Journal Description
Metabolites
Metabolites
is an international, peer-reviewed, open access journal of metabolism and metabolomics, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Biochemistry & Molecular Biology) / CiteScore - Q2 (Endocrinology, Diabetes and Metabolism)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.2 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.1 (2022);
5-Year Impact Factor:
4.5 (2022)
Latest Articles
Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight
Metabolites 2024, 14(6), 325; https://doi.org/10.3390/metabo14060325 (registering DOI) - 8 Jun 2024
Abstract
Epigenetic and metabolic reprogramming alterations are two important features of tumors, and their reversible, spatial, and temporal regulation is a distinctive hallmark of carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, is a new entry point for tumor therapy.
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Epigenetic and metabolic reprogramming alterations are two important features of tumors, and their reversible, spatial, and temporal regulation is a distinctive hallmark of carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, is a new entry point for tumor therapy. Moreover, metabolic reprogramming drives hepatocellular carcinoma (HCC) initiation and progression, highlighting the significance of metabolism in this disease. Exploring the inter-regulatory relationship between tumor metabolic reprogramming and epigenetic modification has become one of the hot directions in current tumor metabolism research. As viral etiologies have given way to metabolic dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it is urgent that complex molecular pathways linking them and hepatocarcinogenesis be explored. However, how aberrant crosstalk between epigenetic modifications and metabolic reprogramming affects MASLD-induced HCC lacks comprehensive understanding. A better understanding of their linkages is necessary and urgent to improve HCC treatment strategies. For this reason, this review examines the interwoven landscape of molecular carcinogenesis in the context of MASLD-induced HCC, focusing on mechanisms regulating aberrant epigenetic alterations and metabolic reprogramming in the development of MASLD-induced HCC and interactions between them while also updating the current advances in metabolism and epigenetic modification-based therapeutic drugs in HCC.
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(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
Open AccessReview
Gut Microbiota and Sinusoidal Vasoregulation in MASLD: A Portal Perspective
by
Gyorgy Baffy and Piero Portincasa
Metabolites 2024, 14(6), 324; https://doi.org/10.3390/metabo14060324 - 7 Jun 2024
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition with heterogeneous outcomes difficult to predict at the individual level. Feared complications of advanced MASLD are linked to clinically significant portal hypertension and are initiated by functional and mechanical changes in the unique
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition with heterogeneous outcomes difficult to predict at the individual level. Feared complications of advanced MASLD are linked to clinically significant portal hypertension and are initiated by functional and mechanical changes in the unique sinusoidal capillary network of the liver. Early sinusoidal vasoregulatory changes in MASLD lead to increased intrahepatic vascular resistance and represent the beginning of portal hypertension. In addition, the composition and function of gut microbiota in MASLD are distinctly different from the healthy state, and multiple lines of evidence demonstrate the association of dysbiosis with these vasoregulatory changes. The gut microbiota is involved in the biotransformation of nutrients, production of de novo metabolites, release of microbial structural components, and impairment of the intestinal barrier with impact on innate immune responses, metabolism, inflammation, fibrosis, and vasoregulation in the liver and beyond. The gut–liver axis is a conceptual framework in which portal circulation is the primary connection between gut microbiota and the liver. Accordingly, biochemical and hemodynamic attributes of portal circulation may hold the key to better understanding and predicting disease progression in MASLD. However, many specific details remain hidden due to limited access to the portal circulation, indicating a major unmet need for the development of innovative diagnostic tools to analyze portal metabolites and explore their effect on health and disease. We also need to safely and reliably monitor portal hemodynamics with the goal of providing preventive and curative interventions in all stages of MASLD. Here, we review recent advances that link portal metabolomics to altered sinusoidal vasoregulation and may allow for new insights into the development of portal hypertension in MASLD.
Full article
(This article belongs to the Special Issue Honorary Special Issue Dedicated to Prof. Giovanni Targher–the Metabolic Fatty Liver Syndromes: MASLD/MAFLD/NAFLD)
Open AccessArticle
Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study
by
Claudia Agabiti Rosei, Anna Paini, Giacomo Buso, Alessandro Maloberti, Cristina Giannattasio, Massimo Salvetti, Edoardo Casiglia, Valerie Tikhonoff, Fabio Angeli, Carlo Maria Barbagallo, Michele Bombelli, Federica Cappelli, Rosario Cianci, Michele Ciccarelli, Arrigo Francesco Giuseppe Cicero, Massimo Cirillo, Pietro Cirillo, Raffaella Dell’Oro, Lanfranco D’Elia, Giovambattista Desideri, Claudio Ferri, Ferruccio Galletti, Loreto Gesualdo, Guido Grassi, Guido Iaccarino, Luciano Lippa, Francesca Mallamaci, Stefano Masi, Maria Masulli, Alberto Mazza, Alessandro Mengozzi, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Roberto Pontremoli, Fosca Quarti-Trevano, Marcello Rattazzi, Gianpaolo Reboldi, Giulia Rivasi, Elisa Russo, Giuliano Tocci, Andrea Ungar, Paolo Verdecchia, Francesca Viazzi, Massimo Volpe, Agostino Virdis, Maria Lorenza Muiesan and Claudio Borghiadd
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Metabolites 2024, 14(6), 323; https://doi.org/10.3390/metabo14060323 - 7 Jun 2024
Abstract
High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study
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High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04–1.27], p < 0.001 and HR 1.25 [1.09–1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.
Full article
(This article belongs to the Special Issue Exploring Uric Acid and Beyond)
Open AccessArticle
Characterization of Urinary N-Acetyltaurine as a Biomarker of Hyperacetatemia in Mice
by
Qingqing Mao, Xiaolei Shi, Yiwei Ma, Yuwei Lu and Chi Chen
Metabolites 2024, 14(6), 322; https://doi.org/10.3390/metabo14060322 - 7 Jun 2024
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Acetate is an important metabolite in metabolic fluxes. Its presence in biological entities originates from both exogenous inputs and endogenous metabolism. Because the change in blood acetate level has been associated with both beneficial and adverse health outcomes, blood acetate analysis has been
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Acetate is an important metabolite in metabolic fluxes. Its presence in biological entities originates from both exogenous inputs and endogenous metabolism. Because the change in blood acetate level has been associated with both beneficial and adverse health outcomes, blood acetate analysis has been used to monitor the systemic status of acetate turnover. The present study examined the use of urinary N-acetyltaurine (NAT) as a marker to reflect the hyperacetatemic status of mice from exogenous inputs and endogenous metabolism, including triacetin dosing, ethanol dosing, and streptozotocin-induced diabetes. The results showed that triacetin dosing increased serum acetate and urinary NAT but not other N-acetylated amino acids in urine. The co-occurrences of increased serum acetate and elevated urinary NAT were also observed in both ethanol dosing and streptozotocin-induced diabetes. Furthermore, the renal cortex was determined as an active site for NAT synthesis. Overall, urinary NAT behaved as an effective marker of hyperacetatemia in three experimental mouse models, warranting further investigation into its application in humans.
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Open AccessArticle
Dietary Cholest-4-en-3-one, a Cholesterol Metabolite of Gut Microbiota, Alleviates Hyperlipidemia, Hepatic Cholesterol Accumulation, and Hyperinsulinemia in Obese, Diabetic db/db Mice
by
Mina Higuchi, Mai Okumura, Sarasa Mitsuta and Bungo Shirouchi
Metabolites 2024, 14(6), 321; https://doi.org/10.3390/metabo14060321 - 3 Jun 2024
Abstract
Previous studies have shown that dietary cholest-4-en-3-one (4-cholestenone, 4-STN) exerts anti-obesity and lipid-lowering effects in mice. However, its underlying mechanisms are not fully understood. In the present study, we evaluated whether 4-STN supplementation would protect obese diabetic db/db mice from obesity-related metabolic disorders.
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Previous studies have shown that dietary cholest-4-en-3-one (4-cholestenone, 4-STN) exerts anti-obesity and lipid-lowering effects in mice. However, its underlying mechanisms are not fully understood. In the present study, we evaluated whether 4-STN supplementation would protect obese diabetic db/db mice from obesity-related metabolic disorders. After four weeks of feeding of a 0.25% 4-STN-containing diet, dietary 4-STN was found to have significantly alleviated hyperlipidemia, hepatic cholesterol accumulation, and hyperinsulinemia; however, the effect was not sufficient to improve hepatic triglyceride accumulation or obesity. Further analysis demonstrated that dietary 4-STN significantly increased the content of free fatty acids and neutral steroids in the feces of db/db mice, indicating that the alleviation of hyperlipidemia by 4-STN was due to an increase in lipid excretion. In addition, dietary 4-STN significantly reduced the levels of desmosterol, a cholesterol precursor, in the plasma but not in the liver, suggesting that normalization of cholesterol metabolism by 4-STN is partly attributable to the suppression of cholesterol synthesis in extrahepatic tissues. In addition, dietary 4-STN increased the plasma and hepatic levels of 4-STN metabolites cholestanol (5α-cholestan-3β-ol) and coprostanol (5β-cholestan-3β-ol). Our results show that dietary 4-STN alleviates obesity-related metabolic disorders, such as hyperlipidemia, hepatic cholesterol accumulation, and hyperinsulinemia, in db/db mice.
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(This article belongs to the Special Issue Impact of Food and Bioactive Compounds on Metabolic Diseases)
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Altered Metabolic Signaling and Potential Therapies in Polyglutamine Diseases
by
Alisha Vohra, Patrick Keefe and Prasanth Puthanveetil
Metabolites 2024, 14(6), 320; https://doi.org/10.3390/metabo14060320 - 31 May 2024
Abstract
Polyglutamine diseases comprise a cluster of genetic disorders involving neurodegeneration and movement disabilities. In polyglutamine diseases, the target proteins become aberrated due to polyglutamine repeat formation. These aberrant proteins form the root cause of associated complications. The metabolic regulation during polyglutamine diseases is
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Polyglutamine diseases comprise a cluster of genetic disorders involving neurodegeneration and movement disabilities. In polyglutamine diseases, the target proteins become aberrated due to polyglutamine repeat formation. These aberrant proteins form the root cause of associated complications. The metabolic regulation during polyglutamine diseases is not well studied and needs more attention. We have brought to light the significance of regulating glutamine metabolism during polyglutamine diseases, which could help in decreasing the neuronal damage associated with excess glutamate and nucleotide generation. Most polyglutamine diseases are accompanied by symptoms that occur due to excess glutamate and nucleotide accumulation. Along with a dysregulated glutamine metabolism, the Nicotinamide adenine dinucleotide (NAD+) levels drop down, and, under these conditions, NAD+ supplementation is the only achievable strategy. NAD+ is a major co-factor in the glutamine metabolic pathway, and it helps in maintaining neuronal homeostasis. Thus, strategies to decrease excess glutamate and nucleotide generation, as well as channelizing glutamine toward the generation of ATP and the maintenance of NAD+ homeostasis, could aid in neuronal health. Along with understanding the metabolic dysregulation that occurs during polyglutamine diseases, we have also focused on potential therapeutic strategies that could provide direct benefits or could restore metabolic homeostasis. Our review will shed light into unique metabolic causes and into ideal therapeutic strategies for treating complications associated with polyglutamine diseases.
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(This article belongs to the Special Issue Cellular Metabolism in Neurological Disorders)
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Phenylpropanoid Metabolism in Phaseolus vulgaris during Growth under Severe Drought
by
Luis Eduardo Peña Barrena, Lili Mats, Hugh J. Earl and Gale G. Bozzo
Metabolites 2024, 14(6), 319; https://doi.org/10.3390/metabo14060319 - 31 May 2024
Abstract
Drought limits the growth and development of Phaseolus vulgaris L. (known as common bean). Common bean plants contain various phenylpropanoids, but it is not known whether the levels of these metabolites are altered by drought. Here, BT6 and BT44, two white bean recombinant
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Drought limits the growth and development of Phaseolus vulgaris L. (known as common bean). Common bean plants contain various phenylpropanoids, but it is not known whether the levels of these metabolites are altered by drought. Here, BT6 and BT44, two white bean recombinant inbred lines (RILs), were cultivated under severe drought. Their respective growth and phenylpropanoid profiles were compared to those of well-irrigated plants. Both RILs accumulated much less biomass in their vegetative parts with severe drought, which was associated with more phaseollin and phaseollinisoflavan in their roots relative to well-irrigated plants. A sustained accumulation of coumestrol was evident in BT44 roots with drought. Transient alterations in the leaf profiles of various phenolic acids occurred in drought-stressed BT6 and BT44 plants, including the respective accumulation of two separate caftaric acid isomers and coutaric acid (isomer 1) relative to well-irrigated plants. A sustained rise in fertaric acid was observed in BT44 with drought stress, whereas the greater amount relative to well-watered plants was transient in BT6. Apart from kaempferol diglucoside (isomer 2), the concentrations of most leaf flavonol glycosides were not altered with drought. Overall, fine tuning of leaf and root phenylpropanoid profiles occurs in white bean plants subjected to severe drought.
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(This article belongs to the Special Issue Metabolic Responses of Plants to Abiotic Stress)
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Stable Isotope Tracing Analysis in Cancer Research: Advancements and Challenges in Identifying Dysregulated Cancer Metabolism and Treatment Strategies
by
Dalton Hilovsky, Joshua Hartsell, Jamey D. Young and Xiaojing Liu
Metabolites 2024, 14(6), 318; https://doi.org/10.3390/metabo14060318 - 31 May 2024
Abstract
Metabolic reprogramming is a hallmark of cancer, driving the development of therapies targeting cancer metabolism. Stable isotope tracing has emerged as a widely adopted tool for monitoring cancer metabolism both in vitro and in vivo. Advances in instrumentation and the development of new
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Metabolic reprogramming is a hallmark of cancer, driving the development of therapies targeting cancer metabolism. Stable isotope tracing has emerged as a widely adopted tool for monitoring cancer metabolism both in vitro and in vivo. Advances in instrumentation and the development of new tracers, metabolite databases, and data analysis tools have expanded the scope of cancer metabolism studies across these scales. In this review, we explore the latest advancements in metabolic analysis, spanning from experimental design in stable isotope-labeling metabolomics to sophisticated data analysis techniques. We highlight successful applications in cancer research, particularly focusing on ongoing clinical trials utilizing stable isotope tracing to characterize disease progression, treatment responses, and potential mechanisms of resistance to anticancer therapies. Furthermore, we outline key challenges and discuss potential strategies to address them, aiming to enhance our understanding of the biochemical basis of cancer metabolism.
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(This article belongs to the Special Issue Isotope-Guided Analytical Strategies for Assessing Metabolic Networks in Cancer)
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The Role of Lysophospholipid Metabolites LPC and LPA in the Pathogenesis of Chronic Obstructive Pulmonary Disease
by
Qiqiang Zhou, Yahong Chen, Ying Liang and Yongchang Sun
Metabolites 2024, 14(6), 317; https://doi.org/10.3390/metabo14060317 - 31 May 2024
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by persistent respiratory symptoms and airflow limitation. While there are some available treatment options, the effectiveness of treatment varies depending on individual differences and the phenotypes of the disease. Therefore, exploring or
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Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by persistent respiratory symptoms and airflow limitation. While there are some available treatment options, the effectiveness of treatment varies depending on individual differences and the phenotypes of the disease. Therefore, exploring or identifying potential therapeutic targets for COPD is urgently needed. In recent years, there has been growing evidence showing that lysophospholipids, namely lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), can play a significant role in the pathogenesis of COPD. Exploring the metabolism of lysophospholipids holds promise for understanding the underlying mechanism of COPD development and developing novel strategies for COPD treatment. This review primarily concentrates on the involvement and signaling pathways of LPC and LPA in the development and progression of COPD. Furthermore, we reviewed their associations with clinical manifestations, phenotypes, and prognosis within the COPD context and discussed the potential of the pivotal signaling molecules as viable therapeutic targets for COPD treatment.
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(This article belongs to the Special Issue Lipidomics in Health and Disease)
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Metabolomic Profiling and In Vivo Antiepileptic Effect of Zygophyllum album Aerial Parts and Roots Crude Extracts against Pentylenetetrazole-Induced Kindling in Mice
by
Asmaa R. Abdel-Hamed, Alaa S. Wahba, Dina M. Khodeer, Maged S. Abdel-Kader, Jihan M. Badr, Sebaey Mahgoub and Dina M. Hal
Metabolites 2024, 14(6), 316; https://doi.org/10.3390/metabo14060316 - 30 May 2024
Abstract
The chemical profiles of both Zygophyllum album (Z. album) aerial parts and roots extracts were evaluated with LC-ESI-TOF-MS/MS analysis. Twenty-four compounds were detected. Among them, some are detected in both the aerial parts and the roots extracts, and others were detected
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The chemical profiles of both Zygophyllum album (Z. album) aerial parts and roots extracts were evaluated with LC-ESI-TOF-MS/MS analysis. Twenty-four compounds were detected. Among them, some are detected in both the aerial parts and the roots extracts, and others were detected in the aerial parts only. The detected compounds were mainly flavonoids, phenolic compounds, triterpenes and other miscellaneous compounds. Such compounds contribute to the diverse pharmacological activities elicited by the Z. album species. This study aimed to elucidate the antiepileptic effect of Z. album aerial parts and roots crude extracts against pentylenetetrazole (PTZ)-induced kindling in mice. Male albino mice were divided into four groups, eight animals each. All groups, except the control group, were kindled with PTZ (35 mg/kg i.p.), once every alternate day for a total of 15 injections. One group was left untreated (PTZ group). The remaining two groups were treated prior to PTZ injection with either Z. album aerial parts or roots crude extract (400 mg/kg, orally). Pretreatment with either extract significantly reduced the seizure scores, partially reversed the histological changes in the cerebral cortex and exerted antioxidant/anti-inflammatory efficacy evinced by elevated hippocampal total antioxidant capacity and SOD and catalase activities, parallel to the decrement in MDA content, iNOS activity and the TXNIB/NLRP3 axis with a subsequent decrease in caspase 1 activation and a release of IL-1β and IL-18. Moreover, both Z. album extracts suppressed neuronal apoptosis via upregulating Bcl-2 expression and downregulating that of Bax, indicating their neuroprotective and antiepileptic potential. Importantly, the aerial parts extract elicited much more antiepileptic potential than the roots extract did.
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(This article belongs to the Section Plant Metabolism)
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Multimodal Mass Spectrometry Imaging of an Osteosarcoma Multicellular Tumour Spheroid Model to Investigate Drug-Induced Response
by
Sophie M. Pearce, Neil A. Cross, David P. Smith, Malcolm R. Clench, Lucy E. Flint, Gregory Hamm, Richard Goodwin, James I. Langridge, Emmanuelle Claude and Laura M. Cole
Metabolites 2024, 14(6), 315; https://doi.org/10.3390/metabo14060315 - 29 May 2024
Abstract
A multimodal mass spectrometry imaging (MSI) approach was used to investigate the chemotherapy drug-induced response of a Multicellular Tumour Spheroid (MCTS) 3D cell culture model of osteosarcoma (OS). The work addresses the critical demand for enhanced translatable early drug discovery approaches by demonstrating
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A multimodal mass spectrometry imaging (MSI) approach was used to investigate the chemotherapy drug-induced response of a Multicellular Tumour Spheroid (MCTS) 3D cell culture model of osteosarcoma (OS). The work addresses the critical demand for enhanced translatable early drug discovery approaches by demonstrating a robust spatially resolved molecular distribution analysis in tumour models following chemotherapeutic intervention. Advanced high-resolution techniques were employed, including desorption electrospray ionisation (DESI) mass spectrometry imaging (MSI), to assess the interplay between metabolic and cellular pathways in response to chemotherapeutic intervention. Endogenous metabolite distributions of the human OS tumour models were complemented with subcellularly resolved protein localisation by the detection of metal-tagged antibodies using Imaging Mass Cytometry (IMC). The first application of matrix-assisted laser desorption ionization–immunohistochemistry (MALDI-IHC) of 3D cell culture models is reported here. Protein localisation and expression following an acute dosage of the chemotherapy drug doxorubicin demonstrated novel indications for mechanisms of region-specific tumour survival and cell-cycle-specific drug-induced responses. Previously unknown doxorubicin-induced metabolite upregulation was revealed by DESI-MSI of MCTSs, which may be used to inform mechanisms of chemotherapeutic resistance. The demonstration of specific tumour survival mechanisms that are characteristic of those reported for in vivo tumours has underscored the increasing value of this approach as a tool to investigate drug resistance.
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(This article belongs to the Special Issue Advanced Metabolomics and Lipidomics Approaches in Studying Human Diseases)
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Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer
by
Muhammad Usman Babar, Ala F. Nassar, Xinxin Nie, Tianxiang Zhang, Jianwei He, Jacky Yeung, Paul Norris, Hideki Ogura, Anne Muldoon, Lieping Chen and Stephania Libreros
Metabolites 2024, 14(6), 314; https://doi.org/10.3390/metabo14060314 - 29 May 2024
Abstract
Acute inflammation is the body’s first defense in response to pathogens or injury that is partially governed by a novel genus of endogenous lipid mediators that orchestrate the resolution of inflammation, coined specialized pro-resolving mediators (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs),
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Acute inflammation is the body’s first defense in response to pathogens or injury that is partially governed by a novel genus of endogenous lipid mediators that orchestrate the resolution of inflammation, coined specialized pro-resolving mediators (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs), include the eicosapentaenoic acid-derived and docosahexaenoic acid-derived Resolvins, Protectins, and Maresins. Herein, we review their biosynthesis, structural characteristics, and therapeutic effectiveness in various diseases such as ischemia, viral infections, periodontitis, neuroinflammatory diseases, cystic fibrosis, lung inflammation, herpes virus, and cancer, especially focusing on therapeutic effectiveness in respiratory inflammation and ischemia-related injuries. Resolvins are sub-nanomolar potent agonists that accelerate the resolution of inflammation by reducing excessive neutrophil infiltration, stimulating macrophage functions including phagocytosis, efferocytosis, and tissue repair. In addition to regulating neutrophils and macrophages, Resolvins control dendritic cell migration and T cell responses, and they also reduce the pro-inflammatory cytokines, proliferation, and metastasis of cancer cells. Importantly, several lines of evidence have demonstrated that Resolvins reduce tumor progression in melanoma, oral squamous cell carcinoma, lung cancer, and liver cancer. In addition, Resolvins enhance tumor cell debris clearance by macrophages in the tumor’s microenvironment. Resolvins, with their unique stereochemical structure, receptors, and biosynthetic pathways, provide a novel therapeutical approach to activating resolution mechanisms during cancer progression.
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(This article belongs to the Special Issue Mass Spectrometry-Based Metabolomics and Lipidomics for Biomarker Discovery and Drug Development)
Open AccessArticle
Utilising A Clinical Metabolomics LC-MS Study to Determine the Integrity of Biological Samples for Statistical Modelling after Long Term −80 °C Storage: A TOFI_Asia Sub-Study
by
Aidan Joblin-Mills, Zhanxuan E. Wu, Ivana R. Sequeira-Bisson, Jennifer L. Miles-Chan, Sally D. Poppitt and Karl Fraser
Metabolites 2024, 14(6), 313; https://doi.org/10.3390/metabo14060313 - 29 May 2024
Abstract
Biological samples of lipids and metabolites degrade after extensive years in −80 °C storage. We aimed to determine if associated multivariate models are also impacted. Prior TOFI_Asia metabolomics studies from our laboratory established multivariate models of metabolic risks associated with ethnic diversity. Therefore,
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Biological samples of lipids and metabolites degrade after extensive years in −80 °C storage. We aimed to determine if associated multivariate models are also impacted. Prior TOFI_Asia metabolomics studies from our laboratory established multivariate models of metabolic risks associated with ethnic diversity. Therefore, to compare multivariate modelling degradation after years of −80 °C storage, we selected a subset of aged (≥5-years) plasma samples from the TOFI_Asia study to re-analyze via untargeted LC-MS metabolomics. Samples from European Caucasian (n = 28) and Asian Chinese (n = 28) participants were evaluated for ethnic discrimination by partial least squares discriminative analysis (PLS–DA) of lipids and polar metabolites. Both showed a strong discernment between participants ethnicity by features, before (Initial) and after (Aged) 5-years of −80 °C storage. With receiver operator characteristic curves, sparse PLS–DA derived confusion matrix and prediction error rates, a considerable reduction in model integrity was apparent with the Aged polar metabolite model relative to Initial modelling. Ethnicity modelling with lipids maintained predictive integrity in Aged plasma samples, while equivalent polar metabolite models reduced in integrity. Our results indicate that researchers re-evaluating samples for multivariate modelling should consider time at −80 °C when producing predictive metrics from polar metabolites, more so than lipids.
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Open AccessReview
Is Lipid Metabolism of Value in Cancer Research and Treatment? Part I- Lipid Metabolism in Cancer
by
Ala F. Nassar, Xinxin Nie, Tianxiang Zhang, Jacky Yeung, Paul Norris, Jianwei He, Hideki Ogura, Muhammad Usman Babar, Anne Muldoon, Stephania Libreros and Lieping Chen
Metabolites 2024, 14(6), 312; https://doi.org/10.3390/metabo14060312 - 29 May 2024
Abstract
For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise and disease development are examples of cellular environment alterations which produce changes
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For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise and disease development are examples of cellular environment alterations which produce changes in these networks. There are indications that alterations in lipid metabolism contribute to the development and progression of a variety of cancers. Measuring such alterations and understanding the pathways involved is critical to fully understand cellular metabolism. The demands for this information have led to the emergence of lipidomics, which enables the large-scale study of lipids using mass spectrometry (MS) techniques. Mass spectrometry has been widely used in lipidomics and allows us to analyze detailed lipid profiles of cancers. In this article, we discuss emerging strategies for lipidomics by mass spectrometry; targeted, as opposed to global, lipid analysis provides an exciting new alternative method. Additionally, we provide an introduction to lipidomics, lipid categories and their major biological functions, along with lipidomics studies by mass spectrometry in cancer samples. Further, we summarize the importance of lipid metabolism in oncology and tumor microenvironment, some of the challenges for lipodomics, and the potential for targeted approaches for screening pharmaceutical candidates to improve the therapeutic efficacy of treatment in cancer patients.
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(This article belongs to the Special Issue Mass Spectrometry-Based Metabolomics and Lipidomics for Biomarker Discovery and Drug Development)
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Machine Learning Metabolomics Profiling of Dietary Interventions from a Six-Week Randomised Trial
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Afroditi Kouraki, Ana Nogal, Weronika Nocun, Panayiotis Louca, Amrita Vijay, Kari Wong, Gregory A. Michelotti, Cristina Menni and Ana M. Valdes
Metabolites 2024, 14(6), 311; https://doi.org/10.3390/metabo14060311 - 29 May 2024
Abstract
Metabolomics can uncover physiological responses to prebiotic fibre and omega-3 fatty acid supplements with known health benefits and identify response-specific metabolites. We profiled 534 stool and 799 serum metabolites in 64 healthy adults following a 6-week randomised trial comparing daily omega-3 versus inulin
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Metabolomics can uncover physiological responses to prebiotic fibre and omega-3 fatty acid supplements with known health benefits and identify response-specific metabolites. We profiled 534 stool and 799 serum metabolites in 64 healthy adults following a 6-week randomised trial comparing daily omega-3 versus inulin supplementation. Elastic net regressions were used to separately identify the serum and stool metabolites whose change in concentration discriminated between the two types of supplementations. Random forest was used to explore the gut microbiome’s contribution to the levels of the identified metabolites from matching stool samples. Changes in serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate and indoleproprionate levels accurately discriminated between fibre and omega-3 (area under the curve (AUC) = 0.87 [95% confidence interval (CI): 0.63–0.99]), while stool eicosapentaenoate indicated omega-3 supplementation (AUC = 0.86 [95% CI: 0.64–0.98]). Univariate analysis also showed significant increases in indoleproprionate with fibre, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, and eicosapentaenoate with omega-3. Out of these, only the change in indoleproprionate was partly explained by changes in the gut microbiome composition (AUC = 0.61 [95% CI: 0.58–0.64] and Rho = 0.21 [95% CI: 0.08–0.34]) and positively correlated with the increase in the abundance of the genus Coprococcus (p = 0.005). Changes in three metabolites discriminated between fibre and omega-3 supplementation. The increase in indoleproprionate with fibre was partly explained by shifts in the gut microbiome, particularly Coprococcus, previously linked to better health.
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(This article belongs to the Collection Advances in Metabolomics)
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Synergistic Fermentation of Pichia kluyveri and Saccharomyces cerevisiae Integrated with Two-Step Sugar-Supplement for Preparing High-Alcohol Kiwifruit Wine
by
Qiang Wu, Qiaoling Yuan, Xi Wang, Lingying Chen, Senlin Yi, Xiaodan Huang, Jun Wang and Xutong Wang
Metabolites 2024, 14(6), 310; https://doi.org/10.3390/metabo14060310 - 28 May 2024
Abstract
Wild yeast suitable for kiwifruit wine fermentation was isolated and purified, and the fermentation process was optimized to increase the alcohol content of the kiwifruit wine. Pichia kluyveri was isolated from kiwifruit pulp by lineation separating, screened by morphological characteristics in Wallerstein Laboratory
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Wild yeast suitable for kiwifruit wine fermentation was isolated and purified, and the fermentation process was optimized to increase the alcohol content of the kiwifruit wine. Pichia kluyveri was isolated from kiwifruit pulp by lineation separating, screened by morphological characteristics in Wallerstein Laboratory Nutrient Agar (WL) medium and microscope observation, and further identified by 26S rDNA D1/D2 domain sequence analysis. Taking alcohol content and sensory evaluation as two indexes, the fermentation condition for kiwifruit wine was optimized by single factor and response surface experiment. The optimal fermentation conditions were optimized as follows: the fermentation temperature was at 24 °C, the initial pH was 3.8, the sugar dosage in second step was 8% (w/w), and the inoculating quantity of Pichia kluyveri and Saccharomyces cerevisiae was 0.15 g/L at equal proportion. Under these optimal conditions, the maximum estimated alcohol content was 15.6 vol%, and the kiwifruit wine was light green in color with strong kiwifruit aroma and mellow taste.
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(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)
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Elucidating the Role of Lipid-Metabolism-Related Signal Transduction and Inhibitors in Skin Cancer
by
Eunjin Kook and Do-Hee Kim
Metabolites 2024, 14(6), 309; https://doi.org/10.3390/metabo14060309 - 28 May 2024
Abstract
Lipids, as multifunctional molecules, play a crucial role in a variety of cellular processes. These include regulating membrane glycoprotein functions, controlling membrane trafficking, influencing apoptotic pathways, and affecting drug transport. In addition, lipid metabolites can alter the surrounding microenvironment in ways that might
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Lipids, as multifunctional molecules, play a crucial role in a variety of cellular processes. These include regulating membrane glycoprotein functions, controlling membrane trafficking, influencing apoptotic pathways, and affecting drug transport. In addition, lipid metabolites can alter the surrounding microenvironment in ways that might encourage tumor progression. The reprogramming of lipid metabolism is pivotal in promoting tumorigenesis and cancer progression, with tumors often displaying significant changes in lipid profiles. This review concentrates on the essential factors that drive lipid metabolic reprogramming, which contributes to the advancement and drug resistance in melanoma. Moreover, we discuss recent advances and current therapeutic strategies that employ small-molecule inhibitors to target lipid metabolism in skin cancers, particularly those associated with inflammation and melanoma.
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(This article belongs to the Special Issue Advances in Cellular Metabolism and Regulation)
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Effects of Increasing Glycerin Levels in Broiler Chickens
by
Elaine de Assis Carvalho, Weslane Justina da Silva, Denise Russi Rodrigues, Ludmilla Faria dos Santos, Camila Ferreira Rezende, Flávio Medeiros Vieites, Fabiana Ramos dos Santos, Fabiano Guimarães Silva and Cibele Silva Minafra
Metabolites 2024, 14(6), 308; https://doi.org/10.3390/metabo14060308 - 28 May 2024
Abstract
Glycerin contributes to the animal’s energy metabolism as an important structural component of triglycerides and phospholipids. The present study was carried out to evaluate the effect of replacing corn with 0, 5, 10, and 15% of glycerin in terms of performance, digestibility, carcass
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Glycerin contributes to the animal’s energy metabolism as an important structural component of triglycerides and phospholipids. The present study was carried out to evaluate the effect of replacing corn with 0, 5, 10, and 15% of glycerin in terms of performance, digestibility, carcass yield, relative weights of gastrointestinal tract (GIT) organs, and nutrient metabolism. Four hundred chickens (40.0 g ± 0.05 g) were distributed in a completely randomized design with four treatments and five replicates. Growth parameters were measured at 7, 14, 21, and 42 days. Digestibility of crude protein and fat, carcass yield, relative weights of GIT organs, and biochemical blood profile were measured. The results were subject to an analysis of variance by Tukey’s HSD test (p > 0.05). The inclusion of 5%, 10%, or 15% of glycerin did not influence performance or affect the crude protein and fat digestibility in broilers (p > 0.05) when compared to that of the basal (0%) diet. Similarly, the supplementation of glycerin levels showed no significant influence (p > 0.05) on the relative GIT organ weights, carcass yield, or nutrient metabolism. Thus, we concluded that glycerin may be included in the broilers’ diets in rations of up to 15%.
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(This article belongs to the Special Issue Animal Nutritional Metabolism and Toxicosis Disease)
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Secondary Metabolites and Antioxidant Activity against Moko Disease as a Defense Mechanism of Musa spp. from the Ecuadorian Coast Area
by
Raluca A. Mihai, Vanessa A. Terán-Maza, Karen A. Portilla-Benalcazar, Lissette E. Ramos-Guaytarilla, María J. Vizuete-Cabezas, Erly J. Melo-Heras, Nelson S. Cubi-Insuaste and Rodica D. Catana
Metabolites 2024, 14(6), 307; https://doi.org/10.3390/metabo14060307 - 28 May 2024
Abstract
The Musa spp. represents the most commonly produced, transitioned, and consumed fruit around the globe, with several important applications in the biotechnology, pharmaceutical, and food industries. Moko disease is produced by Ralstonia solanacearum—a factor with a high impact on all crops in
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The Musa spp. represents the most commonly produced, transitioned, and consumed fruit around the globe, with several important applications in the biotechnology, pharmaceutical, and food industries. Moko disease is produced by Ralstonia solanacearum—a factor with a high impact on all crops in Ecuador, representing one of the biggest phytosanitary problems. Four of the most common varieties of Musa spp. were tested to identify the metabolic reaction of plants facing Moko disease. The phenolic and flavonoid content has been evaluated as a defense system, and the α-diphenyl-α-picrylhydrazyl free-radical-scavenging method (DPPH), free-radical-scavenging activity (ABTS), ferric-reducing antioxidant power (FRAP) assays, and liquid chromatography and mass spectrometry (LC-MS) have been adapted to analyze the active compounds with the antioxidant capacity necessary to counteract the pathogenic attack. Our results indicate that all the studied varieties of Musa spp. react in the same way, such that the diseased samples showed a higher accumulation of secondary metabolites with antioxidant capacity compared with the healthy ones, with high active compound synthesis identified during the appearance of Moko disease symptoms. More than 40 compounds and their derivatives (from kaempferol and quercetin glycosides) with protective roles demonstrate the implication of the Musa spp. defense system against R. solanacearum infection.
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(This article belongs to the Special Issue Metabolomics and Plant Defence)
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Multidimensional Assessment of Sarcopenia and Sarcopenic Obesity in Geriatric Patients: Creatinine/Cystatin C Ratio Performs Better Than Sarcopenia Index
by
Mohamad Khalil, Agostino Di Ciaula, Nour Jaber, Roberta Grandolfo, Flavia Fiermonte and Piero Portincasa
Metabolites 2024, 14(6), 306; https://doi.org/10.3390/metabo14060306 - 27 May 2024
Abstract
The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI) are novel indicators for sarcopenia, but their accuracy may depend on various confounders. To assess CCR and SI diagnostic accuracy, we studied the clinical and biophysical parameters associated with sarcopenia or sarcopenic
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The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI) are novel indicators for sarcopenia, but their accuracy may depend on various confounders. To assess CCR and SI diagnostic accuracy, we studied the clinical and biophysical parameters associated with sarcopenia or sarcopenic obesity. A total of 79 elderly patients (65–99 yrs, 33 females) underwent clinical, anthropometric, body composition, geriatric performance, and blood chemistry evaluation. The CCR and SI accuracy were assessed to identify sarcopenia. Sarcopenia was confirmed in 40.5%, and sarcopenic obesity in 8.9% of the subjects. Sarcopenic patients showed an increased Charlson comorbidity index, cardiovascular disease (CVD) rates and frailty, and decreased physical performance than non-sarcopenic subjects. Patients with sarcopenic obesity had increased body fat and inflammatory markers compared to obese subjects without sarcopenia. Sarcopenia was associated with a decreased CCR and SI. However, when the logistic regression models were adjusted for possible confounders (i.e., age, gender, Charlson comorbidity index, presence of CVD, and frailty score), a significant OR was confirmed for the CCR (OR 0.021, 95% CI 0.00055–0.83) but not for the SI. The AUC for the CCR for sarcopenia discrimination was 0.72. A higher performance was observed in patients without chronic kidney diseases (CKD, AUC 0.83). CCR, more than the SI, is a useful, non-invasive, and cost-effective tool to predict sarcopenia, irrespective of the potential confounders, particularly in subjects without CKD.
Full article
(This article belongs to the Special Issue Systemic Immune-Inflammation Index in Endocrine and Metabolic Disorders)
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