Article
Biochemical Research Methods
Min Su, Kristian Serafimov, Peng Li, Cornelius Knappe, Michael Laemmerhofer
Summary: The chromatographic behavior of mixed-mode and hydrophilic interaction liquid chromatography (HILIC) was assessed in this study for the separation of metabolites from glycolysis and pentose phosphate pathways. Optimization of chromatographic conditions allowed for selective targeted analysis of glycolytic phosphorylated carbohydrate metabolites using liquid chromatography with tandem mass spectrometry (MS/MS). The separation of pentose phosphate isomers was achieved using mixed-mode HILIC/SAX and HILIC BEH Amide columns. HILIC-MS/MS showed challenges in separating hexose monophosphate metabolites, but the BEH Amide column provided the best results for this separation.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Endocrinology & Metabolism
Qingying Si, Jinxiu Guo, Xiumei Yang, Yujin Guo, Linlin Wu, Dadi Xie, Pei Jiang
Summary: This study investigated the metabolic alterations in streptozotocin-induced diabetic rats using gas chromatography-mass spectrometry analysis. The results showed differential expression of metabolites in the serum, heart, liver, kidney, cortex, renal lipid, hippocampus, and brown fat tissues of diabetic rats compared to control rats. Metabolic pathway analysis revealed that these alterations mainly involved amino acid metabolism, organic acid metabolism, sugar metabolism, and lipid metabolism.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemical Research Methods
Dimitrios J. Floros, Kangkang Xu, Franz Berthiller, Heidi Schwartz-Zimmermann
Summary: Metabolomics is gaining popularity in livestock research, and this study compared different chromatographic methods to assess their coverage of mammalian metabolites. The study investigated 354 primary metabolites from various compound classes and optimized selected reaction monitoring transitions on a mass spectrometer. The results showed that hydrophilic interaction liquid chromatography (HILIC) methods had the highest coverage of metabolites, including polar ones such as amino acids and biogenic amines. Combining complementary HILIC and reversed-phase (RP) methods increased the coverage to 92%, and further incorporating anion exchange chromatography (AIC) achieved a coverage of 97%.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Pharmacology & Pharmacy
Tongxi Zhuang, Xinhua Liu, Wen Wang, Jing Song, Le Zhao, Lili Ding, Li Yang, Mingmei Zhou
Summary: The study indicates that herbal polyphenols and flavonoids have multiple beneficial effects on obesity caused by chronic metabolic disorders, and the combination of CQR has significant therapeutic effects in combating obesity. Through urinary metabolomic analysis, it was found that CQR has a significant impact on the metabolites of HFD-induced obese rats.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemical Research Methods
Kristian Serafimov, Michael Laemmerhofer
Summary: In this study, a targeted approach with wide metabolite coverage was developed for cellular metabolomic analysis using a UHPLC-QTrap-MS system operated in the scheduled multiple reaction monitoring (sMRM) mode. The study compared four different cell extraction protocols and developed two HILIC-MS methods. A total of 161 metabolites were successfully detected in ESI+ mode, and 92 were detected in negative ionization mode. The developed methods were calibrated and validated, showing good accuracy and precision.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Nutrition & Dietetics
Laura Mayo-Martinez, Francisco J. Ruperez, Gabriel A. Martos-Moreno, Montserrat Graell, Coral Barbas, Jesus Argente, Antonia Garcia
Summary: AN is a mental disorder affecting mainly young women with intense fear of weight gain, leading to physical, metabolic, and psychological consequences. Metabolomics is proposed as a powerful tool to elucidate disease mechanisms and provide new insights into the diagnosis, treatment, and prognosis of AN. Ongoing research has shifted focus toward gut-microbiota metabolites as possible factors contributing to AN development.
Article
Toxicology
Andrea Gerdemann, Matthias Behrens, Melanie Esselen, Hans-Ulrich Humpf
Summary: Mycotoxins are secondary fungal metabolites that exhibit toxic effects in low concentrations. Metabolic profiling is a powerful tool for evaluating the toxicity of xenobiotics such as mycotoxins.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Environmental Sciences
Sonia Torres, Sara Samino, Pere Rafols, Manuela Martins-Green, Xavier Correig, Noelia Ramirez
Summary: This study investigated the metabolic disorders caused by thirdhand smoke (THS) exposure in the liver of male mice and the effects of antioxidant treatment. Results showed that THS exposure altered 88 metabolites, including amino acids, nucleotides, and various lipids, affecting pathways related to oxidative stress and lipid metabolism. Antioxidant treatment reduced lipid accumulation but did not fully reverse metabolic alterations, indicating THS as a new factor for liver steatosis.
ENVIRONMENT INTERNATIONAL
(2021)
Article
Chemistry, Analytical
Isabelle Kohler, Michel Verhoeven, Rob Haselberg, Andrea F. G. Gargano
Summary: Proteomics and metabolomics have become increasingly important in clinical applications, with RPLC-MS and HILIC-MS techniques playing crucial roles in biomarker discovery and disease diagnosis. While RPLC-MS and HILIC-MS complement each other in resolving the complexity of proteome and metabolites, they also have technical limitations and potential solutions that need to be addressed.
MICROCHEMICAL JOURNAL
(2022)
Article
Physiology
Eden A. Houske, Matthew G. Glimm, Annika R. Bergstrom, Sally K. Slipher, Hope D. Welhaven, Mark C. Greenwood, Greta M. Linse, Ronald K. June, Alan S. L. Yu, Darren P. Wallace, Alyssa K. Hahn
Summary: This study analyzed the urine metabolites of early-stage ADPKD patients and identified metabolic pathway alterations and candidate diagnostic and prognostic biomarkers. The results provide potential therapeutic targets and biomarkers for early diagnosis and tracking disease progression of ADPKD.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Salah Abdelrazig, Catharine A. Ortori, Michael Doherty, Ana M. Valdes, Victoria Chapman, David A. Barrett
Summary: Metabolomics studies have identified potential surrogate biomarkers of knee osteoarthritis in urine, aiding in a better understanding of OA progression and potential targeted treatment.
Article
Chemistry, Physical
Dan Tudor Eniu, Angelica Rita Chiorean, Andreea Iulia Socaciu, Adelina Staicu, Claudiu Rachieriu, Iulian Goidescu, Rares Buiga, Daniela Eniu, Carmen Socaciu, Romeo Chira
Summary: This study identified potential biomarkers in altered metabolic pathways related to breast cancer by analyzing metabolites in blood serum and urine samples. Both polar molecules and lipids were considered significant biomarkers for cancer staging and early diagnosis. Further analysis with larger patient cohorts will be essential for validating these findings.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemical Research Methods
Xue-Man Dong, Pu Wu, Long-Hui Cheng, Lan Shou, Heng Dong, Xiao-Yu Chen, Hao-Jin Gao, Jian-Xiang Chen, Fei Xiang, Qi Zhang, Da-Hong Zhang, Jian-Liang Zhou, Tian Xie
Summary: Metabolic reprogramming of cancer cells is a hallmark of cancer. This study developed a highly selective and sensitive HILIC-MS/MS method for direct determination of polar metabolites in cancer metabolic pathways. The method has been widely verified and can be used for understanding cancer, finding diagnostic biomarkers, and identifying therapeutic targets.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Chemistry, Analytical
Nguyen Phuoc Long, Dayoung Heo, Hee-Yeon Kim, Tae Hyun Kim, Jae-Gook Shin, Anbok Lee, Dong-Hyun Kim
Summary: The study utilized a metabolomics-guided global pathway meta-analysis to investigate metabolic alterations in breast cancer, highlighting the importance of avoiding the loss of functionally relevant information and capturing key changes in the breast cancer metabolome. These alterations in metabolic pathways play crucial roles in breast cancer initiation, progression, metastasis, and drug resistance, providing insights for potential therapeutic targets.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Biochemistry & Molecular Biology
Samuel Bernardo-Bermejo, Elena Sanchez-Lopez, Lei Tan, Selma Benito-Martinez, Zhengjin Jiang, Maria Castro-Puyana, Francisco Javier Lucio-Cazana, Maria Luisa Marina
Summary: Oxygen deficiency can disrupt biological functions and lead to diseases. Kidneys are particularly sensitive to hypoxia, which is linked to acute kidney injury and chronic kidney disease. Understanding hypoxia-induced metabolic alterations is crucial for kidney disease research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ryan J. King, Surendra K. Shukla, Chunbo He, Enza Vernucci, Ravi Thakur, Kuldeep S. Attri, Aneesha Dasgupta, Nina V. Chaika, Scott E. Mulder, Jaime Abrego, Divya Murthy, Venugopal Gunda, Camila G. Pacheco, Paul M. Grandgenett, Audrey J. Lazenby, Michael A. Hollingsworth, Fang Yu, Kamiya Mehla, Pankaj K. Singh
Summary: Metabolic alterations play a crucial role in regulating cancer aggressiveness and immune responses. This study found that elevated expression of CD73, an enzyme involved in generating adenosine, is associated with increased aggressiveness in pancreatic ductal adenocarcinoma (PDAC). Inhibiting CD73 expression led to reduced tumor growth and myeloid-derived suppressor cells (MDSC) in PDAC mouse models. Furthermore, CD73 knockdown resulted in increased IFN-gamma expression by intratumoral CD4(+) and CD8(+) T cells and decreased GM-CSF levels. Depletion of CD4(+) T cells, but not CD8(+) T cells, abolished the beneficial effects of CD73 reduction. Overall, targeting the adenosine axis presents a promising therapeutic strategy for enhancing the immune response against PDAC.
Review
Immunology
Ryan J. King, Pankaj K. Singh, Kamiya Mehla
Summary: Cholesterol plays a role in cancer, atherosclerosis, and autoimmunity by modulating the immune system. Manipulating cholesterol metabolism may improve immunotherapy responses in cancer treatment. It can have both proinflammatory and anti-inflammatory effects in mammals, acting through various immune cell types depending on the context. Understanding the mechanisms of cholesterol-related metabolites can enhance our knowledge of their functions and effects on the immune system, leading to the development of better therapeutic strategies.
TRENDS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Pauline C. Xu, Mikyoung You, Seok-Yeong Yu, Yi Luan, Maya Eldani, Thomas C. Caffrey, Paul M. Grandgenett, Kelly A. O'Connell, Surendra K. Shukla, Chandramohan Kattamuri, Michael A. Hollingsworth, Pankaj K. Singh, Thomas B. Thompson, Soonkyu Chung, So-Youn Kim
Summary: This study found that elevated activin A levels were associated with remodeling of visceral adipose tissue in PDAC patients, characterized by decreased adipocyte diameter and increased fibrotic deposition, without changes in expression of thermogenic marker UCP1.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Venugopal Gunda, Thiago C. Genaro-Mattos, Jyoti B. Kaushal, Ramakanth Chirravuri-Venkata, Gopalakrishnan Natarajan, Kavita Mallya, Paul M. Grandgenett, Karoly Mirnics, Surinder K. Batra, Zeljka Korade, Satyanarayana Rachagani
Summary: This study investigates the significance and consistency of the cholesterol synthesis pathway in pancreatic cancer through the use of preclinical models, in vitro analysis, and clinical specimens, revealing aberrations in sterol metabolite intermediates and related genes.
Article
Nutrition & Dietetics
Gulshan Singh, Yeneneh Haileselassie, Leah Briscoe, Lawrence Bai, Akshar Patel, Elvi Sanjines, Steven Hendler, Pankaj K. Singh, Nandita R. Garud, Berkeley N. Limketkai, Aida Habtezion
Summary: This study found that the use of proton pump inhibitors (PPIs) can disrupt the gut microbiota, but probiotic intervention can mitigate these changes. Additionally, PPIs enhance the colonization of certain probiotic bacterial species. Therefore, combining PPIs with probiotics may be a beneficial strategy.
CLINICAL NUTRITION ESPEN
(2022)
Article
Biochemistry & Molecular Biology
Suravi Pramanik, Yingling Chen, Heyu Song, Irine Khutsishvili, Luis A. Marky, Sutapa Ray, Amarnath Natarajan, Pankaj K. Singh, Kishor K. Bhakat
Summary: This study identifies a novel role for the protein APE1 in regulating stable G4 formation and KRAS expression in PDAC, suggesting that G4 structures could be potential prognostic markers and therapeutic targets for PDAC.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Farina Sultan, Reelina Basu, Divya Murthy, Manisha Kochar, Kuldeep S. Attri, Ayush Aggarwal, Pooja Kumari, Pooja Dnyane, Jyoti Tanwar, Rajender K. Motiani, Archana Singh, Chetan Gadgil, Neel Sarovar Bhavesh, Pankaj K. Singh, Vivek T. Natarajan, Rajesh S. Gokhale
Summary: This study investigates the temporal dynamics of melanogenesis and identifies three dominant phases of metabolic and transcriptional reprogramming. The findings suggest that fatty acid metabolism could be a potential therapeutic target for the treatment of various hyperpigmentary cutaneous diseases.
Article
Multidisciplinary Sciences
Mohammad Mazharul Islam, Andrea Goertzen, Pankaj K. Singh, Rajib Saha
Summary: In this study, a highly curated PDAC genome-scale metabolic model was reconstructed and used to explore the unique metabolic traits of PDAC. New therapeutic targets were identified, providing a better understanding of the metabolic vulnerabilities in PDAC and potential guidance for the development of novel therapeutic strategies.
Article
Oncology
Bhopal C. Mohapatra, Sameer Mirza, Aditya Bele, Channabasavaiah B. Gurumurthy, Mohsin Raza, Irfana Saleem, Matthew D. Storck, Aniruddha Sarkar, Sai Sundeep Kollala, Surendra K. Shukla, Siddesh Southekal, Kay-Uwe Wagner, Fang Qiu, Subodh M. Lele, Mansour A. Alsaleem, Emad A. Rakha, Chittibabu Guda, Pankaj K. Singh, Robert D. Cardiff, Hamid Band, Vimla Band
Summary: Ecdysoneless (ECD) protein is overexpressed in breast cancer and its overexpression predicts shorter survival in patients. In a mouse study, inducible overexpression of ECD led to mammary hyperplasia, pre-neoplastic lesions, heterogeneous tumors, and lung metastasis. ECD overexpression promoted epithelial to mesenchymal transition and cancer stem cell characteristics, and its oncogenic effects were mediated through regulation of c-MYC-mediated glucose metabolism.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yongji Zeng, Ling Yin, Jiuli Zhou, Renya Zeng, Yi Xiao, Adrian R. Black, Tuo Hu, Pankaj K. Singh, Feng Yin, Surinder K. Batra, Fang Yu, Yuanhong Chen, Jixin Dong
Summary: This study identifies MARK2 as a critical regulator for paclitaxel chemosensitivity in PDAC and shows that it controls mitotic progression and paclitaxel cytotoxicity by regulating class IIa HDACs. Inhibition of MARK2 or HDACs enhances paclitaxel cytotoxicity and overcomes chemoresistance. The findings suggest that the MARK2-HDAC axis could be a potential target for overcoming chemoresistance in PDAC.
Article
Oncology
Nicholas J. Mullen, Ravi Thakur, Surendra K. Shukla, Nina Chaika, Sai Sundeep Kollala, Dezhen Wang, Chunbo He, Yuki Fujii, Shikhar Sharma, Scott E. Mulder, David B. Sykes, Pankaj K. Singh
Summary: In this study, we identified CNX-774 as a previously uncharacterized ENT1 inhibitor that could sensitize pancreatic cancer cell lines to the DHODH inhibitor brequinar (BQ). Our results also suggest that N-acetylneuraminic acid accumulation could serve as a potential marker for the therapeutic efficacy of DHODH inhibitors.
Editorial Material
Oncology
Pankaj K. Singh, Kamiya Mehla
Review
Oncology
Nicholas J. J. Mullen, Pankaj K. K. Singh
Summary: Metabolic alterations, specifically the augmented synthesis and use of nucleotide triphosphates, are crucial for cancer cells and contribute to their aggressive behaviors and resistance to therapies. Upregulation of nucleotide biosynthesis is a prerequisite for cancer initiation and progression. Despite the potential of nucleotide synthesis inhibitors, their full efficacy has not been realized. This review discusses recent studies on the diverse roles of hyperactive nucleotide metabolism in cancer and explores opportunities for combination therapies to target these pathways effectively.
NATURE REVIEWS CANCER
(2023)
Article
Chemistry, Medicinal
Benjamin Suenkel, Sergio Valente, Clemens Zwergel, Sandra Weiss, Elisabetta Di Bello, Rossella Fioravanti, Michele Aventaggiato, Joao A. Amorim, Neha Garg, Surinder Kumar, David B. Lombard, Tuo Hu, Pankaj K. Singh, Marco Tafani, Carlos M. Palmeira, David Sinclair, Antonello Mai, Clemens Steegborn
Summary: Sirtuins, a group of NAD+-dependent protein deacylases, play important roles in metabolic regulation and aging-related diseases. This study identifies 1,4-dihydropyridine-based compounds as potential activators for Sirtuin isoforms, including pan activators and specific stimulators for Sirt3 and Sirt5. These compounds can enhance turnover of peptide and protein substrates and activate cellular pathways such as apoptosis and electron transport chain.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)