PubMed

Life (Basel). 2024 Dec 31;15(1):43. doi: 10.3390/life15010043.ABSTRACTZooplanktonic copepods represent a major biological mass in the marine food chain that can be affected by climate change. Monitoring the health of this critical biomass is essential for increasing our understanding of the impact of environmental changes on marine environments. Since the lipidomes of marine organisms are known to adapt to alterations in pH, temperature, and availability of metabolic precursors, lipidomics is one technology that can be used for monitoring copepod adaptations. Among the key lipid parameters that can be monitored are the fatty acid substituents of glycerolipids and glycerophospholipids. We utilized high-resolution tandem mass spectrometry (≤2 ppm mass error) to characterize the fatty acid substituents of triacylglycerols, glycerophosphocholines, ceramides, and sphingomyelins of Labidocerca aestiva. This included monitoring for furan fatty acid substituents, a family of fatty acids unique to marine organisms. These data will contribute to establishing a lipid database of the fatty acid substituents of essential structural lipids. The key findings were that polyunsaturated fatty acids (PUFAs) were only major substituents in glycerophosphocholines with 36 to 44 carbons. Triacylglycerols, ceramides, and sphingomyelins contained minimal PUFA substituents. Furan fatty acids were limited to mono- and di-acylglycerols. In summary, we have built a baseline database of the fatty acid substituents of key structural lipids in Labidocerca aestiva. With this database, we will next evaluate potential seasonal changes in these lipid substituents and long-term effects of climate change.PMID:39859983 | DOI:10.3390/life15010043

Life (Basel). 2024 Dec 24;15(1):6. doi: 10.3390/life15010006.ABSTRACTMancozeb (MZ), an EBDC fungicide, has been found to contaminate agricultural products and cause male reproductive toxicity. The phytochemical compounds of white N. nucifera petal extract (WNPE) and its effects on metabolomic profiles and reproductive function in male rats poisoned with MZ were investigated. Seventy-two mature male Wistar rats were divided into nine groups (n = 8) and, for 30 days, were gavaged with WNPE at doses of 0.55, 1.10, and 2.20 mg/kg; were given distilled water; or were co-gavaged with MZ and WNPE. By evaluating the 1H-NMR of WNPE, myricetin, apigenin, luteolin, ferulic acid, caffeic acid, ascorbic acid, genistein, chlorogenic acid, naringenin, and ellagic acid were found, and the essential minerals were evaluated by AAS. The NMR spectra demonstrated that creatine, carnitine, ACh, and choline in WNPE were significantly higher than that in MZ. The gavaging of the rats with WNPE before poisoning them with MZ improved creatine, carnitine, acetylcholine, progressive sperm motility, sperm viability, and normal sperm morphology compared to rats who only received MZ. It was concluded that MZ had a toxicity effect on the male reproductive system via decreased metabolomic profiles, affecting sperm motility, sperm viability, and normal sperm morphology. Nevertheless, WNPE had plenty of bioactive compounds that could enhance creatine, carnitine, and acetylcholine, which are related to sperm quality in male rats. WNPE should be considered as an alternative dietary supplement that can protect against MZ toxicity and enhance sperm quality in the male rat reproductive system.PMID:39859946 | DOI:10.3390/life15010006

Insects. 2025 Jan 2;16(1):37. doi: 10.3390/insects16010037.ABSTRACTThermal condition affects the development and growth of ectotherms. The stenothermic honeybee brood, particularly the prepupae, are sensitive to low rearing temperature. The fat body plays important roles in energy reserve and metabolism during the honeybee brood development. To date, the fat body metabolic changes in prepupae responding to cold stress have not been completely understood. In this study, the ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS)-based non-target metabolome was analyzed between the cold-treated (CT, 20 °C, 36 h) and control (CK, 35 °C) fat body in prepupal honeybees. The fat body metabolomic data showed that the levels of 1860 and 254 metabolites were significantly increased and decreased, respectively, in cold-stressed prepupae. These altered metabolites, glutamine, glutamic acid, pyroglutamic acid, and oxidized glutathione, were significantly enriched into glutamine metabolism and glutathione metabolism pathways. Furthermore, the expression levels of glutamine metabolism-related genes, glutaminase (GLS), glutamate dehydrogenase (GDH), and gamma-glutamyl transferase (GGT-1 and GGT-7), were significantly decreased in cold-exposed prepupae compared with the control groups. Meanwhile, the oxidized glutathione (GSSG), but not the reduced glutathione (GSH) content, was increased in the cold-exposed group compared with controls. Collectively, our data revealed the fat body metabolomic changes in larva-to-pupa transition when exposed to cold stress. Our data provided new insights into stenothermic honeybee sensitivity to cold, characterized by perturbation of glutamine metabolism and oxidative stress.PMID:39859618 | DOI:10.3390/insects16010037

Int J Mol Sci. 2025 Jan 16;26(2):742. doi: 10.3390/ijms26020742.ABSTRACTBee venom (BV) and its main compound melittin (MLT) have antioxidant, anti-inflammatory, and anti-aging activities; however, very little research has been conducted on their effects on skin aging. In this study, a mouse skin aging model induced by D-galactose was constructed via subcutaneous injection into the scruff of the neck, and different doses of BV and MLT were used as interventions. The anti-aging effects and mechanisms of BV and MLT were explored by detecting the skin morphology and structure, and anti-aging-related factors and performing non-targeted metabolomics of mice. BV and MLT improved dermal and epidermal thickness, boosted the collagen fiber content, increased hydroxyproline and hyaluronic acid levels, and enhanced transcript-level expression of IL-10, Col1a1, and Col3a1, while decreasing that of IL-1β. Metabolomic analysis showed that BV and MLT regulated the levels of some metabolites (compared to those in the skin aging control). BV effectively alleviated skin aging by regulating the pentose phosphate pathway, and pathways associated with carbon, galactose, and β-alanine metabolism, whereas MLT regulated pathways related to lipid metabolism, cholesterol metabolism, and atherosclerosis. This study highlights the potential applicability of BV and MLT in skin aging treatments and cosmetic products.PMID:39859456 | DOI:10.3390/ijms26020742

Int J Mol Sci. 2025 Jan 15;26(2):702. doi: 10.3390/ijms26020702.ABSTRACTA compound fruit drink (CFD) is a functional beverage containing fruits, Chinese herbal medicine, and prebiotic fructose. Previous studies have shown the effect of a CFD on alleviating constipation and its impact on gut microbiota. However, a comprehensive analysis has not been reported in regard to the serum metabolism of CFDs. This study established a mouse constipation model, using loperamide hydrochloride. Herein, based on UHPLC-QTOF/MS analysis, 93 differential metabolites (mainly including phosphoglycerides and amino acid derivatives) among the groups of mice were identified. After CFD treatment, the content of phosphatidylethanolamine, amino acid derivatives (including N-Acetyl-L-aspartate, L-Norleucine, and cis-4-Hydroxy-D-proline), and fumarate increased, while that of esters decreased. Pathway enrichment analysis revealed that the CFD mitigated constipation by modulating nine metabolic pathways, which encompass glycerophospholipid metabolism, the tricarboxylic acid (TCA) cycle, pyruvate metabolism, and tyrosine metabolism. Notably, the glycerophospholipid metabolic pathway was identified as the most pertinent. Collectively, the results provide new ideas for developing functional foods that nourish the intestines and relieve constipation.PMID:39859416 | DOI:10.3390/ijms26020702

Int J Mol Sci. 2025 Jan 15;26(2):701. doi: 10.3390/ijms26020701.ABSTRACTUsing male sterile (MS) lines instead of normal inbred maternal lines in hybrid seed production can increase the yield and quality with lower production costs. Therefore, developing a new MS germplasm is essential for maize hybrid seed production in the future. Here, we reported a male sterility gene ms*-N125, cloned from a newly found MS mutant ms*-N125. This mutant has an underdeveloped tassel that showed impaired glumes and shriveled anthers without pollen grains. The MS locus of ms*-N125 was mapped precisely to a 112-kb-interval on the chromosome 5. This interval contains only three candidate genes, Zm958, Zm959, and Zm960. Sequencing results showed that only candidate Zm960 harbored a 548-bp transposable element (TE) in its 9th exon, and the two other candidate genes were found to have no genetic variations between the mutant and wild type (WT). Thus, Zm960 is the only candidate gene for male sterility of the mutant ms*-N125. In addition, we screened another recessive MS mutant, ms*-P884, which exhibited similar male sterility phenotypes to ms*-N125. Sequencing Zm960 in ms*-P884 showed a 600-bp TE located in its 2nd exon. Zm960 encodes an ATP-binding cassette in the G subfamily of ABC (ABCG) transporters, ZmABCG2a, with both mutants which harbored an Ac/Ds-like transposon in each. To verify the function of ZmABCG2a for male sterility further, we found an ethyl methanesulfonate (EMS) mutant, zmabcg2a*, which displayed male sterility and tassel phenotypes highly similar to ms*-N125 and ms*-P884, confirming that ZmABCG2a must be the gene for male sterility in maize. In addition, the results of lipid metabolome analysis of ms*-N125 young tassels showed that the total lipid content of the mutant was significantly lower than that of the WT, with 15 subclasses of lipids, including PE (phosphatidylethanolamine), PC (phosphatidylcholine), DG (digalactosyldiacylglycerols), and MGDG (monogalactosyldiacylglycerol) which were significantly down-regulated in the ms*-N125 mutant versus its wild type. In summary, we identified alternate mutations of the ZmABCG2a gene, which may be a potential germplasm for hybrid seed production in maize.PMID:39859415 | DOI:10.3390/ijms26020701

Int J Mol Sci. 2025 Jan 14;26(2):668. doi: 10.3390/ijms26020668.ABSTRACTPhlomoides rotata, a traditional medicinal plant, is commonly found on the Tibetan Plateau at altitudes of 3100-5200 m. Its primary active medicinal compounds, flavonoids and phenylethanol glycosides (PhGs), exhibit various pharmacological effects, including hemostatic, anti-inflammatory, antitumor, immunomodulatory, and antioxidant activities. This study analyzed flavonoid and PhG metabolites in the roots of P. rotata collected from Henan County (HN), Guoluo County (GL), Yushu County (YS), and Chengduo County (CD) in Qinghai Province. A total of differentially abundant metabolites (DAMs) including 38 flavonoids and 21 PhGs were identified. Six genes (UFGT1, CHS1, COMT2, C4H3, C4H8, and C4H5) and four enzymes (4CL, C4H, PPO, and ALDH) were found to play key roles in regulating flavonoid and PhG biosynthesis in P. rotata roots. With increasing altitude, the relative content of 15 metabolites, the expression of seven genes, and the activity of four enzymes associated with flavonoid and PhG metabolism increased. These findings enhance our understanding of the regulatory mechanisms of flavonoid and PhG metabolism in P. rotata and provide insights into the potential pharmaceutical applications of its bioactive compounds.PMID:39859384 | DOI:10.3390/ijms26020668

Int J Mol Sci. 2025 Jan 14;26(2):650. doi: 10.3390/ijms26020650.ABSTRACTSphingolipidomic mass spectrometry has provided valuable information-and surprises-about sphingolipid structures, metabolism, and functions in normal biological processes and disease. Nonetheless, many noteworthy compounds are not routinely determined, such as the following: most of the sphingoid bases that mammals biosynthesize de novo other than sphingosine (and sometimes sphinganine) or acquire from exogenous sources; infrequently considered metabolites of sphingoid bases, such as N-(methyl)n-derivatives; "ceramides" other than the most common N-acylsphingosines; and complex sphingolipids other than sphingomyelins and simple glycosphingolipids, including glucosyl- and galactosylceramides, which are usually reported as "monohexosylceramides". These and other subspecies are discussed, as well as some of the circumstances when they are likely to be seen (or present and missed) due to experimental conditions that can influence sphingolipid metabolism, uptake from the diet or from the microbiome, or as artifacts produced during extraction and analysis. If these compounds and factors are kept in mind during the design and interpretation of lipidomic studies, investigators are likely to be surprised by how often they appear and thereby advance knowledge about them.PMID:39859363 | DOI:10.3390/ijms26020650

Int J Mol Sci. 2025 Jan 14;26(2):647. doi: 10.3390/ijms26020647.ABSTRACTSafflower (Carthamus tinctorius L.) is a medicinal and edible cash crop that is widely cultivated worldwide. However, the genetic diversity of safflower germplasm resources and the reasons for the variations in safflower flower colour remain unclear. In this study, we used a combination of agronomic traits and Indel markers to assess the genetic diversity of 614 safflower germplasm resources. The results showed that most of the evaluated agronomic traits had high variability. The mean values of the Shannon's information index (I) and polymorphism information content (PIC) in 50 pairs of Indel markers were 0.551 and 0.296, respectively. The population structure, neighbour-joining phylogeny, and principal coordinate analyses classified all genotypes into four subgroups, and 214 safflower core germplasms were constructed. Multiple analyses of genetic diversity parameters, range conformity, and the percentage of variance difference showed that the core germplasm did not differ significantly and could represent the original germplasm better. Transcriptome and metabolome analyses revealed that flavonoid synthesis-related genes, including CHS, F3H, ANS, and BZ1, were differentially expressed in different coloured safflowers. Most significantly, different genes and metabolite compounds in white safflowers were enriched upstream from the phenylpropanoid metabolic pathway to the production of naringenin, whereas those in red safflowers were concentrated in the downstream pathway from eriodictyol. Meanwhile, the preliminary quantification of anthocyanins and carotenoids extracted from red, orange, and white types of safflower showed that the level of both anthocyanins and carotenoids were highest in red types. This work provides new insights into the formation of different safflower flower colours and in the conservation and management of safflower germplasm.PMID:39859362 | DOI:10.3390/ijms26020647

Int J Mol Sci. 2025 Jan 11;26(2):582. doi: 10.3390/ijms26020582.ABSTRACTThe accumulation of aniline in the natural environment poses a potential threat to crops, and thus, investigating the effects of aniline on plants holds practical implications for agricultural engineering and its affiliated industries. This study combined physiological, transcriptomic, and metabolomic methods to investigate the growth status and molecular-level response mechanisms of rice under stress from varying concentrations of aniline. At a concentration of 1 mg/L, aniline exhibited a slight growth-promoting effect on rice. However, higher concentrations of aniline significantly inhibited rice growth and even caused notable damage to the rice seedlings. Physiological data indicated that under aniline stress, the membrane of rice underwent oxidative damage. Furthermore, when the concentration of aniline was excessively high, the cells suffered severe damage, resulting in the inhibition of antioxidant enzyme synthesis and activity. Transcriptomic and metabolomic analyses indicated that the phenylpropanoid biosynthesis pathway became quite active under aniline stress, with alterations in various enzymes and metabolites related to lignin synthesis. In addition to the phenylpropanoid biosynthesis pathway, amino acid metabolism, lipid metabolism, and purine metabolism were also critical pathways related to rice's response to aniline stress. Significant changes occurred in the expression levels of multiple genes (e.g., PRX, C4H, GST, and ilvH, among others) associated with functions such as antioxidant activity, membrane remodeling, signal transduction, and nitrogen supply. Similarly, notable alterations were observed in the accumulation of various metabolites (for instance, glutamic acid, phosphatidic acid, phosphatidylglycerol, and asparagine, etc.) related to these functions. Our research findings have unveiled the potential of compounds such as phenylpropanoids and amino acids in assisting rice to cope with aniline stress. A more in-depth and detailed exploration of the specific mechanisms by which these substances function in the process of plant resistance to aniline stress (for instance, utilizing carbon-14 isotope tracing to monitor the metabolic pathway of aniline within plants) will facilitate the cultivation of plant varieties that are resistant to aniline. This will undoubtedly benefit activities such as ensuring food production and quality in aniline-contaminated environments, as well as utilizing plants for the remediation of aniline-polluted environments.PMID:39859297 | DOI:10.3390/ijms26020582

Int J Mol Sci. 2025 Jan 10;26(2):565. doi: 10.3390/ijms26020565.ABSTRACTMowing significantly influences nutrient cycling and stimulates metabolic adjustments in plants to promote regrowth. Plant growth-promoting rhizobacteria (PGPR) are crucial for enhancing plant growth, nutrient absorption, and stress resilience; however, whether inoculation with PGPR after mowing can enhance plant regrowth capacity further, as well as its specific regulatory mechanisms, remains unexplored. In this study, PGPR Pantoea eucalyptus (B13) was inoculated into mowed Leymus chinensis to evaluate its effects on phenotypic traits, root nutrient contents, and hormone levels during the regrowth process and to further explore its role in the regrowth of L. chinensis after mowing. The results showed that after mowing, root nutrient and sugar contents decreased significantly, while the signal pathways related to stress hormones were activated. This indicates that after mowing, root resources tend to sacrifice a part of growth and prioritize defense. After mowing, B13 inoculation regulated the plant's internal hormone balance by reducing the levels and signal of JA, SA, and ABA and upregulated the signal transduction of growth hormones in the root, thus optimizing growth and defense in a mowing environment. Transcriptomic and metabolomic analyses indicated that B13 promoted nutrient uptake and transport in L. chinensis root, maintained hormone homeostasis, enhanced metabolic pathways related to carbohydrates, energy, and amino acid metabolism to cope with mowing stress, and promoted root growth and regeneration of shoot. This study reveals the regenerative strategy regulated by B13 in perennial forage grasses, helping optimize resource utilization, increase yield, and enhance grassland stability and resilience.PMID:39859281 | DOI:10.3390/ijms26020565

Int J Mol Sci. 2025 Jan 10;26(2):557. doi: 10.3390/ijms26020557.ABSTRACTLipid droplets (LDs), highly dynamic cellular organelles specialized in lipid storage and maintenance of lipid homeostasis, contain several proteins on their surface, among which the perilipin (Plin) family stands out as the most abundant group of LD-binding proteins. They play a pivotal role in influencing the behavior and functionality of LDs, regulating lipase activity, and preserving a balance between lipid synthesis and degradation, which is crucial in the development of obesity and abnormal accumulation of fat in non-adipose tissues, causing negative adverse biological effects, such as insulin resistance, mitochondrial dysfunction, and inflammation. The expression levels of Plins are often associated with various diseases, such as hepatic steatosis and atherosclerotic plaque formation. Thus, it becomes of interest to investigate the Plin roles by using appropriate "omics" approaches that may provide additional insight into the mechanisms through which these proteins contribute to cellular and tissue homeostasis. This review is intended to give an overview of the most significant omics studies focused on the characterization of Plin proteins and the identification of their potential targets involved in the development and progression of cardiovascular and cardiometabolic complications, as well as their interactors that could be useful for more efficient therapeutic and preventive approaches for patients.PMID:39859272 | DOI:10.3390/ijms26020557

Int J Mol Sci. 2025 Jan 10;26(2):545. doi: 10.3390/ijms26020545.ABSTRACTTo investigate the impact of age on the metabolomic profile of loggerhead sea turtles (Caretta caretta), this study analyzed 100 plasma samples of individuals across two age groups-50 post-hatchlings and 50 juveniles-from various locations along the Mediterranean coastline. Both targeted and untargeted metabolomic analyses were performed on the samples. Our results demonstrated a significant age-related effect on the metabolomic profiles in both analyses. Specifically, post-hatchling turtles exhibited increased levels of urea (p < 0.001), triglyceride (p = 0.0003), cholesterol (p < 0.001), lysoPE (18:1/0:0) (p < 0.001), 7-HDoHE (p = 0.0121), pyrrolidinebutanoic acid (p < 0.001), formiminoglutamic acid (p < 0.001), pyroglutamic acid (p < 0.001), lysoPC (0:0/20:4) (p < 0.001), lysoPE (22:6/0:0) (p < 0.001), 1-acyl-sn-glycero-3-phosphocholine (p < 0.001), DL-homocysteine (p < 0.001) and gamma-Glutamyltyrosine (p < 0.001). Conversely, post-hatchlings showed reduced levels of total protein (p < 0.001), glucose (p = 0.0002), uric acid (p < 0.001), inorganic phosphorus (p = 0.0018) and calcium (p = 0.0410) compared with juveniles. These findings suggest significant physiological changes between the age groups, likely due to differentiated feeding patterns. Further research is needed to better understand the metabolic profiles and complex physiological and nutritional interactions of this species.PMID:39859261 | DOI:10.3390/ijms26020545

Int J Mol Sci. 2025 Jan 10;26(2):544. doi: 10.3390/ijms26020544.ABSTRACTCicadae Periostracum (CP) is a traditional Chinese animal-derived medicine with the potential to treat Parkinson's disease (PD). This study aims to explore the pharmacodynamic mechanisms of CP against PD-based on metabolomics technology and provide a theoretical basis for developing new anti-PD medicine. First, MPP+-induced SH-SY5Y cells were used to evaluate the anti-PD activity of CP. In the animal study, an MPTP-induced PD mouse model was employed to assess CP's therapeutic effects. Immunofluorescence (IF) staining and Western blotting (WB) were used to evaluate its neuroprotective activity on neurons. A Serum metabolomics analysis was conducted to examine CP's regulatory effects on metabolites and to identify vital metabolic pathways. Finally, cellular experiments were performed to validate the critical pathways. Cellular activity experiments demonstrated that CP mitigates MPP+-induced SH-SY5Y cytotoxicity, inhibits apoptosis, and restores mitochondrial homeostasis. Animal experiments revealed that CP significantly alleviates dyskinesia in PD mice, enhances motor performance, and restores neuronal integrity while reducing α-synuclein (α-syn) aggregation in the striatum (STR), showing its strong anti-PD effect. Metabolomic analysis revealed that CP can significantly improve the metabolic disorders of ten biomarkers that are mainly involved in amino acid metabolism and fatty acid β-oxidation and are closely related to oxidative stress pathways. Finally, pathway verification was performed, and the results show that CP exerted neuroprotective effects against PD through the dual signaling pathways of Bcl-2/Bax/Caspase-3 and Nrf2/HO-1. This study provides a comprehensive strategy for elucidating the mechanisms by which CP exerts its therapeutic effects against PD, highlighting its potential in developing anti-PD drugs.PMID:39859260 | DOI:10.3390/ijms26020544

Int J Mol Sci. 2025 Jan 9;26(2):497. doi: 10.3390/ijms26020497.ABSTRACTAn obstacle for many microfluidic developments is the fabrication of its structures, which is often complex, time-consuming, and expensive. Additive manufacturing can help to reduce these barriers. This study investigated whether the results of a microfluidic assay for the detection of the promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) fusion protein (PML::RARA), and thus for the differential diagnosis of acute promyelocytic leukemia (APL), could be transferred from borosilicate glass microfluidic structures to additively manufactured fluidics. Digital light processing (DLP) and stereolithography (SLA) printers as well as different photopolymerizable methacrylate-based resins were tested for fabrication of the fluidics. To assess suitability, both print resolution and various physical properties, serializability, biocompatibility, and functionalization with biological molecules were analyzed. The results show that additively manufactured microfluidics are suitable for application in leukemia diagnostics. This was demonstrated by transferring the microfluidic sandwich enzyme-linked immunosorbent assay (ELISA) for PML::RARA onto the surface of magnetic microparticles from a glass structure to three-dimensional (3D)-printed parts. A comparison with conventional glass microstructures suggests lower sensitivity but highlights the potential of additive manufacturing for prototyping microfluidics. This may contribute to the wider use of microfluidics in biotechnological or medical applications.PMID:39859217 | DOI:10.3390/ijms26020497

Int J Mol Sci. 2025 Jan 8;26(2):474. doi: 10.3390/ijms26020474.ABSTRACTGlioblastoma (GBM), the most prevalent primary malignant brain tumor, remains challenging to treat due to extensive inter- and intra-tumor heterogeneity. This variability demands combination treatments to improve therapeutic outcomes. A significant obstacle in treating GBM is the expression of O6-methylguanine-DNA methyltransferase, a DNA repair enzyme that reduces the efficacy of the standard alkylating agent, temozolomide, in about 50% of patients. This underscores the need for novel, more targeted therapies. Our study investigates the metabolic-epigenetic impact of combining SN-38, a novel topoisomerase inhibitor inducing DNA double-strand breaks, with rabusertib, a checkpoint kinase 1 inhibitor. We identified this synergistic combination through high-throughput drug screening across a panel of GBM cell lines using a cancer drug library combined with SN-38. A secondary metabolic screening with the PEDS algorithm demonstrated a synergistic modulation of purine, one-carbon, and redox metabolism. Furthermore, the combined treatment led to the significant depletion of epigenetically relevant metabolites such as 5-methyl-cytosine, acetyl-lysine, and trimethyl-lysine. Reduced intermediates of the glutathione cycle indicated increased cellular stress following combinatorial treatment. Overall, the combination of SN-38 and rabusertib synergistically disrupts metabolites associated with epigenetic adaptations, leading to cytotoxicity independent of O6-methylguanine-DNA methyltransferase status, thereby underpinning this combination as a promising candidate for combinatorial therapy in GBM.PMID:39859189 | DOI:10.3390/ijms26020474

Microorganisms. 2025 Jan 14;13(1):166. doi: 10.3390/microorganisms13010166.ABSTRACTMany infants consume both human milk and infant formula (mixed-fed); however, few studies have investigated how mixed feeding affects the gut microbiome composition and metabolic profiles compared to exclusive breastfeeding or formula feeding. Herein, how delivery mode and early nutrition affect the microbiome and metabolome of 6-week-old infants in the STRONG Kids2 cohort was investigated. Fecal samples were collected from exclusively breastfed (BF; n = 25), formula-fed (FF; n = 25) or mixed-fed (MF; n = 25) participants. Within each feeding group, infants were either delivered vaginally (VD; n = 13) or by Cesarean section (CS; n = 12). Feeding mode affects the fecal microbiome diversity, composition, and functional potential, as well as metabolomic profiles regardless of delivery mode. Alpha and beta diversity of MF differed from that of BF (p < 0.05) but were comparable to FF infants. Functional analyses have shown 117 potential metabolic pathways differed between BF and FF, 112 between BF and MF, and 8 between MF and FF infants (p < 0.05, q < 0.10). Fecal metabolomic profiles of MF and FF clustered together and separated from BF infants. In total, 543 metabolites differed between BF and FF, 517 between BF and MF, and 3 between MF and FF (p < 0.05, q < 0.10). Delivery mode affected overall microbial composition (p = 0.022) at the genus level and 24 potential functional pathways, with 16 pathways being higher in VD than CS infants (p < 0.05, q < 0.10). Metabolomic analysis identified 47 differential metabolites between CS and VD, with 39 being lower in CS than VD (p < 0.05, q < 0.10). In summary, fecal microbiota composition and function and metabolite profiles of 6-week-old MF infants are closer to FF than BF infants.PMID:39858934 | DOI:10.3390/microorganisms13010166

Microorganisms. 2025 Jan 14;13(1):161. doi: 10.3390/microorganisms13010161.ABSTRACTMetabolic disorders, including type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome, are systemic conditions that profoundly impact the skin microbiota, a dynamic community of bacteria, fungi, viruses, and mites essential for cutaneous health. Dysbiosis caused by metabolic dysfunction contributes to skin barrier disruption, immune dysregulation, and increased susceptibility to inflammatory skin diseases, including psoriasis, atopic dermatitis, and acne. For instance, hyperglycemia in T2DM leads to the formation of advanced glycation end products (AGEs), which bind to the receptor for AGEs (RAGE) on keratinocytes and immune cells, promoting oxidative stress and inflammation while facilitating Staphylococcus aureus colonization in atopic dermatitis. Similarly, obesity-induced dysregulation of sebaceous lipid composition increases saturated fatty acids, favoring pathogenic strains of Cutibacterium acnes, which produce inflammatory metabolites that exacerbate acne. Advances in metabolomics and microbiome sequencing have unveiled critical biomarkers, such as short-chain fatty acids and microbial signatures, predictive of therapeutic outcomes. For example, elevated butyrate levels in psoriasis have been associated with reduced Th17-mediated inflammation, while the presence of specific Lactobacillus strains has shown potential to modulate immune tolerance in atopic dermatitis. Furthermore, machine learning models are increasingly used to integrate multi-omics data, enabling personalized interventions. Emerging therapies, such as probiotics and postbiotics, aim to restore microbial diversity, while phage therapy selectively targets pathogenic bacteria like Staphylococcus aureus without disrupting beneficial flora. Clinical trials have demonstrated significant reductions in inflammatory lesions and improved quality-of-life metrics in patients receiving these microbiota-targeted treatments. This review synthesizes current evidence on the bidirectional interplay between metabolic disorders and skin microbiota, highlighting therapeutic implications and future directions. By addressing systemic metabolic dysfunction and microbiota-mediated pathways, precision strategies are paving the way for improved patient outcomes in dermatologic care.PMID:39858932 | DOI:10.3390/microorganisms13010161

Microorganisms. 2025 Jan 13;13(1):149. doi: 10.3390/microorganisms13010149.ABSTRACTε-poly-l-lysine (ε-PL), a natural food preservative, has garnered widespread attention. It is mainly produced by Streptomyces albulus, but the production by wild-type strains fails to meet the demands of industrialization. To address this issue, adaptive laboratory evolution (ALE) was successfully employed in this study, subjecting S. albulus CICC 11022 to environmental stresses such as acidic pH and antibiotics (rifampicin, gentamicin, and streptomycin). As a result of ALE, an evolutionary strain S. albulus C214 was obtained, exhibiting an increase in ε-PL production and cell growth by 153.23% and 234.51%, respectively, as compared with the original strain. Genomic and metabolic analyses revealed that mutations occurred in genes responsible for transcriptional regulation, transporter, cell envelope, energy metabolism, and secondary metabolite synthesis, as well as the enrichment of metabolites involved in the biosynthesis of ε-PL. These findings hold great significance for elucidating the mechanism underlying ε-PL synthesis.PMID:39858917 | DOI:10.3390/microorganisms13010149

Microorganisms. 2025 Jan 13;13(1):146. doi: 10.3390/microorganisms13010146.ABSTRACTPlasma treatment has emerged as a promising tool for manipulating plant microbiomes and metabolites. This review explores the diverse applications and effects of plasma on these biological systems. It is hypothesized that plasma treatment will not induce substantial changes in the composition of plant microbiomes or the concentration of plant metabolites. We delve into the mechanisms by which plasma can regulate microbial communities, enhance antimicrobial activity, and recruit beneficial microbes to mitigate stress. Furthermore, we discuss the optimization of plasma parameters for effective microbiome interaction and the role of plasmids in plant-microbe interactions. By characterizing plasmidome responses to plasma exposure and investigating transcriptional and metabolomic shifts, we provide insights into the potential of plasma as a tool for engineering beneficial plant-microbe interactions. The review presented herein demonstrates that plasma treatment induces substantial changes in both microbial community composition and metabolite levels, thereby refuting our initial hypothesis. Finally, we integrate plasmidome, transcriptome, and metabolome data to develop a comprehensive understanding of plasma's effects on plant biology and explore future perspectives for agricultural applications.PMID:39858915 | DOI:10.3390/microorganisms13010146