PubMed

Biochim Biophys Acta Mol Basis Dis. 2024 Nov 27:167567. doi: 10.1016/j.bbadis.2024.167567. Online ahead of print.ABSTRACTIt becomes increasingly clear that the tissue specificity of mitochondrial diseases might in part rely on their ability to compensate for mitochondrial defects, contributing to the heterogeneous nature of mitochondrial diseases. Here, we investigated tissue-specific responses to cytochrome c oxidase (CIV or COX) deficiency using a mouse model with heart and skeletal muscle-specific depletion of the COX assembly factor COX10. At three weeks of age, both tissues exhibit pronounced CIV depletion but respond differently to oxidative phosphorylation (OXPHOS) impairment. Heart-specific COX10 depletion caused severe dilated cardiomyopathy, while skeletal muscle experiences less damage. Cardiac CIV deficiency triggered extensive metabolic remodelling and stress response activation, potentially worsening cardiomyopathy, whereas skeletal muscle showed no stress response or significant metabolic changes. Our findings highlight distinct tissue capacities for managing CIV deficiency, explaining how identical primary defects can lead to different phenotypic outcomes and contribute to the heterogeneous progression of mitochondrial diseases.PMID:39613003 | DOI:10.1016/j.bbadis.2024.167567

J Hazard Mater. 2024 Nov 26;483:136668. doi: 10.1016/j.jhazmat.2024.136668. Online ahead of print.ABSTRACT8:2 Chlorinated polyfluoroalkyl ether sulfonate (8:2 Cl-PFESA) is a substitute for perfluorooctane sulfonate and an emerging environmental pollutant, yet its bioaccumulation and health risks are poorly understood. We established a subchronic exposure model in mice (0.04, 0.2, and 1 mg/kg/d) to evaluate its adverse effects. Our findings show extensive distribution of 8:2 Cl-PFESA in various tissues (plasma, liver, kidney, brain, heart, lung, testis, ovary, spleen, thymus, thyroid, uterus, large intestine, small intestine, muscle, and fat), with the highest accumulation in the liver, identified as the primary storage organ. Liver histopathology revealed elevated alanine aminotransferase levels, reduced triglycerides, and ballooning degeneration. Proteomics analysis indicated significant involvement of amino acid metabolism in 8:2 Cl-PFESA-induced hepatotoxicity. Metabolomics analysis further highlighted pronounced alterations in amino acid interconversion. Multi-omics integration revealed disruptions in amino acid metabolism, particularly with alanine, histidine, and tryptophan, identifying key proteins EHHADH, HAL, MAO-A, ALDH3A2, and TDO2 as crucial connectors in these metabolic processes, validated by Western blot experiments. This study provides a comprehensive analysis of 8:2 Cl-PFESA accumulation and distribution in biological systems, demonstrating that hepatotoxicity is primarily mediated through amino acid metabolism disruption, offering insights for pollution mitigation strategies and future toxicological research.PMID:39612878 | DOI:10.1016/j.jhazmat.2024.136668

Food Chem. 2024 Nov 23;466:142219. doi: 10.1016/j.foodchem.2024.142219. Online ahead of print.ABSTRACTIn this study, the flavor of egg whites was significantly improved by lactic acid fermentation, and the metabolic networks of metabolites, volatile compounds, and enzymes were established using gas chromatography-mass spectrometry, metabolomic, and proteomic. Results indicate that among ten types of common lactic acid bacteria, Streptococcus thermophilus endowed egg white with the most pleasant flavor through increasing aldehydes, ketones, alcohols, esters, terpenoids, and aromatic compounds. Amino acid catabolism was the predominant pathway for generating most aldehydes, alcohols, acids, and esters. The changes in the organic acids and derivatives (mainly amino acids, peptides, and analogues) concentration during fermentation are attributed to the hydrolysis of egg white proteins by proteinases and peptidases, and the regulation of enzymes involved in amino acid biosynthesis and other reactions. This study provides a valuable reference for future investigations focusing on regulating the flavor release of egg whites.PMID:39612849 | DOI:10.1016/j.foodchem.2024.142219

Sci Total Environ. 2024 Nov 28;957:177776. doi: 10.1016/j.scitotenv.2024.177776. Online ahead of print.ABSTRACTPropranolol (PRO) has been detected in water bodies worldwide, attributed to the incomplete removal by wastewater treatment processes. Although reports exist on the removal of PRO by wetland plants such as Phragmites communis, research on the impact of PRO on soil organic carbon (SOC) components in these plants' rhizospheres remains scarce. This investigation examined the impacts of 0.5 μg/L and 50 μg/L concentrations of PRO on the rhizosphere of P. communis over a 21-day laboratory experiment. PRO exposure slightly promoted root growth, notably enhancing fine root development at a lower concentration. A notable decrease in SOC content was observed in the PRO-treated samples: specifically, the proportion of mineral-associated organic carbon (MAOC) rose (from 47.90 % to 33.17 %), whereas the proportion of particulate organic carbon (POC) significantly declined following PRO treatment (from 52.10 % to 66.83 %). Moreover, Proteobacteria and Nitrospirae experienced significant promotion in the high-concentration samples while Bacteroidetes and Verrucomicrobia were inhibited. The metabolomic analysis demonstrated that glycine, serine, and threonine metabolism was the principal differential metabolic pathway in varying concentrations of PRO exposure. Additionally, across varying PRO concentrations, plant influence emerged as the predominant factor affecting POC alterations, whereas MAOC changes resulted from the synergistic interaction of plants and associated bacteria. The outcomes of this study mark a critical advancement towards a thorough assessment of PRO's impact on the rhizosphere of wetland plants, bearing significant ramifications for evaluating PRO's environmental effects.PMID:39612712 | DOI:10.1016/j.scitotenv.2024.177776

Poult Sci. 2024 Nov 23;104(1):104556. doi: 10.1016/j.psj.2024.104556. Online ahead of print.ABSTRACTOver the past decade, metabolomic research in livestock and poultry has gained considerable momentum; however, quail metabolomics still lags behind that of livestock species such as chickens, pigs, and cattle. Quails are important models due to their low-cost protein sources-both eggs and meat-and practical benefits such as minimal space requirements, high egg production, disease resistance, and rapid reproduction. Therefore, it is necessary to systematically understand the effects of various factors on quail metabolism to provide a theoretical basis for accurate feeding and breeding practices. In this study, liquid chromatography with tandem mass spectroscopy (LC-MS/MS)-based metabolomics was used to examine the effects of age, breed, and sex on the serum metabolic profile of quails. A total of 550 metabolites were identified. Relative to breed and sex, we found that age played a crucial role in influencing quail serum metabolites. At 20 days of age (D20), quails had high levels of serum thymidine and alpha-D-glucose, while at 70 days of age (D70), the lipids, including 3-isothujone, 15-deoxy-d-12,14-PGJ2, and 2-aminobut-2-enoate dominated the serum. Additionally, xanthine, hypoxanthine, diaminopimelic acid, and 2-deoxy-scyllo-inosose appeared to be specific metabolites of Japanese quail (JAPQ). Serum levels of N-acetylglutamic acid, hydroxypyruvic acid, carnosine, alloepipregnanolone, lumichrome, 6-hydroxynicotinate, and myristic acid were higher in D70 Hengyan white feather quails (HYWQ) than those in D70 JAPQ. Notably, this study also identified 2-hydroxy-2-ethylsuccinic acid and riboflavin as potential specific metabolites in female quails. Furthermore, integration analysis showed that amino acid biosynthesis and metabolism, as well as ABC transporters, were the key pathways distinguishing D20 from D70. Purine metabolism, pyrimidine metabolism, ABC transporters, and TCA cycle were the key pathways distinguishing HYWQ from JAPQ. Differences in energy metabolism and amino acid biosynthesis and metabolism were observed between males and females. These findings enhance our understanding of the dynamic changes in quail serum metabolites influenced by various factors and address the knowledge gap regarding serum metabolic changes at different stages in quails.PMID:39612675 | DOI:10.1016/j.psj.2024.104556

Medicine (Baltimore). 2024 Nov 29;103(48):e40719. doi: 10.1097/MD.0000000000040719.ABSTRACTTo demonstrate the potential for connecting metabolomics with traditional Chinese medicine (TCM) external therapies such as acupuncture and moxibustion, we conducted a literature review on metabolomics as a measurement tool for determining the efficacy of various TCM external therapies. Human research and animal models published in the last 10 years were summarized. The investigation can be classified as follows: Using metabolomics to study metabolic profile changes produced by stimulation of a specific acupoint ST36 indicates the perturbation of metabolites produced by stimulation of acupoints by external TCM treatments can be characterized by metabolomics; and Using metabolomics to reveal the molecular mechanism of various TCM external therapy methods to treat specific diseases such as digestive system disease, cardiovascular disease, neurological disorder, bone disease, and muscle fatigue. We conclude that metabolomics has considerable potential for comprehending TCM external treatment interventions, particularly from a systems perspective. Linking TCM external therapy research with metabolomics can further bridge detailed biological mechanisms with the systematic effect of TCM external therapy, hence providing new paths for gaining a deeper knowledge of the importance of TCM in the treatment and maintenance of health.PMID:39612392 | DOI:10.1097/MD.0000000000040719

mSystems. 2024 Nov 29:e0145024. doi: 10.1128/msystems.01450-24. Online ahead of print.ABSTRACTIt is well known that gut microbial imbalance is a potential factor for the occurrence and development of diabetes mellitus (DM) and its complications. Moreover, the heart and gut microbiota can regulate each other through the gut-metabolite-heart axis. In this study, metagenomics, metabolomics, and transcriptomics were chosen to sequence the changes in gut microbiota, serum metabolite levels, and differentially expressed genes (DEGs) in leptin receptor-deficient db/db mice and analyze the correlation between serum metabolites and gut microbiota or DEGs. According to the results, there were significant differences in the 1,029 cardiac genes and 353 serum metabolites in diabetic mice of the db/db group, including DEGs enriched in the PPAR signaling pathway and increased short-chain carboxylic acids (CAs), when compared with the normal db/m group. According to metagenomics, the gut microbiota of mice in the db/db group were disrupted, and particularly Lachnospiraceae bacteria and Oscillospiraceae bacteria significantly decreased. Also, according to the Pearson correlation analysis, a significant positive correlation was found between CAs and PPAR signaling pathway-related DEGs, and a negative correlation was found between CAs and the abundance of the above-mentioned species. To sum up, type 2 diabetes mellitus (T2DM) can upregulate the expression of partial cardiac genes through the levels of serum short-chain CAs affected by gut microbiota, thus playing a role in the occurrence and development of diabetic cardiomyopathy (DCM).IMPORTANCE: Our research results clearly link the changes in heart genes of T2DM and normal mice with changes in serum metabolites and gut microbiota, indicating that some genes in biological processes are closely related to the reduction of protective microbiota in the gut microbiota. This study provides a theoretical basis for investigating the mechanism of DCM and may provide preliminary evidence for the future use of gut microbiota therapy for DCM.PMID:39611812 | DOI:10.1128/msystems.01450-24

Reproduction. 2024 Nov 1:REP-24-0051. doi: 10.1530/REP-24-0051. Online ahead of print.ABSTRACTTop-down proteomics was employed to construct proteoform atlas of sperm and seminal plasma (SP) from bulls with low (LF) and high (HF) semen freezability. Sperm and seminal proteins were fractionated by tandem size exclusion chromatography (< 30 kDa) and analyzed by reversed-phase liquid chromatography-tandem mass spectrometry. This approach enabled the identification of 299 SP (from 46 families) and 267 sperm proteoforms (from 139 families). Seventy proteoforms belonging to beta-defensin 10, c-type natriuretic peptide (NPPC), caltrin, seminal ribonuclease, osteopontin, and binder of sperm protein (BSP) 3 families were unique to HF bulls' SP. LF seminal proteins had unique 77 proteoforms, including caltrin, NPPC, osteopontin, BSP3, serpin family A member 5, and β-NGF families. Proteoform families of SP in HF and LF bulls were related to Ca2+ uptake, capacitation, acrosome reaction, sperm protection, fertilization and proteolytic processes. Thirty-three proteoforms of NPPC, caltrin, and cylicin-2 families were upregulated in HF sperm. Twenty-two proteoforms of caltrin, cylicin-2, ATP synthases, and malate dehydrogenase families were among those upregulated in LF sperm. Truncated and acetylated histone H2A and non-truncated and acetylated c-Myc binding protein were prevalent in LF sperm. Cylicin-2 proteoforms were observed in HF and LF sperm, and truncated glyceraldehyde-3-phosphate dehydrogenases, only in HF sperm. In silico analyses indicated the enrichment of mitochondrial metabolic pathways in HF sperm, including fatty acid metabolism and TCA cycle. Our study brings an unprecedented description of the bovine SP and sperm proteoforms. Post-translational processing appears to define the bio-properties of semen proteins and their associations with sperm cryoresistance.PMID:39611730 | DOI:10.1530/REP-24-0051

Elife. 2024 Nov 29;13:RP96937. doi: 10.7554/eLife.96937.ABSTRACTBACKGROUND: Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to this disorder are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits.METHODS: In this study, we investigated the impact of severe AUD (sAUD), and of a 3-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 sAUD patients hospitalized for alcohol withdrawal.RESULTS: We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in sAUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol exposure and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine, and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in postmortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue.CONCLUSIONS: Our data allow the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets arising in the management of neuropsychiatric diseases such as sAUD.FUNDING: Gut2Behave project was initiated from ERA-NET NEURON network (Joint Transnational Call 2019) and was financed by Academy of Finland, French National Research Agency (ANR-19-NEUR-0003-03) and the Fonds de la Recherche Scientifique (FRS-FNRS; PINT-MULTI R.8013.19, Belgium). Metabolomics analysis of the TSDS samples was supported by grant from the Finnish Foundation for Alcohol Studies.PMID:39611656 | DOI:10.7554/eLife.96937

Am J Physiol Cell Physiol. 2024 Nov 29. doi: 10.1152/ajpcell.00611.2023. Online ahead of print.ABSTRACTThe TCA cycle serves as a central hub to balance catabolic and anabolic needs of the cell, where carbon moieties can either contribute to oxidative metabolism or support biosynthetic reactions. This differential TCA cycle engagement for glucose-derived carbon has been extensively studied in cultured cells, but the fate of fatty acid (FA)-derived carbons is poorly understood. To fill the knowledge gap, we have developed a strategy to culture cells with long-chain FAs without altering cell viability. By tracing 13C-FA we show that FA oxidation (FAO) is robust in both proliferating and oxidative cells while the metabolic pathway after citrate formation is distinct. In proliferating cells, a significant portion of carbon derived from FAO exits canonical TCA cycle as citrate and converts to unlabeled malate in cytosol. Increasing FA supply or b-oxidation does not change the partition of FA-derived carbon between cytosol and mitochondria. Oxidation of glucose competes with FA derived carbon for the canonical TCA pathway thus promoting FA carbon flowing into the alternative TCA pathway. Moreover, the coupling between FAO and the canonical TCA pathway changes with the state of oxidative energy metabolism.PMID:39611618 | DOI:10.1152/ajpcell.00611.2023

Amyotroph Lateral Scler Frontotemporal Degener. 2024 Nov 29:1-7. doi: 10.1080/21678421.2024.2433578. Online ahead of print.ABSTRACTOBJECTIVE: Over the past years, interest in the role of gut microbiota in neurodegenerative diseases has emerged. Despite numerous publications over the past decade, both in human and pre-clinical studies, there is no clear consensus on the microbiota's role or involvement in ALS. Few studies on mouse models of ALS highlighted a correlation between specific bacteria species and the prognostic or severity of the disease. Still these results lack reproducibility and remain controverted. In this article we present a study of fecal microbiota in the SOD1G93A mouse model associated with a metabolomic analysis of cecum content, compared to controls.METHODS: Intestinal metabolomic profile and fecal microbiota were assessed in two cohorts of SODG93A mice compared to wildtype controls at the terminal stage of the ALS disease.RESULTS: Results showed a significant difference in metabolomic profile in SOD1G93A mice compared to controls but without a marked change in composition and diversity of fecal microbiota. Nevertheless, we observed an increase of Lachnospiraceae family, which are butyrate-producer bacteria, in SOD1G93A mice. Moreover, some metabolites with significantly different intestinal concentrations are partially produced and linked with intestinal bacteria, such as riboflavin, hippurate, and N-acetylputrescine, leaving us convinced of the interest in looking further into the role of the microbiota in ALS.CONCLUSIONS: Despite an alteration of the intestinal metabolome in SOD1G93A mice, microbiota data did not show significant changes, underlying the need for further research.PMID:39611550 | DOI:10.1080/21678421.2024.2433578

New Phytol. 2024 Nov 29. doi: 10.1111/nph.20323. Online ahead of print.ABSTRACTMarine microalgae demonstrate a notable capacity to adapt to high CO2 and warming in the context of global change. However, the dynamics of their evolutionary processes under simultaneous high CO₂ and warming conditions remain poorly understood. Here, we analyze the dynamics of evolution in experimental populations of a model marine diatom Phaeodactylum tricornutum. We conducted whole-genome resequencing of populations under ambient, high-CO2, warming and high CO2 + warming at 2-yr intervals over a 4-yr adaptation period. The common genes selected between 2- and 4-yr adaptation were found to be involved in protein ubiquitination and degradation and the tricarboxylic acid (TCA) cycle, and were consistently selected regardless of the experimental conditions or adaptation duration. The unique genes selected only by 4-yr adaptation function in respiration, fatty acid, and amino acid metabolism, facilitating adaptation to prolonged high CO2 with warming conditions. Corresponding changes at the metabolomic level, with significant alterations in metabolites abundances involved in these pathways, support the genomic findings. Our study, integrating genomic and metabolomic data, demonstrates that long-term adaptation of microalgae to high CO2 and/or warming can be characterized by a complex and dynamic genetic process and may advance our understanding of microalgae adaptation to global change.PMID:39611545 | DOI:10.1111/nph.20323

Biosci Biotechnol Biochem. 2024 Nov 28:zbae182. doi: 10.1093/bbb/zbae182. Online ahead of print.ABSTRACTProper diet is crucial for obesity prevention. Food health research primarily focuses on two aspects: the pathogenesis of lifestyle-related diseases caused by obesity and the identification of dietary components that can aid in the prevention and treatment of lifestyle-related diseases. Substantial knowledge has been accumulated regarding these aspects via health function evaluations based on biological experiments. However, the intricate causal relationships and specific biological metabolites or food compounds that affect health remain unclear. To address these issues, recent my studies have incorporated mass spectrometry data, particularly metabolomic data obtained via comprehensive component analysis, to enhance health function evaluation via biological experiments. These studies have revealed various biological and healthy compounds derived from different food materials for the management of obesity-induced metabolic disorders.PMID:39611358 | DOI:10.1093/bbb/zbae182

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