Article
Engineering, Chemical
Kozue Okamura, Sara Badr, Sei Murakami, Hirokazu Sugiyama
Summary: This paper presents a three-module hybrid approach for studying monoclonal antibody production processes. The approach combines kinetic models, data-driven modules, and consideration of quality aspects, facilitating the design and control of cultivation processes.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2022)
Article
Cell Biology
Feng Cai, Divya Bezwada, Ling Cai, Rohit Mahar, Zheng Wu, Mario C. Chang, Panayotis Pachnis, Chendong Yang, Sherwin Kelekar, Wen Gu, Bailey Brooks, Bookyung Ko, Hieu S. Vu, Thomas P. Mathews, Lauren G. Zacharias, Misty Martin-Sandoval, Duyen Do, K. Celeste Oaxaca, Eunsook S. Jin, Vitaly Margulis, Craig R. Malloy, Matthew E. Merritt, Ralph J. Deberardinis
Summary: Stable isotopes are important tools for evaluating metabolism and can be detected using both mass spectrometry and nuclear magnetic resonance in vivo. We have developed a mass spectrometry method that can report all 16 aspartate and 32 glutamate isotopomers, offering higher sensitivity than nuclear magnetic resonance. This method allows for discrimination between pathways that result in the same number of 13C labels in aspartate and glutamate. Through experiments, we have demonstrated metabolic heterogeneity within human tumors, examined the impact of fumarate hydratase deficiency in renal cancer, and investigated the contributions of tricarboxylic acid cycle turnover and CO2 recycling to in vivo isotope labeling.
Review
Biochemistry & Molecular Biology
Benjamin Strain, James Morrissey, Athanasios Antonakoudis, Cleo Kontoravdi
Summary: With the increasing availability of omics data, Genome-scale metabolic models (GEMs) have become a useful tool for organizing and analyzing mammalian cell and human cell systems. However, the application of GEMs in microbial cells has been more prevalent due to smaller model sizes and ease of experimentation. This article discusses the challenges in accurately analyzing data for mammalian cell systems using GEMs and proposes integrating GEMs with data-driven tools and expanding their application beyond metabolism.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Multidisciplinary Sciences
Nozomu Takata, Jason M. Miska, Marc A. Morgan, Priyam Patel, Leah K. Billingham, Neha Joshi, Matthew J. Schipma, Zachary J. Dumar, Nikita R. Joshi, Alexander V. Misharin, Ryan B. Embry, Luciano Fiore, Peng Gao, Lauren P. Diebold, Gregory S. McElroy, Ali Shilatifard, Navdeep S. Chandel, Guillermo Oliver
Summary: Using eye organoids and mouse models, the authors demonstrate that lactate plays a bioenergetic independent role as a cell signaling molecule during early eye formation in mice. The study reveals the importance of aerobic glycolysis in retinal development and identifies specific glucose transporters and glycolytic genes involved. Lactate-mediated upregulation of eye-field transcription factors is controlled by epigenetic modifications.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Analytical
Fengqiu Zhang, Changsheng Shao, Yahui Wu, Wei Zhao, Xumiao Jing, Cao Fang, Qing Huang
Summary: In this study, a GFP fluorescent probe was utilized to construct a cell model for real-time observation of the dynamic change of glycolysis. It was found that TSA, an HDAC inhibitor, significantly enhanced glycolysis and inhibited cell proliferation. The mechanism of this process was associated with the regulation of HIF-1 alpha and c-Myc.
Article
Plant Sciences
Qing Ji, Ruifang Wang, Kai Chen, Zhengwan Xie, Sunyang Li, Dawei Wang, Ao Zhang, Yumei Xu, Shenghui Li, Junjun Cui, Sha Liu, Jun Zhou, Lihu Wang
Summary: Chinese jujube is an economically important fruit with anti-cancer effects, and rain-proof cultivation enhances sugar content in jujube fruits through regulating gene expression and metabolic activity. The molecular mechanisms underlying the differences in sugar content between rain-proof and open-field cultivation modes are still unknown.
Article
Biotechnology & Applied Microbiology
Quentin Thommen, Julien Hurbain, Benjamin Pfeuty
Summary: In this study, a stochastic simulation algorithm (SSA) derived from the chemical master equation of the isotope labeling system is proposed. The algorithm can compute the time evolution of isotopomer concentrations in non-stationary conditions without being influenced by the number of isotopomers. It is well-suited for comprehensive dataset including parallel labeling experiments and can serve as an alternative approach for metabolic flux analysis.
METABOLIC ENGINEERING
(2023)
Article
Plant Sciences
Jing Yu, Xiaowei Wang, Qianqian Yuan, Jiaxin Shi, Jingyi Cai, Zhichao Li, Hongwu Ma
Summary: The systematic characterization and understanding of plant metabolic behaviors are crucial for plant metabolic engineering and synthetic biology. By constructing a genome-scale metabolic network and combining multiomics analysis, we systematically investigated the impact of in-vitro cultivation on the tobacco metabolic network. We found that in-vitro tobacco showed slower growth, reduced biomass, and suppressed photosynthesis, while showing a significant increase in amino acids content. In silico investigation revealed that in-vitro tobacco downregulated photosynthesis and primary carbon metabolism, while upregulating the GS/GOGAT cycle to meet the demands of in-vitro growth.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Plant Sciences
Guiping Wang, Ru Chen, Xueping Han, Xiaomin Xue
Summary: This study investigated the effects of non-bagging and bagging cultivation on the growth and substance content of Fuji apple fruits. Non-bagging cultivation resulted in increased fruit weight, improved taste and aroma, and enhanced antioxidant capacity. These effects were associated with changes in hormone levels, trace elements, and gene expression.
Article
Biotechnology & Applied Microbiology
Maciek R. Antoniewicz
Summary: Metabolic engineering aims to improve biological production by designing and optimizing metabolic pathways, quantifying metabolic fluxes, and analyzing metabolic network models; essential concepts include metabolic network models and metabolic fluxes; in recent years, advancements in technology and methods have allowed for a deeper understanding of the capabilities of biological systems.
METABOLIC ENGINEERING
(2021)
Article
Oncology
Jun Jiang, DengLiang Huang, Yuan Jiang, Jing Hou, MeiYuan Tian, JianHua Li, Li Sun, YaoGang Zhang, Tao Zhang, ZhiQin Li, ZhongCheng Li, SiXian Tong, YanYan Ma
Summary: Lactate plays a role in modulating cellular metabolism in non-small cell lung cancer by reducing glucose uptake and glycolysis while maintaining mitochondrial homeostasis. The regulation of gene expression through histone lactylation is involved in this metabolic modulation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Marianna Aprile, Simona Cataldi, Caterina Perfetto, Antonio Federico, Alfredo Ciccodicola, Valerio Costa
Summary: This study identified a specific metabolic gene signature in BRAF-mutated tumors, characterized by enhanced glycolysis and increased expression of Hif-1 alpha-modulated glycolytic genes. Inhibitory effects of BRAFi on these genes and on cell viability were counteracted by Hif-1 alpha stabilization. Treatment with BRAFi and diclofenac combination could restrain the glycolytic phenotype and synergistically reduce tumor cells' viability.
BRITISH JOURNAL OF CANCER
(2023)
Article
Engineering, Biomedical
Stefanie Fuchs, Ruben W. J. van Helden, Maury Wiendels, Mees N. S. de Graaf, Valeria V. Orlova, Christine L. Mummery, Berend J. van Meer, Torsten Mayr
Summary: Recent advances in microfluidic engineering have enabled the cultivation of human cells under more realistic physiological conditions. By integrating oxygen and pH sensors into microfluidic devices, cellular physiology can be controlled and monitored in real time. Using highly metabolic human-induced pluripotent stem cells (hiPSCs) as a model, monitoring the extracellular environment allowed for rapid optimization of the seeding protocol and assessment of cell metabolism with the same precision as conventional cell culture methods.
MATERIALS TODAY BIO
(2022)
Article
Multidisciplinary Sciences
Yuefan Huang, Vakul Mohanty, Merve Dede, Kyle Tsai, May Daher, Li Li, Katayoun Rezvani, Ken Chen
Summary: Cells alter metabolic strategies under nutrient-deprived conditions to support their survival and growth. Characterizing metabolic reprogramming in the tumor microenvironment (TME) is important in cancer research and patient care. The computational framework METAFlux is developed to predict metabolic fluxes from single-cell RNA-seq data and has been validated in diverse cancer and immunotherapeutic contexts.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Song-Min Schinn, Carly Morrison, Wei Wei, Lin Zhang, Nathan E. Lewis
Summary: Genome-scale metabolic models that accurately predict the growth rates of mammalian cells require correct parameterization, which includes considerations such as metabolic activity limitations for cellular homeostasis and dynamic changes in cell morphology and viability. Different parameterizations can lead to varying predictions of metabolic phenotypes, with accurate parameter values broadly aligning with experimental measurements. These insights will inform future investigations into mammalian metabolism.
METABOLIC ENGINEERING
(2021)
Article
Biochemical Research Methods
Heeju Noh, Ziyi Hua, Panagiotis Chrysinas, Jason E. Shoemaker, Rudiyanto Gunawan
Summary: Understanding the molecular targets of diseases and drugs is crucial for drug discovery and treatment formulation. High-throughput gene transcription profiling technology provides whole-genome data, but identifying direct gene targets can be challenging due to the complexity of gene regulatory networks. DeltaNeTS+ is a powerful network analysis tool that can infer direct gene targets from gene expression profiles, combining steady-state and time-course data and leveraging gene network structure information.
BMC BIOINFORMATICS
(2021)
Article
Chemistry, Applied
Edith Mawunya Kutorglo, Frantisek Muzika, Fatima Hassouna, Giuseppe Storti, Dusan Kopecky, Roman Bleha, Andriy Synytsya, Ivona Sedlarova, Miroslav Soos
Summary: Immobilizing enzymes on 3D porous materials can enhance stability and reusability, and the 3D porous materials synthesized using a template method with chemically accessible surfaces show potential as biocatalyst supports.
MICROPOROUS AND MESOPOROUS MATERIALS
(2021)
Article
Biotechnology & Applied Microbiology
Ce Shi, Sebastian Vogg, Dong-Qiang Lin, Mattia Sponchioni, Massimo Morbidelli
Summary: A study developed a design procedure (DP) suitable for optimizing both batch frontal chromatography and Flow2 in terms of purity, yield, and productivity. Comparing the two operated at their optimal conditions showed that the Flow2 process demonstrated a more favorable Pareto front of yield and productivity at a specified purity, and exhibited improved robustness compared to the batch process.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Engineering, Chemical
Jose Francisco Wilson, Boleslav Zahradnik, Ondrej Srom, Baptiste Jaquet, Fatima Hassouna, Zdenek Hrdlicka, Juraj Kosek, Miroslav Soos
Summary: The research found that an increase in system temperature leads to an increase in aggregate size of polymer nanoparticles due to increased adhesion between NP surfaces. Additionally, at temperatures above the T-g of the polymer composing the shell, an increase in shear rate causes a reduction in interparticle contact strength, suggesting the presence of a shear-thinning effect during contact.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2021)
Article
Chemistry, Physical
Martina Jezkova, Petr Jelinek, Ivana Sloufova, Miroslav Soos
Summary: Gold snowflake-like particles were prepared via chemical reduction using inorganic salts, showing enhanced electro-optical behavior. The addition of inorganic salts and specific concentration ratios played a key role in determining the size and morphology of the particles. Various reaction parameters were systematically tested to understand their influence on the shape development of the gold particles. A trapping method was developed to efficiently collect individual particles without damaging their surface structure, and their enhanced electro-optical behavior was confirmed through surface-enhanced Raman spectroscopy.
SURFACES AND INTERFACES
(2021)
Article
Engineering, Chemical
Martina Jezkova, Petr Jelinek, Oskar Marelja, Dan Trunov, Marketa Jarosova, Zdenek Slouka, Miroslav Soos
Summary: Multicomponent hollow aggregates were prepared using an emulsion templating method adapted to microfluidic format, with IO and Au NPs in an inner inorganic shell covered with PCL NPs. Smaller aggregates were achieved compared to immiscible phases due to diffusion controlled shrinkage, with surface properties controlled by the mobilities and affinities of IO, Au, and PCL NPs. The biocompatible surface layer and inorganic shell with core space for cargo loading make these constructs advantageous for medicinal applications.
CHEMICAL ENGINEERING SCIENCE
(2022)
Article
Chemistry, Physical
Yannis Vasilopoulos, Jan Heyda, Jan Rohlicek, Eliska Skorepova, Vitek Zvonicek, Miroslav Soos
Summary: This study investigates the kinetics of desolvation in drug manufacturing, focusing on the interaction between solvents and active pharmaceutical ingredients (APIs). The results reveal the role of solvent diffusion and provide insights into the nanoscale interactions between the drug and solvent molecules during desolvation.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biotechnology & Applied Microbiology
Ismaele Fioretti, Thomas Mueller-Spaeth, Richard Weldon, Sebastian Vogg, Massimo Morbidelli, Mattia Sponchioni
Summary: Oligonucleotides (ONs) are a promising class of biotherapeutics in the biopharmaceutical industry due to their unique way of regulating gene expression and influencing protein synthesis. However, their production cost limits large-scale manufacturing, which can be alleviated through process intensification. In this study, an efficient and continuous chromatographic purification process for ONs was developed, improving productivity and buffer consumption compared to traditional batch processes.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Chemistry, Multidisciplinary
Argyro Chatziadi, Eliska Skorepova, Jan Jirat, Jan Rohlicek, Miroslav Soos
Summary: In this study, we successfully synthesized three cocrystals, two solvates, and two coamorphous systems of sofosbuvir using slurry experiments, solution evaporation, and mechanochemistry. We characterized these multicomponent solid forms and determined the crystal structures of sofosbuvir with piperazine, dichloromethane, and chloroform. Our results provide valuable insights into the molecular interactions in these systems.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Pharmacology & Pharmacy
Dominik Svara, Barbora Koprivova, Tomas Picek, Petr Mikes, Anna Kluk, Miroslav Soos
Summary: The purpose of this work is to prepare nanofibrous orally dispersible films (ODFs) using needleless electrospinning. The lamination pressure affects the mechanical properties of ODFs but has no impact on the dissolution kinetics.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Eliska Skorepova, Milos Vaclavik, Jan Jirat, Morgane Poupon, Ludeek Ridvan, Martin Babor, Miroslav Soos
Summary: The aim of this study was to investigate the solid forms of obeticholic acid and characterize their structures. Two possible solvated forms were discovered using X-ray powder diffraction, and further analysis showed that each solvate contains its respective solvent. The two series of solvates are isostructural, and single-crystal X-ray diffraction revealed that both forms are channel solvates.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Chemistry, Multidisciplinary
Jan Jirat, Martin Babor, Ludek Ridvan, Eliska Skorepova, Michal Dusek, Miroslav Soos
Summary: By examining the structure-property relations of apremilast cocrystals and solvates, this study presents a unique and large dataset of multicomponent crystal forms, including previously unpublished forms. The high similarity in crystal packing among these forms makes it easier to evaluate the structure-property relations. Interestingly, a significant correlation was found between the intrinsic dissolution rate of the multicomponent forms and their solubility as well as the solubility of the guest molecules in the dissolution medium. This finding is particularly important for the design of multicomponent forms with desired properties.
Article
Chemistry, Multidisciplinary
Sreela Ramesh, Eliska Skorepova, Vaclav Eigner, Vaisakh Chelod Paingad, Vit Zvonicek, Petr Kuzel, Miroslav Soos
Summary: The aim of this study was to prepare new crystalline salts of cyamemazine, an antipsychotic drug, with dicarboxylic acids, and compare their thermal stabilities, dissolution properties, and structural features. Among the eight acids investigated, novel salts were obtained with four of them. This study provides the first-ever examination of the solid-state landscape and crystal structure of cyamemazine.
CRYSTAL GROWTH & DESIGN
(2023)
Article
Thermodynamics
Pavel Krysa, Miroslav Soos
Summary: This study used computational fluid dynamics (CFD) to predict the breakage and coalescence of bubbles in gas-liquid systems and to predict the bubble size distribution (BSD). The CFD model was validated by comparing the simulation results with experimental data, and a characterization analysis of the system was performed.
INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER
(2022)
Article
Pharmacology & Pharmacy
Georgia Koutentaki, Pavel Krysa, Dan Trunov, Tomas Pekarek, Marketa Pislova, Miroslav Soos
Summary: The properties of paracetamol particles coated with carnauba wax were investigated. Raman mapping technique was used to examine the thickness and homogeneity of the coating layer. The results showed that the wax existed in two forms on the surface of the particles, and the coating thickness had high variability. The ability of carnauba wax to decrease the dissolution rate of paracetamol was confirmed.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2023)