Article
Toxicology
S. G. Rudyak, L. A. Usakin, E. A. Tverye, E. D. Robertson, A. A. Panteleyev
Summary: Aryl hydrocarbon receptor (AhR) expression and stability are influenced by AhR ligands. Treatment with TCDD, FICZ, and I3C caused a decrease in AhR expression. AhR degradation is regulated by proteasomal degradation and the presence of AhR antagonists, and requires the involvement of AhR dimerization partner ARNT. In addition, HDAC inhibition enhances AhR expression.
TOXICOLOGY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
J. Christopher Corton, Jie Liu, Nicole Kleinstreuer, Maureen R. Gwinn, Natalia Ryan
Summary: This article describes a computational approach utilizing high-throughput transcriptomics to predict estrogen receptor activity through a gene expression biomarker, aiming to reduce the reliance on animal tests. The study shows that the ER biomarker model correctly identifies active and inactive ER reference chemicals with high prediction accuracy.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Cell Biology
Tu Nguyen, Mei Zheng, Maura Knapp, Nikola Sladojevic, Qin Zhang, Lizhuo Ai, Devin Harrison, Anna Chen, Albert Sitikov, Le Shen, Frank J. Gonzalez, Qiong Zhao, Yun Fang, James J. K. Liao, Rongxue Wu
Summary: The decline in endothelial ARNT expression contributes to the suppressed angiogenic phenotype in diabetic mice. The cytoprotective effect of ARNT in endothelial cells is partially mediated by declines in ROS production.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Environmental Sciences
Severine A. Degrelle, Ioana Ferecatu, Thierry Fournier
Summary: Aryl hydrocarbon receptor (AHR) is a crucial transcription factor involved in various biological processes. Two new reporter genes have been constructed to improve the study of AHR activity, and their capability to monitor AHR activity in different cell types has been demonstrated.
ENVIRONMENT INTERNATIONAL
(2022)
Review
Pharmacology & Pharmacy
Ziyue Kou, Wei Dai
Summary: Aryl hydrocarbon receptor (AHR) is a cellular protein involved in detoxification of xenobiotic compounds. Research has shown that AHR plays important roles in normal development and homeostasis, and its deficiency can lead to various developmental abnormalities.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Cell Biology
Claudia Rejano-Gordillo, Ana Ordiales-Talavero, Ana Nacarino-Palma, Jaime M. Merino, Francisco J. Gonzalez-Rico, Pedro M. Fernandez-Salguero
Summary: The transcription factor aryl hydrocarbon receptor (AHR) is a key regulator involved in cell functions and tumor progression. It can act as either an oncogene or a tumor suppressor, depending on the specific organ, tissue and cell type. In addition to its role in cell adhesion and migration, AHR has potential as a therapeutic tool, diagnosis and prognosis marker.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Lucia Sladekova, Sridhar Mani, Zdenek Dvorak
Summary: The aryl hydrocarbon receptor (AhR) is a crucial member of the helix-loop-helix transcription factors family, playing a central role in host physiology and various pathophysiologies. Activation of AhR is ligand-driven and the pharmacology of activation is dependent on the type and quantity of ligand. Therefore, understanding AhR ligands is essential for further advancements in the field. This minireview clarifies misconceptions and explores the true nature of AhR activation by discussing selected chemical classes and their qualification as true receptor ligands.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Oncology
Yujing Bi, Qiuli Yang, Zhengchao Li, Yuexin Wang, Yufei Wang, Anna Jia, Zhiyuan Pan, Ruifu Yang, Guangwei Liu
Summary: The lack of aryl hydrocarbon receptor nuclear translocator (ARNT) promotes neutrophil recruitment, neutrophil extracellular trap (NET) development, inflammatory cytokine secretion, and suppressive activities, thereby promoting colorectal cancer growth. The gut microbiota plays a crucial role in the functional alterations of Arnt(-/-) neutrophils. These findings have important implications for the combination of gut microbiota and immunotherapy approaches in colorectal cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Congrong Niu, Bill Smith, Yurong Lai
Summary: This study characterized the gene induction by ligands of CAR and AhR in human hepatocytes, showing distinct effects on metabolizing enzyme and drug transporter genes. Different inducers had varying degrees of effects on specific genes, highlighting the importance of assessing transporter gene inductions alongside metabolizing enzyme genes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Puneet Kumar, Manoj Yadav, Khushi Verma, Ruhi Dixit, Juhi Singh, Satyendra K. Tiwary, Gopeshwar Narayan, V. K. Dixit
Summary: The study reveals that AHRR expression is significantly down-regulated in gallbladder cancer tissue samples compared to controls, and this decreased expression is associated with tumor development and progression, suggesting a potential role for AHRR as a tumor suppressor gene in gallbladder cancer.
SAUDI JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Pharmacology & Pharmacy
Colleen S. Curran, Jeffrey B. Kopp
Summary: The aryl hydrocarbon receptor (AHR) plays an important role in the development of chronic kidney disease (CKD) by binding various endogenous and xenobiotic ligands and regulating kidney stability, transcriptional activity, and cell signaling. AHR activity is closely associated with kidney damage and protection, with its cross-talk with estrogen, peroxisome proliferator-activated receptor-gamma, and NF-kappa B pathways contributing to the diversity of AHR responses in different forms and stages of CKD. Understanding the roles of AHR in kidney fibrosis, metabolism, and the renin-angiotensin system can provide insights into the pathogenesis and therapies of CKD.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Immunology
Xiaoyu Xi, Qinbin Ye, Danping Fan, Xiaoxue Cao, Qiong Wang, Xing Wang, Mengxiao Zhang, Yuan Xu, Cheng Xiao
Summary: Several factors, including genetic, epigenetic, and environmental factors, play important roles in the pathogenesis of rheumatoid arthritis (RA), with polycyclic aromatic hydrocarbons (PAHs) being a recently highlighted environmental factor. This review summarizes the recent progress in understanding the mechanisms of PAHs and aryl hydrocarbon receptors (AHRs) in RA, and discusses the development of therapeutic drugs targeting AHRs. Challenges and prospects of AHR application in the future are also discussed.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Anne-Marie Chausse, Sylvie M. Roche, Marco Moroldo, Christelle Hennequet-Antier, Sebastien Holbert, Florent Kempf, Emilie Barilleau, Jerome Trotereau, Philippe Velge
Summary: This study describes the transcriptomic reprogramming of IEC-6 intestinal epithelial cell line to Salmonella Typhimurium strains that invaded cells by trigger or zipper mechanisms. Regardless of the entry mechanism, the transcriptomic reprogramming of the cell was similar. However, when comparing gene expression between exposed and unexposed cells, the transcriptomic reprogramming of exposed cells was significantly different, indicating the impact of Salmonella infection. The activation of target genes of the aryl hydrocarbon receptor and modulation of extracellular matrix genes were observed during Salmonella infection.
Article
Biochemistry & Molecular Biology
Meei-Ling Sheu, Liang-Yi Pan, Cheng-Ning Yang, Jason Sheehan, Liang-Yu Pan, Weir-Chiang You, Chien-Chia Wang, Hung-Chuan Pan
Summary: Thrombin is closely related to neurodegenerative disorders, and AhR is well expressed in microglia cells involved in inflammatory disorders of the brain. This study found that deleting AhR aggravated the inflammatory response and neurodegenerative processes induced by thrombin in microglia cells, while an AhR agonist could inhibit these responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Andreia Barroso, Joao Vitor Mahler, Pedro Henrique Fonseca-Castro, Francisco J. Quintana
Summary: The aryl hydrocarbon receptor (AHR) was originally identified as the receptor for dioxin and is now known to be a receptor for multiple physiological ligands, playing crucial roles in health and disease. AHR has been found to play a role in the gut-brain axis and could hold potential as a therapeutic target for immune-mediated diseases.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Peter Satzer, Daniel Komuczki, Magdalena Pappenreiter, Alessandro Luigi Cataldo, Bernhard Sissolak, Alois Jungbauer
Summary: This study investigated the impact of different failure rates and scheduling scenarios on the actual productive uptime of an integrated continuous biomanufacturing process using a Monte Carlo approach. The results showed that flexible scheduling for seed fermentation is crucial for maximizing the potential of continuous biomanufacturing, which demonstrated higher productive uptime compared to batch manufacturing.
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Ignacio Montes-Serrano, Peter Satzer, Alois Jungbauer, Astrid Duerauer
Summary: By combining experimental results and CFD simulations, this study determines the volumetric power input and hydrodynamics in MTPs, providing a foundation for direct scale-up from microtiter plates to stirred tank reactors.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biochemical Research Methods
Leo A. A. Jakob, Tomas Mesurado, Alois Jungbauer, Nico Lingg
Summary: The CASPON enzyme is an interesting enzyme for fusion protein processing due to its generation of an authentic N-terminus. However, the high cysteine content in CASPON may lead to aggregation through disulfide-bond formation, which can negatively impact enzymatic activity. Different multimerization states of CASPON were isolated and analyzed to determine their propensity for multimerization and enzymatic activity. The results showed that the dimer state was the most stable and active, with 50% higher enzymatic activity than the tetramer state. Multimerization was mainly mediated by cysteine, and attractive protein-protein interactions were observed in the presence of ammonium sulfate and on a chromatographic stationary phase. These findings provide insights into protein purification and highlight the importance of controlling multimerization to maintain protein activity.
PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY
(2023)
Article
Chemistry, Analytical
Baubek Spanov, Oladapo Olaleye, Tomes Mesurado, Natalia Govorukhina, Alois Jungbauer, Nico C. van de Merbel, Nico Lingg, Rainer Bischoff
Summary: The study found that Pertuzumab undergoes changes in charge heterogeneity, primarily due to deamidation in the Fc domain and N-terminal pyroglutamate formation in the heavy chain. Peptide mapping analysis also showed that clinical samples had 2-3% deamidation in the heavy chain CDR2, 20-25% deamidation in the Fc domain, and 10-15% N-terminal pyroglutamate formation in the heavy chain.
ANALYTICAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Magdalena Pappenreiter, Benjamin Bayer, Marijan Logarusic, Bernhard Sissolak, Alois Jungbauer
Summary: The study investigated the individual impacts of mild and rigorous intra-experimental parameter shifts on the culture performance and cell metabolism of an antibody producing CHO cell line. The results showed significant changes in cell growth, metabolism, and productivity due to intra-experimental parameter shifts. However, if the conditions within an experiment are changed, rigorous parameter shifts should be avoided, as they can lead to irreversible changes in cell behavior, as observed in media blending experiments.
BIOCHEMICAL ENGINEERING JOURNAL
(2023)
Article
Biotechnology & Applied Microbiology
Viktoria Mayer, Anna-Carina Frank, Shirin Preinsperger, Patrick Csar, Petra Steppert, Alois Jungbauer, Patricia Pereira Aguilar
Summary: Host cell DNA, especially chromatin, is an important impurity in downstream processing of enveloped viruses. Endonuclease treatment, using salt-tolerant endonucleases, combined with flow-through chromatography using core-shell particles, showed high purity and purification efficiency in the processing of recombinant measles virus. This strategy has the potential to be applied in other viral platforms.
BIOTECHNOLOGY PROGRESS
(2023)
Article
Biotechnology & Applied Microbiology
Magdalena Pappenreiter, Hubert Schwarz, Bernhard Sissolak, Alois Jungbauer, Veronique Chotteau
Summary: This study tested different process set ups and conditions in low shear TFF systems using magnetic levitation pumps in small-scale perfusion bioreactors. The authors validated a novel concept of applying reverse flow across the hollow fiber using two magnetically levitating pumps. The results showed that product sieving could be improved by 30% with the application of dynamic recirculation flow, and minimal product retention was achieved by reversing the flow of two alternating pumps with short cycle times. Additionally, a correlation was found between the passage of high molecular weight species and the flow direction, as well as the degree of product sieving.
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Astrid Duerauer, Alois Jungbauer, Theresa Scharl
Summary: The biopharmaceutical industry is still running in batch mode due to heavy regulation, but there are initiatives and technologies being developed to move towards automated and autonomous bioprocessing. These include Process Analytical Technologies, Quality by Design, and Continuous Integrated Manufacturing. The ultimate goal is to achieve real-time release and establish a highly predictive and robust biomanufacturing system.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Gabriele Recanati, Magdalena Pappenreiter, Christoph Gstoettner, Patrick Scheidl, Elena Dominguez Vega, Bernhard Sissolak, Alois Jungbauer
Summary: Continuous precipitation coupled with continuous tangential flow filtration is an economical method for capturing recombinant antibodies from cell culture supernatant. By adopting tubular reactors to replace surge tanks, a continuous harvest and mass flow of product can be achieved with a narrow residence time distribution. The combination of CaCl2 precipitation and PEG capture method allows for efficient removal of host-cell DNA and retention of glycosylation profile.
ENGINEERING IN LIFE SCIENCES
(2023)
Article
Biochemical Research Methods
Markus Mozgovicz, Andreas Fischer, Cecile Brocard, Alois Jungbauer, Nico Lingg
Summary: Immobilized metal affinity chromatography (IMAC) is a powerful technique for capturing and purifying biopharmaceuticals. Protein recovery can be compromised due to spreading and unfolding of the protein, leading to fouling of the stationary phase. This study investigates the kinetics of irreversible adsorption of a protease on an IMAC resin and suggests that L-arginine sulfate can decelerate the irreversible adsorption.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Biochemistry & Molecular Biology
Nico Lingg, Markus Mozgovicz, Theresa Schaufler, Alexander Prokup, Amy Carruthers, David Boerema, Laura Keigher, Nathan Brinkman, Alois Jungbauer
Summary: Currently, IVIG is manufactured in batch through cold ethanol precipitation, which leads to a slow process with high space requirements. We have developed a continuous method using a tubular reactor to replace the batch precipitation method. This reactor, filled with static mixers for efficient cooling, allows for complete precipitation with the same yield and purity even with a residence time of only one minute. A tubular reactor with specific dimensions can process 4000 L of plasma per day, providing an opportunity to reduce the plant footprint or intensify existing manufacturing plants.
PROCESS BIOCHEMISTRY
(2023)
Article
Engineering, Chemical
Mafalda S. Santos, Christian Schuster, Harald Rennhofer, Helga C. Lichtenegger, Herwig Peterlik, Tim Causon, Alois Jungbauer
Summary: Efficient recovery of building-block chemicals, such as biobased itaconic acid, produced by microbial processes can be achieved using ultrathin membranes. The composition of the membranes was optimized to improve the separation performance, and membranes with high selectivity for itaconic acid were successfully demonstrated in experiments with synthetic solutions and culture supernatant.
SEPARATION AND PURIFICATION TECHNOLOGY
(2023)
Article
Chemistry, Analytical
Baubek Spanov, Oladapo Olaleye, Tomes Mesurado, Natalia Govorukhina, Alois Jungbauer, Nico C. van de Merbel, Nico Lingg, Rainer Bischoff
Summary: The ion-exchange profile of pertuzumab was evaluated, revealing that deamidation in the Fc domain and N-terminal pyroglutamate formation in the heavy chain were the main contributors to charge heterogeneity. Peptide mapping analysis of clinical samples showed deamidation rates of 2-3% in the heavy chain CDR2, 20-25% in the Fc domain, and N-terminal pyroglutamate formation rates of 10-15% in the heavy chain. These findings suggest that in vitro stress studies can predict in vivo modifications.
ANALYTICAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Hannah Engelmaier, Christoph Dattenboeck, Katerina Petrushevska-Seebach, Alois Jungbauer, Nikolaus Hammerschmidt
Summary: The study presents an integrated, continuous process for the capture of recombinant blood coagulation factors. The developed process consists of three continuous unit operations and has demonstrated successful continuous capture of the factors over a 24-hour duration.
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Maria del Carme Pons Royo, Jean-Luc Beulay, Eric Valery, Alois Jungbauer, Peter Satzer
Summary: Protein solubility is a critical attribute in the development and production of monoclonal antibodies. This study presents a simple and adaptable millidevice design for fast solubility curve determination, which showed consistent and reproducible results compared to manual assays.
REACTION CHEMISTRY & ENGINEERING
(2022)
Article
Cell Biology
Karina A. Pena, Sofya Savransky, Breanna Lewis
Summary: Compartmentalization of GPCR signaling is an emerging topic that emphasizes the importance of spatial bias in signaling for physiological relevance. PTH1R was the first GPCR discovered to signal via cAMP from endosomes, challenging the conventional model of GPCR signaling. The location of cAMP generation determines the physiological outcomes of GPCR signaling.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Cheng-Xu Ma, Xiao-Ni Ma, Jin-Jin Liu, Cong-Hui Guan, Ying-Dong Li, Nan Zhao, Didac Mauricio, Song-Bo Fu
Summary: The downregulation of primary cilia (PCs) due to BRAFV600E mutation contributes to the aggressiveness and lymph node metastasis of Papillary Thyroid Cancer (PTC).
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Kejun Wu, Cuihua Huang, Wenrong Zheng, Yubin Wu, Qintao Huang, Menghua Lin, Ruonan Gao, Liqin Qi, Guanlian He, Xiaoying Liu, Xiaohong Liu, Linxi Wang, Zhou Chen, Libin Liu
Summary: Recurrent non-severe hypoglycemia in patients with diabetes is associated with cognitive impairment. This study found that this condition is associated with reduced mitophagy in the hippocampus, leading to mitochondrial dysfunction and neurological impairment.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Yifei Lv, Yizhou Huang, Huiyu Fan, Yunxiu Zhao, Linjuan Ma, Yibing Lan, Chunming Li, Peiqiong Chen, Zheng Lou, Jianhong Zhou
Summary: Before menopause, females have a lower incidence of cardiovascular disease than age-matched males, possibly due to the protective effects of sex hormones. 17 beta-E2 inhibits THBS1 expression, preventing cell senescence and apoptosis, and counteracts oxidative stress by suppressing the TGF-beta/Smad signaling pathway.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Ana C. L. Camargo, Flavia B. Constantino, Sergio A. A. Santos, Ketlin T. Colombelli, Luiz M. F. Portela, Matheus N. Fioretto, Luisa A. Barata, Guilherme T. Valente, Carlos S. Moreno, Luis A. Justulin
Summary: This study examined the effects of maternal malnutrition on the transcriptomic landscape of the ventral prostate in rats. It found that changes in molecular pathways related to cellular development and tissue morphogenesis were associated with maternal malnutrition. The Abcg1 gene was found to be deregulated in both malnourished rats and prostate cancer models and patients.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Sandra Romero-Cordoba, Mayel Chirinos, Nancy Noyola-Martinez, Nayeli Torres-Ramirez, Mitzi Garcia-Olivares, Juan Pablo Aragon-Hernandez, Ixchel Ramirez-Camacho, Rosa Zuniga, Fernando Larrea, Ali Halhali, David Barrera
Summary: This study analyzed the effects of calcitriol, TGF-131, and their combination on human trophoblast cells. The results showed that the combination treatment modified the transcriptional landscape and mainly affected the storage, activity, and metabolism of lipids, which may have an impact on placental development.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Traver J. Wright, Richard B. Pyles, Melinda Sheffield-Moore, Rachel R. Deer, Kathleen M. Randolph, Kristen A. Mcgovern, Christopher P. Danesi, Charles R. Gilkison, Weston W. Ward, Jayson A. Vargas, Peyton A. Armstrong, Sarah E. Lindsay, Mohammed F. Zaidan, Justin Seashore, Tamara L. Wexler, Brent E. Masel, Randall J. Urban
Summary: This study investigates the persistent neurologic symptoms in COVID-19 patients after recovery and explores the association between these symptoms and disrupted growth hormone secretion and gastrointestinal discomfort.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Li-Li Chen, Ya-Qin Li, Zhi-Hui Kang, Xuan Zhang, Su-Yan Gu, Na Wang, Xue-Yan Shen
Summary: Defects in trophoblastic EMT caused by dysregulation of circTNRC18's interaction with LIN28A play a vital role in the development of preeclampsia. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, while LIN28A knockdown promotes them. Furthermore, circTNRC18 regulates the intracellular distribution of LIN28A and the expression of insulin-like growth factor II, affecting cell migration and invasion. Targeting the circTNRC18-LIN28A regulatory axis may provide a novel treatment approach for preeclampsia.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
