Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Genetic polymorphisms and expression of Rhesus blood group RHCE are associated with 2,3-bisphosphoglycerate in humans at high altitude

Tue, 26/12/2023 - 12:00
Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2315930120. doi: 10.1073/pnas.2315930120. Epub 2023 Dec 26.ABSTRACTRed blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity.PMID:38147558 | DOI:10.1073/pnas.2315930120

Long-term effects of oil contamination on soil quality and metabolic function

Tue, 26/12/2023 - 12:00
Environ Geochem Health. 2023 Dec 26;46(1):13. doi: 10.1007/s10653-023-01779-2.ABSTRACTWidespread soil contamination with oil and the toxicity of petroleum hydrocarbons to soil biota make it extremely important to study microbial responses to oil stress. Soil metabolites reflect the main metabolic pathways in the soil microbial community. The examination of changes in the soil metabolic profile and metabolic function is essential for a better understanding of the nature of the pollution and restoration of the disturbed soils. The present study aimed to assess the long-term effect of oil on the ecological state of the soil, evaluate quantitative and qualitative differences in metabolite composition between soil contaminated with oil and non-contaminated soil, and reveal biologically active metabolites that are related to oil contamination and can be used for contamination assessment. A long-term field experiment was conducted to examine the effects of various oil concentrations on the biochemical properties and metabolic profile of the soil. Podzolic soil contaminated with oil demonstrated the long-term inhibition of soil biological activity and vegetation. Oil affected the metabolic activity of soil fungi increasing the production of toxic metabolites. A metabolomic approach was employed to determine soil metabolites. The metabolite profile was found to vary greatly between oil-contaminated and non-contaminated soils. Carbohydrates had the largest number of metabolites negatively affected by oil, while the content of organic acids, phenolic compounds, and terpenoids was mainly increased in oil-contaminated soil. The evaluation of the long-term impact of oil on microbial metabolism can make a valuable contribution to the assessment of soil quality and the activity of soil microorganisms being under stress from oil pollution. The results contribute to a further understanding of the role of microorganisms in the ecological functions of contaminated soil, which can be useful in the development of rehabilitation strategies for disturbed sites.PMID:38147148 | DOI:10.1007/s10653-023-01779-2

Intercropping of Narrow-Leafed Lupin (<em>Lupinus angustifolius</em> L.) and Barley (<em>Hordeum vulgare</em> L.) Affects the Flavonoid Composition of Both Crops

Tue, 26/12/2023 - 12:00
J Agric Food Chem. 2023 Dec 26. doi: 10.1021/acs.jafc.3c03684. Online ahead of print.ABSTRACTBarley (Hordeum vulgare L.) is a common cereal crop in agricultural production and is often included in legume-cereal intercropping. Flavonoids, a major class of secondary metabolites found in barley, are involved in plant defense and protection. However, the effect of intercropping on barley flavonoids remains unknown. Herein, an intercropping system involving barley and lupin (Lupinus angustifolius L.) was studied. Intercropping increased the level of luteolin in lupin roots. Lupin-barley intercropping considerably increased genistein, rutin, and apigenin in barley shoots. Genistein and apigenin were also detected in intercropped barley roots and rhizosphere soil. The three flavonoids have been reported as defense compounds, suggesting that lupin triggers a defense response in barley to strengthen its survival ability.PMID:38146912 | DOI:10.1021/acs.jafc.3c03684

Metabolomics at the tumor microenvironment interface: Decoding cellular conversations

Tue, 26/12/2023 - 12:00
Med Res Rev. 2023 Dec 26. doi: 10.1002/med.22010. Online ahead of print.ABSTRACTCancer heterogeneity remains a significant challenge for effective cancer treatments. Altered energetics is one of the hallmarks of cancer and influences tumor growth and drug resistance. Studies have shown that heterogeneity exists within the metabolic profile of tumors, and personalized-combination therapy with relevant metabolic interventions could improve patient response. Metabolomic studies are identifying novel biomarkers and therapeutic targets that have improved treatment response. The spatial location of elements in the tumor microenvironment are becoming increasingly important for understanding disease progression. The evolution of spatial metabolomics analysis now allows scientists to deeply understand how metabolite distribution contributes to cancer biology. Recently, these techniques have spatially resolved metabolite distribution to a subcellular level. It has been proposed that metabolite mapping could improve patient outcomes by improving precision medicine, enabling earlier diagnosis and intraoperatively identifying tumor margins. This review will discuss how altered metabolic pathways contribute to cancer progression and drug resistance and will explore the current capabilities of spatial metabolomics technologies and how these could be integrated into clinical practice to improve patient outcomes.PMID:38146814 | DOI:10.1002/med.22010

Preterm Birth: Screening and Prediction

Tue, 26/12/2023 - 12:00
Int J Womens Health. 2023 Dec 21;15:1981-1997. doi: 10.2147/IJWH.S436624. eCollection 2023.ABSTRACTPreterm birth (PTB) affects approximately 10% of births globally each year and is the most significant direct cause of neonatal death and of long-term disability worldwide. Early identification of women at high risk of PTB is important, given the availability of evidence-based, effective screening modalities, which facilitate decision-making on preventative strategies, particularly transvaginal sonographic cervical length (CL) measurement. There is growing evidence that combining CL with quantitative fetal fibronectin (qfFN) and maternal risk factors in the extensively peer-reviewed and validated QUanititative Innovation in Predicting Preterm birth (QUiPP) application can aid both the triage of patients who present as emergencies with symptoms of preterm labor and high-risk asymptomatic women attending PTB surveillance clinics. The QUiPP app risk of delivery thus supports shared decision-making with patients on the need for increased outpatient surveillance, in-patient treatment for preterm labor or simply reassurance for those unlikely to deliver preterm. Effective triage of patients at preterm gestations is an obstetric clinical priority as correctly timed administration of antenatal corticosteroids will maximise their neonatal benefits. This review explores the predictive capacity of existing predictive tests for PTB in both singleton and multiple pregnancies, including the QUiPP app v.2. and discusses promising new research areas, which aim to predict PTB through cervical stiffness and elastography measurements, metabolomics, extracellular vesicles and artificial intelligence.PMID:38146587 | PMC:PMC10749552 | DOI:10.2147/IJWH.S436624

Current Status and Influencing Factors of Snakebite Diagnosis and Treatment Knowledge Among Medical Staff in China: A Cross-Sectional Study

Tue, 26/12/2023 - 12:00
Int J Public Health. 2023 Dec 11;68:1606601. doi: 10.3389/ijph.2023.1606601. eCollection 2023.ABSTRACTObjectives: This study aimed to determine the current status of the knowledge of diagnosis and treatment of snakebites among medical staff in China and its influencing factors. Methods: A cross-sectional survey of 12,581 medical staff was conducted in 12 provinces in China between June 2022 and February 2023. We analyzed the results using descriptive statistics, T-tests or analysis of variance, and a generalized linear model. Results: The average score of snakebite diagnosis and treatment knowledge among medical staff in China was 3.15 ± 2.15 out of a total score of 12. Through a generalized linear regression model, we found that gender, occupation, region, hospital level, work department, work tenure, training received in the diagnosis and treatment of snakebite, experience in snakebite diagnosis and treatment, availability of antivenom in the unit, and self-evaluation of snakebite treatment ability all affected the medical staff's scores of snakebite diagnosis and treatment knowledge. Conclusion: The knowledge level of snakebite diagnosis and treatment among Chinese medical staff is generally low, so it is imperative to conduct standardized snakebite diagnosis and treatment training for medical staff.PMID:38146482 | PMC:PMC10749458 | DOI:10.3389/ijph.2023.1606601

Metabolomic study of the estrogenic and anti-osteoporotic potential of Erythrina bidwillii leaf

Tue, 26/12/2023 - 12:00
Biomed Chromatogr. 2023 Dec 25:e5810. doi: 10.1002/bmc.5810. Online ahead of print.ABSTRACTErythrina bidwillii Lindl., Leguminosae, constitutes a valuable crop for horticulture and medicine; however, it is rarely investigated. Menopause is a crucial transitional period in women's health. Women worldwide consider the use of phytoestrogens as a safe hormone replacement therapy to alleviate detrimental menopausal symptoms. Thus, the discovery of novel phytoestrogens is highly demanded. The present study aimed to investigate, for the first time, the metabolomic profile and the estrogenic potential of E. bidwillii Lindl. leaf. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and gas chromatography-mass spectrometry metabolite profiling revealed the prevalence of alkaloids, flavonoids, isoflavonoids and fatty acids. Additionally, five erythrinan alkaloids, cristanine A (1), 8-oxoerythraline (2), (+)-erythrinine (3), (+)-erythraline (4) and 8-oxoerythrinine (5), along with the isoflavonoid genistin (6), were isolated. Erythrina bidwillii leaf extract exhibited significant in vivo estrogenic, anti-osteoporotic, anti-hyperlipidemic, hepatoprotective, and nephroprotective activities, utilizing ovariectomized rat model. Moreover, ethyl acetate and hexane fractions possessed significant in vitro estrogeic potential on MCF-7 cell lines. An in silico study of the isolated metabolites revealed that (+)-erythrinine (3) and 8-oxoerythrinine (5) exhibited the highest affinity for ERα and ERβ, respectively, modeling them as potential estrogenic lead metabolites. Therefore, E. bidwillii leaf could be employed as promising hormone replacement therapy for postmenopausal women after thorough clinical trials.PMID:38146195 | DOI:10.1002/bmc.5810

Enhancement of the organic acid content and antioxidant capacity of yellow whey through fermentation with Lacticaseibacillus casei YQ336

Mon, 25/12/2023 - 12:00
World J Microbiol Biotechnol. 2023 Dec 26;40(2):53. doi: 10.1007/s11274-023-03874-z.ABSTRACTFermentation is considered an effective tool for improving the functional characteristics of food. In this study, Lacticaseibacillus casei YQ336 was used to ferment yellow whey, and physical and chemical analysis was performed to identify the changes in the nutritional components and antioxidant activity of the fermented yellow whey. Non-targeted metabolomics was used to study the transformation of small molecular substances in the fermented yellow whey. After 48 h of pure culture fermentation with L. casei YQ336, the pH of yellow whey decreased significantly (p < 0.05). Meanwhile, the content of total acids, organic acids, sugars, total phenols, and total flavonoids and the antioxidant activity showed a significant increase (p < 0.05). A total of 628 differential metabolites were identified between fermented and unfermented yellow whey samples, of which 293 were upregulated and 335 were downregulated. After fermentation, due to the growth and metabolic activity of L. casei YQ336, meaningful metabolites such as homovanillic acid, lactic acid, oxalic acid, L-glutamic acid, and phenylalanine, as well as phenyllactic acid, gallic acid, and genistein were produced. This increased the organic acid content and antioxidant activity of yellow whey. The findings provide a theoretical and practical basis for further research on the bio-functional activity of yellow whey and the recycling and utilization of food by-products.PMID:38146044 | DOI:10.1007/s11274-023-03874-z

Choline metabolism in regulating inflammatory bowel disease-linked anxiety disorders: A multi-omics exploration of the gut-brain axis

Mon, 25/12/2023 - 12:00
Neurobiol Dis. 2023 Dec 23:106390. doi: 10.1016/j.nbd.2023.106390. Online ahead of print.ABSTRACTAnxiety and depression caused by inflammatory bowel disease (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis (GBA) mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. Therefore, it's vital to conduct comprehensive research on the GBA in IBD. Multi-omics studies can provide an understanding of the pathological mechanisms of the GBA in the development of IBD, helping to uncover the mechanisms underlying the onset and progression of the disease. Thus, we analyzed the prefrontal cortex (PFC) of Dextran Sulfate Sodium Salt (DSS)-induced IBD mice using transcriptomics and metabolomics. We observed increased mRNA related to acetylcholine synthesis and secretion, along with decreased phosphatidylcholine (PC) levels in the PFC of DSS group compared to the control group. Fecal metagenomics also revealed abnormalities in the microbiome and lipid metabolism in the DSS group. Since both acetylcholine and PC are choline metabolites, we posited that the DSS group may experience choline deficiency and choline metabolism disorders. Subsequently, when we supplemented CDP-choline, IBD mice exhibited improvements, including decreased anxiety-like behaviors, reduced PC degradation, and increased acetylcholine synthesis in the PFC. In addition, administration of CDP-choline can restore imbalances in the gut microbiome and disruptions in lipid metabolism caused by DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a crucial role in the development and treatment of mood disorders in IBD. Choline and its metabolites appear to have a significant role in maintaining the stability of the GBA.PMID:38145852 | DOI:10.1016/j.nbd.2023.106390

Microbiota-mediated metabolic perturbations in the gut and brain of mice after microplastic exposure

Mon, 25/12/2023 - 12:00
Chemosphere. 2023 Dec 23:141026. doi: 10.1016/j.chemosphere.2023.141026. Online ahead of print.ABSTRACTMicroplastics (MPs), emerging environmental toxicants, have drawn attention because of their wide distribution in the environment. Exposure to MPs induces gut microbiota dysbiosis, intestinal barrier dysfunction, metabolic perturbations, and neurotoxicity in different rodents. However, the relationship between MPs, gut microbiota, and the metabolome of the gut and brain in mice remains unclear. In this study, female C57BL/6 mice were orally gavaged with vehicle, 200 nm MP, and 800 nm MP three times per week for four weeks. Cecal contents were collected for gut microbiota analysis using 16S rRNA gene sequencing. Intestinal and brain tissues from mice were used to determine metabolic profiles using liquid chromatography-mass spectrometry (LC-MS). The results showed that MP altered microbiota composition, accompanied by metabolic perturbations in the mouse gut and brain. Specifically, Firmicutes and Bacteroidetes were suggested to be important phyla for MP exposure, partially dominating further metabolite alterations. Simultaneously, MP-induced metabolic profiles were associated with energy homeostasis and bile acid, nucleotide, and carnitine metabolic pathways. The results of the mediation analysis further revealed an MP-microbiota-metabolite relationship. Our results indicate that MPs can induce gut dysbiosis and disturb metabolic dysfunction in the mouse brain and/or intestine. Integrative omics approaches have the potential to monitor MP-induced molecular responses in various organs and systematically elucidate the complex mechanisms of human health effects.PMID:38145850 | DOI:10.1016/j.chemosphere.2023.141026

METABOLITES, IONS, AND THE MECHANISMS BEHIND SEASONAL COLD HARDENING OF PYROCHROA COCCINEA (PYROCHROIDAE) LARVAE

Mon, 25/12/2023 - 12:00
J Insect Physiol. 2023 Dec 23:104610. doi: 10.1016/j.jinsphys.2023.104610. Online ahead of print.ABSTRACTThe larvae of the black headed cardinal beetle Pyrochroa coccinea, overwinters under the bark of dead logs in northern European dioecious forests, and are thus exposed to temperatures below the melting point of their bodily fluids. Here we explore the mechanisms behind their seasonal cold hardening by characterising field samples collected monthly throughout the year. Both the lower lethal temperature and supercooling point dropped as much as 10℃ in the second half of November, reaching values around -15℃ by the beginning of December. This change was accompanied by a 320 mosmol/kg increase in hemolymph osmolality, which is a doubling compared to the summer levels. We used NMR metabolomics to identify and measure the absolute concentration of the responsible cryoprotective C-H containing metabolites in the hemolymph. The largest increase was found to be in either glucose or trehalose, with an average total increase of 120 mM. Proline, alanine, and choline concentrations were found to increase by around 10 mM each. Contrarily, phosphocholine and phosphoethanolamine were halved, resulting in a total decrease of around 50 mM. These measurements were complemented with ion exchange chromatography measurements. This allowed us to account for all the osmotic pressure in the summer hemolymph, and the measured concentration changes explained as much as 40% of the observed osmolality increase upon cold hardening. Preliminary results indicate that the remainder may be explained by non-colligative protein contributions.PMID:38145824 | DOI:10.1016/j.jinsphys.2023.104610

Unbiased Single-Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation

Mon, 25/12/2023 - 12:00
Adv Sci (Weinh). 2023 Dec 25:e2304539. doi: 10.1002/advs.202304539. Online ahead of print.ABSTRACTAplastic anemia (AA) is a bone marrow (BM) failure syndrome mediated by hyperactivated T-cells with heterogeneous pathogenic factors. The onset of BM failure cannot be accurately determined in humans; therefore, exact pathogenesis remains unclear. In this study, a cellular atlas and microenvironment interactions is established using unbiased single-cell RNA-seq, along with multi-omics analyses (mass cytometry, cytokine profiling, and oxidized fatty acid metabolomics). A new KIR+ CD8+ regulatory T cells (Treg) subset is identified in patients with AA that engages in immune homeostasis. Conventional CD4+ T-cells differentiate into highly differentiated T helper cells with type 2 cytokines (IL-4, IL-6, and IL-13), GM-SCF, and IL-1β. Immunosuppressive homeostasis is impaired by enhanced apoptosis of activated Treg cells. Pathological Vδ1 cells dominated the main fraction of γδ T-cells. The B/plasma, erythroid, and myeloid lineages also exhibit substantial pathological features. Interactions between TNFSF12-TNFRSF12A, TNF-TNFRSF1A, and granzyme-gasdermin are associated with the cell death of hematopoietic stem/progenitor (HSPCs), Treg, and early erythroid cells. Ferroptosis, a major driver of HSPCs destruction, is identified in patients with AA. Furthermore, a case of twins with AA is reported to enhance the persuasiveness of the analysis. These results collectively constitute the cellular atlas and microenvironment interactions in patients with AA and provide novel insights into the development of new therapeutic opportunities.PMID:38145351 | DOI:10.1002/advs.202304539

Metabolome analysis reveals that cyclic adenosine diphosphate ribose contributes to the regulation of differentiation in mice adipocyte

Mon, 25/12/2023 - 12:00
FASEB J. 2024 Jan;38(1):e23391. doi: 10.1096/fj.202300850RR.ABSTRACTAdipocytes play a key role in energy storage and homeostasis. Although the role of transcription factors in adipocyte differentiation is known, the effect of endogenous metabolites of low molecular weight remains unclear. Here, we analyzed time-dependent changes in the levels of these metabolites throughout adipocyte differentiation, using metabolome analysis, and demonstrated that there is a positive correlation between cyclic adenosine diphosphate ribose (cADPR) and Pparγ mRNA expression used as a marker of differentiation. We also found that the treatment of C3H10T1/2 adipocytes with cADPR increased the mRNA expression of those marker genes and the accumulation of triglycerides. Furthermore, inhibition of ryanodine receptors (RyR), which are activated by cADPR, caused a significant reduction in mRNA expression levels of the marker genes and triglyceride accumulation in adipocytes. Our findings show that cADPR accelerates adipocytic differentiation via RyR pathway.PMID:38145327 | DOI:10.1096/fj.202300850RR

Effects of Delaying Post-hatch Feeding on the Plasma Metabolites of Broiler Chickens Revealed by Targeted and Untargeted Metabolomics

Mon, 25/12/2023 - 12:00
J Poult Sci. 2023 Dec 22;60:2023032. doi: 10.2141/jpsa.2023032. eCollection 2023.ABSTRACTExogenous nutrients are essential for body and skeletal muscle growth in newly hatched chicks, and delaying post-hatch feeding negatively affects body growth, meat yield, and meat quality. The aim of this study was to investigate the effects of delayed post-hatch feeding on the metabolic profiles of broiler chickens using a combination of targeted and untargeted metabolomics. Newly hatched chicks had either immediate free access to feed (freely fed chicks) or no access to feed from 0 to 2 days of age (delayed-fed chicks); both groups were subsequently provided feed ad libitum until 13 days of age. Untargeted metabolomic analysis was performed using gas chromatography-mass spectrometry, whereas targeted metabolomic analysis of amino acids was performed using high-performance liquid chromatography with ortho-phthalaldehyde derivatization. Delayed feeding increased the plasma levels of sucrose, maltose, serotonin, lactitol, gentiobiose, xylitol, threonic acid, and asparagine, and decreased the plasma levels of creatinine, aspartic acid, and glutamic acid. In addition, the digestibility of the nitrogen-free extract (starch and sugar) and the cecal butyric acid concentration increased in chicks subjected to delayed feeding. In contrast, delayed feeding did not affect muscle protein degradation or digestibility in chicks. Taken together, our results indicate that delaying feeding until 48 h post-hatch alters multiple metabolic pathways, which are accompanied by changes in intestinal carbohydrate digestion and cecal butyric acid content in broiler chickens.PMID:38145205 | PMC:PMC10730121 | DOI:10.2141/jpsa.2023032

Metabolite profiling of <em>Trichinella spiralis</em> adult worms and muscle larvae identifies their excretory and secretory products

Mon, 25/12/2023 - 12:00
Front Cell Infect Microbiol. 2023 Dec 8;13:1306567. doi: 10.3389/fcimb.2023.1306567. eCollection 2023.ABSTRACTHuman trichinellosis is a parasitic infection caused by roundworms belonging to the genus Trichinella, especially Trichinella spiralis. Early and accurate clinical diagnoses of trichinellosis are required for efficacious prognosis and treatment. Current drug therapies are limited by antiparasitic resistance, poor absorption, and an inability to kill the encapsulating muscle-stage larvae. Therefore, reliable biomarkers and drug targets for novel diagnostic approaches and anthelmintic drugs are required. In this study, metabolite profiles of T. spiralis adult worms and muscle larvae were obtained using mass spectrometry-based metabolomics. In addition, metabolite-based biomarkers of T. spiralis excretory-secretory products and their related metabolic pathways were characterized. The metabolic profiling identified major, related metabolic pathways involving adenosine monophosphate (AMP)-dependent synthetase/ligase and glycolysis/gluconeogenesis in T. spiralis adult worms and muscle larvae, respectively. These pathways are potential drug targets for the treatment of the intestinal and muscular phases of infection. The metabolome of larva excretory-secretory products was characterized, with amino acid permease and carbohydrate kinase being identified as key metabolic pathways. Among six metabolites, decanoyl-l-carnitine and 2,3-dinor-6-keto prostaglandin F1α-d9 were identified as potential metabolite-based biomarkers that might be related to the host inflammatory processes. In summary, this study compared the relationships between the metabolic profiles of two T. spiralis growth stages. Importantly, the main metabolites and metabolic pathways identified may aid the development of novel clinical diagnostics and therapeutics for human trichinellosis and other related helminthic infections.PMID:38145042 | PMC:PMC10749202 | DOI:10.3389/fcimb.2023.1306567

Effectiveness of L-serine supplementation in children with a <em>GRIN2B</em> loss-of-function mutation: Rationale and protocol for single patient (n-of-1) multiple cross-over trials

Mon, 25/12/2023 - 12:00
Contemp Clin Trials Commun. 2023 Nov 17;36:101233. doi: 10.1016/j.conctc.2023.101233. eCollection 2023 Dec.ABSTRACTRATIONALE: Loss-of-function (LoF) mutations in GRIN2B result in neurologic abnormalities due to N-methyl-D-aspartate receptor (NMDAR) dysfunction. Affected persons present with various symptoms, including intellectual developmental disability (IDD), hypotonia, communication deficits, motor impairment, complex behavior, seizures, sleep disorders and gastrointestinal disturbance. Recently, in vitro experiments showed that D-serine mitigates function to GluN2B (mutation)-containing NMDARs. 11 previous case reports are published on (experimental) L-serine treatment of patients between 1.5 and 12 years old with GRIN2B missense or null mutations, some of whom showed notable improvement in motor and cognitive performance, communication, behavior and abnormalities on electro encephalography (EEG). Our objective is to further evaluate the effectiveness of L-serine for GRIN2B-related neurodevelopmental disorder (GRIN2B-NDD), using an n-of-1 trial design, increasing the level of evidence.METHODS/DESIGN: These n-of-1 trials, consisting of 2 cycles of 6 months, will be performed to evaluate the effect of L-serine compared to placebo in 4 patients with a GRIN2B LoF mutation. The aggregation of multiple n-of-1 trials will provide an estimate of the average treatment effects.The primary outcome is the Perceive-Recall-Plan-Perform of Task Analysis, assessing developmental skills. Secondary outcomes include Goal Attainment Scaling, seizure log books, EEGs, sleep log books, the irritability subscale of the Aberrant Behavior Checklist, the Bristol Stool Scale and the Pediatric Quality of Life Inventory.CONCLUSION: This study employs an innovative methodological approach to evaluate the effectiveness of L-serine for patients with a GRIN2B LoF mutation. The results will establish a foundation for implementing L-serine as a disease-modifying treatment in GRIN2B-NDD.PMID:38144875 | PMC:PMC10746402 | DOI:10.1016/j.conctc.2023.101233

An overview of analytical methods employed for quality assessment of <em>Crocus sativus</em> (saffron)

Mon, 25/12/2023 - 12:00
Food Chem X. 2023 Nov 14;20:100992. doi: 10.1016/j.fochx.2023.100992. eCollection 2023 Dec 30.ABSTRACTThis paper reviews qualitative and quantitative analytical methodologies used for the appraisal of saffron quality, as the most expensive spice. Due to the chemical diversity of biologically active compounds of the Crocus genus, analytical methods with different features are required for their complete analysis. However, screening of the main components, such as carotenoids and flavonoids, appears to be sufficient for quality control, a more precise examination needs evaluation of minor compounds, including anthocyanins and fatty acids. High-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), ultraviolet-visible spectroscopy (UV), nuclear magnetic resonance spectroscopy (NMR), and thin-layer chromatography (TLC), are elementary and applicable methods in quality control analysis, whereas HPLC provides metabolite fingerprint and monitoring multi-compound instances at preparative and analytical levels. Combination approaches like metabolomics using different methods could classify saffron types, identify its adulterations, contaminants and provide a comprehensive metabolite map for quality control of selected compounds.PMID:38144850 | PMC:PMC10740065 | DOI:10.1016/j.fochx.2023.100992

Metabolic profiling provides insights into the accumulation patterns of flavonoids and phenolic acids in different parts of <em>Lactuca indica</em> L

Mon, 25/12/2023 - 12:00
Food Chem X. 2023 Nov 22;20:101012. doi: 10.1016/j.fochx.2023.101012. eCollection 2023 Dec 30.ABSTRACTLactuca indica L. contains high amounts of flavonoids and phenolic acids. However, there is limited information on the composition of these compounds in different parts of the plant. The present study analyzed the secondary metabolite profiles of the stem, leaf, flower, and seed of Lactuca indicaL.cv. Mengzao (LIM) using a widely targeted metabolomic approach. A total of 576 secondary metabolites were identified, including 218, 267, 232, 286, 302, and 308 differentially accumulated metabolites (DAMs) in the stem_vs_leaf, stem_vs_flower, stem_vs_seed, leaf_vs_flower, leaf_vs_seed, and flower_vs_seed comparisons. In particular, considerable differences were detected in the flavonoids and phenolic acids, five flavonoids, five phenolic acids, one triterpenoid and one alkaloid being differentially accumulated in the four parts. Compared to the stem and flower, the leaf and seed had higher total flavonoid content and total phenolic content. Thses findings provide comprehensive insights into utilizing different parts of LIM in developing functional food products.PMID:38144821 | PMC:PMC10739775 | DOI:10.1016/j.fochx.2023.101012

Proteomic and metabolomic analysis of ageing beef exudate to determine that iron metabolism enhances muscle protein and lipid oxidation

Mon, 25/12/2023 - 12:00
Food Chem X. 2023 Nov 30;20:101038. doi: 10.1016/j.fochx.2023.101038. eCollection 2023 Dec 30.ABSTRACTThe study aimed to assess differences in proteomic and metabolite profiles in ageing (1, 2, 4, and 6 days at 4 °C) beef exudates and determine their relationship with beef muscle iron metabolism and oxidation. Proteomic and metabolomic analyses identified 877 metabolites and 1957 proteins. The joint analysis identified 24 differential metabolites (DMs) and 56 differentially expressed proteins (DEPs) involved in 15 shared pathways. Ferroptosis was identified as the only iron metabolic pathway, and 4 DMs (l-glutamic acid, arachidonic acid, glutathione and gamma-glutamylcysteine) and 5 DEPs (ferritin, phospholipid hydroperoxide glutathione peroxidase, heme oxygenase 1, major prion protein, and acyl-CoA synthetase long chain family member 4) were involved in iron metabolism by regulating heme and ferritin degradation, Fe2+ and Fe3+ conversion, arachidonic acid oxidation and inactivation of glutathione peroxidase (GPX) 4, leading to increased levels of free iron, ROS, protein and lipid oxidation (P < 0.05). Overall, abnormal iron metabolism during ageing induced oxidative stress in muscle tissue.PMID:38144814 | PMC:PMC10739755 | DOI:10.1016/j.fochx.2023.101038

Analysis of dipeptides in Chinese liquors based on dansylation combined with liquid chromatography-mass spectrometry

Mon, 25/12/2023 - 12:00
Food Chem X. 2023 Oct 12;20:100933. doi: 10.1016/j.fochx.2023.100933. eCollection 2023 Dec 30.ABSTRACTDipeptides have been shown to be an important taste substance in alcoholic beverages. However, the characterization of dipeptides in Chinese liquors was poor. Here, dansylation combined with liquid chromatography - mass spectrometry was employed to analyze dipeptides in eight liquors of two flavors. Consequently, 35 dipeptides were identified from liquors and 32 of them were quantified. Dipeptide quantification showed LODs smaller than 2.5 ng/mL. The calibration curves showed concentration spans from two to three orders of magnitude with satisfactory linearity. The matrix effects in low and high concentrations were from -25.71 % to 24.19 % and -14.82 % to 20.73 %, respectively. Intra- and inter-day precision is lower than 15 % for both low and high concentrations. The dipeptide contents in sauce flavor liquors were higher than those in strong flavor liquors. Ala- and -Phe dipeptides showed their unique trends between sauce and strong flavor liquors. This study provides new clues to evaluate taste of liquors.PMID:38144804 | PMC:PMC10739968 | DOI:10.1016/j.fochx.2023.100933

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