PubMed

Autophagy. 2024 Dec 11. doi: 10.1080/15548627.2024.2440842. Online ahead of print.ABSTRACTCholesterol serves as a vital lipid that regulates numerous physiological processes. Nonetheless, its role in regulating cell death processes remains incompletely understood. In this study, we investigated the role of cholesterol trafficking in immunogenic cell death. Through cell-based drug screening, we identified two antidepressants, sertraline and indatraline, as potent inducers of the nuclear translocation of TFEB (transcription factor EB). Activation of TFEB was mediated through the autophagy-independent lipidation of MAP1LC3/LC3 (microtubule associated protein 1 light chain 3). Both compounds promoted cholesterol accumulation within lysosomes, resulting in lysosomal membrane permeabilization, disruption of autophagy and cell death that could be reversed by cholesterol depletion. Molecular docking analysis indicated that sertraline and indatraline have the potential to inhibit cholesterol binding to the lysosomal cholesterol transporters, NPC1 (NPC intracellular cholesterol transporter 1) and NPC2. This inhibitory effect might be further enhanced by the upregulation of NPC1 and NPC2 expression by TFEB. Both antidepressants also upregulated PLA2G15 (phospholipase A2 group XV), an enzyme that elevates lysosomal cholesterol. In cancer cells, sertraline and indatraline elicited immunogenic cell death, converting dying cells into prophylactic vaccines that were able to confer protection against tumor growth in mice. In a therapeutic setting, a single dose of each compound was sufficient to significantly reduce the outgrowth of established tumors in a T-cell-dependent manner. These results identify sertraline and indatraline as immunostimulatory agents for cancer treatment. More generally, this research shed light on novel therapeutic avenues harnessing lysosomal cholesterol transport to regulate immunogenic cell death.PMID:39663580 | DOI:10.1080/15548627.2024.2440842

Autophagy. 2024 Dec 11. doi: 10.1080/15548627.2024.2437649. Online ahead of print.ABSTRACTDBI/ACBP is a phylogenetically ancient hormone that stimulates appetite and lipo-anabolism. In response to starvation, DBI/ACBP is secreted through a noncanonical, macroautophagy/autophagy-dependent pathway. The physiological hunger reflex involves starvation-induced secretion of DBI/ACBP from multiple cell types. DBI/ACBP concentrations subsequently increase in extracellular fluids to stimulate food intake. Recently, we observed that glucocorticoids, which are endogenous stress hormones as well as anti-inflammatory drugs, upregulate DBI/ACBP expression at the transcriptional level and stimulate autophagy in hepatocytes, thereby causing a surge in circulating DBI/ACBP levels. Prolonged increase in glucocorticoid concentrations causes an extreme form of metabolic syndrome, dubbed "Cushing syndrome", which is characterized by clinical features including hyperphagia, hyperdipsia, dyslipidemia, hyperinsulinemia, insulin resistance, lipodystrophy, visceral adiposity, steatosis, sarcopenia and osteoporosis. Mice and patients with Cushing syndrome exhibit supraphysiological DBI/ACBP plasma levels. Of note, neutralization of extracellular DBI/ACBP protein with antibodies or mutation of the DBI/ACBP receptor (i.e. the GABRG2 subunit of GABR [gamma-aminobutyric acid type A receptor]) renders mice resistant to the induction of Cushing syndrome. Similarly, knockout of Dbi/Acbp in hepatocytes suppresses the corticotherapy-induced surge in plasma DBI/ACBP concentrations and prevents the manifestation of most of the characteristics of Cushing syndrome. We conclude that autophagy-mediated secretion of DBI/ACBP by hepatocytes constitutes a critical step of the pathomechanism of Cushing syndrome. It is tempting to speculate that stress-induced chronic elevations of endogenous glucocorticoids also compromise human health due to the protracted augmentation of circulating DBI/ACBP concentrations.PMID:39663572 | DOI:10.1080/15548627.2024.2437649

Rapid Commun Mass Spectrom. 2025 Mar 15;39(5):e9939. doi: 10.1002/rcm.9939.ABSTRACTRATIONALE: Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease typically coexisting with intestinal microbiota dysbiosis, oxidative stress, and an inflammatory response. Although its underlying mechanism of action is unclear, Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) have demonstrated significant therapeutic efficacy for UC.METHODS: The mechanism of action of MMRAC in the treatment of UC model was investigated by combining metabolomics, transcriptomics, and intestinal microbiota detection techniques.RESULTS: The high-dose group of MMRAC was determined as the best therapeutic dose by pathological changes and biochemical indexes. Transcriptome analysis revealed that 360 genes were differentially altered after MMRAC treatment. Metabolomic analysis using colon tissue yielded 14 colon tissue metabolites with significant differences. Intestinal flora analysis showed that 26 major microorganisms were identified at the genus level.CONCLUSIONS: Based on a thorough multi-omics analysis of transcriptomics, metabolomics, and gut flora, it was determined that MMRAC regulated cysteine and methionine metabolism, arginine biosynthesis, and sphingolipid metabolism and their respective genes BHMT, PHGDH, iNOS, and SPHK1, which in turn served to inhibit UC-generated inflammatory responses and oxidative stress. Additionally, MMRAC regulated the abundance of Coprococcus, Helicobacter, Sutterella, Paraprevotella, and Roseburia in the intestinal tracts of UC mice, which was regulated toward normal levels, thereby restoring normal intestinal function.PMID:39663538 | DOI:10.1002/rcm.9939

Nature. 2024 Dec;636(8042):322-331. doi: 10.1038/s41586-024-08280-5. Epub 2024 Dec 11.ABSTRACTThe human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies. Recent advances in proteomic technology and computational sciences now provide opportunities to investigate the intricate biology of the human body at unprecedented resolution and scale. Here we introduce a big-science endeavour called π-HuB (proteomic navigator of the human body). The aim of the π-HuB project is to (1) generate and harness multimodality proteomic datasets to enhance our understanding of human biology; (2) facilitate disease risk assessment and diagnosis; (3) uncover new drug targets; (4) optimize appropriate therapeutic strategies; and (5) enable intelligent healthcare, thereby ushering in a new era of proteomics-driven phronesis medicine. This ambitious mission will be implemented by an international collaborative force of multidisciplinary research teams worldwide across academic, industrial and government sectors.PMID:39663494 | DOI:10.1038/s41586-024-08280-5

J Ethnopharmacol. 2024 Dec 9:119232. doi: 10.1016/j.jep.2024.119232. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis (SR), an ancient antiviral herbal medicine, is widely used in treating viral pneumonia and its active constituents, baicalin and baicalein, have been reported to have antiviral activity.AIM OF THE STUDY: However, reports on Q-markers of SR for antiviral pneumonia are still scarce. This study aims to screen for Q-markers using a comprehensive strategy that integrates identification of chemical profiles, in vivo absorption, metabolic regulation and predicted target.MATERIALS AND METHODS: First, the markers were screened by chemical profile identification and pharmacokinetics using HPLC-MS/MS. Then, the therapeutic effects and differential metabolites of SR on viral pneumonia rats were evaluated by HE staining, assessment of inflammation levels and metabolomics analysis. Finally, the mechanisms of action between Q-markers and metabolites were exploited based on network pharmacology.CONCLUSION: A total of 139 compounds were identified in SR, of which 35 and 41 were found in rat plasma and urine, respectively. Pharmacokinetic screening identified baicalin, baicalein, wogonin, wogonoside and oroxylin A as potential markers of SR. Furthermore, SR significantly improved interstitial and alveolar oedema, hemorrhage and alveolar collapse after modelling, while reducing the expression of inflammatory factors. Metabolomics revealed that SR significantly regulated the expression of 37 metabolites, mainly involving phenylalanine, tyrosine and tryptophan biosynthesis pathways. Network pharmacology showed that these five biomarkers can regulate the expression of metabolites through the key target SRC, ESR1, HSP90AA1, EGFR, thereby exerting antiviral effects against pneumonia. The study results suggest that baicalin, baicalein, wogonin, wogonoside and oroxylin A serve as primary Q-markers of SR in the treatment of viral pneumonia.PMID:39662860 | DOI:10.1016/j.jep.2024.119232

Exp Neurol. 2024 Dec 9:115108. doi: 10.1016/j.expneurol.2024.115108. Online ahead of print.NO ABSTRACTPMID:39662793 | DOI:10.1016/j.expneurol.2024.115108

Microb Pathog. 2024 Dec 9:107216. doi: 10.1016/j.micpath.2024.107216. Online ahead of print.ABSTRACTIncreasing evidence suggests that immune cell clearance is closely linked to cellular metabolism. Neurosyphilis, a severe neurological disorder caused by Treponema pallidum (T. pallidum) infection, significantly impacts the brain. Microglia, the innate immune cells of the central nervous system, play a critical role in neuroinflammation and immune surveillance. However, the inability of the nervous system to fully eliminate T. pallidum points to a compromised clearance function of microglia. This study investigates how T. pallidum alters the immune clearance ability of microglia and explores the underlying metabolic mechanisms. RNA sequencing (RNA seq), LC-MS metabolomics, and XFe96 Seahorse assays were employed to assess metabolic activity in microglial cells. Western blotting, qPCR, and immunofluorescence imaging were utilized to evaluate autophagy flux and extent of T. pallidum infections. Transcriptomic analysis revealed that T. pallidum alters the transcription expression of key glycolytic enzymes, including hexokinase 1 (HK1), hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), leading to significant metabolic dysregulation. Specifically, metabolomic analysis showed reduced levels of phosphoenolpyruvate and citrate, while lactate production was notably increased. Functional assays confirmed that T. pallidum impairs glycolytic activity in microglial, as evidenced by decreased glycolytic flux, glycolytic reserve capacity, and maximum glycolytic capacity. Moreover, our results indicate that HK2, a crucial glycolytic enzyme, is closely associated with the autophagy. T. pallidum infection inhibits HK2 expression, which in turn suppresses autophagic flux by reducing the formation of lysosome-associated membrane protein 2 (LAMP2) and disrupting autophagosome- lysosome fusion. These findings suggest that T. pallidum hijacks microglial metabolic pathways, specifically glycolysis, to evade immune clearance. By inhibiting the glycolytic enzyme HK2, T. pallidum modulates autophagy and enhances immune evasion, providing a novel insight into the pathogenesis of neurosyphilis. This study paves the way for further investigations into the role of metabolic reprogramming in the immune escape mechanisms of T. pallidum.PMID:39662785 | DOI:10.1016/j.micpath.2024.107216

Biochim Biophys Acta Mol Basis Dis. 2024 Dec 9:167618. doi: 10.1016/j.bbadis.2024.167618. Online ahead of print.ABSTRACTInflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.PMID:39662756 | DOI:10.1016/j.bbadis.2024.167618

Int J Biol Macromol. 2024 Dec 9:138625. doi: 10.1016/j.ijbiomac.2024.138625. Online ahead of print.ABSTRACTStilbenes constitute a class of naturally occurring polyphenolic compounds that have been identified in a wide range of plants. In wine, stilbenes play crucial roles in humans, exhibiting anti-cancer, anti-inflammatory, antioxidant properties, and aiding in the prevention of cardiovascular diseases. Therefore, studies on the synthesis and regulatory mechanisms of styrene compounds in grapes are of great economic importance. In this study, we discovered that BS (BSISTER) transcript factors, a member of the MADS-BOX gene family, regulate the biosynthesis of stilbenes in grapevine. Comprehensive transcriptome and phenolic metabolome analysis were conducted on wild-type grapevine callus, as well as on transgenic callus overexpressing 35S::VviBS1-GFP and 35S: VviBS2-GFP under the control of the 35S promoter. The results showed that VviBS1 and VviBS2 down-regulate the synthesis of stilbenes. We screened seven STS differential genes from the transcriptome and further examined the expression of these differential genes in grapevine callus by RT-qPCR, and found that VviSTS48 was the most highly expressed compared to other STS genes. In addition, yeast one-hybrid assay, dual luciferase assay, and Chip-qPCR assay were performed for validation. The results of these experiments indicate that VviBS1 and VviBS2 down-regulate astragalus synthesis by directly binding to the promoter of VviSTS48. In conclusion, our researches provide new insight into the regulatory mechanisms of stilbenes biosynthesis in grapevine, which could be effectively employed for metabolic engineering to regulate stilbenes content and represent a useful reference for further study of BS function.PMID:39662544 | DOI:10.1016/j.ijbiomac.2024.138625

Neurobiol Dis. 2024 Dec 9:106762. doi: 10.1016/j.nbd.2024.106762. Online ahead of print.ABSTRACTLipidomic alterations have been associated with various neurological diseases. Examining temporal changes in serum lipidomic profiles, irrespective of injury type, reveals promising prognostic indicators. In this longitudinal prospective observational study, serum samples were collected early (46 ± 24 h) and late (142 ± 52 h) post-injury from 70 patients with ischemic stroke, aneurysmal subarachnoid hemorrhage, and traumatic brain injury that had outcomes dichotomized as favorable (modified Rankin Scores (mRS) 0-3) and unfavorable (mRS 4-6) three months post-injury. Lipidomic profiling of 1153 lipids, analyzed using statistical and machine learning methods, identified 153 lipids with late-stage significant outcome differences. Supervised machine learning pinpointed 12 key lipids, forming a combinatory prognostic equation with high discriminatory power (AUC 94.7 %, sensitivity 89 %, specificity 92 %; p < 0.0001). Enriched functions of the identified lipids were related to sphingolipid signaling, glycerophospholipid metabolism, and necroptosis (p < 0.05, FDR-corrected). The study underscores the dynamic nature of lipidomic profiles in acute brain injuries, emphasizing late-stage distinctions and proposing lipids as significant prognostic markers, transcending injury types. These findings advocate further exploration of lipidomic changes for a comprehensive understanding of pathobiological roles and enhanced prediction for recovery trajectories.PMID:39662533 | DOI:10.1016/j.nbd.2024.106762

Ecotoxicol Environ Saf. 2024 Dec 10;289:117475. doi: 10.1016/j.ecoenv.2024.117475. Online ahead of print.ABSTRACTPerfluorodecanoic acid (PFDA) is a typical perfluoroalkyl substances frequently encountered in populations, posing significant risks to human health. However, research on the effects of PFDA exposure on organism metabolism and related pathogenic mechanisms is severely lacking. In this study, serum and liver samples of C57BL/6 J mice exposed to different doses of PFDA were analyzed by UPLC-HRMS-based metabolomics and lipidomics techniques. Both 1 mg/kg and 10 mg/kg PFDA exposure induced liver damage, while only 10 mg/kg PFDA exposure caused weight loss. Metabolomics analysis revealed that 330 and 515 metabolites were significantly altered in the serum and liver of mice after PFDA exposure, respectively. Most amino acids and peptides increased in the serum but decreased in the liver. Lipidomics analysis indicated that 281 and 408 lipids experienced significant alterations in the serum and liver after PFDA exposure, respectively. Most lipids, particularly multiple triacylglycerols, were downregulated in a dose-dependent manner in both serum and liver. Taken together, PFDA can induce changes in the amino acid metabolism pathway, disrupt fatty acid β-oxidation, and down-regulate glycolipid pathways in mice, resulting in disturbances in energy metabolism. These findings suggested that the liver is a critical target organ for PFDA exposure, and will also help inform future risk assessment.PMID:39662454 | DOI:10.1016/j.ecoenv.2024.117475

Sci Total Environ. 2024 Dec 10;958:177982. doi: 10.1016/j.scitotenv.2024.177982. Online ahead of print.ABSTRACTOxybenzone (BP-3), a common sunscreen ingredient, has been detected in marine ecosystems and shown to be toxic to various marine species, raising environmental concerns. However, its effects on macroalgae remain largely unknown. This study investigated the toxicity of BP-3 on two macroalgae species: Hormosira banksii and Ulva lactuca. A chronic germination-inhibition experiment with H. banksii and an acute study with mature U. lactuca were conducted using BP-3 concentrations ranging from 0.03 to 27 mg/L. Results revealed significant inhibition of H. banksii spore germination at 3, 9, and 27 mg/L BP-3 at 72 h, with a 10 % effect concentration of 0.363 mg/L (95 % confidence interval: 0.27-0.45 mg/L). For U. lactuca, relative growth rate decreased by 20-70 % compared to controls in treatments of 0.1, 3, 9, and 27 mg/L BP-3 after 72 h. Exposure to ≥0.3 mg/L BP-3 resulted in lower chlorophyll a and b concentrations and higher lipid peroxidation, with significant differences observed between the control and ≥9 mg/L BP-3 treatments. Exposure to 1 mg/L BP-3 induced significant alterations in several key metabolic pathways associated with stress response mechanisms, energy metabolism, and cellular signalling in U. lactuca. These findings suggest that BP-3 does not pose an acute risk to mature U. lactuca or a chronic risk to H. banksii at concentrations typically observed in the marine environment, as in both cases effect concentrations exceeded BP-3 concentrations typically observed in marine environmental water samples. However, further research is needed to assess potential risks associated with chronic exposure to environmentally relevant concentrations. These toxicity data contribute valuable information for future risk assessments of BP-3 and aid in setting water quality guidelines for this widely used organic UV filter.PMID:39662409 | DOI:10.1016/j.scitotenv.2024.177982

J Chromatogr A. 2024 Dec 6;1740:465588. doi: 10.1016/j.chroma.2024.465588. Online ahead of print.ABSTRACTThe analysis of ionic compounds by liquid chromatography is challenging due to the interaction of analytes with the metal surface of the instrument and the column, leading to poor peak shape and decreased sensitivity. The use of bioinert materials in the chromatographic system minimizes these unrequired interactions. In this work, the ultrahigh-performance liquid chromatography (UHPLC) with bioinert components was connected to a high-resolution mass spectrometer to develop a method for untargeted metabolomic analysis. 81 standards of metabolites were used for the development and optimization of the method. In comparison to the conventional chromatographic system, the application of bioinert technology resulted in significantly improved peak shapes and increased sensitivity, especially for metabolites containing phosphate groups. The calibration curves were constructed for the evaluation of the method performance, showing a wide dynamic range, low limit of detection, and linear regression coefficients higher than 0.99 for all standards. The optimized method was applied to the analysis of NIST SRM 1950 human plasma, which allowed the detection of 156 metabolites and polar lipids based on the combination of mass accuracy in the full-scan mass spectra in both polarity modes, characteristic fragment ions in MS/MS, and logical chromatographic behavior leading to the high confidence level of annotation/identification. We have demonstrated an improvement in the peak shapes and sensitivity of ionic metabolites using bioinert technology, which indicates the potential for the analysis of other ionic compounds, e.g., molecules containing phosphate groups.PMID:39662336 | DOI:10.1016/j.chroma.2024.465588

Poult Sci. 2024 Dec 5;104(1):104623. doi: 10.1016/j.psj.2024.104623. Online ahead of print.ABSTRACTEggshell translucency is the common problem on eggshell that become more severe with age. They are important because it influence consumer preferences and the economic value of eggs. The reason for the eggshell translucency is currently believed to be the eggshell membrane (ESM). In this study, we screened translucency eggs and normal eggs and used metabolomics to study liver metabolism in different eggshell translucency and discuss important liver lipids and phosphatidyl metabolites. Liver samples were taken for Liquid Chromatograph Mass Spectrometer (LC-MS) during the formation of eggshell membranes in hens, that is, when eggs form eggshell membranes in the oviduct isthmus. The results showed that we identified two essential metabolic pathways through differential metabolite pathway analysis, which were glycine, serine, and threonine metabolism related to amino acids metabolism and the PPAR metabolic pathway related to lipid metabolism. Furthermore, this study helps us understand the process of translucency egg production in poultry. This laid the foundation for in-depth research on eggshell translucency. These results may and provide support for future breeding.PMID:39662257 | DOI:10.1016/j.psj.2024.104623

Poult Sci. 2024 Dec 5;104(1):104643. doi: 10.1016/j.psj.2024.104643. Online ahead of print.ABSTRACTOmics techniques, including genomics, transcriptomics, proteomics, metabolomics, and lipidomics, analyze entire sets of biological molecules to seek comprehensive knowledge on a particular phenotype. These approaches have been extensively utilized to identify both biomarkers and biological mechanisms for various physiological conditions in livestock and poultry. The purpose of this symposium was not only to focus on how recent omics technologies can be used to gather, integrate, and interpret data produced by various methodologies in poultry research, but also to highlight how omics and bioinformatics have increased our understanding of poultry meat quality problems and other complex traits. This Poultry Science Association symposium paper includes 5 sections that cover: 1) functional annotation of cis-regulatory elements in the genome informs genetic control of complex traits in poultry, 2) mass spectrometry for proteomics, metabolomics, and lipidomics, 3) proteomic approaches to investigate meat quality, 4) spatial transcriptomics and metabolomics studies of wooden breast disease, and 5) multiomics analyses on chicken meat quality and spaghetti meat. These topics provide insights into the molecular components that contribute to the structure, function, and dynamics of the underlying mechanisms influencing meat quality traits, including chicken breast myopathies. This information will ultimately contribute to improving the quality and composition of poultry products.PMID:39662255 | DOI:10.1016/j.psj.2024.104643

J Photochem Photobiol B. 2024 Dec 8;262:113079. doi: 10.1016/j.jphotobiol.2024.113079. Online ahead of print.ABSTRACTDespite increasing evidence suggesting that red light photobiomodulation (R-PBM) and leonurus play important roles in analgesic and anti-inflammatory processes, data on their combined effect on primary dysmenorrhea (PD) are scarce. In this study, we reported the pain assessment of red light at various modes combined with leonurus on the oxytocin-induced model of PD mice. The combined intervention of pulsed R-PBM and leonurus decreased pain responses and PGF2α/PGE2 levels, alleviated uterine swelling and inflammatory infiltration, enhanced antioxidant levels (T-AOC, GSH-PX, SOD), and reduced lipid peroxidation (MDA, LPO) in the uterus, with its synergistic effect surpassing either treatment alone or the combination of continuous wave R-PBM with leonurus. Transcriptomic analysis demonstrated significant changes in differentially expressed genes associated with calcium signaling (Cav1, Cacna1c, Kcnmb1, Cnn1, and Myh11) and inflammatory response (Ptgs2, Jun, Fos, IL1rn, and IL17b) in the combination group, with concurrent downregulation of MLCK, COX-2, p-JNK/JNK, and IL17b protein levels, and upregulation of IL1rn, suggesting that the combined intervention of pulsed R-PBM and leonurus may alleviate pain through disruption of calcium homeostasis and induction of ROS-mediated inflammatory responses. Metabolomics studies of plasma revealed significant changes in lipid metabolism after the combined intervention, consistent with the transcriptomic findings. Hence, pulsed R-PBM combined leonurus has the potential to be an effective therapeutic approach for PD, as well as an alternative option for painful and inflammatory diseases; however, further exploration of its underlying mechanism is still necessary.PMID:39662253 | DOI:10.1016/j.jphotobiol.2024.113079

Food Chem. 2024 Dec 4;467:142368. doi: 10.1016/j.foodchem.2024.142368. Online ahead of print.ABSTRACTPecan (Carya illinoinensis) is a globally important nut crop, yet the processes of lipid biosynthesis and spatial lipid distribution within its embryo remain poorly understood. This study employed UHPLC-MS/MS and MALDI-MSI to profile lipids in developing pecan embryos, identifying 401 lipid molecules, including a high abundance of glycerolipids (148) and glycerophospholipids (144). Differential diacylglycerols showed gradual uptrends, highlighting their role in synthesizing glycerolipids and glycerophospholipids. Unsaturated fatty acids, especially oleic, linoleic, and linolenic acids, were enriched in triacylglycerols, diacylglycerols, phosphatidylethanolamines, and phosphatidylcholines. MALDI-MSI revealed the spatial distribution of phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), suggesting heterogeneous lipid distribution within embryos. The proportion of linoleic and linolenic acids is higher in the kernel coat, whereas the proportion of oleic acid is relatively higher in the cotyledons. Differences in lipid content were also observed between the inner and outer cotyledons. This study provides the first comprehensive map of lipid distribution in pecan embryos, offering new insights into lipid metabolism regulation.PMID:39662248 | DOI:10.1016/j.foodchem.2024.142368

Clin Nutr. 2024 Dec 6;44:124. doi: 10.1016/j.clnu.2024.12.010. Online ahead of print.NO ABSTRACTPMID:39662117 | DOI:10.1016/j.clnu.2024.12.010

Kidney Blood Press Res. 2024 Dec 11:1-21. doi: 10.1159/000542263. Online ahead of print.ABSTRACTINTRODUCTION: Urolithiasis is characterized by a high morbidity and recurrence rate, primarily attributed to metabolic disorders. The identification of more metabolic biomarkers would provide valuable insights into the etiology of stone formation and the assessment of disease risk. The present study aimed to seek potential organic acid (OA) biomarkers from morning urine samples and explore new methods based on machine learning (ML) for metabolic risk prediction of urolithiasis.METHODS: Morning urine samples were collected from 117 healthy controls and 156 urolithiasis patients. Gas chromatography-mass spectrometry (GC-MS) was used to obtain metabolic profiles. Principal component analysis (PCA) and ML were carried out to screen robust markers and establish a prediction evaluation model.RESULTS: There were 25 differential metabolites identified, such as palmitic acid, L-pyroglutamic acid, glyoxylate, and ketoglutarate, mainly involving arginine and proline metabolism, fatty acid degradation, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylic acid metabolism. The urinary organic acid markers significantly improved the performance of the ML model. The sensitivity and specificity were up to 87.50% and 84.38%, respectively. The area under the receiver operating characteristic curve (AUC) was significantly improved (AUC = 0.9248).CONCLUSION: The results suggest that OA profiles in morning urine can improve the accuracy of predicting urolithiasis risk, and possibly help to understand the involvement of metabolic perturbations in metabolic pathways of stone formation and to provide new insights.PMID:39662072 | DOI:10.1159/000542263

Clin Lab. 2024 Dec 1;70(12). doi: 10.7754/Clin.Lab.2024.240717.ABSTRACTBACKGROUND: Neonatal birth/perinatal asphyxia is a critical condition that can adversely affect many different bodily tissues, particularly the brain; depending on duration and severity of asphyxia, leading to difficulties and lifelong disabilities. These can be avoided by early detection of the biochemical derangements and prompt intervention. Serum alpha-ketoglutarate (α-KG) and cord blood lactate have been found to be associated with birth asphyxia and may have potential to act as biomarkers for birth asphyxia.METHODS: Serum levels of α-KG and cord blood lactate were estimated in 34 birth asphyxiated neonates with clinical evidence of asphyxia. The levels were also analyzed in 46 apparently healthy controls, and data was compared among different groups by using appropriate statistical analysis. Serum α-KG was estimated by enzyme-linked immunosorbent assay (ELISA) and cord blood lactate by blood gas autoanalyzer (BGA) in the serum samples.RESULTS: Serum α-KG levels were found to be increased in birth asphyxiated neonates as compared to healthy controls (p-value = 0.06). Correlation of serum α-ketoglutarate (ng/mL) levels with outcome (discharged/expired) in birth asphyxiated neonates was not found to be statistically significant (r value = 0.156, p-value = 0.384). A statisti-cally significant correlation was not found between severity of birth asphyxia and levels of serum α-ketoglutarate (ng/mL) (r value = 0.029, p-value = 0.86). Also, correlation of cord blood lactate levels (mmol/L) with severity in birth asphyxiated neonates was not found to be statistically significant (r value = 0.326, p-value = 0.10). Correlation between cord blood lactate levels (mmol/L) and outcome in birth asphyxiated neonates (discharged/ expired) was not found to be statistically significant (r value = 0.03, p-value = 0.87), while correlation of cord pH levels and severity of birth asphyxia in cases was found to be highly statistically significant (r value = -0.60, p-value < 0.01) Conclusions: Serum α-KG and cord blood lactate bear the potential to act as biomarkers in neonates with birth asphyxia.PMID:39662007 | DOI:10.7754/Clin.Lab.2024.240717