PubMed

Sci Rep. 2024 Mar 1;14(1):5110. doi: 10.1038/s41598-024-55406-w.ABSTRACTPlatostoma palustre is an annual herb and an important medicinal and edible plant in southern China. Plastic-film mulching is an effective agronomic practice in the cultivation system of P. palustre, of which black-film mulching is the most common. However, fewer researches have been focused on the use of other colors of plastic films in P. palustre cultivation. In this study, different colors (white, black, red, and green) of plastic film were adopted, and the effects of different colors of plastic film mulching on the soil temperature, yield, and metabolites of P. palustre were investigated. The results showed that the fresh weight of a single plant of the green film treatment was significantly higher than that of the white film treatment (n = top 28). Based on the results of three temperature measurements, the soil temperature was almost the highest in the red film treatment and lowest in the white film treatment. The metabolomic analysis revealed that a total of 103 differential metabolites were identified. Among these, the gluconic acid, deoxyribose, and N-Acetylmannosamine in the red film treatment presented the highest abundance compared with the other treatments, meanwhile, the abundances of the five monosaccharides in the red film treatment were significantly higher than those of the green film treatment. Moreover, the sucrose, trehalose, and D-(+)-trehalose in the green film treatment exhibited the highest abundance, and the abundances of eight different amino acids in the red film treatment were almost the lowest while those in the black film treatment were almost the highest. Further analysis of the membership function values indicated that the black and red film treatments might be more suitable for the cultivation and quality production of P. palustre in comparison with the other two treatments. This study will provide a theoretical basis for improving the efficient cultivation technology of P. palustre and forming a theoretical system of P. palustre film mulching cultivation.PMID:38429397 | DOI:10.1038/s41598-024-55406-w

Sci Rep. 2024 Mar 1;14(1):5113. doi: 10.1038/s41598-024-53502-5.ABSTRACTInflammation is a part of the body's intricate biological reaction to noxious stimuli and defensive reactions. So, the aim of this investigation was to study the anti-inflammatory activity of exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats. A halophilic bacterial strain was isolated from marine sediments in the Red Sea in Egypt. The isolate has been visually and physiologically recognized, as well as by analyzing its 16S rRNA gene, which confirms Kocuria sp. clone Asker4. This particular isolate can be referenced using the accession number OL798051.1. EPSSM was subjected to purification and fractionation by a DEAE-cellulose column. Preliminary chemical analysis of EPSSM indicated that the monosaccharides were fructose, glucuronic acid, and xylose, with 2.0, 0.5, and 1.0, respectively. The antioxidant potential of EPSSM was investigated, and it was discovered that the level of activity increased independently of the concentrations, reaching a maximum threshold of 94.13% at 100 µg/mL of EPSSM for 120 min. Also, EPSSM at 50 mg/kg orally produced a significant anti-inflammatory effect on the carrageenan model at 2, 3, and 4 intervals. The EPSSM intervention resulted in reductions in the levels of catalase and superoxide dismutase enzymes, as well as a decrease in glutathione. Furthermore, the levels of nitric oxide, lipid peroxidation, and reactive oxygen species resulting from carrageenan-induced edema showed a significant reduction subsequent to the administration of EPSSM. Moreover, the findings indicated that the protein expression levels of cyclooxygenase-2 and interleukin-6 were reduced following treatment with EPSSM, resulting in a reduction of paw edema.PMID:38429312 | DOI:10.1038/s41598-024-53502-5

Biochem Pharmacol. 2024 Feb 28:116103. doi: 10.1016/j.bcp.2024.116103. Online ahead of print.ABSTRACTLiver is a major organ that metabolizes sulfur amino acids cysteine, which is the substrate for the synthesis of many essential cellular molecules including GSH, taurine, and coenzyme A. Bile acid-activated farnesoid x receptor (FXR) inhibits cysteine dioxygenase type 1 (CDO1), which mediates hepatic cysteine catabolism and taurine synthesis. To define the impact of bile acid inhibition of CDO1 on hepatic sulfur amino acid metabolism and antioxidant capacity, we developed hepatocyte-specific CDO1 knockout mice (Hep-CDO1 KO) and hepatocyte specific CDO1 transgenic mice (Hep-CDO1 Tg). Liver metabolomics revealed that genetic deletion of hepatic CDO1 reduced de novo taurine synthesis but had no impact on hepatic taurine abundance or bile acid conjugation. Consistent with reduced cysteine catabolism, Hep-CDO1 KO mice showed increased hepatic cysteine abundance but unaltered methionine cycle intermediates and coenzyme A synthesis. Upon acetaminophen overdose, Hep-CDO1 KO mice showed increased GSH synthesis capacity and alleviated liver injury. In contrast, hepatic CDO1 overexpression in Hep-CDO1 Tg mice stimulated hepatic cysteine to taurine conversion, resulting in reduced hepatic cysteine abundance. However, Hep-CDO1 Tg mice and WT showed similar susceptibility to acetaminophen-induced liver injury. Hep-CDO1 Tg mice showed similar hepatic taurine and coenzyme A compared to WT mice. In summary, these findings suggest that bile acid and FXR signaling inhibition of CDO1-mediated hepatic cysteine catabolism preferentially modulates hepatic GSH synthesis capacity and antioxidant defense, but has minimal effect on hepatic taurine and coenzyme A abundance. Repression of hepatic CDO1 may contribute to the hepatoprotective effects of FXR activation under certain pathologic conditions.PMID:38428825 | DOI:10.1016/j.bcp.2024.116103

Am J Clin Nutr. 2024 Feb 28:S0002-9165(24)00167-9. doi: 10.1016/j.ajcnut.2024.02.021. Online ahead of print.ABSTRACTBACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood.OBJECTIVE: Our goal was to investigate the weight loss effects of a 1-year lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared to an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular risk factors METHODS: A total of 400 participants (200 from each study group), aged 55-75 years, and at high cardiovascular risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 year of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota.RESULTS: Compared to the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular risk factors. We identified intervention effects on four stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular risk factors. Additionally, we observed a reduction in the abundance of the genera Eubacterium Hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 year of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular risk factors.CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome.CLINICAL TRIAL REGISTRY NUMBER: ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).PMID:38428742 | DOI:10.1016/j.ajcnut.2024.02.021

Am J Clin Nutr. 2024 Feb 28:S0002-9165(24)00165-5. doi: 10.1016/j.ajcnut.2024.02.019. Online ahead of print.ABSTRACTBACKGROUND: Distinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis.OBJECTIVES: We investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates.METHODS: This study included adults with overweight or obesity (n=536) who participated in a randomized weight-loss diet intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 months after weight-loss diet interventions. The ASCVD risk estimates were calculated by the validated equations.RESULTS: At baseline, higher levels of specific BA subtypes were related to higher levels of atherogenic VLDL lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in primary BAs were related to larger reductions of triglycerides and total cholesterol (every 1-SD decrease of glycocholate, glycochenodeoxycholate, or taurochenodeoxycholate was related to β [SE] -3.3 [1.3], -3.4 [1.3], or -3.8 [1.3] mg/dl, respectively; PFDR <0.05 for all). Greater decreases in specific secondary BA subtypes were also associated with improved lipid metabolism at 6 months; there was β -4.0 [1.1] mg/dl per 1-SD decrease of glycoursodeoxycholate (PFDR=0.003) for changes in LDL cholesterol. We found significant interactions (Pinteraction <0.05) between dietary fat intake and changes in BA subtypes on changes in ASCVD risk estimates; decreases in primary and secondary BAs (such as conjugated cholate or deoxycholate) were significantly associated with improved ASCVD risk after consuming a high-fat diet but not after a low-fat diet.CONCLUSIONS: Decreases in distinct BA subtypes were associated with improved lipid profiles and ASCVD risk estimates, highlighting the importance of changes in circulating BA subtypes as significant factors linked to improved lipid metabolism and ASCVD risk estimates in response to weight-loss dietary interventions. Habitual dietary fat intake may modify the associations of changes in BAs with ASCVD risk.PMID:38428740 | DOI:10.1016/j.ajcnut.2024.02.019

Biochim Biophys Acta Mol Basis Dis. 2024 Feb 28:167105. doi: 10.1016/j.bbadis.2024.167105. Online ahead of print.ABSTRACTCongenital diaphragmatic hernia (CDH) represents a developmental anomaly that profoundly impacts the embryonic development of both the respiratory and cardiovascular systems. Understanding the influences of developmental defects, their origins, and clinical consequences is of paramount importance for further research and the advancement of therapeutic strategies for this condition. In recent years, groundbreaking studies in the fields of metabolomics and genomics have significantly expanded our knowledge regarding the pathogenic mechanisms of CDH. These investigations introduce novel diagnostic and therapeutic avenues. CDH implies a scarcity of available information within this domain. Consequently, a comprehensive literature review has been undertaken to synthesize existing data, providing invaluable insights into this rare disease. Improved comprehension of the molecular underpinnings of CDH has the potential to refine diagnostic precision and therapeutic interventions, thus potentially enhancing clinical outcomes for CDH patients. The identification of potential biomarkers assumes paramount significance for early disease detection and risk assessment in CDH, facilitating prompt recognition and the implementation of appropriate interventions. The process of translating research findings into clinical practice is significantly facilitated by an exhaustive literature review. It serves as a pivotal step, enabling the integration of novel, more effective diagnostic and therapeutic modalities into the management of CDH patients.PMID:38428682 | DOI:10.1016/j.bbadis.2024.167105

J Ethnopharmacol. 2024 Feb 28:117995. doi: 10.1016/j.jep.2024.117995. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) presents a risk of carcinogenesis, which escalates with the duration of IBD. Persistent histological inflammation is considered to be the driving factor of colitis carcinogenesis. Effective control of inflammation is helpful to prevent and treat colitis-related colorectal cancer (CAC). Anchang Yuyang Decoction (AYD), a traditional Chinese medicine (TCM) formula, is originated from the ancient prescription of TCM for treating colitis and colorectal cancer. AYD has demonstrated efficacy in treating IBD and potential anti-carcinogenic properties.AIM OF THE STUDY: This research aims to assess the therapeutic efficacy of AYD in ameliorating experimental colitis-related carcinogenesis induced by AOM/DSS. It further seeks to elucidate its potential mechanisms by integrating multiple omics sequencing approaches.MATERIALS AND METHODS: A rat model for colitis-related carcinogenesis was developed using azoxymethane (AOM)/dextran sulfate sodium (DSS). UPLC-MS identified AYD's chemical constituents. Rats were administered varying doses of AYD (18.37, 9.19 and 4.59 g/kg) orally for 53 days, with mesalazine as a positive control. The study evaluated anti-carcinogenic effects by examining adenoma number, adenoma load, abnormal crypt foci (ACF), histopathological damage, and tumor-related protein expression. Anti-inflammatory and reparative effects were assessed through body weight, disease activity index (DAI), colon length, spleen index, inflammatory cytokine levels, and tight junction protein expression. The effects on intestinal microbiota and host metabolism were explored through 16S rRNA sequencing, targeted short-chain fatty acid (SCFA) metabonomics, and non-targeted colon metabolomics. Potential AYD targets were identified through transcriptomic sequencing and validated by qRT-PCR and western blotting.RESULTS: AYD significantly reduced adenoma number, adenoma load, neoplasm-associated lesions, ACF, and tumor-related protein expression (e.g., p53, PCNA) in AOM/DSS-induced rats, thus impeding colitis-related carcinogenesis progression. AYD also alleviated histopathological damage and inflammation, promoting intestinal mucosal barrier repair. Furthermore, AYD modulated intestinal flora structure, enhanced SCFA production, and regulated colon metabolites. Transcriptomic sequencing revealed a significant impact on the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Subsequent qRT-PCR and western blotting experiments indicated AYD's influence in up-regulating PPAR-γ and down-regulating PPAR-α, PPAR-β/δ, and related proteins (thrombomodulin [Thbd], fatty acid binding protein 5 [Fabp5], stearoyl-CoA desaturase 2 [Scd2], phospholipid transfer protein [Pltp]).CONCLUSIONS: This study demonstrates AYD's ability to inhibit experimental colitis-related carcinogenesis induced by AOM/DSS. Its mechanism likely involves modulation of the PPAR signaling pathway, impacting intestinal microbiota and host metabolic equilibrium.PMID:38428656 | DOI:10.1016/j.jep.2024.117995

Brain Stimul. 2024 Feb 28:S1935-861X(24)00029-9. doi: 10.1016/j.brs.2024.02.014. Online ahead of print.ABSTRACTTemporal interference (TI) electric field brain stimulation is a novel neuromodulation technique that enables the non-invasive modulation of deep brain regions, but few advances about TI stimulation effectiveness and mechanisms have been reported. Conventional transcranial alternating current stimulation (tACS) can enhance motor skills, whether TI stimulation has an effect on motor skills in mice has not been elucidated. In the present study, TI stimulation was proved to stimulating noninvasively primary motor cortex (M1) of mice, and that TI stimulation with an envelope wave frequency of 20 Hz (Δ f = 20 Hz) once a day for 20 min for 7 consecutive days significantly improved the motor skills of mice. The mechanism of action may be related to regulating of neurotransmitter metabolism, increasing the expression of synapse-related proteins, promoting neurotransmitter release, increasing dendritic spine density, enhancing the number of synaptic vesicles and the thickness of postsynaptic dense material, and ultimately enhance neuronal excitability and plasticity. It is the first report about TI stimulation promoting motor skills of mice and describing its mechanisms.PMID:38428583 | DOI:10.1016/j.brs.2024.02.014

J Dairy Sci. 2024 Feb 28:S0022-0302(24)00514-9. doi: 10.3168/jds.2023-23610. Online ahead of print.ABSTRACTThe composition of milk lipids varies across different ethnic sources. The lipidome profiles of Chinese Han human milk (HHM) and Chinese Korean human milk (KHM) were investigated in this study. A total of 741 lipids were identified in HHM and KHM. Twenty-eight differentially expressed lipids (DELs) were screened between the 2 milk groups; among these, 6 triacylglycerols (TGs), 13 diacylglycerols (DGs), 7 free fatty acids (FFAs), and 1 monoglyceride (MG) were upregulated in KHM. Carnitine (CAR) was upregulated in HHM. Most DELs showed a single peak distribution in both groups. The correlations, related pathways and diseases of these DELs were further analyzed. The results demonstrated that DG, MG, and FFAs showed highly positive correlations with each other (r >0.8). The most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) and Human Metabolome Database (HMDB) pathways were inositol phosphate metabolism, and α-linolenic acid and linolenic acid metabolism, respectively. Major depressive disorder-related FFA (20:5) and FFA (22:6) were more abundant in KHM, while HHM showed more obesity-related CAR. These data potentially provide lipidome information regarding human milk from different ethnicities in China.PMID:38428489 | DOI:10.3168/jds.2023-23610

Mol Genet Metab. 2024 Feb 27;142(1):108360. doi: 10.1016/j.ymgme.2024.108360. Online ahead of print.ABSTRACTThe Mendelian disorders of chromatin machinery (MDCMs) represent a distinct subgroup of disorders that present with neurodevelopmental disability. The chromatin machinery regulates gene expression by a range of mechanisms, including by post-translational modification of histones, responding to histone marks, and remodelling nucleosomes. Some of the MDCMs that impact on histone modification may have potential therapeutic interventions. Two potential treatment strategies are to enhance the intracellular pool of metabolites that can act as substrates for histone modifiers and the use of medications that may inhibit or promote the modification of histone residues to influence gene expression. In this article we discuss the influence and potential treatments of histone modifications involving histone acetylation and histone methylation. Genomic technologies are facilitating earlier diagnosis of many Mendelian disorders, providing potential opportunities for early treatment from infancy. This has parallels with how inborn errors of metabolism have been afforded early treatment with newborn screening. Before this promise can be fulfilled, we require greater understanding of the biochemical fingerprint of these conditions, which may provide opportunities to supplement metabolites that can act as substrates for chromatin modifying enzymes. Importantly, understanding the metabolomic profile of affected individuals may also provide disorder-specific biomarkers that will be critical for demonstrating efficacy of treatment, as treatment response may not be able to be accurately assessed by clinical measures.PMID:38428378 | DOI:10.1016/j.ymgme.2024.108360

Water Res. 2024 Feb 22;253:121354. doi: 10.1016/j.watres.2024.121354. Online ahead of print.ABSTRACTDNA-based monitoring of microbial communities that are responsible for the performance of anaerobic digestion of sewage wastes has the potential to improve resource recoveries for wastewater treatment facilities. By treating sludge with propidium monoazide (PMA) prior to amplicon sequencing, this study explored how the presence of DNA from dead microbial biomass carried over with feed sludge may mislead process-relevant biomarkers, and whether primer choice impacts such assessments. Four common primers were selected for amplicon preparation, also to determine if universal primers have sufficient taxonomic or functional coverage for monitoring ecological performance; or whether two domain-specific primers for Bacteria and Archaea are necessary. Anaerobic sludges of three municipal continuously stirred-tank reactors in Victoria, Australia, were sampled at one time-point. A total of 240 amplicon libraries were sequenced on a Miseq using two universal and two domain-specific primer pairs. Untargeted metabolomics was chosen to complement biological interpretation of amplicon gene-based functional predictions. Diversity, taxonomy, phylogeny and functional potentials were systematically assessed using PICRUSt2, which can predict community wide pathway abundance. The two chosen universal primers provided similar diversity profiles of abundant Bacteria and Archaea, compared to the domain-specific primers. About 16 % of all detected prokaryotic genera covering 30 % of total abundances and 6 % of PICRUSt2-estimated pathway abundances were affected by PMA. This showed that dead biomass in the anaerobic digesters impacted DNA-based assessments, with implications for predicting active processes, such as methanogenesis, denitrification or the identification of organisms associated with biological foams. Hence, instead of running two sequencing runs with two different domain-specific primers, we propose conducting PMA-seq with universal primer pairs for routine performance monitoring. However, dead sludge biomass may have some predictive value. In principal component analysis the compositional variation of 239 sludge metabolites resembled that of 'dead-plus-alive' biomass, suggesting that dead organisms contributed to the potentially process-relevant sludge metabolome.PMID:38428359 | DOI:10.1016/j.watres.2024.121354

Anim Reprod Sci. 2024 Feb 27;263:107448. doi: 10.1016/j.anireprosci.2024.107448. Online ahead of print.ABSTRACTThe egg production of captive African penguins differs considerably between individuals. An understanding of the physiological differences in African penguins with relatively greater and lesser egg production is meaningful for the captive breeding program of this endangered species. The objective of this study was to investigate differential microbial composition and metabolites in captive African penguins with different egg production. Fecal samples were collected from captive female African penguins during the breeding season. The results of 16 S rRNA gene sequencing showed that African penguins with different egg production had similar microbial diversities, whereas a significant difference was observed between their microbial community structure. African penguins with relatively greater egg production exhibited a higher relative abundance of Alphaproteobacteria, Rhizobiales, Bradyrhizobiaceae, Bradyrhizobium and Bosea. Meanwhile, penguins with relatively lesser egg production had an increased proportion of Klebsiella and Plesiomonas. We further identified a total of 1858 metabolites in female African penguins by liquid chromatography-mass spectrometry analysis. Among these metabolites, 13 kinds of metabolites were found to be significantly differential between African penguins with different egg production. In addition, the correlation analysis revealed that the egg production had significant correlations with most of the differential microbial bacteria and metabolites. Our findings might aid in understanding the potential mechanism underlying the phenomenon of abnormal egg production in captive African penguins, and provide novel insights into the relationship between gut microbiota and reproduction in penguins.PMID:38428346 | DOI:10.1016/j.anireprosci.2024.107448

J Pharm Biomed Anal. 2024 Feb 23;243:116068. doi: 10.1016/j.jpba.2024.116068. Online ahead of print.ABSTRACTThe formidable challenge posed by the presence of extremely high amounts of compounds and large differences in concentrations in plasma significantly complicates non-targeted metabolomics analyses. In this study, a comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry (GC×GC-qMS) method with a solid-state modulator (SSM) for non-targeted metabolomics in beagle plasma was first established based on a GC-MS method, and the qualitative and quantitative performance of the two platforms were compared. Identification of detected compounds was accomplished utilizing NIST database match scores, retention indices (RIs) and standards. Semi-quantification involved the calculation of peak area ratios to internal standards. Metabolite identification sheets were generated for plasma samples on both analytical platforms, featuring 22 representative metabolites chosen for validating qualitative accuracy, and for conducting comparisons of linearity, accuracy, precision, and sensitivity. The outcomes revealed a threefold increase in the number of identifiable metabolites on the GC×GC-MS platform, with lower limits of quantitation (LLOQs) reduced to 0.5-0.05 times those achieved on the GC-MS platform. Accuracy in quantification for both GC×GC-MS and GC-MS fell within the range of 85-115%, and the vast majority of intra- and inter-day precisions were within the range of 20%. These findings underscore that relative to the conventional GC-MS method, the GC×GC-MS method developed in this study, combined with SSM, exhibits enhanced qualitative capabilities, heightened sensitivity, and comparable accuracy and precision, rendering it more suitable for non-targeted metabolomics analyses.PMID:38428247 | DOI:10.1016/j.jpba.2024.116068

Food Chem. 2024 Feb 28;446:138852. doi: 10.1016/j.foodchem.2024.138852. Online ahead of print.ABSTRACTFoodomics has become a popular methodology in food science studies. Mass spectrometry (MS) based metabolomics and proteomics analysis played indispensable roles in foodomics research. So far, several methodologies have been developed to detect the metabolites and proteins in diets and consumers, including sample preparation, MS data acquisition, annotation and interpretation. Moreover, multiomics analysis integrated metabolomics and proteomics have received considerable attentions in the field of food safety and nutrition, because of more comprehensive and deeply. In this context, we intended to review the emerging strategies and their applications in MS-based foodomics, as well as future challenges and trends. The principle and application of multiomics were also discussed, such as the optimization of data acquisition, development of analysis algorithm and exploration of systems biology.PMID:38428078 | DOI:10.1016/j.foodchem.2024.138852

Sci Adv. 2024 Mar;10(9):eadk8123. doi: 10.1126/sciadv.adk8123. Epub 2024 Mar 1.ABSTRACTBesides recent advances in neonatal care, preterm newborns still develop sex-biased behavioral alterations. Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal growth hormone in utero, and low IGF-1 serum levels correlate with preterm poor neurodevelopmental outcomes. Here, we mimicked IGF-1 deficiency of preterm newborns in mice by perinatal administration of an IGF-1 receptor antagonist. This resulted in sex-biased brain microstructural, functional, and behavioral alterations, resembling those of ex-preterm children, which we characterized performing parallel mouse/human behavioral tests. Pharmacological enhancement of GABAergic tonic inhibition by the U.S. Food and Drug Administration-approved drug ganaxolone rescued functional/behavioral alterations in mice. Establishing an unprecedented mouse model of prematurity, our work dissects the mechanisms at the core of abnormal behaviors and identifies a readily translatable therapeutic strategy for preterm brain disorders.PMID:38427732 | DOI:10.1126/sciadv.adk8123

Methods Mol Biol. 2024;2785:221-260. doi: 10.1007/978-1-0716-3774-6_14.ABSTRACTRecent research has revealed the potential of lipidomics and metabolomics in identifying new biomarkers and mechanistic insights for neurodegenerative disorders. To contribute to this promising area, we present a detailed protocol for conducting an integrated lipidomic and metabolomic profiling of brain tissue and biofluid samples. In this method, a single-phase methanol extraction is employed for extracting both nonpolar and highly polar lipids and metabolites from each biological sample. The extracted samples are then subjected to liquid chromatography-mass spectrometry-based assays to provide relative or semiquantitative measurements for hundreds of selected lipids and metabolites per sample. This high-throughput approach enables the generation of new hypotheses regarding the mechanistic and functional significance of lipid and metabolite alterations in neurodegenerative disorders while also facilitating the discovery of new biomarkers to support drug development.PMID:38427197 | DOI:10.1007/978-1-0716-3774-6_14

Methods Mol Biol. 2024;2785:75-86. doi: 10.1007/978-1-0716-3774-6_6.ABSTRACTThe integration of complementary analytical platforms is nowadays the most common strategy for comprehensive metabolomics analysis of complex biological systems. In this chapter, we describe methods and tips for the application of a mass spectrometry multi-platform in Alzheimer's disease research, based on the combination of direct mass spectrometry and orthogonal hyphenated approaches, namely, reversed-phase ultrahigh-performance liquid chromatography and gas chromatography. These procedures have been optimized for the analysis of multiple biological samples from human patients and transgenic animal models, including blood serum, various brain regions (e.g., hippocampus, cortex, cerebellum, striatum, olfactory bulbs), and other peripheral organs (e.g., liver, kidney, spleen, thymus).PMID:38427189 | DOI:10.1007/978-1-0716-3774-6_6

Metabolomics. 2024 Mar 1;20(2):33. doi: 10.1007/s11306-024-02098-y.ABSTRACTINTRODUCTION: Because cerebrospinal fluid (CSF) samples are difficult to obtain for paediatric HIV, few studies have attempted to profile neurometabolic dysregulation.AIM AND OBJECTIVE: The aim of this exploratory study was to profile the neurometabolic state of CSF from a South African paediatric cohort using GCxGC-TOF/MS. The study included 54 paediatric cases (< 12 years), 42 HIV-negative controls and 12 HIV-positive individuals.RESULTS: The results revealed distinct metabolic alterations in the HIV-infected cohort. In the PLS-DA model, 18 metabolites significantly discriminated between HIV-infected and control groups. In addition, fold-change analysis, Mann-Whitney U tests, and effect size measurements verified these findings. Notably, lactose, myo-inositol, and glycerol, although not significant by p-value alone, demonstrated practical significance based on the effect size.CONCLUSIONS: This study provided valuable insights on the impact of HIV on metabolic pathways, including damage to the gut and blood-brain barrier, disruption of bioenergetics processes, gliosis, and a potential marker for antiretroviral therapy. Nevertheless, the study recognized certain constraints, notably a limited sample size and the absence of a validation cohort. Despite these limitations, the rarity of the study's focus on paediatric HIV research underscores the significance and unique contributions of its findings.PMID:38427142 | DOI:10.1007/s11306-024-02098-y

Clin Exp Med. 2024 Mar 1;24(1):49. doi: 10.1007/s10238-024-01309-z.ABSTRACTIn the dynamic process of metastasis, circulating tumor cells (CTCs) emanate from the primary solid tumor and subsequently acquire the capacity to disengage from the basement membrane, facilitating their infiltration into the vascular system via the interstitial tissue. Given the pivotal role of CTCs in the intricate hematogenous metastasis, they have emerged as an essential resource for a deeper comprehension of cancer metastasis while also serving as a cornerstone for the development of new indicators for early cancer screening and new therapeutic targets. In the epoch of precision medicine, as CTC enrichment and separation technologies continually advance and reach full fruition, the domain of CTC research has transcended the mere straightforward detection and quantification. The rapid advancement of CTC analysis platforms has presented a compelling opportunity for in-depth exploration of CTCs within the bloodstream. Here, we provide an overview of the current status and research significance of multi-omics studies on CTCs, including genomics, transcriptomics, proteomics, and metabolomics. These studies have contributed to uncovering the unique heterogeneity of CTCs and identifying potential metastatic targets as well as specific recognition sites. We also review the impact of various states of CTCs in the bloodstream on their metastatic potential, such as clustered CTCs, interactions with other blood components, and the phenotypic states of CTCs after undergoing epithelial-mesenchymal transition (EMT). Within this context, we also discuss the therapeutic implications and potential of CTCs.PMID:38427120 | DOI:10.1007/s10238-024-01309-z

Diabetologia. 2024 Mar 1. doi: 10.1007/s00125-024-06116-5. Online ahead of print.ABSTRACTAIMS/HYPOTHESIS: As a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia.METHODS: Eighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic-euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure.RESULTS: While glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (p<0.001). Metabolomics revealed an increase in the most common NEFAs (p<0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant.CONCLUSIONS/INTERPRETATION: In conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes.TRIAL REGISTRATION: ClinicalTrials.gov NCT05095259.PMID:38427076 | DOI:10.1007/s00125-024-06116-5