PubMed

Front Cardiovasc Med. 2024 Nov 14;11:1491046. doi: 10.3389/fcvm.2024.1491046. eCollection 2024.ABSTRACTINTRODUCTION: The incidence of adverse short-term outcomes for infants who undergo complex congenital heart disease (CHD) surgery with cardiopulmonary bypass (CPB) is still high. Early identification and treatment of high-risk patients remain challenging, especially because clinical risk factors often fail to explain the different outcomes of this vulnerable population. Metabolomics offers insight into the phenotype of the patient and the complex interplay between the genetic substrate and the environmental influences at the time of sampling. For these reasons, it may be helpful to identify the mechanisms of physio-pathological disruptions experienced in neonates undergoing congenital heart surgery and to identify potential therapeutic targets.METHODS: We conducted a systematic review (PROSPERO: ID 565112) of studies investigating the association between targeted or untargeted metabolomic analysis of infants undergoing elective surgery with CPB for CHD and clinical outcomes. The PRISMA guidelines were followed. We searched MEDLINE via PubMed, EMBASE via Ovid, the Cochrane Central Register of Controlled Trials, the Cochrane Library, ClinicalTrials.gov and the World Health Organization's International Trials Registry and Platform.RESULTS: Seven studies involving 509 children (aged 1 day to 21.3 months), all of whom underwent cardiac surgery requiring CPB, were included for qualitative analysis. We found associations between metabolomic profiles and various clinical outcomes, such as mortality, acute kidney injury (AKI), and neurological outcomes. Specific metabolites (mainly amino acids, their metabolic products and fatty acids) were identified as potential biomarkers for these outcomes, demonstrating the utility of metabolomics in predicting certain postoperative complications.CONCLUSION: The quality of the evidence was limited due to heterogeneity in study designs and small sample sizes, but the findings are promising and suggest that further research is warranted to confirm these associations.SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, PROSPERO ID 565112.PMID:39610977 | PMC:PMC11602462 | DOI:10.3389/fcvm.2024.1491046

Front Oncol. 2024 Nov 14;14:1454161. doi: 10.3389/fonc.2024.1454161. eCollection 2024.ABSTRACTPrimary liver cancer (PLC), which includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a leading cause of cancer-related death worldwide. Chronic liver diseases, such as hepatitis B and C infections and metabolic dysfunction-associated steatotic liver disease (MASLD), are key risk factors for PLC. Metabolic reprogramming, a defining feature of cancer, enables liver cancer cells to adapt to the demands of rapid proliferation and the challenging tumor microenvironment (TME). This manuscript examines the pivotal role of metabolic reprogramming in PLC, with an emphasis on the alterations in glucose, lipid, and amino acid metabolism that drive tumor progression. The Warburg effect, marked by increased glycolysis, facilitates rapid energy production and biosynthesis of cellular components in HCC. Changes in lipid metabolism, including elevated de novo fatty acid synthesis and lipid oxidation, support membrane formation and energy storage essential for cancer cell survival. Amino acid metabolism, particularly glutamine utilization, supplies critical carbon and nitrogen for nucleotide synthesis and maintains redox homeostasis. These metabolic adaptations not only enhance tumor growth and invasion but also reshape the TME, promoting immune escape. Targeting these metabolic pathways presents promising therapeutic opportunities for PLC. This review underscores the interaction between metabolic reprogramming and tumor immunity, suggesting potential metabolic targets for innovative therapeutic strategies. A comprehensive understanding of PLC's intricate metabolic landscape may lead to more effective treatments and better patient outcomes. Integrating metabolomics, genomics, and proteomics in future research will be vital for identifying precise therapeutic targets and advancing personalized therapies for liver cancer.PMID:39610917 | PMC:PMC11602425 | DOI:10.3389/fonc.2024.1454161

Biochem Biophys Rep. 2024 Nov 11;40:101868. doi: 10.1016/j.bbrep.2024.101868. eCollection 2024 Dec.ABSTRACTYin deficiency syndrome is a theoretical concept of traditional Chinese medicine (TCM) that claims an imbalance between Yin and Yang serves as a potential etiological factor disrupting physiological homeostasis. Its diagnosis in TCM is hindered by the intricate and diverse etiology, resulting in the absence of quantification and standardization. Hence, this study developed a hydrocortisone (HC) induced Yin deficiency syndrome model to investigate the intricate network underlying TCM and elucidate its intervention mechanism. In the findings, the model was characterized by weight loss, elevated drinking water, yellow urination, dry stools, variations in inflammatory factors, and higher levels of oxidative stress. Based on metabolomics, 56 metabolites showed different expressions; among them, 19 were upregulated, and 37 were downregulated. Bioinformatics analysis revealed that identified metabolites are mainly involved in glycerol phospholipid metabolism, pyrimidine metabolism, amino acid biosynthesis, arginine and proline metabolism, and arachidonic acid metabolism pathways. Finally, the metabolic network association confirmed the diagnostic accuracy of the Yin deficiency syndrome as established by HC. We propose for the first time an animal model of Yin deficiency syndrome induced by hydrocortisone in TCM clinical state. This research presents experimental evidence for establishing TCM symptoms and serves as a fundamental basis for the scientific awareness of their etiology.PMID:39610834 | PMC:PMC11603011 | DOI:10.1016/j.bbrep.2024.101868

RSC Adv. 2024 Nov 28;14(51):37911-37924. doi: 10.1039/d4ra06732k. eCollection 2024 Nov 25.ABSTRACTDamnacanthus indicus is a widely used folk medicine in China, renowned for its various bioactivities. The key active components, anthraquinones, have not been comprehensively profiled due to their complex chemical nature. Establishing a high-throughput strategy to systematically characterize these anthraquinones is essential. Additionally, the cultivation of D. indicus across various provinces results in significant quality differences in the harvested herbs. Thus, developing an effective strategy to distinguish herbs from different regions and identify characteristic chemical markers for quality evaluation and control is crucial. In this study, a strategy based on ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed to systematically characterize the chemical composition of D. indicus. Mass spectrometry molecular networking was utilized to rapidly recognize and identify anthraquinones. Principal component analysis (PCA) was applied to cluster the herbs from different habitats, while partial least square discriminant analysis (PLS-DA) was used to screen for chemical markers distinguishing herb origins. The result showed that a total of 112 anthraquinones and 66 non-anthraquinone compounds were identified in D. indicus. The biosynthetic pathways of anthraquinones in this herb were proposed. PCA grouped 15 batches of herbs from different origins into three clusters, corresponding to the climate types of their habitats. PLS-DA identified 27 significant chemical markers that could robustly distinguish the geographical origins of the herbs. This study provides a valuable reference for the quality evaluation and control of D. indicus and offers a scientific basis for the pharmacological research and rational utilization of these medicinal resources.PMID:39610812 | PMC:PMC11603343 | DOI:10.1039/d4ra06732k

J Diabetes Metab Disord. 2024 Sep 23;23(2):2279-2287. doi: 10.1007/s40200-024-01495-3. eCollection 2024 Dec.ABSTRACTOBJECTIVES: The efficacy and safety of drug treatments vary widely due to genetic variations. Pharmacogenomics investigates the impact of genetic variations on patient drug response. This research investigates the frequency of UGT1A1 genetic variations in the Iranian population, comparing them with global data to provide insights into the pharmacogenomic approach in the Iranian population.METHODS: The study was conducted using the data of the Bushehr Elderly Health (BEH) program, a population-based cohort study of the elderly population aged ≥ 60 years. Genotyping of three UGT1A1 variant alleles (UGT1A1*6, UGT1A1*27, and UGT1A1*80) was performed on a group of 2730 elderly Iranian participants with the Infinium Global Screening Array.RESULTS: The genotyping analysis revealed significant differences compared to major global populations that were addressed in the gnomAD database. UGT1A1*80 was found at a high frequency (32.34%), and followed by UGT1A1*6 (0.76%) and UGT1A1*27 (0.018) at a low frequency in the Iranian group.CONCLUSIONS: The UGT1A1*80 was the more prevalent allele between investigated alleles in the present study which can be considered as an important allele for pharmacogenomic testing.PMID:39610552 | PMC:PMC11599689 | DOI:10.1007/s40200-024-01495-3

J Diabetes Metab Disord. 2024 Aug 1;23(2):2401-2405. doi: 10.1007/s40200-024-01480-w. eCollection 2024 Dec.ABSTRACTINTRODUCTION: Heterozygous mutations in the GCK gene result in mildly elevated glucose levels from birth, and the homozygous loss-of-function mutations leads to permanent neonatal diabetes. In the present study we aim to investigate the cause of diabetes in an adult female patient with unusual course of diabetes.CASE PRESENTATION: We evaluate a female patient who previously encountered significant hyperglycemia during the infancy and subsequently experienced a relatively uneventful childhood. In later years, she faced significant hyperglycemia and retinopathy that required laser photocoagulation. Her treatment history included periods of oral hypoglycemic agents or insulin, which occasionally led to hypoglycemia, as well as extended intervals without treatment. However, she never required hospitalization for diabetic ketoacidosis. The patient's family history was significant, with her parents being cousins and having a history of prediabetes and gestational diabetes in several family members. Autoantibody tests for type 1 diabetes were negative. Next-generation sequencing analysis of the coding regions and conserved splice sites of several genes identified a homozygous GCK (T/T) missense (His424Tyr) variant, which was validated by Sanger sequencing. Heterozygous C/T mutations were revealed in the parents.DISCUSSION AND CONCLUSION: This case highlights the importance of considering homozygous GCK mutations as a potential cause of persistent neonatal diabetes, especially in patients with a history of elevated glucose levels from infancy, a family history of early-onset non-progressive diabetes and gestational diabetes, and parental consanguinity. Genetic testing can help identify the underlying genetic etiology in such cases. Early diagnosis is crucial to guide appropriate treatment and management strategies.PMID:39610513 | PMC:PMC11599641 | DOI:10.1007/s40200-024-01480-w

J Diabetes Metab Disord. 2023 Aug 28;23(2):1853-1861. doi: 10.1007/s40200-023-01281-7. eCollection 2024 Dec.ABSTRACTBACKGROUND: Gestational diabetes (GD) is associated with a variety of numerous metabolic changes. Discovering related biomarkers by the metabolomic studies can provide a better understanding of the pathological processes involved in the development and progression of GD.METHODS: Blood samples were taken from 400 naturally conceived healthy women aged 25-40 years old in the first trimester of pregnancy. Participants were followed up again at 28 weeks of gestation and reevaluated for GD based on American Diabetes Association (ADA) criteria. After identifying 32 women with GD as the case group, 32 healthy matched women selected as the control group. Plasma samples in the first and third trimester, were sent for nuclear magnetic resonance (NMR) testing. Altered biochemical pathways were identified in MetaboAnalyst 4.0 using Human Metabolism Database (HMDB). The comparison of altered metabolomes in two groups was assessed using multivariate logistic regression analysis in SPSS 23 software.RESULTS: In the first trimester, the amount of increase in steroid hormones level was greater in women who progressed to GD (Impact = 0.344). In the third trimester, although we had lower levels of steroid hormones, prostaglandins and bile acids in the diabetic group vs healthy subjects, however the level of glycine conjugated bile acid was higher in affected women by GD (P = 0.016).CONCLUSIONS: For the first time, we reported new disrupted pathways such as steroid hormone pathways and their related altered metabolites in a group of Iranian population with GD. This may provide a better and faster way to predict, diagnose and prevent GDM in the future. Surely, further studies are required for the validation of the results.PMID:39610512 | PMC:PMC11599657 | DOI:10.1007/s40200-023-01281-7

J Diabetes Metab Disord. 2024 Jun 6;23(2):1871-1877. doi: 10.1007/s40200-024-01436-0. eCollection 2024 Dec.ABSTRACTPURPOSE: While only a few postmenopausal women exhibit biochemical signs of hypovitaminosis D, it has been shown that vitamin D insufficiency has detrimental effects on the overall skeleton mineralization, bone turnover rate, and may be a significant risk factor for osteoporosis and fracture. We evaluated the concurrent effect of Vitamin D levels and biochemical markers of bone turnover on bone health of postmenopausal women.METHODS: The present study was conducted within the framework of the Bushehr Elderly Health (BEH) program, a population-based prospective cohort study being conducted in Bushehr, a southern province of Iran. In summary, 400 persons from participants of the second stage were selected; serum bone turnover markers (bone-specific alkaline phosphatase (bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin (OC), tartrate-resistant acid phosphatase isoenzyme 5b (TRAP)) and vitamin D were measured. Vitamin D deficiency was defined as serum 25(OH) D below 20 ng/ml, and Bone health was considered in terms of Osteoporosis and degraded bone microarchitecture.RESULTS: The number of partially or significantly degraded microstructure based on TBS was higher than the number of osteoporotic women based on BMD. Women with higher CTX levels were more prone to being degraded microarchitecture. Although we couldn't find any association between vitamin D deficiency and bone health, when we considered the vitamin D levels in univariable modelling, the effect of it was significant.CONCLUSIONS: In this study, only CTX was found to be significantly correlated with TBS while BMD was associated with CTX, OC, and TRAP.PMID:39610511 | PMC:PMC11599691 | DOI:10.1007/s40200-024-01436-0

J Diabetes Metab Disord. 2021 Mar 16;23(2):1461-1467. doi: 10.1007/s40200-020-00674-2. eCollection 2024 Dec.ABSTRACTDue to the limitations of organ transplantation and the urgent need for treatment of chronic diseases, the benefit of stem cells for treatment has been studied and evaluated as an effective approach worldwide. One of the leading countries in this field is Iran. In this respect, several research and treatment institutes, including endocrinology and metabolism research institute are active in the use of stem cells in Iran. Herein, the aim is to review strategies, challenges, and opportunities for stem cell research and treatment in endocrinology and metabolism research institute.PMID:39610510 | PMC:PMC11599503 | DOI:10.1007/s40200-020-00674-2

J Diabetes Metab Disord. 2021 Jan 20;23(2):1809-1816. doi: 10.1007/s40200-020-00714-x. eCollection 2024 Dec.ABSTRACTBACKGROUND: Endocrinology and Metabolism Research Institute (EMRI) is one of the biggest research institutes in Iran that was established to develop research strategies for managing endocrine and metabolic disorders such as diabetes. The aim of this study was to provide an overview of diabetes related research activities and achievements in the EMRI since its foundation.METHOD: A comprehensive search was conducted in the PubMed, Scopus, and EMBASE to find out diabetes-related research studies performed in the EMRI. After data extraction, articles were categorized based on their document types, levels of evidence, diabetes types, and subject areas and were presented in various charts.RESULT: After removing duplications and screening, 228 remained documents were categorized. The majority of diabetes investigations performed in the Diabetes Research Center (DRC) was on type 2 diabetes (T2D) (37%). Based on document types, most of these publications were original articles. Moreover, clinical studies constituted the greatest amount of evidence in the literature. According to the subject areas, most of the articles were on basic sciences and diabetes-related associated factors, followed by studies related to the management and prevention of diabetes.CONCLUSIONS: As one of the most comprehensive research institute, the EMRI has developed its national and international research activities to improve diabetes management and cure through developing new treatment strategies, improving translational research, and applying new emerging technologies such as regenerative medicine.PMID:39610497 | PMC:PMC11599651 | DOI:10.1007/s40200-020-00714-x

J Diabetes Metab Disord. 2024 Jul 20;23(2):2031-2042. doi: 10.1007/s40200-024-01462-y. eCollection 2024 Dec.ABSTRACTOBJECTIVES: Diabetic retinopathy (DR), an earnest complication of diabetes, is one of the most common causes of blindness worldwide. This study aimed to investigate the altered metabolites in the serum of non-DR (NDR) and DR including non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) subjects.METHODS: In this study, the 1HNMR platform was applied to reveal the discriminating serum metabolites in three diabetic groups based on the status of their complications: T2D or NDR (n = 15), NPDR, (n = 15), and PDR (n = 15) groups. Multivariate analyses include principal component analysis (PCA) and Partial Least Structures-Discriminant Analysis (PLS-DA) analysis that were performed using R software. The main metabolic pathways were also revealed by KEGG pathway enrichment analysis.RESULTS: The results revealed the significantly different metabolites include 10 metabolites of the NPDR versus PDR group, 24 metabolites of the PDR versus NDR group, and 25 metabolites of the NPDR versus NDR group. The results showed that the significantly altered metabolites in DR compared with NDR serum samples mainly belonged to amino acids. The most important pathways between NPDR/PDR, and NDR/DR groups include ascorbate and aldarate metabolism, galactose metabolism, glutathione metabolism, and tryptophan metabolism, respectively. In addition, some metabolites were detected for the first time.CONCLUSIONS: We created a metabolomics profile for NDR, PDR and NPDR groups. The impairment in the ascorbate/aldarate, galactose, and especially amino acids metabolism was identified as metabolic dysregulation associated with DR, which may provide new insights into potential pathogenesis pathways for DR.PMID:39610496 | PMC:PMC11599686 | DOI:10.1007/s40200-024-01462-y

J Diabetes Metab Disord. 2021 Jan 19;23(2):1539-1544. doi: 10.1007/s40200-021-00727-0. eCollection 2024 Dec.ABSTRACTOBJECTIVE: The aim of this study was to evaluate the status of scientific research output of omics in regards to human diseases with more attention shifted toward endocrine and metabolism disorders in Iran, in order to find scientific gaps and also to design future plans for further investigations in this field.METHODS: Extensive search was performed in the electronic databases of Scopus and PubMed, and documents published by Iranian authors up to 27 December 2020 were extracted. Articles related to human diseases were included and categorized based on their types and topics.RESULTS: A total of 904 publications were found. Followed by checking their titles and abstracts, 327 studies were included. The trend of publication has been increasing during the past years. Regarding this subject, the highest number of publications was in the field of malignant disorders with 82 publications followed by reproductive system diseases and infectious diseases with 33 publications in each subject. Only 12 articles were found in the field of endocrinology and metabolism. The most popular techniques used in those reports were two-dimensional electrophoresis coupled with mass spectrometry (34.4 %) followed by NMR (22.6 %), LC/MS/MS (15 %).CONCLUSIONS: Omics studies in Iran are a relatively new approach and the number of original articles regarding endocrine disorders in humans is limited. Providing appropriate infrastructures including lab facilities with high technology instruments can improve the quality and quantity of basic and clinical researches in this field.PMID:39610495 | PMC:PMC11599483 | DOI:10.1007/s40200-021-00727-0

Public Health Nutr. 2024 Nov 29:1-13. doi: 10.1017/S1368980024002271. Online ahead of print.ABSTRACTOBJECTIVE: Neural tube defects (NTDs) are serious, life-threatening birth defects. Staple food fortification with folic acid (vitamin B9) is a proven, effective intervention to reduce NTD birth prevalence. Mandatory food fortification with folic acid was implemented in South Africa (SA) in 2003. This article provides an overview of NTD birth prevalence in SA, pre- and post-fortification, and evaluates current folic acid fortification regulations.DESIGN: Fortification effectiveness data in SA were reviewed using published studies and national reports on NTD birth prevalence pre- and post-folic acid fortification. Current folic acid fortification regulations in SA were evaluated by experts.SETTING: Regulations were assessed using national health guidelines, legislation and regulations. NTD birth prevalence data were sourced from the published literature.PARTICIPANTS: None.RESULTS: Significant reductions in the birth prevalence of spina bifida and anencephaly, and improved maternal folate levels have been achieved following the introduction of folic acid fortification in SA. However, there is poor overall regulatory compliance in some instances and a gap in current regulations that excludes the fortification of cake flour in SA.CONCLUSIONS: While the SA NTD birth prevalence has decreased post-fortification, the regulatory exclusion of cake flour fortification is a significant and growing issue. Proposed 2016 regulatory amendments to address this gap urgently require finalisation and enactment by government to prevent negating benefits achieved to date and to ensure continued improvement. Fortification monitoring requires strengthening to ensure widespread compliance with policies, particularly in underserved areas.PMID:39610362 | DOI:10.1017/S1368980024002271

Diabetes Metab J. 2024 Nov;48(6):1047-1055. doi: 10.4093/dmj.2024.0659. Epub 2024 Nov 21.ABSTRACTThe consumption of ultra-processed foods (UPFs) has surged globally, raising significant public health concerns due to their associations with a range of adverse health outcomes. This review aims to elucidate potential health impacts of UPF intake and underscore the importance of considering diet quality when interpreting study findings. UPF group, as classified by the Nova system based on the extent of industrial processing, contains numerous individual food items with a wide spectrum of nutrient profiles, as well as differential quality as reflected by their potential health effects. The quality of a given food may well misalign with the processing levels so that a UPF food can be nutritious and healthful whereas a non-UPF food can be of low quality and excess intake of which may lead to adverse health consequences. The current review argues that it is critical to focus on the nutritional content and quality of foods and their role within the overall dietary pattern rather than only the level of processing. Further research should dissect health effects of diet quality and food processing, investigate the health impacts of ingredients that render the UPF categorization, understand roles of metabolomics and the gut microbiome in mediating and modulating the health effects of food processing, and consider environmental sustainability in UPF studies. Emphasizing nutrient-dense healthful foods and dietary patterns shall remain the pivotal strategy for promoting overall health and preventing chronic diseases.PMID:39610133 | DOI:10.4093/dmj.2024.0659

Neural Regen Res. 2025 Oct 1;20(10):2982-2997. doi: 10.4103/NRR.NRR-D-23-01979. Epub 2024 Jun 26.ABSTRACTJOURNAL/nrgr/04.03/01300535-202510000-00028/figure1/v/2024-11-26T163120Z/r/image-tiff Alzheimer's disease not only affects the brain, but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota. The aim of this study was to investigate systemic changes that occur in Alzheimer's disease, in particular the association between changes in peripheral organ metabolism, changes in gut microbial composition, and Alzheimer's disease development. To do this, we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1 (APP/PS1) transgenic and control mice at 3, 6, 9, and 12 months of age. Twelve-month-old APP/PS1 mice exhibited cognitive impairment, Alzheimer's disease-related brain changes, distinctive metabolic disturbances in peripheral organs and fecal samples (as detected by untargeted metabolomics sequencing), and substantial changes in gut microbial composition compared with younger APP/PS1 mice. Notably, a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice. These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer's disease development, indicating potential new directions for therapeutic strategies.PMID:39610107 | DOI:10.4103/NRR.NRR-D-23-01979

Environ Health. 2024 Nov 28;23(1):105. doi: 10.1186/s12940-024-01145-4.ABSTRACTBACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure has been associated with metabolic diseases, however, the underlying molecular pathogenesis remains to be understood. Integrated PFAS and lipidomic analysis has the potential to identify alterations in lipid metabolism pathways for exposome research.METHODS: A targeted LC-MS/MS method was developed for the quantification of 14 PFAS from human plasma samples (n = 96). Concurrently, high coverage lipidomics was conducted for the quantification of 665 lipid species in the same plasma samples. Linear regression models were implemented to study the association of PFAS with plasma lipidome.RESULTS: Women had lower levels of PFAS compared to men and Asian-Indians had lower levels of PFAS compared to both Chinese and Malay subjects. PFAS were positively associated with a number of lipid species from lysophospholipid, ceramide and triacylglycerol lipid classes. Phosphatidylinositol, acylcarnitine and sphingosine-1-phosphate were negatively associated with PFAS. Association studies revealed both shared and distinct relationship of PFAS with plasma lipids.CONCLUSIONS: We demonstrate that the circulating levels of PFAS vary with age, ethnicity and sex within a multi-ethnic Asian population with potential implications in future biomonitoring and mitigation. Our comprehensive lipidomics methodology and association studies enabled us to characterize the relationship of circulating PFAS and lipidomic profiles. These results will help in better understanding of the molecular basis of PFAS exposure on human health outcomes.PMID:39609840 | DOI:10.1186/s12940-024-01145-4

Cell Biosci. 2024 Nov 28;14(1):145. doi: 10.1186/s13578-024-01322-5.ABSTRACTBACKGROUND: The increasing incidence of childhood obesity annually has led to a surge in physical and mental health risks, making it a significant global public health concern. This study aimed to discover novel biomarkers of childhood simple obesity through integrative multi-omics analysis, uncovering their potential connections and providing fresh research directions for the complex pathogenesis and treatment strategies.METHODS: Transcriptome, untargeted metabolome, and 16 S rDNA sequencing were conducted on subjects to examine transcripts, metabolites in blood, and gut microflora in stool.RESULTS: Transcriptomic analysis identified 599 differentially expressed genes (DEGs), of which 25 were immune-related genes, and participated in immune pathways such as antimicrobial peptides, neutrophil degranulation, and interferons. The optimal random forest model based on these genes exhibited an AUC of 0.844. The metabolomic analysis examined 71 differentially expressed metabolites (DEMs), including 12 immune-related metabolites. Notably, lauric acid showed an extremely strong positive correlation with BMI and showed a good discriminative power for obesity (AUC = 0.82). DEMs were found to be significantly enriched in four metabolic pathways, namely "Aminoacyl-tRNA biosynthesis", "Valine leucine and isoleucine biosynthesis, and Glycine", "Serine and threonine metabolism", and "Biosynthesis of unsaturated fatty acids". Microbiome analysis revealed 12 differential gut microbiotas (DGMs) at the phylum and genus levels, with p_Firmicutes dominating in the obese group and g_Escherichia-Shigella in the normal group. Subsequently, a Random Forest model was developed based on the DEMs, immune-related DEGs, and metabolites with an AUC value of 0.912. The 14 indicators identified by this model could potentially serve as a set of biomarkers for obesity. The analysis of the inter-omics correlation network found 233 pairs of significant correlations. DEGs BPIFA1, BPI, and SAA1, DEMs Dimethy(tetradecyl)amine, Deoxycholic acid, Pathalic anhydride, and DL-Alanine, and DGMs g_Intestinimonas and g_Turicibacter showed strong connectivity within the network, constituting a large proportion of interactions.CONCLUSION: This study presents the first comprehensive description of the multi-omics characteristics of childhood simple obesity, recognizing promising biomarkers. Immune-related markers offer a new perspective for researching the immunological mechanisms underlying obesity and its associated complications. The revealed interactions among these biomarkers contribute to a deeper understanding the intricate biological regulatory networks associated with obesity.PMID:39609876 | DOI:10.1186/s13578-024-01322-5

IMA Fungus. 2024 Nov 28;15(1):38. doi: 10.1186/s43008-024-00167-4.ABSTRACTFungi are known to produce many chemically diversified metabolites, yet their ecological roles are not always fully understood. The blue cheese fungus Penicillium roqueforti thrives in different ecological niches and is known to produce a wide range of metabolites, including mycotoxins. Three P. roqueforti populations have been domesticated for cheese production and two populations thrive in other anthropized environments, i.e., food, lumber and silage. In this study, we looked for differences in targeted and untargeted metabolite production profiles between populations using HPLC-HR-Q-TOF and UHPLC-Q-TOF-HR-MS/MS. The non-cheese populations produced several fatty acids and different terpenoids, lacking in cheese strains. The Termignon cheese population displayed intermediate metabolite profiles between cheese and non-cheese populations, as previously shown for other traits. The non-Roquefort cheese population with the strongest domestication syndrome, produced the lowest quantities of measured metabolites, including mycophenolic acid (MPA), andrastin A and PR toxin. Its inability to produce MPA was due to a deletion in the mpaC gene, while a premature stop codon in ORF 11 of the PR toxin gene cluster explained PR toxin absence and the accumulation of its intermediates, i.e., eremofortins A and B. In the Roquefort population, we detected no PR toxin nor eremofortins A or B, but found no indel or frameshift mutation, suggesting downregulation. The hypotoxigenic trait of domesticated cheese populations can be hypothesized to be linked to the loss of this ability through trait degeneration and/or the selection of low toxin producers. It may also be due to the fact that populations from other anthropized environments maintained high metabolite diversity as the bioactivities of these compounds are likely important in these ecological niches.PMID:39609866 | DOI:10.1186/s43008-024-00167-4

J Transl Med. 2024 Nov 28;22(1):1077. doi: 10.1186/s12967-024-05796-2.ABSTRACTBACKGROUND: Although research has indicated correlations between lipids, cerebrospinal fluid (CSF) metabolites, and Late-Onset Alzheimer's Disease (LOAD), the specific causal relationships among these elements, as well as the roles and mechanisms of the cerebrospinal fluid metabolites, remain unclear.METHODS: Statistical datasets derived from Genome-Wide Association Studies (GWAS) were utilized to assess the bidirectional causal relationships between lipids and LOAD. Subsequently, genetic variants associated with CSF metabolites and established lipids underwent a two-step Mendelian randomization (MR) analysis to explore potential mediators and analyze mediation effects. Sensitivity analyses were employed to assess the robustness of the detection systems.RESULTS: Genetically predicted cholesterol (IVW OR = 0.989; 95% CI 0.982-0.996) was found to reduce the risk of LOAD, whereas Phosphatidylcholine (PC) (18:1_0:0) (IVW OR = 1.015; 95% CI 1.005-1.025) posed a risk factor. The potential mediator, CSF metabolite N-acetylneuraminate (NeuAC), was identified with a mediation proportion of 21.02% (3.25%, 45.50%). No pleiotropy or heterogeneity was detected across MR analyses.CONCLUSIONS: The findings underscore the pivotal role of CSF metabolomics in elucidating the lipid-mediated pathogenesis of LOAD, highlighting potential diagnostic and preventative biomarkers.PMID:39609832 | DOI:10.1186/s12967-024-05796-2

Sci Rep. 2024 Nov 28;14(1):29621. doi: 10.1038/s41598-024-81321-1.ABSTRACTDiet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD; high in refined carbohydrates, cholesterol and saturated fat), relative to a heart-healthy diet (HHD; high in unrefined carbohydrates, polyunsaturated fat and fiber, and low in cholesterol) on brain microvessel transcriptomics and brain metabolomics of the temporal region in Ossabaw minipigs. Thirty-two pigs (16 male and 16 females) were fed a WD or HHD starting at the age of 4 months for a period of 6 months. The WD and HHD were isocaloric and had a similar macronutrient content but differed in macronutrient quality. Within each dietary group, half of the pigs also received atorvastatin. Relative to HHD-fed pigs, WD-fed pigs had 175 genes differentially expressed (fold change > 1.3, FDR < 0.05) by diet, 46 upregulated and 129 downregulated. Gene Set Enrichment Analysis identified 22 gene sets enriched in WD-fed pigs, comprising pathways related to inflammation, angiogenesis, and apoptosis, and 53 gene sets enriched in the HHD-fed pigs, including cell energetics, neurotransmission, and inflammation resolution pathways. Metabolite analysis showed enrichment in arginine, tyrosine, and lysine in WD-fed pigs, and ergothioneine and S-adenosyl methionine in HHD-fed pigs. Atorvastatin treatment did not affect gene expression. These results suggest a likely contribution of diet to brain pathologies characterized by neuroinflammation and neurodegeneration.PMID:39609531 | DOI:10.1038/s41598-024-81321-1