10;14(4):538. doi: 10.3390/plants14040538.ABSTRACTAlthough metabolomics is widely used to assess the detrimental effects of antibiotics and characterize stress response, the relationships between metabolites and biological endpoints following antibiotics remain unknown. In our study, we exposed ryegrass seeds to sulfamethoxazole for five days. The results showed that sulfamethoxazole inhibited plant growth (by 12.90-85.83%). It also decreased chlorophyll content (by 35.40-93.32%), carotenoid content (by 32.76-90.18%), and root cell permeability (by 98.43-99.29%), but increased root reactive oxygen species (ROS) concentration (increasing rate: 11.32- to 137.36-times). Moreover, high sulfamethoxazole concentrations increased superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities. To elucidate the association between metabolites and biological endpoints, we conducted an orthogonal partial least squares analysis. The results showed that sulfamethoxazole significantly altered six metabolic pathways. Among the metabolites modulated by sulfamethoxazole, amino acids mainly affected root growth and ROS concentration, whereas carbohydrates were substantially associated with the effect of sulfamethoxazole on cell permeability. Many metabolites had contrasting effects. For example, some metabolites increased root fresh weight and improved cell permeability by decreasing ROS levels and SOD, POD, and CAT activities. By contrast, some metabolites negatively affected root fresh weight and cell permeability by increasing ROS levels and SOD, POD, and CAT activities. These observations bring new insights into ryegrass responses to sulfamethoxazole-induced stress.PMID:40006797 | DOI:10.3390/plants14040538
Metabolite Profiling of the Resurrection Grass <em>Eragrostis nindensis</em> During Desiccation and Recovery
Plants (Basel). 2025 Feb 9;14(4):531. doi: 10.3390/plants14040531.ABSTRACTResurrection plants employ unique metabolic mechanisms to protect themselves against damage caused by desiccation. This study aimed to identify metabolites, using gas chromatography-mass spectrometry, which were differentially abundant in Eragrostis nindensis at different stages of dehydration and rehydration in leaves which are destined to senesce on desiccation termed "senescent tissue" (ST) and those which remain desiccation-tolerant during water deficit and are termed "non-senescent tissue" (NST). Furthermore, the study compared the shoot and root systems during extreme water deficit and recovery therefrom to unravel similarities and differences at the whole plant level in overcoming desiccation. Shoot metabolomics data showed differentially abundant metabolites in NST, including raffinose, sucrose, glutamic acid, aspartic acid, proline, alpha-ketoglutaric acid, and allantoin, which act as major drivers for plant desiccation tolerance and aid the plant post-rehydration. The metabolites which accumulated in the ST-indicated initiation of programmed cell death (PCD) leading to senescence. The roots accumulated fewer metabolites than the shoots, some exclusive to the root tissues with functions such as osmoprotection, reactive oxygen species quenching, and signaling, and thus proposed to minimize damage in leaf tissues during dehydration and desiccation. Collectively, this work gives further insight into the whole plant responses of E. nindensis to extreme dehydration conditions and could serve as a model for future improvements of drought sensitive crops.PMID:40006790 | DOI:10.3390/plants14040531
STEAP3 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by Regulating Fatty Acid and Lipid Droplet Synthesis
Vet Sci. 2025 Feb 8;12(2):147. doi: 10.3390/vetsci12020147.ABSTRACTPorcine Reproductive and Respiratory Syndrome (PRRS) is a contagious disease that impacts swine health worldwide. Lipid metabolism plays a vital role in energy production and is regulated by various genes involved in lipogenesis and lipolysis. In this study, we found that PRRSV infection significantly reduced the protein expression of STEAP3. The overexpression of STEAP3 can notably inhibit PRRSV replication. Additionally, we utilized transcriptomics and metabolomics to examine the effects of STEAP3 on PRRSV replication, identifying important pathways associated with energy metabolism and lipogenesis. We subsequently found that STEAP3 can suppress PRRSV replication by regulating fatty acid synthesis and enhancing lipid droplet formation. Overall, these findings indicate that STEAP3 could be a potential target for developing strategies to manage PRRSV infection by modulating lipid metabolism.PMID:40005907 | DOI:10.3390/vetsci12020147
Feline Calicivirus Infection Manipulates Central Carbon Metabolism
Vet Sci. 2025 Feb 7;12(2):138. doi: 10.3390/vetsci12020138.ABSTRACTViruses can manipulate the host metabolism to achieve optimal replication conditions, and central carbon metabolism (CCM) pathways are often crucial in determining viral infections. Feline calicivirus (FCV), a diminutive RNA viral agent, induces upper respiratory tract infections in feline hosts, with highly pathogenic strains capable of precipitating systemic infections and subsequent host cell necrosis, thereby presenting a formidable challenge to feline survival and protection. However, the relationship between FCV and host cell central carbon metabolism (CCM) remains unclear, and the precise pathogenic mechanisms of FCV are yet to be elucidated. Upon FCV infection of Crandell-Rees Feline Kidney (CRFK) cells, an enhanced cellular uptake of glucose and glutamine was observed. Metabolomics analyses disclosed pronounced alterations in the central carbon metabolism of the infected cells. FCV infection was found to augment glycolytic activity while sustaining the tricarboxylic acid (TCA) cycle flux, with cellular ATP levels remaining invariant. Concurrently, both glutamine metabolism and the flux of the pentose phosphate pathway (PPP) were noted to be intensified. The application of various inhibitory agents targeting glycolysis, glutamine metabolism, and the PPP resulted in a significant suppression of FCV proliferation. Experiments involving glucose and glutamine deprivation demonstrated that the absence of either nutrient markedly curtailed FCV replication. Collectively, these findings suggest a critical interplay between central carbon metabolism and FCV proliferation. FCV infection stimulates CRFK cells to augment glucose and glutamine uptake, thereby supplying the necessary metabolic substrates and energy for viral replication. During the infection, glutamine emerges as the primary energy substrate, ensuring ATP production and energy homeostasis, while glucose is predominantly channeled into the pentose phosphate pathway to facilitate nucleotide synthesis.PMID:40005898 | DOI:10.3390/vetsci12020138
Differential Analysis of Fecal SCFAs and Their Contribution to Adipogenesis in UCP1 Knock-In Pigs
Vet Sci. 2025 Feb 1;12(2):102. doi: 10.3390/vetsci12020102.ABSTRACTThis study aimed to investigate the changes in fecal short-chain fatty acids (SCFAs) content in UCP1 knock-in pigs (KI pigs) and their effect on adipogenesis. Fecal samples from five 6-month-old wild-type (WT) and KI pigs were collected for targeted metabolomics and 16s rRNA sequencing analyses to identify differences in SCFAs and gut microbiota that may contribute to regulating fat deposition in pigs. The metabolome of pig fecal samples targeted for an analysis of SCFAs identified seven SCFAs, with caproic acid (except isovaleric acid) being the significantly different one. The results of the fecal 16s rRNA analysis demonstrated a notable reduction in the abundance of Streptococcus spp. in the KI pigs in comparison to the WT pigs, with a statistically significant difference. Correlation analyses demonstrated a statistically significant positive correlation between the abundance of Streptococcus spp. and SCFAs, as well as pig body weight and fatness. It was postulated that the reduction in SCFAs in the intestinal tracts of KI pigs may be associated with a reduction in Streptococcus spp. abundance. Compared to WT pigs, the concentration of fecal SCFAs in KI pigs was significantly reduced, which may be related to the decreased abundance of Streptococcus. The in vitro experiments showed that caproic acid could significantly enhance the differentiation efficiency of porcine SVF cells into mature adipocytes by activating the FFAR4 gene.PMID:40005862 | DOI:10.3390/vetsci12020102
Impact of Calcium Propionate Supplementation on the Lactation Curve and Milk Metabolomic Analysis on Rambouillet Ewes
Vet Sci. 2025 Jan 22;12(2):79. doi: 10.3390/vetsci12020079.ABSTRACTIn lactating ewes, energy demand increases for milk production, reserve mobilizations, and body weight maintenance. For reconversion to energy, ruminants require ruminal propionate production because it is the most predominant substrate for gluconeogenesis and one of the most relevant pathways since it allows an adequate supply of glucose. Calcium propionate supplementation is an alternative to increase glucose production by an external additive. Thus, the objective was to evaluate the effect of calcium propionate (CaPr) on milk production and milk metabolomic profile on lactating ewes. Sixteen Rambouillet (65.3 ± 6.2 kg BW; three years old) were randomly assigned one of two experimental treatments: (a) basal diet without supplementation (CP/0S) and (b) basal diet + 30 g d-1 of CaPr (CP/30S). The experimental period was from parturition day until day 60 (baby lamb weaning). A completely randomized design was used and analyzed with a mixed model. Initial and final lactating weight and milk production differed statistically (p < 0.05) between treatments. CP/30S led to differential changes (p < 0.05) in the lactation curve, showing significant milk production over eight-week measurements. Lactation peak (mL), maximum production (mL), and lactational persistency (d) were superior (p < 0.05) for supplemented ewes. An 11.4% variability was shown in a principal component analysis between treatments. For CP/0S, 63 bioactive compounds were detected, and 55 for CP/30S treatment. The metabolites detected in CP/0S showed that only fatty acid biosynthesis, biosynthesis of unsaturated fatty acids, and fatty acid elongation pathways were affected (p < 0.05) in milk. However, for CP/30S, metabolic pathways related (p < 0.05) were fatty acid biosynthesis, biosynthesis of unsaturated fatty acids, fatty acid elongation, phenylalanine metabolism, and steroid metabolism in milk samples. Calcium propionate supplementation increases milk performance and lactation persistency-induced changes in specific metabolic milk production pathways.PMID:40005839 | DOI:10.3390/vetsci12020079
Vertical Stratification Reduces Microbial Network Complexity and Disrupts Nitrogen Balance in Seasonally Frozen Ground at Qinghai Lake in Tibet
Microorganisms. 2025 Feb 19;13(2):459. doi: 10.3390/microorganisms13020459.ABSTRACTGlobal climate change has accelerated the reduction of permafrost regions across different altitude gradients, shortening the duration of the freezing period to varying extents. However, the response of the soil microorganisms of frozen soils along altitude gradients remains unclear. In this study, we employed 16S rRNA sequencing and LC-MS metabolomics to investigate the response of soil microbial communities and soil metabolites to vertical stratification in the permafrost soils of the Qinghai Lake region. The results indicated that Proteobacteria, Firmicutes, and Actinobacteria were key soil bacterial phyla in the permafrost soils of Qinghai Lake during the freezing period, with Proteobacteria and Firmicutes showing significant sensitivity to vertical stratification (p < 0.05). The majority of the physicochemical factors exhibited a trend of initially increasing and then decreasing with increasing altitude, whereas pH showed the opposite trend. pH and moisture content were identified as the most important environmental factors influencing soil bacterial community structure. Deterministic processes dominated the assembly of bacterial communities of frozen soils in the Qinghai Lake basin. Co-occurrence network analysis showed that increasing altitude gradients led to a higher average degree of the bacterial network, while reducing network complexity and inter-species connectivity. Soil metabolomics analysis revealed that vertical stratification altered the metabolic profiles of 27 metabolites, with the significantly changed metabolites primarily associated with carbohydrate and amino acid metabolism. In conclusion, the characteristics of the Qinghai Lake permafrost were regulated by regional vertical stratification, which further influenced microbial community structure and soil metabolic characteristics, thereby altering carbon and nitrogen stocks. Specifically, higher altitudes were more favorable for the retention of the carbon and nitrogen stocks of frozen soils in the Qinghai Lake basin.PMID:40005823 | DOI:10.3390/microorganisms13020459
Metagenomic and Metabolomic Analyses Reveal the Role of a Bacteriocin-Producing Strain of Enterococcus faecalis DH9003 in Regulating Gut Microbiota in Mice
Microorganisms. 2025 Feb 8;13(2):372. doi: 10.3390/microorganisms13020372.ABSTRACTTo investigate the regulatory effect of a bacteriocin-producing strain of Enterococcus faecalis DH9003 on the gut microbiota of mice, 15 healthy C57 male mice were randomly administered an equal volume of sterile normal saline (HD, control group, n = 7) and E. faecalis DH9003 (YD, treatment group, n = 8) via gavage. Metagenomic and metabolomic analyses were performed to determine the composition and metabolic function of the intestinal microbiota in mice. The results showed that the relative abundance of Firmicutes continuously increased over time in YD compared to HD. The number of E. faecalis DH9003 increased slowly and remained steady from days 7 to 28, indicating that E. faecalis DH9003 could colonize a considerable number of mouse guts via intragastric administration. Supplementation with E. faecalis DH9003 demonstrated a regulatory effect on the intestinal microbiota composition of mice, causing a shift in the relative abundance of Bacteroidetes and Firmicutes at the phylum level. In addition, a total of 2426 different metabolites were found in mouse feces, including 1286 and 1140 metabolites in positive and negative modes, respectively. Vitamin B6 and succinate were the most regulated and downregulated metabolites in negative ion mode, and the most upregulated and downregulated metabolites in positive ion mode were N-methyl-glutamic acid and N-octanoyl sphingosine. In conclusion, E. faecalis DH9003 can colonize mice gut, affecting the gut microbiota and metabolic competence. This strain therefore offers considerable potential for application as a probiotic.PMID:40005739 | DOI:10.3390/microorganisms13020372
Mixotrophy in Marine Microalgae to Enhance Their Bioactivity
Microorganisms. 2025 Feb 5;13(2):338. doi: 10.3390/microorganisms13020338.ABSTRACTPhotosynthetic microorganisms, such as microalgae, are remarkable for their ability to harness sunlight, fix carbon dioxide, and produce a variety of bioactive compounds. These organisms are pivotal in climate mitigation strategies as they can absorb carbon dioxide while generating valuable biomolecules. Among the diverse cultivation approaches, mixotrophic growth combines light energy with both inorganic and organic carbon sources, offering a unique strategy to enhance biomass production and metabolic diversity in microalgae. Here, microalgal species such as Nannochloropsis granulata, Phaeodactylum tricornutum, and Chlorella sp. were investigated for their potential applications under different cultivation methods, including phototrophy and mixotrophy. Mixotrophic conditions significantly improved biomass production across all tested species. Among these, Phaeodactylum tricornutum, a marine diatom, emerged as a promising candidate for bioactive compound production, exhibiting higher antiproliferative activity against human melanoma cells and antibacterial effects against Staphylococcus aureus. Importantly, Chlorella sp. was also found to possess antibacterial activity against Staphylococcus aureus, broadening its potential applications. Additionally, metabolomics analysis was performed on Chlorella sp. and Phaeodactylum tricornutum to identify the compounds responsible for the observed bioactivity. This study highlights the value of mixotrophic cultivation in enhancing the productivity and bioactivity of microalgae, positioning them as versatile organisms for sustainable biotechnological applications.PMID:40005705 | DOI:10.3390/microorganisms13020338
Exploring Competitive Relationship Between Haemophilus parainfluenzae and Mitis Streptococci via Co-Culture-Based Molecular Diagnosis and Metabolomic Assay
Microorganisms. 2025 Jan 26;13(2):279. doi: 10.3390/microorganisms13020279.ABSTRACTVarious bacterial strains with nitrate-reducing capacity (NRC), such as Haemophilus, Actinomyces, and Neisseria, are known to promote NH3 production, control pH in the oral cavity, and inhibit the growth of aciduric bacteria. However, experimental evidence on various estimated bacterial networks within the salivary microbiome is insufficient. This study aims to explore potential bacterial compositional competition observed within saliva samples from dental caries patients through a co-culture assay of mitis Streptococci, which is a primary colonizer in the salivary microbiome, and nitrate-reducing bacteria Haemophilus parainfluenzae. We investigated bacterial growth efficiency change by co-culture time using the qRT-PCR method. In addition, we applied LC/Q-TOF-based metabolites screening to confirm metabolic interactions between oral bacterial species and their association with dental caries from a metabolomics perspective. As a result, we first found that the nitrate reduction ability of H. parainfluenzae is maintained even in a co-culture environment with the mitis Streptococci group through a nitrate reduction test. However, nitrate reduction efficiency was hindered when compared with monoculture-based nitrate reduction test results. Next, we designed species-specific primers, and we confirmed by qRT-PCR that there is an obvious competitive relationship in growth efficiency between H. parainfluenzae and two mitis Streptococci (S. australis and S. sanguinis). Furthermore, although direct effects of nitrate reduction on competition have not been identified, we have potentially confirmed through LC/Q-TOF-based metabolite screening analysis that the interaction of various metabolic compounds synthesized from mitis Streptococci is driving inter-strain competition. In particular, we constructed a basic reference core-metabolites list to understand the metabolic network between each target bacterial species (H. parainfluenzae and mitis Streptococci) within the salivary microbiome, which still lacks accumulated research data. Ultimately, we suggest that our data have potential value to be referenced in further metagenomics and metabolomics-based studies related to oral health care.PMID:40005646 | DOI:10.3390/microorganisms13020279
Combined Analysis of Transcriptomes and Metabolomes Reveals Key Genes and Substances That Affect the Formation of a Multi-Species Biofilm by Nine Gut Bacteria
Microorganisms. 2025 Jan 22;13(2):234. doi: 10.3390/microorganisms13020234.ABSTRACTBiofilms are one of the ways microorganisms exist in natural environments. In recent years, research has gradually shifted its focus to exploring the complexity and interactions of multi-species biofilms. A study showed that nine gut bacteria can form a multi-species biofilm on wheat fibers (M9 biofilm). However, the previous study did not clarify the reasons why M9 exhibited a better biofilm formation ability than the mono-species biofilms. In this study, the gene expression levels and metabolic accumulation of the M9 multi-species biofilm and biofilms of each individual bacterium were analyzed using transcriptomes and metabolomes. The differentially expressed genes (DEGs) showed that there were 740 common DEGs that existed in all of the nine groups, and they could regulate five pathways related to bacterial motility, cellular communication, and signal transduction. The metabolome results revealed that many peptides/amino acids and derivatives were produced in the M9 biofilm. Furthermore, purine metabolism was significantly enhanced in the M9 biofilm. L-arginine, l-serine, guanosine, and hypoxanthine were the common differentially accumulated metabolites (DAMs). The combined analysis of the transcriptomes and metabolomes showed that there were 26 common DEGs highly correlated with the four common DAMs, and they were involved in five metabolic pathways related to amino acids and purines. These results indicate that M9 can regulate multi-species biofilm formation by modulating genes related to bacterial motility, cellular communication, signal transduction, and the metabolism of amino acids and purines. This study provides insights into the interactions of microbial biofilms.PMID:40005603 | DOI:10.3390/microorganisms13020234
Understanding Host-Pathogen Interactions in Congenital Chagas Disease Through Transcriptomic Approaches
Pathogens. 2025 Jan 22;14(2):106. doi: 10.3390/pathogens14020106.ABSTRACTChagas disease, caused by Trypanosoma cruzi, is a parasitic zoonosis with significant health impacts, particularly in Latin America. While traditionally associated with vector-borne transmission, increased migration has expanded its reach into urban and non-endemic regions. Congenital transmission has become a critical route of infection, involving intricate maternal-fetal immune interactions that challenge diagnosis and treatment. This review synthesizes findings from three RNA-seq studies that explore the molecular underpinnings of congenital Chagas disease, emphasizing differentially expressed genes (DEGs) implicated in host-pathogen interactions. The DAVID tool analysis highlighted the overexpression of genes associated with the innate immune response, including pro-inflammatory cytokines that drive chemotaxis and neutrophil activation. Additionally, calcium-dependent pathways critical for parasite invasion were modulated. T. cruzi exploits the maternal-fetal immune axis to establish a tolerogenic environment conducive to congenital transmission. Alterations in placental angiogenesis, cellular regeneration, and metabolic processes further demonstrate the parasite's ability to manipulate host responses for its survival and persistence. These findings underscore the complex interplay between the host and pathogen that facilitates disease progression. Future research integrating transcriptomic, proteomic, and metabolomic approaches is essential to unravel the molecular mechanisms underlying congenital Chagas disease, with a particular focus on the contributions of genetic diversity and non-coding RNAs in immune evasion and disease pathogenesis.PMID:40005483 | DOI:10.3390/pathogens14020106
Non-Invasive Biomarkers for Early Diagnosis of Kidney Allograft Dysfunction: Current and Future Applications in the Era of Precision Medicine
Medicina (Kaunas). 2025 Feb 4;61(2):262. doi: 10.3390/medicina61020262.ABSTRACTKidney transplantation stands as the preferred treatment for end-stage kidney disease, significantly improving both the quality and longevity of life compared to dialysis. In recent years, the survival rates for patients and grafts have markedly increased thanks to innovative strategies in desensitization protocols for incompatible transplants and advancements in immunosuppressive therapies. For kidney transplant recipients, preventing allograft rejection is of paramount importance, necessitating the use of immunosuppressive medications. Regular follow-up appointments are essential, as monitoring the function of the kidney allograft is critical. Currently, established biomarkers such as serum creatinine, estimated Glomerular Filtration Rate (eGFR), proteinuria, and albuminuria are commonly employed to assess allograft function. However, these biomarkers have limitations, as elevated levels often indicate significant allograft damage only after it has occurred, thereby constraining treatment options and the potential for restoring graft function. Additionally, kidney biopsies, while considered the gold standard for diagnosing rejection, are invasive and carry associated risks. Consequently, the identification and development of new, sensitive, and specific biomarkers like dd-cfDNA, microRNAs (e.g., miR-21, miR-155), and sCD30 for allograft rejection are crucial. To tackle this challenge, intensive ongoing research employing cutting-edge technologies, including "omics" approaches, like genomic techniques, proteomics, or metabolomics, is uncovering a variety of promising new biomarkers.PMID:40005378 | DOI:10.3390/medicina61020262
Cytochalasins from the Ash Endophytic Fungus <em>Nemania diffusa</em> DSM 116299
Molecules. 2025 Feb 19;30(4):957. doi: 10.3390/molecules30040957.ABSTRACTThe secondary metabolome of Nemania diffusa, isolated as an ash endophytic fungus, was analyzed in detail. From its cultures, a previously undescribed cytochalasin 1 was isolated using preparative HPLC, together with six known congeners: 18-dehydroxy-cytochalasin E (2), cytochalasins Z7 (3), Z8 (4), and E (5), 18-dehydroxy-17-didehydro-cytochalasin E (6), and K Steyn (7). The structures of these compounds were determined using data from high-resolution mass spectrometry (HR-MS), in combination with 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Metabolites 1-4 share a characteristic 12-membered lactone moiety, placing them within a rarely examined cytochalasin subclass. Thus, the compounds were incorporated into our ongoing screening campaign to study the structure-activity relationship of this metabolite family. We initially determined their cytotoxicity in eukaryotic mouse fibroblast L929 cells using an MTT-based colorimetric assay, and further investigated their effect on the cellular actin dynamics of the human osteosarcoma cell line U-2OS in detail. Unexpectedly, we discovered a high number of irreversible compounds (1, 2, and 4). Additionally, we highlighted specific structural features within the 12-membered cytochalasin subclass that may play a role in directing the reversibility of these compounds.PMID:40005267 | DOI:10.3390/molecules30040957
Dynamic Environmental Interactions Shape the Volatile Compounds of Agarwood Oils Extracted from <em>Aquilaria sinensis</em> Using Supercritical Carbon Dioxide
Molecules. 2025 Feb 18;30(4):945. doi: 10.3390/molecules30040945.ABSTRACTAquilaria spp. are a highly valuable plant species found in the Chinese herbal medicine and agarwood fragrance supplement industries for fumigation, combustion and perfume. The phytochemical composition of agarwood oils (extracts) was derived from Aquilaria sinensis and its subspecies 'Qi-Nan' using supercritical CO2 extraction technology. Gas chromatography connected with a mass spectrometry apparatus was employed for qualitative and quantitative analyses. Comparing the agarwood oils from six planting areas, 12 common components were obtained, among which sesquiterpenes and chromones had the highest relative content. Genetic and environmental factors had the greatest impact on the three chromones, especially on 2-phenyl-4H-chromen-4-one. According to the PCA and PLS-DA models, the 'Qi-Nan' was derived from a variety selected from the native A. sinensis, and the difference in the volatile components was able to indirectly prove that it was genetically heterogeneous with the native A. sinensis. Using the 73 components obtained from GC-MS analysis, the VIP values and S-plots were generated using the OPLS-DA model. Seven components with VIP values > 1.0 were selected from two groups of agarwood oils of the native A. sinensis and 'Qi-Nan' subspecies. In addition, by analyzing 12 common components, the differential components with VIP values > 1 were 2-phenyl-4H-chromen-4-one and 2-(4-methoxyphenethyl)-4H-chromen-4-one. Chromones were the main component of agarwood oils extracted by supercritical CO2, and 2-phenyl-4H-chromen-4-one could be used as a volatile marker, especially in the 'Qi-Nan' subspecies, where this marker exhibited more prominent characteristics.PMID:40005255 | DOI:10.3390/molecules30040945
What Happens Inside the Germinating Grain After Microbial Decontamination by Pulsed Electric Field? Data-Driven Multi-Omics Helps Find the Answer
Molecules. 2025 Feb 17;30(4):924. doi: 10.3390/molecules30040924.ABSTRACTPulsed electric field (PEF) has previously been recognized as a method of gentle food processing, and its use has been shown to be helpful in reducing the levels of toxigenic Fusarium micromycetes developed during malting. The aim of this study was to describe the effects of PEF on gene expression and metabolite production at the pre-finishing stage of barley malting by using a novel multi-omics data-driven approach. The study helps to uncover the processes occurring in the germinated grain and discusses the up-/downregulation of genes and metabolites in relation to fungal infection and/or PEF-induced abiotic stress. Among the factors upregulated by PEF and previously described as supportive against Fusarium diseases, we identified the increased expression of genes encoding vegetative gp1-like protein, which positively correlated with flavonoids, (methylsulfanyl)prop-2-enoates, triterpenoid glycosides, and indole alkaloids. On the other hand, some genes associated with barley resistance to fungal infection were also overexpressed in the untreated control (in particular, genes encoding ethylene response factor 3-like, putrescine hydroxycinnamoyltransferase 3-like, and dirigent protein 21-like). This study provides the first 'data-driven' basic research results that contribute to the understanding of the role of PEF as an effective fungal decontamination strategy and allows the formulation of new hypotheses related to Fusarium pathogen crosstalk.PMID:40005235 | DOI:10.3390/molecules30040924
Comparison of the Immune Enhancing Activity and Chemical Constituents Between Imitation Wild and Cultivated Astragali Radix
Molecules. 2025 Feb 17;30(4):923. doi: 10.3390/molecules30040923.ABSTRACTAstragali Radix (AR), a traditional food and medicinal herb used for thousands of years, is widely recognized for its role in enhancing immunity, particularly when combined with adjuvant chemotherapy. The two primary types of AR available in the market are imitation wild AR (grown for seven years) and cultivated AR (grown for two years). However, whether differences exist in their immune-enhancing effects and chemical constituents remains unclear. In this study, a comparative analysis was performed to evaluate the immune activity and chemical composition of cultivated and imitation wild AR. Immune activity was assessed through in vivo animal studies, while metabolomic analysis was used to characterize their chemical profiles. The results demonstrate that AR possesses significant antitumor and immune-enhancing activities, with imitation wild AR showing superior efficacy compared with cultivated AR. Following 16 days of daily AR treatment, both the thymus and spleen coefficients were significantly increased, effectively reversing the immune dysfunction induced by cyclophosphamide (CTX). Moreover, the administration of AR showed no significant toxicity, as evidenced by the stable liver and kidney function indicators, including ALT, UREA, and CRE levels. To investigate chemical differences, a customized chemotaxonomic-based in-house library containing 215 compounds was developed and integrated with the Progenesis QI informatics platform for metabolite annotation. Using multivariate analysis, 48 constituents were identified in total: 46 unique to the imitation wild AR and 45 specific to the cultivated AR. The correlation between chemical constituents and the pharmacological effects of AR was evaluated. Based on orthogonal partial least-squares discriminant analysis (OPLS-DA) and S-plot analysis, five potential biomarkers were identified, including Calycosin-7-glucoside, Rhamnocitrin-3-O-β-D-glucopyranoside, Ononin, 3,5-Dicaffeoylquinic acid, and Acetylastragaloside I. These biomarkers likely account for the differences in immune-enhancing effects between the two AR types. This study provides a scientific foundation for the rational use of Astragali Radix.PMID:40005233 | DOI:10.3390/molecules30040923
Untargeted Lipidomic Reveals Potential Biomarkers in Plasma Samples for the Discrimination of Patients Affected by Parkinson's Disease
Molecules. 2025 Feb 12;30(4):850. doi: 10.3390/molecules30040850.ABSTRACTNowadays, the diagnosis of Parkinson's disease (PD) remains essentially clinical, based on the subjective observations of clinicians. In addition, misdiagnosis with other neuro disorders, such as Alzheimer's (AD), can occur. Herein, an untargeted lipidomic analysis of 75 plasma samples was performed to identify lipid species capable of discriminating between these two neuro groups. Therefore, PLS-DA and OPLS-DA analysis revealed significant differences in patient profiles in the sphingolipid and glycerophospholipid categories. As a result, a putative lipid biomarker panel was developed, which included HexCer (40:1; O2) and PC (O-32:0), with an area under the receiver operating characteristic curve (AUC) > 80, respectively. This panel was effective in discriminating between diseased and healthy subjects, but most importantly, it could discriminate between two neurodegenerative disorders that can present similar symptoms, namely PD and AD. Together, these findings suggest that the dysregulated metabolism of lipids plays a critical role in AD and PD pathology and may represent a valuable clinical tool for their diagnosis. Thus, further targeted studies are encouraged to better understand the underlying mechanisms of PD and confirm the diagnostic potency of the identified lipid metabolites.PMID:40005161 | DOI:10.3390/molecules30040850