Jorine C. van der Weerd, Annemiek M. J. van Wegberg, Theo S. Boer, Udo F. H. Engelke, Karlien L. M. Coene, Ron A. Wevers, Stephan J. L. Bakker, Pim de Blaauw, Joost Groen, Francjan J. van Spronsen, M Rebecca Heiner-Fokkema
Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann–Whitney U test, p < 0.05) analyses. Results: Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. Conclusions: This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason.
{"title":"Impact of Phenylketonuria on the Serum Metabolome and Plasma Lipidome: A Study in Early-Treated Patients","authors":"Jorine C. van der Weerd, Annemiek M. J. van Wegberg, Theo S. Boer, Udo F. H. Engelke, Karlien L. M. Coene, Ron A. Wevers, Stephan J. L. Bakker, Pim de Blaauw, Joost Groen, Francjan J. van Spronsen, M Rebecca Heiner-Fokkema","doi":"10.3390/metabo14090479","DOIUrl":"https://doi.org/10.3390/metabo14090479","url":null,"abstract":"Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann–Whitney U test, p < 0.05) analyses. Results: Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. Conclusions: This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"7 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emad Ali Albadawi, Naweed SyedKhaleel Alzaman, Yasir Hassan Elhassan, Heba M. Eltahir, Mekky M. Abouzied, Muayad Saud Albadrani
The increasing incidence of hypospadias and cryptorchidism, coupled with the widespread presence of endocrine-disrupting chemicals (EDCs), has raised concerns about the potential impact of these environmental factors on male urogenital development. This systematic review and meta-analysis aims to evaluate the association between maternal exposure to various EDCs and the risk of hypospadias and cryptorchidism. We conducted a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases from inception until May 2024. We included case-control and cohort studies that examined the association between maternal EDC exposure and hypospadias or cryptorchidism, reporting adjusted odds ratios (aOR) or crude odds ratios (cOR). Data were extracted and pooled using a random effects model, and heterogeneity was assessed using the Q test and I-square statistics. The risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS). A total of 48 studies were included in the systematic review, with 46 studies included in the meta-analysis. The pooled analysis revealed a significant association between maternal EDC exposure and an increased risk of hypospadias (aOR = 1.26, 95% CI: 1.18–1.35, p < 0.0001) and cryptorchidism (aOR = 1.37, 95% CI: 1.19–1.57, p < 0.001). Subgroup analyses showed that exposure to pesticides, phthalates, alkyl phenolic compounds (ALKs), and heavy metals significantly increased the risk of hypospadias. In contrast, polychlorinated biphenyls (PCBs) did not show a significant association. Significant associations were found with pesticide and PCB exposure for cryptorchidism, but not with phthalate, ALK, or heavy metal exposure. Maternal exposure to certain EDCs is associated with an increased risk of hypospadias and cryptorchidism in male children. These findings underscore the importance of addressing environmental and occupational exposures during pregnancy to mitigate potential risks. Further research is needed to elucidate the mechanisms by which EDCs affect urogenital development and to develop effective interventions to reduce exposure among vulnerable populations.
尿道下裂和隐睾症的发病率不断上升，再加上干扰内分泌的化学品（EDCs）的广泛存在，引起了人们对这些环境因素对男性泌尿生殖系统发育的潜在影响的关注。本系统综述和荟萃分析旨在评估母体暴露于各种 EDCs 与尿道下裂和隐睾症风险之间的关联。我们对 PubMed、Scopus、Web of Science 和 Cochrane 数据库进行了全面检索，检索时间从开始到 2024 年 5 月。我们纳入了研究母体暴露于 EDC 与尿道下裂或隐睾症之间关系的病例对照和队列研究，并报告了调整后的几率比（aOR）或粗略几率比（cOR）。采用随机效应模型提取和汇总数据，并使用 Q 检验和 I 方统计量评估异质性。偏倚风险采用纽卡斯尔-渥太华量表（NOS）进行评估。共有 48 项研究被纳入系统综述，46 项研究被纳入荟萃分析。汇总分析显示，母体接触 EDC 与尿道下裂（aOR = 1.26，95% CI：1.18-1.35，p < 0.0001）和隐睾（aOR = 1.37，95% CI：1.19-1.57，p < 0.001）风险增加之间存在显著关联。分组分析表明，接触杀虫剂、邻苯二甲酸盐、烷基酚化合物（ALKs）和重金属会显著增加尿道下裂的风险。与此相反，多氯联苯（PCBs）并未显示出明显的关联性。研究发现，隐睾症与农药和多氯联苯暴露有显著关联，但与邻苯二甲酸盐、ALK 或重金属暴露无显著关联。母亲暴露于某些 EDC 与男性尿道下裂和隐睾症的风险增加有关。这些发现强调了解决孕期环境和职业暴露问题以降低潜在风险的重要性。还需要进一步研究，以阐明 EDC 影响泌尿生殖系统发育的机制，并制定有效的干预措施，减少易感人群的接触。
{"title":"The Association between Maternal Endocrine-Disrupting Chemical Exposure during Pregnancy and the Incidence of Male Urogenital Defects: A Systematic Review and Meta-Analysis","authors":"Emad Ali Albadawi, Naweed SyedKhaleel Alzaman, Yasir Hassan Elhassan, Heba M. Eltahir, Mekky M. Abouzied, Muayad Saud Albadrani","doi":"10.3390/metabo14090477","DOIUrl":"https://doi.org/10.3390/metabo14090477","url":null,"abstract":"The increasing incidence of hypospadias and cryptorchidism, coupled with the widespread presence of endocrine-disrupting chemicals (EDCs), has raised concerns about the potential impact of these environmental factors on male urogenital development. This systematic review and meta-analysis aims to evaluate the association between maternal exposure to various EDCs and the risk of hypospadias and cryptorchidism. We conducted a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases from inception until May 2024. We included case-control and cohort studies that examined the association between maternal EDC exposure and hypospadias or cryptorchidism, reporting adjusted odds ratios (aOR) or crude odds ratios (cOR). Data were extracted and pooled using a random effects model, and heterogeneity was assessed using the Q test and I-square statistics. The risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS). A total of 48 studies were included in the systematic review, with 46 studies included in the meta-analysis. The pooled analysis revealed a significant association between maternal EDC exposure and an increased risk of hypospadias (aOR = 1.26, 95% CI: 1.18–1.35, p < 0.0001) and cryptorchidism (aOR = 1.37, 95% CI: 1.19–1.57, p < 0.001). Subgroup analyses showed that exposure to pesticides, phthalates, alkyl phenolic compounds (ALKs), and heavy metals significantly increased the risk of hypospadias. In contrast, polychlorinated biphenyls (PCBs) did not show a significant association. Significant associations were found with pesticide and PCB exposure for cryptorchidism, but not with phthalate, ALK, or heavy metal exposure. Maternal exposure to certain EDCs is associated with an increased risk of hypospadias and cryptorchidism in male children. These findings underscore the importance of addressing environmental and occupational exposures during pregnancy to mitigate potential risks. Further research is needed to elucidate the mechanisms by which EDCs affect urogenital development and to develop effective interventions to reduce exposure among vulnerable populations.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"6 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amy Thachil, Li Wang, Rupasri Mandal, David Wishart, Tom Blydt-Hansen
Discrepant sample processing remains a significant challenge within blood metabolomics research, introducing non-biological variation into the measured metabolome and biasing downstream results. Inconsistency during the pre-analytical phase can influence experimental processes, producing metabolome measurements that are non-representative of in vivo composition. To minimize variation, there is a need to create and adhere to standardized pre-analytical protocols for blood samples intended for use in metabolomics analyses. This will allow for reliable and reproducible findings within blood metabolomics research. In this review article, we provide an overview of the existing literature pertaining to pre-analytical factors that influence blood metabolite measurements. Pre-analytical factors including blood tube selection, pre- and post-processing time and temperature conditions, centrifugation conditions, freeze–thaw cycles, and long-term storage conditions are specifically discussed, with recommendations provided for best practices at each stage.
{"title":"An Overview of Pre-Analytical Factors Impacting Metabolomics Analyses of Blood Samples","authors":"Amy Thachil, Li Wang, Rupasri Mandal, David Wishart, Tom Blydt-Hansen","doi":"10.3390/metabo14090474","DOIUrl":"https://doi.org/10.3390/metabo14090474","url":null,"abstract":"Discrepant sample processing remains a significant challenge within blood metabolomics research, introducing non-biological variation into the measured metabolome and biasing downstream results. Inconsistency during the pre-analytical phase can influence experimental processes, producing metabolome measurements that are non-representative of in vivo composition. To minimize variation, there is a need to create and adhere to standardized pre-analytical protocols for blood samples intended for use in metabolomics analyses. This will allow for reliable and reproducible findings within blood metabolomics research. In this review article, we provide an overview of the existing literature pertaining to pre-analytical factors that influence blood metabolite measurements. Pre-analytical factors including blood tube selection, pre- and post-processing time and temperature conditions, centrifugation conditions, freeze–thaw cycles, and long-term storage conditions are specifically discussed, with recommendations provided for best practices at each stage.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"11 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Claire Connolly, Mark Timlin, Sean A. Hogan, Tom F. O’Callaghan, André Brodkorb, Michael O’Donovan, Deirdre Hennessy, Ellen Fitzpatrick, Kieran McCarthy, John P. Murphy, Lorraine Brennan
A pasture or concentrate-based dietary regime impacts a variety of factors including both ruminal health and function, and consequently milk production and quality. The objective of this study was to examine the effect of feeding differing pasture levels on the metabolite composition of bovine ruminal fluid. Ruminal fluid was obtained from rumen-cannulated spring-calving cows (N = 9, Holstein-Friesian breed, average lactation number = 5) fed one of three diets across a full lactation season. Group 1 (pasture) consumed perennial ryegrass supplemented with 5% concentrates; group 2 received a total mixed ration (TMR) diet; and group 3 received a partial mixed ration (PMR) diet which included pasture and a TMR. Samples were taken at two timepoints: morning and evening. Metabolomic analysis was performed using nuclear magnetic resonance (1H-NMR) spectroscopy. Statistical analysis revealed significant changes across the dietary regimes in both morning and evening samples, with distinct alterations in the metabolite composition of ruminal fluid from pasture-fed cows (FDR-adjusted p-value < 0.05). Acetate and butyrate were significantly higher in samples derived from a pasture-based diet whereas sugar-related metabolites were higher in concentrate-based samples. Furthermore, a distinct diurnal impact on the metabolite profile was evident. This work lays the foundation for understanding the complex interaction between dietary regime and ruminal health.
{"title":"The Impact of Varying Pasture Levels on the Metabolomic Profile of Bovine Ruminal Fluid","authors":"Claire Connolly, Mark Timlin, Sean A. Hogan, Tom F. O’Callaghan, André Brodkorb, Michael O’Donovan, Deirdre Hennessy, Ellen Fitzpatrick, Kieran McCarthy, John P. Murphy, Lorraine Brennan","doi":"10.3390/metabo14090476","DOIUrl":"https://doi.org/10.3390/metabo14090476","url":null,"abstract":"A pasture or concentrate-based dietary regime impacts a variety of factors including both ruminal health and function, and consequently milk production and quality. The objective of this study was to examine the effect of feeding differing pasture levels on the metabolite composition of bovine ruminal fluid. Ruminal fluid was obtained from rumen-cannulated spring-calving cows (N = 9, Holstein-Friesian breed, average lactation number = 5) fed one of three diets across a full lactation season. Group 1 (pasture) consumed perennial ryegrass supplemented with 5% concentrates; group 2 received a total mixed ration (TMR) diet; and group 3 received a partial mixed ration (PMR) diet which included pasture and a TMR. Samples were taken at two timepoints: morning and evening. Metabolomic analysis was performed using nuclear magnetic resonance (1H-NMR) spectroscopy. Statistical analysis revealed significant changes across the dietary regimes in both morning and evening samples, with distinct alterations in the metabolite composition of ruminal fluid from pasture-fed cows (FDR-adjusted p-value < 0.05). Acetate and butyrate were significantly higher in samples derived from a pasture-based diet whereas sugar-related metabolites were higher in concentrate-based samples. Furthermore, a distinct diurnal impact on the metabolite profile was evident. This work lays the foundation for understanding the complex interaction between dietary regime and ruminal health.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"5 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sally Wu, Kristoffer J. Panganiban, Jiwon Lee, Dan Li, Emily C.C. Smith, Kateryna Maksyutynska, Bailey Humber, Tariq Ahmed, Sri Mahavir Agarwal, Kristen Ward, Margaret Hahn
Metabolic dysfunction is commonly observed in schizophrenia spectrum disorders (SSDs). The causes of metabolic comorbidity in SSDs are complex and include intrinsic or biological factors linked to the disorder, which are compounded by antipsychotic (AP) medications. The exact mechanisms underlying SSD pathophysiology and AP-induced metabolic dysfunction are unknown, but dysregulated lipid metabolism may play a role. Lipidomics, which detects lipid metabolites in a biological sample, represents an analytical tool to examine lipid metabolism. This systematic review aims to determine peripheral lipid signatures that are dysregulated among individuals with SSDs (1) with minimal exposure to APs and (2) during AP treatment. To accomplish this goal, we searched MEDLINE, Embase, and PsychINFO databases in February 2024 to identify all full-text articles written in English where the authors conducted lipidomics in SSDs. Lipid signatures reported to significantly differ in SSDs compared to controls or in relation to AP treatment and the direction of dysregulation were extracted as outcomes. We identified 46 studies that met our inclusion criteria. Most of the lipid metabolites that significantly differed in minimally AP-treated patients vs. controls comprised glycerophospholipids, which were mostly downregulated. In the AP-treated group vs. controls, the significantly different metabolites were primarily fatty acyls, which were dysregulated in conflicting directions between studies. In the pre-to-post AP-treated patients, the most impacted metabolites were glycerophospholipids and fatty acyls, which were found to be primarily upregulated and conflicting, respectively. These lipid metabolites may contribute to SSD pathophysiology and metabolic dysfunction through various mechanisms, including the modulation of inflammation, cellular membrane permeability, and metabolic signaling pathways.
精神分裂症谱系障碍（SSD）患者通常会出现代谢功能障碍。导致精神分裂症谱系障碍代谢并发症的原因很复杂，包括与精神分裂症有关的内在或生物因素，而抗精神病药物（AP）又会加重这些因素。SSD病理生理学和抗精神病药物诱发代谢功能障碍的确切机制尚不清楚，但脂质代谢失调可能是其中的一个原因。脂质组学可检测生物样本中的脂质代谢物，是研究脂质代谢的一种分析工具。本系统综述旨在确定 SSD 患者（1）在极少接触 APs 的情况下和（2）在 AP 治疗期间发生失调的外周脂质特征。为了实现这一目标，我们检索了 2024 年 2 月的 MEDLINE、Embase 和 PsychINFO 数据库，以确定作者在 SSD 患者中进行脂质组学研究的所有英文全文文章。据报道，与对照组相比，或与 AP 治疗有关，SSD 患者的脂质特征存在明显差异，调节失调的方向也作为结果被提取出来。我们确定了 46 项符合纳入标准的研究。与对照组相比，经 AP 治疗的微量患者的脂质代谢物存在明显差异，其中大部分是甘油磷脂，它们大多被下调。在 AP 治疗组与对照组中，差异显著的代谢物主要是脂肪酰基，不同研究中脂肪酰基的失调方向相互矛盾。在 AP 治疗前与 AP 治疗后的患者中，受影响最大的代谢物是甘油磷脂和脂肪酰，这两种代谢物分别被发现主要上调和相互冲突。这些脂质代谢物可能通过各种机制，包括炎症、细胞膜通透性和代谢信号通路的调节，导致 SSD 病理生理学和代谢功能障碍。
{"title":"Peripheral Lipid Signatures, Metabolic Dysfunction, and Pathophysiology in Schizophrenia Spectrum Disorders","authors":"Sally Wu, Kristoffer J. Panganiban, Jiwon Lee, Dan Li, Emily C.C. Smith, Kateryna Maksyutynska, Bailey Humber, Tariq Ahmed, Sri Mahavir Agarwal, Kristen Ward, Margaret Hahn","doi":"10.3390/metabo14090475","DOIUrl":"https://doi.org/10.3390/metabo14090475","url":null,"abstract":"Metabolic dysfunction is commonly observed in schizophrenia spectrum disorders (SSDs). The causes of metabolic comorbidity in SSDs are complex and include intrinsic or biological factors linked to the disorder, which are compounded by antipsychotic (AP) medications. The exact mechanisms underlying SSD pathophysiology and AP-induced metabolic dysfunction are unknown, but dysregulated lipid metabolism may play a role. Lipidomics, which detects lipid metabolites in a biological sample, represents an analytical tool to examine lipid metabolism. This systematic review aims to determine peripheral lipid signatures that are dysregulated among individuals with SSDs (1) with minimal exposure to APs and (2) during AP treatment. To accomplish this goal, we searched MEDLINE, Embase, and PsychINFO databases in February 2024 to identify all full-text articles written in English where the authors conducted lipidomics in SSDs. Lipid signatures reported to significantly differ in SSDs compared to controls or in relation to AP treatment and the direction of dysregulation were extracted as outcomes. We identified 46 studies that met our inclusion criteria. Most of the lipid metabolites that significantly differed in minimally AP-treated patients vs. controls comprised glycerophospholipids, which were mostly downregulated. In the AP-treated group vs. controls, the significantly different metabolites were primarily fatty acyls, which were dysregulated in conflicting directions between studies. In the pre-to-post AP-treated patients, the most impacted metabolites were glycerophospholipids and fatty acyls, which were found to be primarily upregulated and conflicting, respectively. These lipid metabolites may contribute to SSD pathophysiology and metabolic dysfunction through various mechanisms, including the modulation of inflammation, cellular membrane permeability, and metabolic signaling pathways.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"13 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Baraah T. Abu AlSel, Abdelrahman A. Mahmoud, Elham O. Hamed, Noor A. Hakim, Abdulmajeed A. A. Sindi, Najlaa M. M. Jawad, Amani M. T. Gusti, Manal S. Fawzy, Noha M. Abd El-Fadeal
Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis—including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio—and MetS. In this descriptive cross-sectional study, 209 participants aged 24–70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment—Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.
{"title":"Iron Homeostasis-Related Parameters and Hepcidin/Ferritin Ratio: Emerging Sex-Specific Predictive Markers for Metabolic Syndrome","authors":"Baraah T. Abu AlSel, Abdelrahman A. Mahmoud, Elham O. Hamed, Noor A. Hakim, Abdulmajeed A. A. Sindi, Najlaa M. M. Jawad, Amani M. T. Gusti, Manal S. Fawzy, Noha M. Abd El-Fadeal","doi":"10.3390/metabo14090473","DOIUrl":"https://doi.org/10.3390/metabo14090473","url":null,"abstract":"Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis—including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio—and MetS. In this descriptive cross-sectional study, 209 participants aged 24–70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment—Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"12 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Swati Nagar, Amale Hawi, Thomas Sciascia, Ken Korzekwa
Nalbuphine (NAL) is a mixed κ-agonist/μ-antagonist opioid with extensive first-pass metabolism. A phase 1 open-label study was conducted to characterize the pharmacokinetics (PKs) of NAL and select metabolites following single oral doses of NAL extended-release tablets in subjects with mild, moderate, and severe hepatic impairment (Child–Pugh A, B, and C, respectively) compared to healthy matched subjects. NAL exposures were similar for subjects with mild hepatic impairment as compared to healthy subjects and nearly three-fold and eight-fold higher in subjects with moderate and severe hepatic impairment, respectively. Datasets obtained for healthy, moderate, and severe hepatic impaired groups were modeled with a mechanistic model that incorporated NAL hepatic metabolism and enterohepatic recycling of NAL and its glucuronidated metabolites. The mechanistic model includes a continuous intestinal absorption model linked to semi-physiological liver–gallbladder–compartmental PK models based on partial differential equations (termed the PDE-EHR model). In vitro studies indicated that cytochromes P450 CYP2C9 and CYP2C19 are the major CYPs involved in NAL oxidation, with glucuronidation mainly catalyzed by UGT1A8 and UGT2B7 isozymes. Complex formation and elimination kinetics of NAL and four main metabolites was well predicted by PDE-EHR. The model is expected to improve predictions of drug interactions and complex drug disposition.
{"title":"Disposition of Oral Nalbuphine and Its Metabolites in Healthy Subjects and Subjects with Hepatic Impairment: Preliminary Modeling Results Using a Continuous Intestinal Absorption Model with Enterohepatic Recirculation","authors":"Swati Nagar, Amale Hawi, Thomas Sciascia, Ken Korzekwa","doi":"10.3390/metabo14090471","DOIUrl":"https://doi.org/10.3390/metabo14090471","url":null,"abstract":"Nalbuphine (NAL) is a mixed κ-agonist/μ-antagonist opioid with extensive first-pass metabolism. A phase 1 open-label study was conducted to characterize the pharmacokinetics (PKs) of NAL and select metabolites following single oral doses of NAL extended-release tablets in subjects with mild, moderate, and severe hepatic impairment (Child–Pugh A, B, and C, respectively) compared to healthy matched subjects. NAL exposures were similar for subjects with mild hepatic impairment as compared to healthy subjects and nearly three-fold and eight-fold higher in subjects with moderate and severe hepatic impairment, respectively. Datasets obtained for healthy, moderate, and severe hepatic impaired groups were modeled with a mechanistic model that incorporated NAL hepatic metabolism and enterohepatic recycling of NAL and its glucuronidated metabolites. The mechanistic model includes a continuous intestinal absorption model linked to semi-physiological liver–gallbladder–compartmental PK models based on partial differential equations (termed the PDE-EHR model). In vitro studies indicated that cytochromes P450 CYP2C9 and CYP2C19 are the major CYPs involved in NAL oxidation, with glucuronidation mainly catalyzed by UGT1A8 and UGT2B7 isozymes. Complex formation and elimination kinetics of NAL and four main metabolites was well predicted by PDE-EHR. The model is expected to improve predictions of drug interactions and complex drug disposition.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gigi Baker, Shiyang Zhao, Jennifer G. Klutsch, Guncha Ishangulyyeva, Nadir Erbilgin
The recent mountain pine beetle outbreaks have caused widespread mortality among lodgepole pine trees in western North America, resulting in a reduced population of surviving trees. While previous studies have focused on the cascading impacts of these outbreaks on the physiology and growth of the surviving trees, there remains a need for a comprehensive study into the interactions among various physiological traits and the growth in post-outbreak stands. Specifically, the relationship between chemical (primarily terpenes) and anatomical (mainly resin ducts) defences, as well as the allocation of non-structural carbohydrates (NSCs) to support these defence modalities, is poorly understood. To address these gaps, we conducted a field survey of surviving lodgepole pine trees in post-mountain pine beetle outbreak stands in western Canada. Our retrospective analysis aimed at determining correlations between the post-outbreak concentrations of monoterpenes, diterpenes, and NSCs in the phloem and the historical resin duct characteristics and growth traits before and after the outbreak. We detected strong correlations between the post-outbreak concentrations of monoterpenes and historical resin duct characteristics, suggesting a possible link between these two defence modalities. Additionally, we found a positive relationship between the NSCs and the total concentrations of monoterpenes and diterpenes, suggesting that NSCs likely influence the production of these terpenes in lodgepole pine. Furthermore, historical tree growth patterns showed strong positive correlations with many individual monoterpenes and diterpenes. Interestingly, while surviving trees had enhanced anatomical defences after the outbreak, their growth patterns did not vary before and after the outbreak conditions. The complexity of these relationships emphasizes the dynamics of post-outbreak stand dynamics and resource allocations in lodgepole pine forests, highlighting the need for further research. These findings contribute to a broader understanding of conifer defences and their coordinated responses to forest insect outbreaks, with implications for forest management and conservation strategies.
{"title":"The Legacy Effect of Mountain Pine Beetle Outbreaks on the Chemical and Anatomical Defences of Surviving Lodgepole Pine Trees","authors":"Gigi Baker, Shiyang Zhao, Jennifer G. Klutsch, Guncha Ishangulyyeva, Nadir Erbilgin","doi":"10.3390/metabo14090472","DOIUrl":"https://doi.org/10.3390/metabo14090472","url":null,"abstract":"The recent mountain pine beetle outbreaks have caused widespread mortality among lodgepole pine trees in western North America, resulting in a reduced population of surviving trees. While previous studies have focused on the cascading impacts of these outbreaks on the physiology and growth of the surviving trees, there remains a need for a comprehensive study into the interactions among various physiological traits and the growth in post-outbreak stands. Specifically, the relationship between chemical (primarily terpenes) and anatomical (mainly resin ducts) defences, as well as the allocation of non-structural carbohydrates (NSCs) to support these defence modalities, is poorly understood. To address these gaps, we conducted a field survey of surviving lodgepole pine trees in post-mountain pine beetle outbreak stands in western Canada. Our retrospective analysis aimed at determining correlations between the post-outbreak concentrations of monoterpenes, diterpenes, and NSCs in the phloem and the historical resin duct characteristics and growth traits before and after the outbreak. We detected strong correlations between the post-outbreak concentrations of monoterpenes and historical resin duct characteristics, suggesting a possible link between these two defence modalities. Additionally, we found a positive relationship between the NSCs and the total concentrations of monoterpenes and diterpenes, suggesting that NSCs likely influence the production of these terpenes in lodgepole pine. Furthermore, historical tree growth patterns showed strong positive correlations with many individual monoterpenes and diterpenes. Interestingly, while surviving trees had enhanced anatomical defences after the outbreak, their growth patterns did not vary before and after the outbreak conditions. The complexity of these relationships emphasizes the dynamics of post-outbreak stand dynamics and resource allocations in lodgepole pine forests, highlighting the need for further research. These findings contribute to a broader understanding of conifer defences and their coordinated responses to forest insect outbreaks, with implications for forest management and conservation strategies.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"41 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Early pregnancy diagnostic techniques are of significant importance in livestock farming, particularly in dairy farming. This study aimed to screen artificially inseminated cows for potential biomarkers at day 21 of pregnancy using microbiota–metabolomics analysis. The microbiome analysis revealed significant changes (p < 0.05) in the composition and abundance of the vaginal microbiota in cows after pregnancy. Notably, there was an increase in the abundance of [Eubacterium]_hallii_group (p < 0.05) associated with the production of short-chain fatty acids in the pregnant group compared with the non-pregnant group. Furthermore, significant alterations were observed in the serum metabolome, with notable changes in the concentrations of prolyl-hydroxyproline (Pro-Hyp) (p < 0.01) and bonactin (p < 0.01). The majority of differential metabolites clustered within the pathways of amino acid metabolism and lipid metabolism, with lipid metabolism exhibiting a higher proportion and playing a pivotal role in early pregnancy. An enzyme-linked immunosorbent assay was employed to quantify three key metabolites of the arachidonic acid pathway. The results demonstrated significant decreases in serum concentrations of leukotriene B4 (LTB4) (p < 0.05) and prostaglandin F2α (PGF2α) (p < 0.01) and no significant changes in arachidonic acid (AA) (NS) concentrations after 21 days of gestation in cows. Spearman’s correlation analysis was utilized to investigate the interrelationship between the vaginal microbiota and serum metabolites. In conclusion, the present study demonstrated that biomaterials such as bonactin, Pro-hyp, LTB4, PGF2α in serum metabolites and [Eubacterium]_hallii_group in the vaginal flora of cows could be utilized as potential biomarkers for 21 days of gestation in cows.
{"title":"Combining the Vaginal Microbiome and Serum Metabolome to Screen for Potential Biomarkers of Early Pregnancy in Cows","authors":"Yan Luo, Zhen Wang, Xin Zhao, Jiankang Xing, Zhiliang Chen, Wenxue Zhao, Xiaoqing Long, Yanbing Zhang, Yongbin Shao","doi":"10.3390/metabo14090469","DOIUrl":"https://doi.org/10.3390/metabo14090469","url":null,"abstract":"Early pregnancy diagnostic techniques are of significant importance in livestock farming, particularly in dairy farming. This study aimed to screen artificially inseminated cows for potential biomarkers at day 21 of pregnancy using microbiota–metabolomics analysis. The microbiome analysis revealed significant changes (p < 0.05) in the composition and abundance of the vaginal microbiota in cows after pregnancy. Notably, there was an increase in the abundance of [Eubacterium]_hallii_group (p < 0.05) associated with the production of short-chain fatty acids in the pregnant group compared with the non-pregnant group. Furthermore, significant alterations were observed in the serum metabolome, with notable changes in the concentrations of prolyl-hydroxyproline (Pro-Hyp) (p < 0.01) and bonactin (p < 0.01). The majority of differential metabolites clustered within the pathways of amino acid metabolism and lipid metabolism, with lipid metabolism exhibiting a higher proportion and playing a pivotal role in early pregnancy. An enzyme-linked immunosorbent assay was employed to quantify three key metabolites of the arachidonic acid pathway. The results demonstrated significant decreases in serum concentrations of leukotriene B4 (LTB4) (p < 0.05) and prostaglandin F2α (PGF2α) (p < 0.01) and no significant changes in arachidonic acid (AA) (NS) concentrations after 21 days of gestation in cows. Spearman’s correlation analysis was utilized to investigate the interrelationship between the vaginal microbiota and serum metabolites. In conclusion, the present study demonstrated that biomaterials such as bonactin, Pro-hyp, LTB4, PGF2α in serum metabolites and [Eubacterium]_hallii_group in the vaginal flora of cows could be utilized as potential biomarkers for 21 days of gestation in cows.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"6 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Su-Min Yun, Cheol-Soo Kim, Jeung-Joo Lee, Jung-Sung Chung
Salt stress is one of the environmental stresses that significantly reduces crop productivity and quality worldwide. Methods to overcome salt stress include developing salt-resistant crops by inserting various resistance genes or to diagnosing and responding to the effects of salt stress at an early stage. In this study, we investigate the effects of salinity stress on growth, photosynthetic efficiency, and metabolic changes in Brussels sprouts (Brassica oleracea var. gemmifera). Fresh weight and leaf area decreased significantly with increasing NaCl concentration, indicating that salinity stress has a detrimental effect on plant growth. However, chlorophyll fluorescence parameters did not show significant changes, suggesting that photosynthetic efficiency was not significantly affected over 10 days. Fourier transform infrared (FTIR) spectroscopy revealed notable metabolic adjustments, especially in lipids, plastids, proteins, and carbohydrates, indicating biosynthesis of protective compounds such as anthocyanins and proline in response to salinity stress. Pearson correlation analysis confirmed a strong relationship between NaCl concentration and the observed physiological and metabolic changes. The findings highlight the potential of FTIR spectroscopy as a non-destructive tool for early detection of salinity stress and timely intervention to improve crop resilience and yield. This study highlights the widespread application of FTIR spectroscopy in agricultural research to manage abiotic stresses in crops.
盐胁迫是严重降低全球作物产量和质量的环境胁迫之一。克服盐胁迫的方法包括通过插入各种抗性基因来开发抗盐作物，或在早期诊断和应对盐胁迫的影响。本研究调查了盐胁迫对球芽甘蓝（Brassica oleracea var. gemmifera）生长、光合效率和代谢变化的影响。鲜重和叶面积随着 NaCl 浓度的增加而显著下降，表明盐胁迫对植物生长有不利影响。然而，叶绿素荧光参数并未出现明显变化，这表明光合作用效率在 10 天内并未受到明显影响。傅立叶变换红外光谱（FTIR）显示了显著的代谢调整，尤其是脂质、质体、蛋白质和碳水化合物，表明花青素和脯氨酸等保护性化合物的生物合成对盐胁迫做出了反应。皮尔逊相关分析证实，NaCl 浓度与观察到的生理和代谢变化之间存在密切关系。研究结果凸显了傅立叶变换红外光谱作为一种非破坏性工具的潜力，可用于早期检测盐渍胁迫并及时干预，以提高作物的抗逆性和产量。这项研究强调了傅立叶变换红外光谱技术在农业研究中的广泛应用，以管理作物的非生物胁迫。
{"title":"Application of ATR-FTIR Spectroscopy for Analysis of Salt Stress in Brussels Sprouts","authors":"Su-Min Yun, Cheol-Soo Kim, Jeung-Joo Lee, Jung-Sung Chung","doi":"10.3390/metabo14090470","DOIUrl":"https://doi.org/10.3390/metabo14090470","url":null,"abstract":"Salt stress is one of the environmental stresses that significantly reduces crop productivity and quality worldwide. Methods to overcome salt stress include developing salt-resistant crops by inserting various resistance genes or to diagnosing and responding to the effects of salt stress at an early stage. In this study, we investigate the effects of salinity stress on growth, photosynthetic efficiency, and metabolic changes in Brussels sprouts (Brassica oleracea var. gemmifera). Fresh weight and leaf area decreased significantly with increasing NaCl concentration, indicating that salinity stress has a detrimental effect on plant growth. However, chlorophyll fluorescence parameters did not show significant changes, suggesting that photosynthetic efficiency was not significantly affected over 10 days. Fourier transform infrared (FTIR) spectroscopy revealed notable metabolic adjustments, especially in lipids, plastids, proteins, and carbohydrates, indicating biosynthesis of protective compounds such as anthocyanins and proline in response to salinity stress. Pearson correlation analysis confirmed a strong relationship between NaCl concentration and the observed physiological and metabolic changes. The findings highlight the potential of FTIR spectroscopy as a non-destructive tool for early detection of salinity stress and timely intervention to improve crop resilience and yield. This study highlights the widespread application of FTIR spectroscopy in agricultural research to manage abiotic stresses in crops.","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"848 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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