Article
Biochemistry & Molecular Biology
Danuta Drozdowska, Dawid Maliszewski, Agnieszka Wrobel, Artur Ratkiewicz, Michal Sienkiewicz
Summary: Eleven new benzamides were synthesized and one derivative showed the strongest inhibitory activity against acetylcholinesterase and beta-secretase. Molecular modeling revealed that the compound increased the enzyme's stiffness and reduced its flexibility to inhibit the enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Dajiang Zou, Renzheng Liu, Yangjing Lv, Jianan Guo, Changjun Zhang, Yuanyuan Xie
Summary: Alzheimer's disease (AD) is a progressive brain disease that results in memory loss and cognitive impairment, leading to death. This review focuses on the development of dual inhibitors that target both acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B), which are considered to contribute to AD pathologies. The inhibitors are classified into six groups based on their parent structures, and their design strategies, structure-activity relationships (SARs), and molecular docking studies with AChE and MAO-B are analyzed. The review provides valuable insights for the future development of AChE and MAO-B dual inhibitors, while also addressing the challenges and providing corresponding solutions.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Lanyu Liu, Qian Liu, Yan Wang, Yu Yuan, Feifan Xie
Summary: This study aimed to evaluate different combinations of polyanion-metal ion based solution system for phospholipids removal and elimination of matrix effects in human plasma. The optimized ZrOCl2-Ludox/DSS systems provided efficient phospholipids removal and adequate analyte recovery, and they also correctly eliminated ion suppression or enhancement of the non-polar and polar drugs.
ANALYTICA CHIMICA ACTA
(2023)
Article
Cell & Tissue Engineering
Yejoo Choi, Sungho Shin, Hyo Jin Son, Na-Hee Lee, Su Hyeon Myeong, Cheolju Lee, Hyemin Jang, Soo Jin Choi, Hee Jin Kim, Duk L. Na
Summary: This study identified two proteins (RCN3 and FSTL3) that may be potential biomarkers for predicting the response to MSCs in AD patients, and four proteins (SCRG1, NPDC1, ApoE, and CysC) that may be potential biomarkers for monitoring the response to MSCs in AD patients.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Pharmacology & Pharmacy
Jiaojiao Lu, Qiongqun Pan, Jieqiang Zhou, Yan Weng, Kaili Chen, Lv Shi, Guanxiu Zhu, Chunlin Chen, Liang Li, Meiyu Geng, Zhenqing Zhang
Summary: This study systematically investigated the pharmacokinetics, tissue distribution, and excretion of sodium oligomannate in animals. The results showed that sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport, resided in circulating body fluids, and could penetrate the blood-cerebrospinal fluid barrier. The excretion of sodium oligomannate was predominantly renal.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2022)
Article
Clinical Neurology
Irep Uras, Merve Karayel-Basar, Betul Sahin, Ahmet Tarik Baykal
Summary: Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by memory deficit and dementia. In this study, the spatial proteomic differences in the neonatal 5xFAD brain tissue were investigated using MALDI-MSI coupled to LC-MS/MS, and the differentially expressed proteins (DEPs) associated with AD were identified. The results showed a remarkable resemblance in the protein expression profiles of neonatal 5xFAD brain compared to AD patient specimens or AD mouse models, suggesting that molecular alterations in the AD brain existed even at birth and certain proteins may serve as neurodegenerative presages in neonatal AD brain.
ALZHEIMERS & DEMENTIA
(2023)
Article
Pharmacology & Pharmacy
Hui Wang, Jian-Ying Dai, Yu-Zhen He, Zhe-Wei Xia, Xiao-Fei Chen, Zhan-Ying Hong, Yi-Feng Chai
Summary: This study examined the therapeutic effect and mechanism of Anemarrhenae Rhizoma (AR) on AD model rats using serum metabolomics. The results showed that AR significantly affected the levels of multiple metabolites involved in various metabolic pathways in the serum of AD model rats. These findings were consistent with the results of behavior study, histopathological observations, and biochemical analyses, providing a scientific basis for the application of AR in the prevention and treatment of AD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemical Research Methods
Tanja R. Zijp, Tim J. Knobbe, Kai van Hateren, Jan Roggeveld, Hans Blokzijl, C. Tji Gan, Stephan J. L. Bakker, Erwin M. Jongedijk, Daan J. Touw
Summary: A straightforward and rapid method was developed for determination of plasma tacrolimus in solid organ transplant recipients, using liquid chromatography tandem mass spectrometry (LC-MS/MS). This method is suitable for measurement of tacrolimus in plasma and will facilitate ongoing observational and prospective studies on the relationship of plasma tacrolimus concentrations with clinical outcomes.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lea Wagmann, Aline C. Vollmer, Lucas Lauder, Felix Mahfoud, Markus R. Meyer
Summary: The study aimed to monitor adherence to antihypertensive medication by developing a quantification procedure for drug concentrations in blood plasma. Results showed that plasma concentration interpretation is more complex than urine screening but can effectively assess adherence. Further data is needed to determine if plasma quantification is superior in assessing adherence to antihypertensive medication.
Review
Biochemistry & Molecular Biology
Debojyoti Halder, Subham Das, Alex Joseph
Summary: Alzheimer's disease (AD) is a neurological disorder affecting millions of people worldwide. Current treatments focus on managing symptoms and slowing disease progression with drugs like AChE inhibitors and the NMDA receptor antagonist memantine. However, natural biological macromolecules have shown promise in AD treatment, with ongoing preclinical and clinical trials. This review highlights the structure-activity relationship (SAR) and mechanisms of action of these molecules, such as peptides, proteins, enzymes, and polysaccharides, providing insights for future development. The research in this field offers hope for individuals affected by this devastating disease.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Applied
Feifei Sun, Peixu Wu, Mohamed F. Abdallah, Haiguang Tan, Yi Li, Shupeng Yang
Summary: This study proposed and validated a novel strategy of one sample multi-point calibration curve (OSCC) using multiple isotopologue reaction monitoring (MIRM) for quantitative LC-MS bioanalysis. The developed OSCC methodology exhibited good performance in selectivity, sensitivity, accuracy, and precision, and could realize sample dilution by monitoring the MIRM channel. The advantages of excluding the preparation of multi-sample external calibration curve (MSCC) and sample dilution in OSCC make this strategy widely applicable in various fields.
Article
Biochemistry & Molecular Biology
Yury Kostyukevich, Elena Stekolshikova, Anna Levashova, Anna Kovalenko, Anna Vishnevskaya, Anton Bashilov, Albert Kireev, Boris Tupertsev, Lidiia Rumiantseva, Philipp Khaitovich, Sergey Osipenko, Eugene Nikolaev
Summary: The administration of low doses of D2O has been used for decades to investigate metabolic pathways and measure compound turnover rate. Previously, the uptake of deuterium in lipids was mainly studied using GC-MS instruments, but recent untargeted LC-MS/MS lipidomics approaches have been employed. In this study, the deuterium uptake in over 500 lipids was investigated in 13 organs and body fluids of mice after 4 days of 100% D2O administration. The highest deuteration was observed in the liver, plasma, and lung, while lower levels were found in the brain and heart. The incorporation of deuterium in palmitic and stearic fragments in lipids was demonstrated using MS/MS, but not in the corresponding free forms. The results were analyzed based on lipid metabolic pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Food Science & Technology
Zhen Ge, Jun-Cai Liu, Jian-An Sun, Xiang-Zhao Mao
Summary: This study aimed to isolate and analyze tyrosinase inhibitory peptides in royal jelly enzymatic digestion products. The D4 fraction showed the most significant tyrosinase inhibitory activity. The IC50 values of the three strongest tyrosinase inhibitory peptides were obtained as 7.59 mg/mL, 6.16 mg/mL, and 9.25 mg/mL, respectively. The results suggest that the new peptide extracted from royal jelly has the potential to be used in food products with health-promoting properties.
Article
Biochemical Research Methods
P. Poorna Basuri, R. Vijayakumar
Summary: The measurement of drug concentration in biological matrices is crucial for determining bioavailability and bioequivalence. In this study, a robust UHPLC-MS/MS method was developed and validated for the quantification of Minoxidil in human plasma. The method demonstrated high sensitivity and accuracy, and was successfully applied in a bioequivalence study.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2022)
Article
Biochemical Research Methods
Tarang Jadav, Niraj Rajput, Amit Kumar Sahu, Pinaki Sengupta
Summary: A sensitive mass spectrometry-based bioanalytical method was established to quantify the antiretroviral drug bictegravir (BTG) in both rat peripheral blood mononuclear cells (PBMCs) and plasma. The method was validated and showed a moderate correlation between plasma and PBMC concentration of BTG. The study suggests the inclusion of a quantification plan for BTG in its therapeutic target site in future research and development work.
ANALYTICAL BIOCHEMISTRY
(2023)
Article
Chemistry, Analytical
Jessica Medina, Rebecca Borreggine, Tony Teav, Liang Gao, Shanshan Ji, Justin Carrard, Christina Jones, Niek Blomberg, Martin Jech, Alan Atkins, Claudia Martins, Arno Schmidt-Trucksass, Martin Giera, Amaury Cazenave-Gassiot, Hector Gallart-Ayala, Julijana Ivanisevic
Summary: This study presents a targeted LC-MS/MS approach for high-throughput quantification of complex lipid species. The method achieved high precision measurements within and across multiple batches. The method can distinguish between different sample sources and reveal sex-specific differences in the serum lipidome.
ANALYTICAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Sarantos Kostidis, Elena Sanchez-Lopez, Martin Giera
Summary: Lipidomics, a new addition to the Omics landscape, is increasingly recognized as a valuable tool for identifying potential drug targets and biochemical markers. This review highlights recent advances in lipid analysis for drug discovery and development, including state-of-the-art technologies that continue to evolve for improved sensitivity and selectivity. The versatility of lipidomics analysis is demonstrated through important examples, and the integration of lipidomics with other Omics technologies, stem cell technologies, and metabolic flux analysis is expected to expand our understanding of pathophysiological mechanisms and lead to the discovery of novel targets and biomarkers.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jose A. Inia, Geurt Stokman, Elsbet J. Pieterman, Martine C. Morrison, Aswin L. Menke, Lars Verschuren, Martien P. M. Caspers, Martin Giera, J. Wouter Jukema, Anita M. van den Hoek, Hans M. G. Princen
Summary: Patients with metabolic syndrome are often prescribed statins to prevent cardiovascular disease, but their effects on NASH are lacking. This study found that atorvastatin can significantly reduce hepatic steatosis, inflammation, and fibrosis, as well as prevent cholesterol crystal formation and NLRP3 inflammasome activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Edgar Dawkins, Rico J. E. Derks, Martina Schifferer, Johannes Trambauer, Edith Winkler, Mikael Simons, Dominik Paquet, Martin Giera, Frits Kamp, Harald Steiner
Summary: Membrane remodeling can enhance the activity of gamma-secretase, leading to increased production of beneficial A beta species in Alzheimer's disease. However, the effects of membrane remodeling vary in different types of gamma-secretase, highlighting the importance of lipid-based AD treatment strategies.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Samuel Bernardo-Bermejo, Jingchuan Xue, Linh Hoang, Elizabeth Billings, Bill Webb, M. Willy Honders, Sanne Venneker, Bram Heijs, Maria Castro-Puyana, Maria Luisa Marina, Erik B. van den Akker, Marieke Griffioen, Gary Siuzdak, Martin Giera, Elena Sanchez-Lopez
Summary: Analytical techniques with high sensitivity and selectivity are crucial in clinical sample analysis. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is the standard method, but it is expensive. This study demonstrates that similar results can be achieved using a simpler single mass spectrometry detector combined with enhanced in-source fragmentation/annotation and correlated ion monitoring. The protocol provides step-by-step instructions for optimizing the conditions for this technique, making it broadly applicable and cost-effective for quantifying small molecules.
Article
Clinical Neurology
Jelle Y. Broos, Floor C. Loonstra, Lodewijk R. J. de Ruiter, Mariam Gouda, Wing Hee Fung, Menno M. Schoonheim, Marieke Heijink, Eva M. M. Strijbis, Charlotte Teunissen, Joep Killestein, Helga E. de Vries, Martin Giera, Bernard M. J. Uitdehaag, Gijs Kooij
Summary: This study investigated the association between bioactive lipid mediators (LMs) and clinical, biochemical, and MRI parameters in patients with multiple sclerosis (MS). The LM profiles of patients with progressive MS (PMS) were significantly different from those of patients with relapsing remitting MS (RRMS) and healthy controls (HCs), particularly with elevated levels of arachidonic acid (AA) derivatives. Specifically, 15-hydroxyeicosatetraenoic acid (HETE) was correlated with clinical and biochemical parameters and associated with neurodegenerative processes in PMS patients.
Article
Cell Biology
Anaisa V. Ferreira, Sarantos Kostidis, Laszlo A. Groh, Valerie A. C. M. Koeken, Mariolina Bruno, Ilayda Baydemir, Gizem Kilic, Ozlem Bulut, Theano Andriopoulou, Victoria Spanou, Kalliopi D. Synodinou, Theologia Gkavogianni, Simone J. C. F. M. Moorlag, L. Charlotte de Bree, Vera P. Mourits, Vasiliki Matzaraki, Werner J. H. Koopman, Frank L. van de Veerdonk, Georgios Renieris, Martin Giera, Evangelos J. Giamarellos-Bourboulis, Boris Novakovic, Jorge Dominguez-Andres
Summary: Dimethyl itaconate can induce long-term trained immunity, enhancing responsiveness to microbial stimulation and improving survival rate in infection.
Article
Pharmacology & Pharmacy
Laura M. de Jong, Soukayna Boussallami, Elena Sanchez-Lopez, Martin Giera, Maarten E. Tushuizen, Menno Hoekstra, Lukas J. A. C. Hawinkels, Robert Rissmann, Jesse J. Swen, Martijn L. Manson
Summary: The CYP2C19 genotype has an impact on the outcome of CYP2C19-dependent drug-drug interactions (DDIs), but there is substantial inconsistency between predicted and observed phenotypes, which may be influenced by disease-related factors.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Zhuang Li, Enchen Zhou, Cong Liu, Hope Wicks, Sena Yildiz, Farhana Razack, Zhixiong Ying, Sander Kooijman, Debby P. Y. Koonen, Marieke Heijink, Sarantos Kostidis, Martin Giera, Ingrid M. J. G. Sanders, Ed J. Kuijper, Wiep Klaas Smits, Ko Willems van Dijk, Patrick C. N. Rensen, Yanan Wang
Summary: This study found that short-chain fatty acids, including butyrate, do not have multiple metabolic benefits in individuals with metabolic syndrome. However, the underlying mechanisms are still unclear. The researchers used antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) to investigate the role of gut microbiota in the metabolic benefits of dietary butyrate. They found that dietary butyrate reduced appetite and ameliorated high-fat diet-induced weight gain, and these effects were dependent on the presence of gut microbiota.
Article
Nutrition & Dietetics
Vivien Chavanelle, Cedric Langhi, Arnaud Michaux, Doriane Ripoche, Yolanda F. Otero, Florian Le Joubioux, Thierry Maugard, Bruno Guigas, Martin Giera, Sebastien Peltier, Pascal Sirvent
Summary: The prevalence of obesity and type 2 diabetes is increasing globally. This study investigates the effects of a botanical supplementation composed of plant extracts on obese mice fed a high-fat diet. The results show that the supplementation can reduce circulating triglycerides, improve glucose metabolism, and enhance lipid tolerance.
NUTRITION RESEARCH
(2023)
Article
Medicine, General & Internal
Zhixiong Ying, Robin van Eenige, Xiaoke Ge, Christy van Marwijk, Joost M. Lambooij, Bruno Guigas, Martin Giera, Jan Freark de Boer, Tamer Coskun, Hongchang Qu, Yanan Wang, Mariette R. Boon, Patrick C. N. Rensen, Sander Kooijman
Summary: This study investigated the effects of combined glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP1R) agonism on nonalcoholic fatty liver disease (NAFLD) development. The results showed that combined GIPR/GLP1R agonism can reduce body weight, lower plasma levels of glucose, triglycerides, and total cholesterol. Additionally, it can also reduce hepatic lipid accumulation and inflammation. This study suggests that combined GIPR/GLP1R agonism may be a promising approach to attenuate NAFLD progression in humans.
Article
Biochemistry & Molecular Biology
Juan Carlos Alarcon Barrera, Alejandro Ondo-Mendez, Martin Giera, Sarantos Kostidis
Summary: The poor availability of oxygen and nutrients in malignant tumors drives the activation of various molecular responses and metabolic reprogramming in cancer cells. Understanding the metabolic changes occurring during hypoxia and reoxygenation is crucial for improving therapy efficacy. In this study, alterations in mitochondrial metabolism, redox status, lipid classes, and structural characteristics of lipids were observed during hypoxia and reoxygenation.
Article
Immunology
Elien Grajchen, Melanie Loix, Paulien Baeten, Beatriz F. Corte-Real, Ibrahim Hamad, Sam Vanherle, Mansour Haidar, Jonas Dehairs, Jelle Y. Broos, James M. Ntambi, Robert Zimmermann, Rolf Breinbauer, Piet Stinissen, Niels Hellings, Sanne G. S. Verberk, Gijs Kooij, Martin Giera, Johannes V. Swinnen, Bieke Broux, Markus Kleinewietfeld, Jerome J. A. Hendriks, Jeroen F. J. Bogie
Summary: The imbalance between pathogenic and protective T cell subsets is a key feature of autoimmune disorders such as multiple sclerosis (MS). The molecular mechanisms underlying the impact of fatty acid metabolism on T cell physiology and autoimmunity are poorly understood. The study reveals that fatty acid desaturation by SCD1 acts as an endogenous brake on regulatory T-cell differentiation and enhances autoimmunity, suggesting potential therapeutic strategies for autoimmune disorders such as MS.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Laurence Pirotton, Marie Octave, Audrey Ginion, Valentine Robaux, Sophie Lepropre, Shakeel Kautbally, Yotis Senis, Zoltan Nagy, Jerome Ambroise, Bruno Guigas, Martin Giera, Luc Bertrand, Christophe Beauloye, Sandrine Horman
Meeting Abstract
Gastroenterology & Hepatology
Eveline Gart, Wim van Duyvenvoorde, Jessica Snabel, Christa de Ruiter, Joline Attema, Martien P. M. Caspers, Serene Lek, Bertie Joan van Heuven, Arjen Speksnijder, Martin Giera, Aswin L. Menke, Kanita Salic, Kendra Bence, Gregory Tesz, Jaap Keijer, Robert Kleemann, Martine C. Morrison
JOURNAL OF HEPATOLOGY
(2023)
