Search Results (116)

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated on three laboratory substrates (glass, polystyrene, and polydimethylsiloxane) and under planktonic conditions. Our results revealed metabolic differences between adherent and planktonic cultures, particularly concerning the lipid and carbohydrate contents. Adherent cultures showed a metabolic profile with an increase in betaine lipids (DGTA/S), fatty acids (tetradecanoic and octadecenoic acids), and sugars (myo-inositol and ribose), suggesting modifications in membrane composition and lipid remodeling, which play a potential role in adhesion. In contrast, planktonic cultures displayed a higher content of cellobiose, specialized metabolites such as dihydroactinidiolide, quinic acid, catechol, and terpenes like phytol, confirming different membrane composition, energy storage capacity, osmoregulation, and stress adaptation. The adaptative strategies do not only concern adherent and planktonic states, but also different adherent culture conditions, with variations in lipid, amino acid, terpene, and carbohydrate contents depending on the physical properties of the support. Our results highlight the importance of metabolic adaptation in adhesion, which could explain the fouling process. Full article

A novel actinobacterial strain, designated E54^T, was isolated from a hyper-arid desert soil sample collected from the Kumtagh Desert in Dunhuang, Gansu Province, China. Phylogenetic analysis based on 16S rRNA gene sequences placed strain E54^T within the genus Lentzea, showing highest similarity to Lentzea waywayandensis DSM 44232^T (98.9%) and Lentzea flava NBRC 15743^T (98.5%). However, whole-genome comparisons revealed that the average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between E54^T and these related strains were below the thresholds for species delineation. Strain E54^T exhibited typical morphological characteristics of the genus Lentzea, forming a branched substrate. It grew optimally at 28–30 °C, pH 7.0–9.0, and tolerated up to 10% NaCl. The cell wall contained meso-diaminopimelic acid, the predominant menaquinone was MK-9(H₄), and major fatty acids included iso-C_16:0. The polar lipid profile comprised diphosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl inositol, hydroxyphosphatidyl ethanolamine, and an unidentified lipid. The characteristic amino acid type of the cell wall was meso-DAP. Whole-cell hydrolysis experiments revealed the characteristic cell wall sugar fractions: ribose and galactose. The genome of strain E54^T is approximately 8.0 Mb with a DNA G+C content of 69.38 mol%. Genome mining revealed 39 biosynthetic gene clusters (BGCs), including non-ribosomal peptide synthetases (NRPS), polyketide synthases (PKS), terpenes, and siderophores. Comparative antiSMASH-based genome analysis across 38 Lentzea strains further demonstrated the genus’ remarkable biosynthetic diversity. NRPS and type I PKS (T1PKS) were the most prevalent BGC types, indicating a capacity to synthesize structurally complex and pharmacologically relevant metabolites. Together, these findings underscore the untapped biosynthetic potential of the genus Lentzea and support the proposal of strain E54^T as a novel species. The strain E54^T (=JCM 34936^T = GDMCC 4.216^T) should represent a novel species, for which the name Lentzea xerophila sp. nov. is proposed. Full article

The Phosphoinositide Specific-Phospholipase C (PI-PLC) family of enzymes plays a crucial role in various cellular processes by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), which are essential messengers mediating critical intracellular signaling pathways. Herein, we carry out a comprehensive analysis of the structure, function, regulation, and implications of the PI-PLC family enzymes in both physiological and pathological contexts. More specifically, we discuss the structural features of PI-PLCs, elucidating their conserved domains and catalytic mechanisms. Furthermore, we explore the multifaceted roles of PI-PLCs in signal transduction, cellular homeostasis, and membrane dynamics, whilst highlighting the intricate regulatory mechanisms governing their activity such as protein–protein interactions, post-translational modifications, and lipid modulation. Lastly, we assess the involvement of PI-PLCs in various diseases, such as cancer, neurological disorders, immune dysregulation, and male infertility, emphasizing their potential as therapeutic targets. Full article

Pontocerebellar hypoplasia (PCH) encompasses a group of autosomal recessive neurodegenerative disorders marked by cerebellar and pontine atrophy. Multiple subtypes of PCH have been identified, among which the rare subtype PCH type 16 is caused by MINPP1 genetic variants. MINPPI encodes an enzyme essential for inositol polyphosphate dephosphorylation, regulating calcium and iron homeostasis. We conducted genome sequencing on a proband from the consanguineous family, who presented with a severe neurodegenerative disorder, to identify the underlying cause of disease. A comprehensive clinical assessment in addition to neuroradiological findings are described. We performed the functional validation of the identified variant and conducted untargeted metabolomic analyses. The clinical and radiological assessment of the patient showed a congenital brain anomaly and neurodegenerative symptoms. Further genetic analysis identified a homozygous loss-of-function variant (c.1401del, p.Ser468Valfs10*) in MINPP1, providing molecular confirmation of a clinical PCH diagnosis. While real-time quantitative PCR (RT-qPCR) showed that MINPP1 gene expression was unaffected in the proband, Western blot analysis demonstrated reduced protein abundance, supporting a pathogenic role of the variant. Metabolomic profiling revealed elevated lipid levels and disrupted inositol metabolism, providing further insights into the disease mechanism. These findings establish the pathogenicity of the p.Ser468Valfs10* variant in MINPP1 and highlight inositol metabolism as a potential pathway involved in PCH16, advancing the understanding of the pathophysiology of the disease. Full article

Polygonati Rhizoma, widely used as a traditional functional food and herbal medicine, is well known for its health-promoting activities after the process of “nine cycles of steaming-drying”. Based on UPLC-MS/MS, 1369 secondary metabolites were identified in P. cyrtonema rhizomes, mainly alkaloids, amino acids and derivatives, flavonoids, organic acids, phenolic acids, and saccharides. The P. cyrtonema rhizomes were rich in xylose, arabinose, glucose, sorbose, mannose, galactose, rhamnose, inositol, fucose, sedoheptulose, phosphorylated monosaccharides, sugar acid, and sugar alcohols. Particularly, 23 types of modifications were detected for amino acids, while the most frequent modifications were acetylation, methylation (nono-, di-, and tri-), cyclo-, homo-, and hydroxylation. Based on the metabolic profile, samples from the third cycle (Tre-3) and the sixth cycle (Tre-6) were firstly clustered together due to similar metabolites and then grouped with samples from the ninth cycle (Tre-9). Differentially accumulated metabolites were mainly enriched in “Metabolic pathways”, “Biosynthesis of cofactors”, “Biosynthesis of secondary metabolites”, “Flavonoid biosynthesis”, “Purine metabolism”, “ABC transporters”, “Biosynthesis of amino acids”, and “Nucleotide metabolism” pathways. During repeated steaming–drying processes, 39 metabolites occurred, including alkaloids, amino acids and derivatives, flavonoids, lignans and coumarins, lipids, nucleotides and derivatives, organic acids, phenolic acids, and terpenoids. This research will provide a critical scientific basis for postharvest processing of P. cyrtonema rhizomes. Full article

Plasma membrane plays a pivotal role in orchestrating motility and invasive processes, as well as mitosis and genome expression. Indeed, specialized regions of the plasma membrane enriched in phosphoinositides—namely PIP2 and PIP3—can accommodate the requirements of the dynamic interface, which mediates the interplay between cells and their microenvironment. The fine-tuned balance between the two phosphoinositides is instrumental in regulating cytoskeleton organization, motility, ion channel activation, and membrane traffic. The balanced expression of PIP2/PIP3 fulfills these functions by activating pathways through several transporter and receptor proteins. These dynamic interactions modulate the interplay with the extracellular environment by decreasing/increasing their exposure on the cell surface. In this way, lipid structures can rapidly either dismiss or recruit specific proteins, eventually favoring their cooperation with membrane receptors and ion channels. Particularly, exposure of proteins can be managed through the internalization of plasma membrane segments, while receptor signaling can be desensitized by their removal from the cell surface. Notably, the equilibrium between PIP2 and PIP3 is largely dependent on inositol availability, as inositol addition enhances PIP2 content while reducing PIP3 via PI3K inhibition. Pharmacological modulation of PIP2/PIP3 balance promises to be an interesting target in different clinical settings. Full article

Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways, and inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is still poorly understood. Since skeletal muscle is a major contributor to energy homeostasis, we have developed a mouse model in which skeletal muscle IPMK is specifically deleted and examined how a loss of IPMK affects whole-body metabolism. Here, we report that skeletal-muscle-specific IPMK knockout mice exhibited a ~12% increase in body weight compared to WT controls (p < 0.05). These mice also showed a significantly impaired glucose tolerance, as indicated by their ~50% higher blood glucose levels during GTT. Additionally, exercise capacity was reduced by ~45% in IPMK-MKO mice, demonstrating a decline in endurance. Moreover, these metabolic alterations were accompanied by a 2.5-fold increase in skeletal muscle triglyceride accumulation, suggesting impaired lipid metabolism. Further analysis revealed that IPMK-deficient myocytes exhibited 30% lower β-oxidation rates. Thus, our results suggest that IPMK mediates whole-body metabolism by regulating muscle metabolism and may be potentially targeted for the treatment of metabolic syndromes. Full article

Boosting evidence indicated lipids play important roles in plants. To explore lipid function in cotton fiber development, the lipid composition and content were detected by untargeted and targeted lipidomics. Compared with rapid elongation fibers, the lipid intensity of 16 sub-classes and 56 molecular species decreased, while only 7 sub-classes and 26 molecular species increased in the fibers at the stage of secondary cell wall deposition. Unexpectedly, at the rapid elongation stage, 20 sub-classes and 60 molecular species increased significantly, while only 5 sub-classes and 8 molecular species decreased in the ligon lintless-1 (li-1) mutant compared with its wild-type Texas Maker-1 (TM-1). Particularly, campesteryl, sitosteryl, and total steryl ester increased by 21.8-, 48.7-, and 45.5-fold in the li-1 fibers, respectively. All the molecular species of sphingosine-1-P, phytoceramide-OHFA, and glucosylceramide increased while all sphingosine, phytosphingosine, and glycosyl inositol phospho ceramides decreased in the li-1 fibers. Similarly, the different expression genes between the mutant and wild type were enriched in many pathways involved in the lipid metabolism. Furthermore, the number of lipid droplets also increased in the li-1 leaf and fiber cells when compared with the wild type. These results illuminated that fiber cell elongation being blocked in the li-1 mutant was not due to a lack of lipids, but rather lipid over-accumulation (obesity), which may result from the disruption of sphingolipid and sterol metabolism. This study provides a new perspective for further studying the regulatory mechanisms of fiber development. Full article

Background/Objectives: This study evaluated metabolites and lipid composition in the calf muscles of Type 2 diabetes mellitus (T2DM) patients and age-matched healthy controls using multi-dimensional MR spectroscopic imaging. We also explored the association between muscle metabolites, lipids, and intra-abdominal fat in T2DM. Methods: Participants included 12 T2DM patients (60.3 ± 8.6 years), 9 age-matched healthy controls (AMHC) (60.9 ± 7.8 years), and 10 young healthy controls (YHC) (28.3 ± 1.8 years). We acquired the 2D MR spectra of calf muscles using an enhanced accelerated 5D echo-planar correlated spectroscopic imaging (EP-COSI) technique and abdominal MRI with breath-hold 6-point Dixon sequence. Results: In YHC, choline levels were lower in the gastrocnemius (GAS) and soleus (SOL) muscles but higher in the tibialis anterior (TA) compared to AMHC. YHC also showed a higher unsaturation index (U.I.) of extramyocellular lipids (EMCL) in TA, intramyocellular lipids (IMCL) in GAS, carnosine in SOL, and taurine and creatine in TA. T2DM patients exhibited higher choline in TA and myo-inositol in SOL than AMHC, while triglyceride fat (TGFR2) levels in TA were lower. Correlation analyses indicated associations between IMCL U.I. and various metabolites in muscles with liver, pancreas, and abdominal fat estimates in T2DM. Conclusions: This study highlights distinct muscle metabolite and lipid composition patterns across YHC, AMHC, and T2DM subjects. Associations between IMCL U.I. and abdominal fat depots underscore the interplay between muscle metabolism and adiposity in T2DM. These findings provide new insights into metabolic changes in T2DM and emphasize the utility of advanced MR spectroscopic imaging in characterizing muscle-lipid interactions. Full article

This study aimed to investigate the effects of dietary supplementation with methylsulfonylmethane (MSM) and myo-inositol (MI) on hair quality, fecal microbiota, and metabolome in poodles. Thirty-two adult poodles categorized based on initial body weight and sex were randomly assigned to four groups. These groups (designated the CON, MSM, MI, and MSM + MI groups) received a basal diet, the same diet supplemented with 0.2% MSM + 0% MI, the same diet supplemented with 0% MSM + 0.2% MI, or the same diet supplemented with 0.2% MSM + 0.2% MI, respectively. The study lasted for 65 days. During the entire study period, body weight, average daily weight gain, feed intake, energy intake, and fecal output were normal in all the animals and did not differ significantly among the treatment groups. Hair scale thickness was lower in the MI and MSM + MI groups than in the CON group on Day 65 (p < 0.05). An amino acid analysis of the hair revealed higher sulfur content in the MI and MSM + MI groups on Day 65 than on Day 0 (p < 0.05). Moreover, the poodles in the MSM, MI, and MSM + MI groups presented significantly lower levels of Proteobacteria_unclassified and Candidatus Phytoplasma than did those in the CON group. The relative abundance of Gammaproteobacteria_unclassified was greater in the MSM and MI groups than in the CON group (p < 0.05). The MSM group presented a greater abundance of Glucerabacter than the CON group (p < 0.05). Compared with those in the CON and MSM + MI groups, the abundances of Paramuribaculum and Hafnia in the MSM group were greater (p < 0.05). The abundances of Enterobacter and Kineothrix were greater (p < 0.05) in the MI group than in the CON and MSM + MI groups. The poodles in the MI group presented significantly greater abundances of Bacteroidales_unclassified, Halanaerobium, Mycobacterium, and Erysipelotrichaceae_unclassified than did poodles in the CON, MSM, and MSM + MI groups. Fecal metabolomics analysis revealed that MSM, MI, and MSM + MI treatment markedly affected carbohydrate metabolism. MSM + MI treatment also influenced lipid metabolism. These findings suggest that dietary supplementation with MSM and MI can improve the hair quality of poodles. Full article

Background: The aim of the present study was to evaluate the effectiveness and safety of a nutraceutical combination given to insulin-resistant overweight patients with altered lipid profiles. To this end, an observational study was designed in which 74 individuals (50 females and 24 males) underwent an observational period of 3 months. Methods: During this time, a specific nutraceutical combination containing myo-inositol, glycine, Coprinus comatus, α-lipoic acid, phlorizin, zinc, vitamin B⁶, and chromium picolinate was administered. Patients were asked not to modify their lifestyles so that no variable that might interfere with results was introduced. Results: After the 3-month period, the obtained data revealed that insulin levels significantly decreased with respect to the baseline, while glucose levels exhibited a trend towards lower concentrations, which was not significant. In addition, HOMA-IR index, body weight, BMI, and abdominal circumference values all decreased significantly. Regarding lipid profiles, the data obtained before and after the 3-month period showed statistically significant decreases in concentrations of total cholesterol, LDL cholesterol, and triglyceride, as well as a small but statistically significant concomitant increase in HDL cholesterol. Conclusions: Thus, on the basis of these data, it may be stated that the specific nutraceutical combination used in the present study significantly ameliorated a number of metabolic parameters without measurable side effects. The efficacy and safety of the product were, therefore, confirmed in our group of patients. Full article

This paper describes the synthesis of two 6-azido-6-deoxy derivatives of phosphatidylinositol (PI), which contained different fatty acid chains. These syntheses, starting from methyl α-d-glucopyranoside, employed multiple regioselective transformations with Ferrier rearrangement as one of the key steps. The PI derivatives contained different fatty acid chains in the lipids and an azido group in the inositol residue to facilitate their further functionalization under bioorthogonal conditions. Therefore, they should be useful probes for the investigation of PI and related biology, such as PI phosphorylation, PI interaction with other molecules in cells, and the functions of lipid structures in these processes. Full article

Phospholipids are the main building components of cell membranes and are also used for cell signaling and as energy storages. Cancer cells alter their lipid metabolism, which ultimately leads to an increase in phospholipids in cancer tissue. Surgical energy instruments use electrical or vibrational energy to heat tissues, which causes intra- and extracellular water to expand rapidly and degrade cell structures, bursting the cells, which causes the formation of a tissue aerosol or smoke depending on the amount of energy used. This gas phase analyte can then be analyzed via gas analysis methods. Differential mobility spectrometry (DMS) is a method that can be used to differentiate malignant tissue from benign tissues in real time via the analysis of surgical smoke produced by energy instruments. Previously, the DMS identification of cancer tissue was based on a ‘black box method’ by differentiating the 2D dispersion plots of samples. This study sets out to find datapoints from the DMS dispersion plots that represent relevant target molecules. We studied the ability of DMS to differentiate three subclasses of phospholipids (phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine) from a control sample using a bovine skeletal muscle matrix with a 5 mg addition of each phospholipid subclass to the sample matrix. We trained binary classifiers using linear discriminant analysis (LDA) and support vector machines (SVM) for sample classification. We were able to identify phosphatidylcholine, -inositol, and -ethanolamine with SVM binary classification accuracies of 91%, 73%, and 66% and with LDA binary classification accuracies of 82%, 74%, and 72%, respectively. Phosphatidylcholine was detected with a reliable classification accuracy, but ion separation setups should be adjusted in future studies to reliably detect other relevant phospholipids such as phosphatidylinositol and phosphatidylethanolamine and improve DMS as a microanalysis method and identify other phospholipids relevant to cancer tissue. Full article

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with myocardial fatty acid metabolism. Carnitine palmitoyltransferase-1β (CPT-1β) is the rate-limiting enzyme responsible for β-oxidation of long-chain fatty acids. Intermedin (IMD) is a pivotal bioactive small molecule peptide, participating in the protection of various cardiovascular diseases. However, the role and underlying mechanisms of IMD in DCM are still unclear. In this study, we investigated whether IMD alleviates DCM via regulating CPT-1β. A rat DCM model was established by having rats to drink fructose water for 12 weeks. A mouse DCM model was induced by feeding mice a high-fat diet for 16 weeks. We showed that IMD and its receptor complexes levels were significantly down-regulated in the cardiac tissues of DCM rats and mice. Reduced expression of IMD was also observed in neonatal rat cardiomyocytes treated with palmitic acid (PA, 300 μM) in vitro. Exogenous and endogenous IMD mitigated cardiac hypertrophy, fibrosis, dysfunction, and lipid accumulation in DCM rats and IMD-transgenic DCM mice, whereas knockout of IMD worsened these pathological processes in IMD-knockout DCM mice. In vitro, IMD alleviated PA-induced cardiomyocyte hypertrophy and cardiac fibroblast activation. We found that CPT-1β enzyme activity, mRNA and protein levels, and acetyl-CoA content were increased in T2DM patients, rats and mice. IMD up-regulated the CPT-1β levels and acetyl-CoA content in T2DM rats and mice. Knockdown of CPT-1β blocked the effects of IMD on increasing acetyl-CoA content and on inhibiting cardiomyocyte hypertrophy and cardiac fibroblast activation. IMD receptor antagonist IMD_17–47 and the phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (Akt) inhibitor LY294002 reversed the effects of IMD on up-regulating CPT-1β and acetyl-CoA expression and on inhibiting cardiomyocyte hypertrophy and cardiac fibroblast activation. We revealed that IMD alleviates DCM by up-regulating CPT-1β via calcitonin receptor-like receptor/receptor activity-modifying protein (CRLR/RAMP) receptor complexes and PI3K/Akt signaling. IMD may serve as a potent therapeutic target for the treatment of DCM. Full article

Fever is one of the most common clinical conditions and is characterized by pyrogenic infection, malignancy, inflammation, and tissue damage, among others. Ellagic acid (EA) can inhibit the expression of related proteins on the pathway by blocking the nuclear factor kappa-B(NF-κB) signaling pathway, inhibit the levels of pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), increase the level of anti-inflammatory factor IL-10, and effectively alleviate inflammatory symptoms. In addition, EA can also reduce the levels of malondialdehyde(MDA) and nitric oxide(NO) in the body, increase the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase(CAT), scavenge oxidative free radicals, inhibit lipid oxidation, and achieve antipyretic and anti-inflammatory effects. The purpose of this study was to establish the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, prostaglandin E2(PGE₂), and cyclic adenosine monophosphate(cAMP), and clarify the mechanism of the cyclooxidase-2(COX-2)/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Compared to lipopolysaccharide (LPS)- treated animals, subsequent administration of EA significantly lowered the LPS-induced rectal temperature increase (p < 0.05 or p < 0.01), significantly increased serum SOD and GSH levels (p < 0.05 or p < 0.01), and significantly decreased serum MDA, IL-1β, IL-6, and TNF-α levels (p < 0.05 or p < 0.01). In addition, compared to LPS-treated animals, subsequent administration of EA significantly decreased cerebrospinal fluid cAMP and PGE₂ levels (p < 0.05 or p < 0.01), significantly decreased cAMP, significantly increased 5-HT levels (p < 0.05 or p < 0.01), and significantly down-regulated p-NF-κB p65 and COX-2 protein levels in the hypothalamus. Subsequent gas chromatography mass spectrometry(GC-MS) metabolite analysis indicated that 12 differential metabolites were detected in serum isolated 4 h after LPS treatment, and 10 differential metabolites were detected in serum collected 7 h after LPS treatment. Next, Pearson correlation analysis was used to systematically characterize the relationship between the identified metabolites and TNF-α, IL-6, MDA, SOD, PGE₂, and cAMP. The levels of propionic acid, pyridine, and L-valine were up-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α and increased the activity of GSH. The levels of inositol, urea, and 2-monopalmitin were down-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α, increased the activity of SOD and GSH, reduced the inflammatory response, and alleviated the oxidative stress state. Combined with the results of the metabolic pathway analysis, we suggest that the pathways of the galactose metabolism, synthesis and degradation of ketone bodies, as well as ascorbic acid and aldehyde acid metabolism are closely related to the antipyretic and anti-inflammatory effects of EA. Our study established the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, PGE₂, and cAMP, and clarified the mechanism of the COX-2/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Full article