PubMed

Cell Mol Biol Lett. 2023 Aug 5;28(1):63. doi: 10.1186/s11658-023-00479-0.ABSTRACTBACKGROUND: Nitrogen (N), phosphorus (P) and potassium (K) are critical macronutrients in crops, such that deficiency in any of N, P or K has substantial effects on crop growth. However, the specific commonalities of plant responses to different macronutrient deficiencies remain largely unknown.METHODS: Here, we assessed the phenotypic and physiological performances along with whole transcriptome and metabolomic profiles of rapeseed seedlings exposed to N, P and K deficiency stresses.RESULTS: Quantities of reactive oxygen species were significantly increased by all macronutrient deficiencies. N and K deficiencies resulted in more severe root development responses than P deficiency, as well as greater chlorophyll content reduction in leaves (associated with disrupted chloroplast structure). Transcriptome and metabolome analyses validated the macronutrient-specific responses, with more pronounced effects of N and P deficiencies on mRNAs, microRNAs (miRNAs), circular RNAs (circRNAs) and metabolites relative to K deficiency. Tissue-specific responses also occurred, with greater effects of macronutrient deficiencies on roots compared with shoots. We further uncovered a set of common responders with simultaneous roles in all three macronutrient deficiencies, including 112 mRNAs and 10 miRNAs involved in hormonal signaling, ion transport and oxidative stress in the root, and 33 mRNAs and 6 miRNAs with roles in abiotic stress response and photosynthesis in the shoot. 27 and seven common miRNA-mRNA pairs with role in miRNA-mediated regulation of oxidoreduction processes and ion transmembrane transport were identified in all three macronutrient deficiencies. No circRNA was responsive to three macronutrient deficiency stresses, but two common circRNAs were identified for two macronutrient deficiencies. Combined analysis of circRNAs, miRNAs and mRNAs suggested that two circRNAs act as decoys for miR156 and participate in oxidoreduction processes and transmembrane transport in both N- and P-deprived roots. Simultaneously, dramatic alterations of metabolites also occurred. Associations of RNAs with metabolites were observed, and suggested potential positive regulatory roles for tricarboxylic acids, azoles, carbohydrates, sterols and auxins, and negative regulatory roles for aromatic and aspartate amino acids, glucosamine-containing compounds, cinnamic acid, and nicotianamine in plant adaptation to macronutrient deficiency.CONCLUSIONS: Our findings revealed strategies to rescue rapeseed from macronutrient deficiency stress, including reducing the expression of non-essential genes and activating or enhancing the expression of anti-stress genes, aided by plant hormones, ion transporters and stress responders. The common responders to different macronutrient deficiencies identified could be targeted to enhance nutrient use efficiency in rapeseed.PMID:37543634 | DOI:10.1186/s11658-023-00479-0

Nat Commun. 2023 Aug 5;14(1):4711. doi: 10.1038/s41467-023-40392-w.ABSTRACTLegumes can utilize atmospheric nitrogen via symbiotic nitrogen fixation, but this process is inhibited by high soil inorganic nitrogen. So far, how high nitrogen inhibits N2 fixation in mature nodules is still poorly understood. Here we construct a co-expression network in soybean nodule and find that a dynamic and reversible transcriptional network underlies the high N inhibition of N2 fixation. Intriguingly, several NAC transcription factors (TFs), designated as Soybean Nitrogen Associated NAPs (SNAPs), are amongst the most connected hub TFs. The nodules of snap1/2/3/4 quadruple mutants show less sensitivity to the high nitrogen inhibition of nitrogenase activity and acceleration of senescence. Integrative analysis shows that these SNAP TFs largely influence the high nitrogen transcriptional response through direct regulation of a subnetwork of senescence-associated genes and transcriptional regulators. We propose that the SNAP-mediated transcriptional network may trigger nodule senescence in response to high nitrogen.PMID:37543605 | DOI:10.1038/s41467-023-40392-w

Cell Mol Life Sci. 2023 Aug 5;80(8):241. doi: 10.1007/s00018-023-04885-7.ABSTRACTSpinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene resulting in reduced levels of the SMN protein. Nusinersen, the first antisense oligonucleotide (ASO) approved for SMA treatment, binds to the SMN2 gene, paralogue to SMN1, and mediates the translation of a functional SMN protein. Here, we used longitudinal high-resolution mass spectrometry (MS) to assess both global proteome and metabolome in cerebrospinal fluid (CSF) from ten SMA type 3 patients, with the aim of identifying novel readouts of pharmacodynamic/response to treatment and predictive markers of treatment response. Patients had a median age of 33.5 [29.5; 38.25] years, and 80% of them were ambulant at time of the enrolment, with a median HFMSE score of 37.5 [25.75; 50.75]. Untargeted CSF proteome and metabolome were measured using high-resolution MS (nLC-HRMS) on CSF samples obtained before treatment (T0) and after 2 years of follow-up (T22). A total of 26 proteins were found to be differentially expressed between T0 and T22 upon VSN normalization and LIMMA differential analysis, accounting for paired replica. Notably, key markers of the insulin-growth factor signaling pathway were upregulated after treatment together with selective modulation of key transcription regulators. Using CombiROC multimarker signature analysis, we suggest that detecting a reduction of SEMA6A and an increase of COL1A2 and GRIA4 might reflect therapeutic efficacy of nusinersen. Longitudinal metabolome profiling, analyzed with paired t-Test, showed a significant shift for some aminoacid utilization induced by treatment, whereas other metabolites were largely unchanged. Together, these data suggest perturbation upon nusinersen treatment still sustained after 22 months of follow-up and confirm the utility of CSF multi-omic profiling as pharmacodynamic biomarker for SMA type 3. Nonetheless, validation studies are needed to confirm this evidence in a larger sample size and to further dissect combined markers of response to treatment.PMID:37543540 | DOI:10.1007/s00018-023-04885-7

EBioMedicine. 2023 Jul 21:104733. doi: 10.1016/j.ebiom.2023.104733. Online ahead of print.ABSTRACTBACKGROUND: Autonomous cortisol secretion (ACS), resulting from cortisol-producing adenomas (CPA), causes endogenous steroid-induced osteoporosis (SIOP). However, the risk of endogenous SIOP cannot be explained by cortisol excess alone, and how other steroid metabolites affect bone status is unclear.METHODS: ACS was diagnosed as serum cortisol ≥1.8 μg/dL after the 1-mg dexamethasone suppression test (DST-cortisol). Using liquid chromatography tandem mass spectrometry, 21 plasma steroid metabolites were measured in 73 patients with ACS and 85 patients with non-functioning adrenal tumors (NFAT). Expression of steroidogenic enzymes and relevant steroid metabolites were analyzed in some of CPA tissues.FINDINGS: Discriminant and principal component analyses distinguished steroid profiles between the ACS and NFAT groups in premenopausal women. Premenopausal women with ACS exhibited higher levels of a mineralocorticoid metabolite, 11-deoxycorticosterone (11-DOC), and lower levels of androgen metabolites, dehydroepiandrosterone-sulfate, and androsterone-glucuronide. In premenopausal women with ACS, DST-cortisol negatively correlated with trabecular bone score (TBS). Additionally, 11-DOC negatively correlated with lumbar spine-bone mineral density, whereas androsterone-glucuronide positively correlated with TBS. The CPA tissues showed increased 11-DOC levels with increased expression of CYP21A2, essential for 11-DOC synthesis. Adrenal non-tumor tissues were atrophied with reduced expression of CYB5A, required for androgen synthesis.INTERPRETATION: This study demonstrates that unbalanced production of adrenal steroid metabolites, derived from both adrenal tumor and non-tumor tissues, contributes to the pathogenesis of endogenous SIOP in premenopausal women with ACS.FUNDING: JSPS KAKENHI, Secom Science and Technology Foundation, Takeda Science Foundation, Japan Foundation for Applied Enzymology, AMED-CREST, JSTA-STEP, JST-Moonshot, and Ono Medical Research Foundation.PMID:37543511 | DOI:10.1016/j.ebiom.2023.104733

Brain Behav Immun. 2023 Aug 3:S0889-1591(23)00215-5. doi: 10.1016/j.bbi.2023.07.022. Online ahead of print.ABSTRACTThe field of psychoneuroimmunology (PNI) has grown substantially in both relevance and prominence over the past 40 years. Notwithstanding its impressive trajectory, a majority of PNI studies are still based on a relatively small number of analytes. To advance this work, we suggest that PNI, and health research in general, can benefit greatly from adopting a multi-omics approach, which involves integrating data across multiple biological levels (e.g., the genome, proteome, transcriptome, metabolome, lipidome, and microbiome/metagenome) to more comprehensively profile biological functions and relate these profiles to clinical and behavioral outcomes. To assist investigators in this endeavor, we provide an overview of multi-omics research, highlight recent landmark multi-omics studies investigating human health and disease risk, and discuss how multi-omics can be applied to better elucidate links between psychological, nervous system, and immune system activity. In doing so, we describe how to design high-quality multi-omics PNI studies, decide which biological samples (e.g., blood, stool, urine, saliva, solid tissue) are most relevant, incorporate behavioral and wearable sensing data into multi-omics research, and understand key data quality, integration, analysis, and interpretation issues. PNI researchers are addressing some of the most interesting and important questions at the intersection of psychology, neuroscience, and immunology. Applying a multi-omics approach to this work will greatly expand the horizon of what is possible in PNI and has the potential to revolutionize our understanding of mind-body medicine.PMID:37543247 | DOI:10.1016/j.bbi.2023.07.022

J Nutr. 2023 Aug 3:S0022-3166(23)72527-3. doi: 10.1016/j.tjnut.2023.08.003. Online ahead of print.ABSTRACTBACKGROUND: Milk composition is complex and includes numerous components essential for offspring growth and development. In addition to the high abundance of miR-30b microRNA, milk produced by the transgenic mouse model of miR-30b-mammary deregulation displays a significantly altered fatty acid profile. Moreover, wild-type adopted pups fed miR-30b milk present an early growth defect.OBJECTIVE: This study aimed to investigate the consequences of miR-30b milk feeding on the duodenal development of wild-type neonates, a prime target of suckled milk, along with comprehensive milk phenotyping.METHODS: The duodenum of wild-type pups fed miR-30b milk was extensively characterized at postnatal day (PND)-5, PND-6, and PND-15 using histological, transcriptomic, proteomic, and duodenal permeability analyses, and compared to pups fed wild-type milk. Milk of miR-30b foster dams collected at mid-lactation was extensively analyzed using proteomic, metabolomic, and lipidomic approaches and hormonal immunoassays.RESULTS: At PND-5, wild-type pups fed miR-30b milk showed maturation of their duodenum (1.5-fold (p<0.05) and 1.3-fold (p<0.10) increase expression of Claudin-3 and Claudin-4, respectively; changes in eight duodenal protein; p<0.10), with an earlier reduction in paracellular and transcellular permeability (183 ng/mL FSA and 12 ng/ml HRP, respectively, compared to 5,700 ng/mL FSA and 90 ng/ml HRP in wild-type; p<0.001). Compared to wild-type milk, miR-30b milk displayed an increase in total lipid (219 g/L compared to 151 g/L; p<0.05), ceramide (17.6 μM compared to 6.9 μM; p<0.05), sphingomyelin levels (163.7 μM compared to 76.3 μM; p<0.05), the over-expression of nine proteins involved in the gut barrier (p<0.1) and higher insulin and leptin levels (1.88 ng/ml and 2.04 ng/ml, respectively, compared to 0.79 ng/ml and 1.06 ng/ml; p<0.01).CONCLUSIONS: miR-30b milk displays significant changes in bioactive components associated with neonatal duodenal integrity and maturation which could be involved in the earlier intestinal closure phenotype of the wild-type pups associated with a lower growth rate.PMID:37543213 | DOI:10.1016/j.tjnut.2023.08.003

J Pharm Biomed Anal. 2023 Jul 29;235:115610. doi: 10.1016/j.jpba.2023.115610. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is a progressive disease with continuous brain changes and has caused a severe burden on families and society. Huanglian Jiedu Decoction (HLJD) is a classic traditional Chinese medicine formula that can improve AD animals' cognitive impairment. This study recruited 50 AD patients who were divided into two groups, one receiving donepezil (DON) treatment and the other receiving DON + HLJD treatment for 3 months. The curative effect, inflammatory and oxidative stress levels were analyzed. The PES-D/11, MMSE, and ADL scales were used to evaluate traditional Chinese medicine syndrome elements, cognitive function, mental state, and life ability. There were no significant differences between the two groups in baseline characteristics and vital sign indicators. After drug treatment, the results showed that AD patients with HLJD combined with DON treatment didn't increase the adverse effects and had good compliance. HLJD combined with DON could improve the disease syndrome, making the differences in PES-D/11, MMSE, and ADL scores before and after the intervention larger. Furthermore, both DON and DON+HLJD treatment inhibited the levels of IL-6, IL-1β, TNF-α, and MDA, raised SOD level, and HLJD enhances the inhibitory effect of DON on inflammation and oxidative stress. IL-6, IL-1β, TNF-α, and MDA levels were significantly correlated with curative effect. Moreover, this study found 107 (206) up-regulated metabolites and 1430 (145) down-regulated metabolites in urine (serum) and conducted differential metabolite screening and correlation analysis suggesting that HLJD may interfere with oxidative stress and inflammation in AD by regulating lipid metabolism and glutamic acid metabolism. Arachidonic acid, diaminopimelic acid, and 1-Aminocyclopropanecarboxylic acid may play an important role in HLJD to improve AD.PMID:37542831 | DOI:10.1016/j.jpba.2023.115610

J Pharm Biomed Anal. 2023 Jul 29;235:115611. doi: 10.1016/j.jpba.2023.115611. Online ahead of print.ABSTRACTEnrichment of pharmaceutically important vinca alkaloids, vinblastine and vincristine, in the leaves of Madagascar periwinkle (Catharanthus roseus) plants through different pre- or postharvest treatments or cultivation conditions, e.g., exposing the plants to UV-irradiation, has been in focus for decades. Controlled LED environment in the visible light range offers the possibility of monitoring the changes in the concentration of metabolites in the vinca alkaloid-related pathway without involving UV-related abiotic stress. In the frame of our targeted metabolomics approach, 64 vinca alkaloids and metabolites were screened with the help of a UPLC-ESI-QTOF-MS instrumental setup from the leaf extracts of C. roseus plants grown in chambers under control (medium light), low light, and high blue / high red/ high far-red conditions. Out of the 14 metabolites that could be assigned either unambiguously with authentic standards or tentatively with high resolution mass spectrometry-based methods, all three dimer vinca alkaloids, that is, 3',4'-anhydrovinblastine, vinblastine and vincristine showed an at least nine-fold enrichment under high blue irradiation when compared with the control conditions: final concentrations of 961 mg kg-1 dry weight, 33.8 mg kg-1 dry weight, and 11.7 mg kg-1 dry weight could be achieved, respectively. As supported by multivariate statistical analysis, the key metabolites of the vinca alkaloid pathway were highly represented among the metabolites that were specifically stimulated by high blue light application.PMID:37542828 | DOI:10.1016/j.jpba.2023.115611

BMC Biol. 2023 Aug 4;21(1):166. doi: 10.1186/s12915-023-01650-x.ABSTRACTBACKGROUND: The extracellular space between the cell wall and plasma membrane is a battlefield in plant-pathogen interactions. Within this space, the pathogen employs its secretome to attack the host in a variety of ways, including immunity manipulation. However, the role of the plant secretome is rarely studied for its role in disease resistance.RESULTS: Here, we examined the secretome of Verticillium wilt-resistant Gossypium hirsutum cultivar Zhongzhimian No.2 (ZZM2, encoding 95,327 predicted coding sequences) to determine its role in disease resistance against the wilt causal agent, Verticillium dahliae. Bioinformatics-driven analyses showed that the ZZM2 genome encodes 2085 secreted proteins and that these display disequilibrium in their distribution among the chromosomes. The cotton secretome displayed differences in the abundance of certain amino acid residues as compared to the remaining encoded proteins due to the localization of these putative proteins in the extracellular space. The secretome analysis revealed conservation for an allotetraploid genome, which nevertheless exhibited variation among orthologs and comparable unique genes between the two sub-genomes. Secretome annotation strongly suggested its involvement in extracellular stress responses (hydrolase activity, oxidoreductase activity, and extracellular region, etc.), thus contributing to resistance against the V. dahliae infection. Furthermore, the defense response genes (immunity marker NbHIN1, salicylic acid marker NbPR1, and jasmonic acid marker NbLOX4) were activated to varying degrees when Nicotina benthamiana leaves were agro-infiltrated with 28 randomly selected members, suggesting that the secretome plays an important role in the immunity response. Finally, gene silencing assays of 11 members from 13 selected candidates in ZZM2 displayed higher susceptibility to V. dahliae, suggesting that the secretome members confer the Verticillium wilt resistance in cotton.CONCLUSIONS: Our data demonstrate that the cotton secretome plays an important role in Verticillium wilt resistance, facilitating the development of the resistance gene markers and increasing the understanding of the mechanisms regulating disease resistance.PMID:37542270 | PMC:PMC10403859 | DOI:10.1186/s12915-023-01650-x

Biol Res. 2023 Aug 5;56(1):44. doi: 10.1186/s40659-023-00456-z.ABSTRACTBACKGROUND: Malignant cells adopt anoikis resistance to survive anchorage-free stresses and initiate cancer metastasis. It is still unknown how varying periods of anchorage loss contribute to anoikis resistance, cell migration, and metabolic reprogramming of cancerous cells.RESULTS: Our study demonstrated that prolonging the anchorage-free lifetime of non-small-cell lung cancer NCI-H460 cells for 7 days strengthened anoikis resistance, as shown by higher half-life and capability to survive and grow without anchorage, compared to wild-type cells or those losing anchorage for 3 days. While the prolonged anchorage-free lifetime was responsible for the increased aggressive feature of survival cells to perform rapid 3-dimensional migration during the first 3 h of a transwell assay, no significant influence was observed with 2-dimensional surface migration detected at 12 and 24 h by a wound-healing method. Metabolomics analysis revealed significant alteration in the intracellular levels of six (oxalic acid, cholesterol, 1-ethylpyrrolidine, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, β-alanine, and putrescine) among all 37 identified metabolites during 7 days without anchorage. Based on significance values, enrichment ratios, and impact scores of all metabolites and their associated pathways, three principal metabolic activities (non-standard amino acid metabolism, cell membrane biosynthesis, and oxidative stress response) offered potential links with anoikis resistance.CONCLUSIONS: These findings further our insights into the evolution of anoikis resistance in lung cancer cells and identify promising biomarkers for early lung cancer diagnosis.PMID:37542350 | DOI:10.1186/s40659-023-00456-z

Expert Rev Anticancer Ther. 2023 Aug 4. doi: 10.1080/14737140.2023.2245144. Online ahead of print.ABSTRACTINTRODUCTION: Liquid biopsies are used for the detection of tumor-specific elements in body fluid. Their application in prognosis and diagnosis of muscle/non-muscle invasive bladder cancer (MIBC/NMIBC) or upper tract urothelial cancer (UTUC) remains poorly known and rarely mentioned in clinical guidelines.AREAS COVERED: Herein, we provide an overview of current data regarding the use of liquid biopsies in urothelial tumors.EXPERT OPINION: Studies that were included analyzed liquid biopsies using the detection of circulating tumor cells (CTCs), deoxyribonucleic acid (DNA), ribonucleic acid (RNA), exosomes or metabolomics. The sensitivity of blood CTC detection in patients with localized cancer was 35% and raised to 50% in patients with metastatic cancer. In NMIBC patients, blood CTC was associated with poor prognosis (time to recurrence and progression), whereas discrepancies were seen in MIBC patients. Circulating plasma DNA presented a superior sensitivity to urine. Moreover, it was a good indicator for diagnosis, follow-up, and oncological outcome. In urine, specific bladder cancer (BC) microRNA had an overall sensitivity of 85% and a specificity of 86% in the diagnosis of urothelial cancer. These results support the growing evidence for the use of liquid biopsies to provide biomarkers for the diagnosis, follow-up or prognosis of urothelial cancer. Further development and understanding on the use of liquid biopsies are needed in order to include it as part of urothelial cancer management.PMID:37542214 | DOI:10.1080/14737140.2023.2245144

Am J Surg. 2023 Jul 28:S0002-9610(23)00374-4. doi: 10.1016/j.amjsurg.2023.07.040. Online ahead of print.ABSTRACTBACKGROUND: The interactions of polytrauma, shock, and traumatic brain injury (TBI) on thromboinflammatory responses remain unclear and warrant investigation as we strive towards personalized medicine in trauma. We hypothesized that comprehensive omics characterization of plasma would identify unique metabolic and thromboinflammatory pathways following TBI.METHODS: Patients were categorized as TBI vs Non-TBI, and stratified into Polytrauma or minimally injured. Discovery 'omics was employed to quantify the top differently expressed proteins and metabolites of TBI and Non-TBI patient groups.RESULTS: TBI compared to Non-TBI showed gene enrichment in coagulation/complement cascades and neuronal markers. TBI was associated with elevation in glycolytic metabolites and conjugated bile acids. Division into isolated TBI vs polytrauma showed further distinction of proteomic and metabolomic signatures.CONCLUSION: Identified mediators involving in neural inflammation, blood brain barrier disruption, and bile acid building leading to TBI associated coagulopathy offer suggestions for follow up mechanistic studies to target personalized interventions.PMID:37541795 | DOI:10.1016/j.amjsurg.2023.07.040

J Adv Res. 2023 Aug 2:S2090-1232(23)00206-0. doi: 10.1016/j.jare.2023.08.002. Online ahead of print.ABSTRACTINTRODUCTION: Entry into the viable but nonculturable (VBNC) state is a survival strategy adopted by bacteria to survive harsh environment. Although VBNC cells still have metabolic activity, they lose the ability to form colonies on nonselective culture media. Thus, conventional bacterial detection methods, such as plate counting, are unable to detect the presence of VBNC cells. When the environmental conditions are appropriate, VBNC cells can initiate resuscitation, posing a great risk to the safety of public health. The study of the VBNC resuscitation mechanism could provide new insights into the prevention and control of VBNC resuscitation.OBJECTIVES: Uncovering the molecular mechanism of VBNC cell resuscitation by investigating the role of O-antigen ligase (RfaL) in inhibiting the resuscitation of Escherichia coli O157:H7 in the VBNC state.METHODS: RfaL was screened and verified as a resuscitation inhibitor of VBNC Escherichia coli O157:H7 by detecting resuscitation curve and time-lapse microscopy. The mechanism of RfaL impacts VBNC E. coli resuscitation was investigated by detecting the single cell ATP content, metabolomic changes, NAD(H) content and new protein biosynthesis of WT and ΔrfaL at different stage of resuscitation.RESULTS: Mutation of rfaL, which encoded an O-antigen ligase, markedly shortened the resuscitating lag phase. Further studies indicated that ΔrfaL VBNC cells contained higher ATP levels, and ATP consumption during the resuscitating lag phase was highly correlated with resuscitation efficiency. Metabolomic analysis revealed that ATP was utilized to activate the Handler and salvage pathways to synthesize NAD+, balancing redox reactions to recover cell activity and promote cell resuscitation.CONCLUSION: Our findings revealed a strategy employed by VBNC cells for revival, that is, using residual ATP to primarily recover metabolic activity, driving cells to exit dormancy. The synthesis pathway of lipopolysaccharide (LPS) in rfaL null mutant was inhibited and could supply more ATP to synthesis NAD+ and promote resuscitation.PMID:37541583 | DOI:10.1016/j.jare.2023.08.002

J Nutr. 2023 Aug 2:S0022-3166(23)72524-8. doi: 10.1016/j.tjnut.2023.08.001. Online ahead of print.ABSTRACTBACKGROUND: Dairy consumption is related to chronic disease risk, yet the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake.OBJECTIVES: We aimed to identify associations between dietary intake of dairy (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in two independent study populations of U.S. adults.METHODS: Dietary intake was assessed with food frequency questionnaires. Multivariable linear regression models were used to estimate cross-sectional associations between dietary intake of dairy and 360 serum metabolites analyzed in two subgroups of the Atherosclerosis Risk in Communities study (ARIC; n= 3776). Results from the two subgroups were meta-analyzed using fixed effects meta-analysis. Significant meta-analyzed associations in the ARIC study were then tested in the Bogalusa Heart Study (BHS; n= 785).RESULTS: In the ARIC study and BHS, respectively, mean age was 54 and 48 years, 61% and 29% were Black, and mean dairy intake was 1.7 and 1.3 servings/day. Twenty-nine significant associations between dietary intake of dairy and serum metabolites were identified in the ARIC study (total dairy, n=14; low-fat dairy, n=10; high-fat dairy, n=5). Three associations were also significant in BHS: myristate (14:0) was associated with high-fat dairy and pantothenate was associated with total dairy and low-fat dairy, but 23 of the 27 associations significant in the ARIC study and tested in BHS were not associated with dairy in BHS.CONCLUSIONS: We identified metabolomic associations with dietary intake of dairy, including three associations found in two independent cohort studies. These results suggest that myristate (14:0) and pantothenate (vitamin B5) are candidate biomarkers of dairy consumption.PMID:37541543 | DOI:10.1016/j.tjnut.2023.08.001

J Nutr. 2023 Aug 2:S0022-3166(23)72523-6. doi: 10.1016/j.tjnut.2023.07.014. Online ahead of print.ABSTRACTBACKGROUND: Dyslipidemia is important due to its association with various metabolic complications. Numerous studies have sought to obtain scientific evidence for managing dyslipidemia patients.OBJECTIVES: This study aims to identify differences in the nutritional traits of dyslipidemia subjects based on metabolite pattern.METHODS: Dyslipidemia (n = 73) and control (n = 80) subjects were included. Dyslipidemia was defined as triglycerides ≥ 200 mg/dL, total cholesterol ≥ 240 mg/dL, low-density lipoprotein cholesterol ≥ 160 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL (men) or 50 mg/dL (women), or lipid-lowering medicine use. Nontargeted metabolomics based on ultra high performance liquid chromatography-mass spectrometry identified plasma metabolites, and K-means clustering was used to reconstitute groups based on the similarity of metabolomic patterns across all subjects. Then, with eXtreme Gradient Boosting (XGBoost), metabolites significantly contributing to the new grouping were selected. Statistical analysis was conducted to analyze traits demonstrating appreciable differences between the groups.RESULTS: Dyslipidemia subjects were divided into two groups based on whether they were (n = 24) or were not (n = 56) in a similar metabolic state as the controls by K-means clustering. The considerable contribution of four metabolites (3-hydroxybutyrylcarnitine, 2-octenal, 1,3,5-heptatriene, and 5 β-cholanic acid) to this new subset of dyslipidemia was confirmed by XGBoost. Furthermore, fiber intake was significantly higher in dyslipidemia subjects whose metabolic state was similar to that of the control than in the dissimilar group (p = 0.002). Moreover, significant correlations were observed between the four metabolites and fiber intake. Regression analysis determined that the ideal cutoff for fiber intake was 17.28 g/day.CONCLUSIONS: Dyslipidemia patients who consume 17.28 g/day or more of dietary fiber may maintain similar metabolic patterns to healthy individuals, with substantial effects on the changes in the levels of four metabolites. Our findings could be applied to developing dietary guidelines for dyslipidemia patients.PMID:37541542 | DOI:10.1016/j.tjnut.2023.07.014

Prog Neuropsychopharmacol Biol Psychiatry. 2023 Aug 2:110836. doi: 10.1016/j.pnpbp.2023.110836. Online ahead of print.ABSTRACTAlong with the typical biochemical alterations that occur during pregnancy, certain metabolic changes might be associated with the development of several psychiatric disorders, including postpartum depression (PPD), which is the most common type of psychiatric disorder during pregnancy or first postpartum year, and it develops in about 15% of women. Metabolomics is a rapidly developing discipline that deals with the metabolites as the final products of all genetically controlled biochemical pathways, highly influenced by external and internal changes. The aim of this paper was to review the published studies whose results suggest or deny a possible association between the fine regulation of the metabolome and PPD, enabling conclusions about whether metabolomics could be a useful tool in defining the biochemical pathways directly involved in the etiology, diagnosis and course of PPD. Beside numerous hormonal changes, a lot of different metabolic pathways have been discovered to be affected in women with PPD or associated with its development, including alterations in the energy metabolism, tryptophan and amino acid metabolism, steroid metabolism, purine cycle, as well as neurotransmitter metabolism. Additionally, metabolomics helped in defining the association between PPD and the exposure to various endocrine disrupting metabolites during pregnancy. Finally, metabolome reflects different PPD therapies and exposure of fetus or breastfed infants to pharmacotherapy prescribed to a mother suffering from PPD. This review can help in creating the picture about metabolomics' broad application in PPD studies, but it also implies that its potential is still not completely used.PMID:37541332 | DOI:10.1016/j.pnpbp.2023.110836

Cell Stem Cell. 2023 Aug 3;30(8):1054-1071.e8. doi: 10.1016/j.stem.2023.07.010.ABSTRACTWhite matter injuries (WMIs) are the leading cause of neurologic impairment in infants born premature. There are no treatment options available. The most common forms of WMIs in infants occur prior to the onset of normal myelination, making its pathophysiology distinctive, thus requiring a tailored approach to treatment. Neonates present a unique opportunity to repair WMIs due to a transient abundance of neural stem/progenitor cells (NSPCs) present in the germinal matrix with oligodendrogenic potential. We identified an endogenous oxysterol, 20-αHydroxycholesterol (20HC), in human maternal breast milk that induces oligodendrogenesis through a sonic hedgehog (shh), Gli-dependent mechanism. Following WMI in neonatal mice, injection of 20HC induced subventricular zone-derived oligodendrogenesis and improved myelination in the periventricular white matter, resulting in improved motor outcomes. Targeting the oligodendrogenic potential of postnatal NSPCs in neonates with WMIs may be further developed into a novel approach to mitigate this devastating complication of preterm birth.PMID:37541211 | DOI:10.1016/j.stem.2023.07.010

J Hazard Mater. 2023 Jul 20;459:132097. doi: 10.1016/j.jhazmat.2023.132097. Online ahead of print.ABSTRACTThe accumulation of microplastics (MPs) in sediments could pose risks to benthic organisms and their progeny. Here, we examined effects on traditional apical endpoints along with changes to whole body metabolite profiles induced by irregular shaped polyethylene MPs (1-45 µm) at environmentally relevant concentrations (125, 250, 500 and 1000 MPs/kg sediment) in Chironomus tepperi using a two-generation exposure regime. Survival and emergence of C. tepperi were negatively affected in the parental generation at the two highest concentrations, whereas endpoints associated with growth were only impacted at 1000 MPs/kg sediment. Metabolites associated with several amino acid and energy metabolism pathways were present at lower abundances at the highest exposure concentration suggesting an overall impact on bioenergetics which relates to the inhibition of food acquisition or nutrient assimilation caused by ingestion of MPs, rather than a traditional receptor-mediated toxicity response. In contrast, no significant effects on apical endpoints were observed in the continuous exposure of first filial generation, and lactic acid was the only metabolite that differed significantly between groups. Larvae in unexposed conditions showed no differences in survival or metabolite profiles suggesting that effects in the parental generation do not carry over to the next filial generation. The findings provide evidence on the underlying impacts of MP ingestion and potential adaption to MP exposure of C. tepperi.PMID:37541122 | DOI:10.1016/j.jhazmat.2023.132097

J Chromatogr A. 2023 Jul 22;1706:464239. doi: 10.1016/j.chroma.2023.464239. Online ahead of print.ABSTRACTCationic, anionic, zwitterionic and, partially polar metabolites are very important constituents of blood serum. Several of these metabolites underpin the core metabolism of cells (e.g., Krebs cycle, urea cycle, proteins synthesis, etc.), while others might be considered ancillary but still important to grasp the status of any organism through blood serum analysis. Due to its wide chemical diversity, modern metabolomics analysis of serum is still struggling to provide a complete and comprehensive picture of the polar metabolome, due to the limitations of each specific analytical method. In this study, two metabolomics-based analytical methods using the most successful techniques for polar compounds separation in human serum samples, namely hydrophilic interaction liquid chromatography (HILIC) and capillary electrophoresis (CE), are evaluated, both coupled to a high-resolution time-of-flight mass spectrometer via electrospray ionization (ESI-Q-TOF-MS). The performance of the two methods have been compared using five terms of comparison, three of which are specific to metabolomics, such as (1) compounds' detectability (2) Pezzatti score (Pezzatti et al. 2018), (3) intra-day precision (repeatability), (4) ease of automatic analysis of the data (through a common deconvolution alignment and extrapolation software, MS-DIAL, and (5) time & cost analysis. From this study, HILIC-MS proved to be a better tool for polar metabolome analysis, while CE-MS helped identify some interesting variables that gave it interest in completing metabolome coverage in metabolomics studies. Finally, in this framework, MS-DIAL demonstrates for the first time its ability to process CE data for metabolomics, although it is not designed for it.PMID:37541059 | DOI:10.1016/j.chroma.2023.464239

Arch Oral Biol. 2023 Jul 27;154:105776. doi: 10.1016/j.archoralbio.2023.105776. Online ahead of print.ABSTRACTOBJECTIVE: The present study aims to investigate the variations in dental caries (DC) related microbiome abnormality and metabolomics shift in children.DESIGN: The patients were divided into two groups healthy control (C) and highly affected DC children based on inclusion and exclusion criteria. Saliva samples were collected and used for the taxonomic and functional characterization of oral microbiota.RESULTS: Metatranscriptomics analysis revealed the alterations and composition of oral microbiota in the C and DC groups. Relative abundance in the C group was associated with Firmicutes, Actinobacteria, and Bacteroidetes. Whereas, the microbial composition in the DC group was found to be considerably altered with increases in the abundance of the Proteobacteria (25%), Fusobacteria (15%), and Cyanobacteria (8%) while decreases in the abundance of Firmicutes (10%) and Bacteroidetes (23%). Alterations in the phylum composition were positively and negatively correlated with several metabolites of sugars (such as fructose, sorbose, ribose, allose, and mannose) and amino acids (such as arginine, lysine, tryptophan, and proline). Moreover, in comparison with the C group, the metabolic shift of the DC group was different with an increase in certain tricarboxylic acid cycle intermediates levels, and a decrease in fatty acid. Such alterations can enhance the growth of oral pathogens and contribute to DC development.CONCLUSIONS: The findings of this study suggest that an altered abundance of Actinobacillus, Fusobacterium, and Shuttleworthia can serve as biomarkers of DC in children.PMID:37540967 | DOI:10.1016/j.archoralbio.2023.105776