Article
Microbiology
Jan Stephan Wichers, Paolo Mesen-Ramirez, Gwendolin Fuchs, Jing Yu-Strzelczyk, Jan Staecker, Heidrun von Thien, Arne Alder, Isabelle Henshall, Benjamin Liffner, Georg Nagel, Christian Loew, Danny Wilson, Tobias Spielmann, Shiqiang Gao, Tim-Wolf Gilberger, Anna Bachmann, Jan Strauss
Summary: This study investigated the subcellular localization and essentiality of several membrane transport proteins in Plasmodium falciparum parasites. Four of the membrane transport proteins were found to be essential for asexual development, and the plasma membrane resident transporter 1 was shown to be essential for gametocytogenesis.
Article
Developmental Biology
Ryan C. V. Lintao, Ananth Kumar Kammala, Natasha Vora, Jerome L. Yaklic, Ramkumar Menon
Summary: This study found that nutrient transporter genes and proteins are expressed in human fetal membrane tissues and cells, with similar expression patterns to placental tissues and BeWo cells. These findings contribute to our understanding of nutrient uptake kinetics during pregnancy.
Article
Biochemistry & Molecular Biology
Yaolei Mi, Xue Cao, Xuewen Zhu, Weiqiang Chen, Xiangxiao Meng, Huihua Wan, Wei Sun, Sifan Wang, Shilin Chen
Summary: This study identified and characterized 113 ABC transporters in C. sativa, and proposed seven core transporters that may participate in cannabinoid transport. These candidate genes showed high correlation with cannabinoid biosynthetic pathway genes and content, and were highly expressed in cannabinoid biosynthesis and accumulation sites.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Biochemistry & Molecular Biology
Laszlo Homolya
Summary: Mutations and polymorphisms in the human ABCG2 transporter can lead to reduced function, potentially causing hyperuricemia and toxic reactions. The genetic alterations in ABCG2 can affect the body's defense mechanisms and the absorption, distribution, and excretion of toxic substances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Brittany N. Araj, Bruce Swihart, Robert Morrison, Patricia Gonzales Hurtado, Andrew Teo, Almahamoudou Mahamar, Oumar Attaher, Bacary S. Diarra, Santara Gaoussou, Djibrilla Issiaka, Alassane Dicko, Patrick E. Duffy, Michal Fried
Summary: The study utilized proteomic analyses of PfEMP1 from clinical parasite isolates collected from Malian children to identify targets of immunity. Peptide-specific antibody responses in children were examined, and it was found that high antibody levels to specific PfEMP1 domains correlated with decreased parasite burden in future infections. These findings suggest that certain PfEMP1 domains play a role in protective immunity against malaria.
Article
Medical Laboratory Technology
Simin Yu, Zhen Xiao, Xiaoliang O. U. Yang, Xiuping Wang, Deng Zhang, Chunming Li
Summary: This study investigated the abnormal metabolites and metabolic pathways in patients with moderate-to-severe acne vulgaris. LC-MS/MS analysis of plasma metabolites was conducted on acne patients and healthy controls, identifying significant differential metabolites and metabolic pathways. The top three metabolites, namely 2-oxoadipic acid, Myo-inositol, and Citrate, were found to be highly associated with acne vulgaris. The most closely related metabolic pathways included ATP-binding cassette (ABC) transporters and sphingolipid signaling pathway. These findings provide new insight into the link between plasma metabolic changes and acne vulgaris.
CLINICA CHIMICA ACTA
(2022)
Article
Biochemical Research Methods
Ryuichi Hirota, Zen-ichiro Katsuura, Naoki Momokawa, Hiroki Murakami, Satoru Watanabe, Takenori Ishida, Takeshi Ikeda, Hisakage Funabashi, Akio Kuroda
Summary: In this study, it was found that under specific conditions, a phosphite-dependent strain of Escherichia coli can generate escape mutants. The mutation occurs at position 210 of the transmembrane domain protein HtxC of the phosphorus compound transporter HtxBCDE. The replacement of a specific amino acid residue at this position can reduce the rate of escape mutant generation.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Jose Pedro Gil, Claudia Fancony
Summary: The lethal Plasmodium falciparum parasite's ability to develop resistance against anti-malarial drugs is a central challenge in global malaria control and elimination efforts. Drug transporters like MRPs play a pivotal role in this process by handling a wide range of substrates, potentially contributing to the development of multi-drug resistance phenotypes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Pei-Fen Zhang, Zi-Yi Wu, Wen-Bin Zhang, Yong-Qiao He, Kexin Chen, Tong-Min Wang, Haixin Li, Hong Zheng, Dan-Hua Li, Da-Wei Yang, Ting Zhou, Chang-Mi Deng, Ying Liao, Wen-Qiong Xue, Lian-Jing Cao, Xi-Zhao Li, Jiang-Bo Zhang, Si-Qi Dong, Fang Wang, Mei-Qi Zheng, Wen-Li Zhang, Jianbing Mu, Wei-Hua Jia
Summary: Researchers have discovered a potential biomarker, oncofetal chondroitin sulfate (ofCS), for pan-cancer detection. They developed a sensitive plasma detection method to quantitate the levels of ofCS and found that cancer patients have significantly higher levels of ofCS. The study suggests that developing multi-cancer early detection tests based on cfDNA or protein markers holds great promise.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Louise Breuil, Nora Ziani, Sarah Leterrier, Gaelle Hugon, Fabien Caille, Viviane Bouilleret, Charles Truillet, Maud Goislard, Myriam El Biali, Martin Bauer, Oliver Langer, Sebastien Goutal, Nicolas Tournier
Summary: This study investigated the impact of CYP inducers and inhibitors on the brain and plasma kinetics of [C-11]metoclopramide using PET imaging. The results showed that CYP induction or inhibition had negligible effects on the plasma kinetics and metabolism of [C-11]metoclopramide, but ritonavir significantly increased brain penetration.
Review
Environmental Sciences
Silvia Simonetti, Valerio Zupo, Maria Cristina Gambi, Till Luckenbach, Ilaria Corsi
Summary: This review comprehensively investigates and summarizes the species and adaptive mechanisms in naturally low water pH conditions, and provides guidance for predicting the potential impact of future ocean acidification on marine biodiversity.
MARINE POLLUTION BULLETIN
(2022)
Article
Microbiology
Andrew E. Maclean, Hannah R. Bridges, Mariana F. Silva, Shujing Ding, Jana Ovciarikova, Judy Hirst, Lilach Sheiner
Summary: The study reveals the composition of the Toxoplasma mitochondrial electron transport chain (mETC) and F1Fo-ATP synthase using complexome profiling proteomic approach, with a particular focus on complexes II and III. The identification of new parasite-specific complex III subunits sheds light on the essential role of these proteins in parasite survival and proper functioning of the mETC. This highlights the diverse subunit composition of the apicomplexan mETC and F1Fo-ATP synthase complexes, setting the stage for future structural and drug discovery studies.
Article
Plant Sciences
Ting Qian, Xiaoshan Wang, Jingjing Liu, Mengyun Shi, Jing Zhao, Peipei Sun, Guanghui Zheng, Congbing Fang, Xingbin Xie
Summary: This study uncovered that anthocyanin transport in strawberry fruits may be mediated by ABCC transporter ABCC8 and its expression is regulated by MYB10, bHLH33, and MYC1 transcription factors.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Qingshan Luo, Huigang Shi, Xueqing Xu
Summary: Lipopolysaccharide (LPS) is a crucial component of the outer membrane in most Gram-negative bacteria, and its transport from the inner membrane to the outer membrane is facilitated by seven lipopolysaccharide transport proteins. This study presents the cryo-EM structures of LptB(2)FG and LptB(2)FGC from Klebsiella pneumoniae, highlighting the detailed interactions between LPS and the transporter.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Gangyang Wang, Lingling Cao, Yafei Jiang, Tao Zhang, Hongsheng Wang, Zhuoying Wang, Jing Xu, Min Mao, Yingqi Hua, Zhengdong Cai, Xiaojun Ma, Shuo Hu, Chenghao Zhou
Summary: This study demonstrates that anlotinib can reverse multidrug resistance in osteosarcoma cells by inhibiting the efflux function of P-glycoprotein 1 (PGP1) and increasing the intracellular accumulation of chemotherapeutic agents. Anlotinib also stimulates the ATPase activity of PGP1. In animal studies, anlotinib combined with doxorubicin shows a significant decrease in tumor growth rate and tumor size.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Carlijn H. C. Litjens, Laurens F. M. Verscheijden, Celine Bolwerk, Rick Greupink, Jan B. Koenderink, Petra H. H. van den Broek, Jeroen J. M. W. van den Heuvel, Elin M. Svensson, Martin J. Boeree, Cecile Magis-Escurra, Wouter Hoefsloot, Reinout van Crevel, Arjan van Laarhoven, Jakko van Ingen, Saskia Kuipers, Rovina Ruslami, David M. Burger, Frans G. M. Russel, Rob E. Aarnoutse, Lindsey H. M. Te Brake
Summary: The study investigated the pharmacokinetic interaction of moxifloxacin with rifampicin in tuberculosis treatment, providing new insights and potential therapeutic strategies. Simulations demonstrated that increasing the dose of moxifloxacin could restore plasma exposure in patients.
JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tim Brecklinghaus, Wiebke Albrecht, Franziska Kappenberg, Julia Duda, Nachiket Vartak, Karolina Edlund, Rosemarie Marchan, Ahmed Ghallab, Cristina Cadenas, Georgia Gunther, Marcel Leist, Mian Zhang, Iain Gardner, Jorg Reinders, Frans G. M. Russel, Alison J. Foster, Dominic P. Williams, Amruta Damle-Vartak, Melanie Grandits, Gerhard Ecker, Naim Kittana, Jorg Rahnenfuehrer, Jan G. Hengstler
Summary: A method was introduced to assess the risk of human drug induced liver injury based on oral doses and blood concentrations of drugs using in vitro/in silico approaches. The addition of an assay that measures the inhibition of bile acid export carriers improved the differentiation of hepatotoxic and non-hepatotoxic compounds. Integration of the CMFDA assay with an in vitro test battery enhanced the separation of hepatotoxic from non-hepatotoxic compounds.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Toxicology
Gaby A. M. Eliesen, Milou Fransen, Nina Kooijman, Petra H. H. van den Broek, Frans G. M. Russel, Rick Greupink
Summary: Tumor necrosis factor (TNF) plays a role in regulating trophoblast turnover during placental syncytium formation and may be affected by xenobiotics. High levels of TNF increase gene expression in undifferentiated BeWo cells, while physiological levels of TNF positively affect cell viability without affecting functional markers.
TOXICOLOGY IN VITRO
(2022)
Article
Infectious Diseases
Saskia I. Johanns, Richard G. Gantin, Bawoubadi Wangala, Kossi Komlan, Wemboo A. Halatoko, Meba Banla, Potchoziou Karabou, Adrian J. F. Luty, Hartwig Schulz-Key, Carsten Koehler, Peter T. Soboslay
Summary: The repeated use of ivermectin has been shown to prevent onchocerciasis infections and enhance immune responses in patients. However, it may also lead to decreased specific antibody responses, which could weaken the immune defense against tissue-dwelling O. volvulus larvae. On the other hand, increased cellular chemokine responses could enhance the elimination of O. volvulus larvae.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Infectious Diseases
Noe Patrick M'Bondoukwe, Reinne Moutongo, Komi Gbedande, Jacques Mari Ndong Ngomo, Tatiana Hountohotegbe, Rafiou Adamou, Jeanne Vanessa Koumba Lengongo, Kowir Pambou Bello, Denise Patricia Mawili-Mboumba, Adrian John Frederick Luty, Marielle Karine Bouyou-Akotet
Summary: The study aimed to investigate the potential role of co-endemic parasites on malaria susceptibility by comparing cytokine levels and ratios among populations with different parasitic profiles. Results showed higher IL-6 and IL-10 levels and IL-10/TNF-alpha ratio in individuals with Plasmodium falciparum infection. This suggests a potential impact of intestinal protozoa and helminths on antimalarial immunity and susceptibility to malaria.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Medicine, Research & Experimental
Eva J. Streekstra, Marton Kiss, Jeroen van den Heuvel, Johan Nicolai, Petra van den Broek, Sanne M. B. I. Botden, Martijn W. J. Stommel, Lara van Rijssel, Anna-Lena Ungell, Evita van de Steeg, Frans G. M. Russel, Saskia N. de Wildt
Summary: The Ussing chamber methodology is a suitable model to assess pediatric intestinal drug absorption, revealing higher drug transport in adult tissues compared to pediatric tissues, with no clear correlation for efflux transport across different age groups in children.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Infectious Diseases
Odilon Nouatin, Javier Ibanez, Rolf Fendel, Ulysse A. Ngoa, Freia-Raphaella Lorenz, Jean-Claude Dejon-Agobe, Jean Ronald Edoa, Judith Fluegge, Sina Brueckner, Meral Esen, Michael Theisen, Stephen L. Hoffman, Kabirou Moutairou, Adrian J. F. Luty, Bertrand Lell, Peter G. Kremsner, Ayola A. Adegnika, Benjamin Mordmueller
Summary: In a vaccine trial investigating the malaria vaccine candidate GMZ2, it was found that the GMZ2-specific antibody response increased after vaccination but was not correlated to protection. However, antibody responses to several Plasmodium falciparum antigens and the broadness of malaria-specific antibody response were significantly higher in protected study participants.
Article
Medicine, General & Internal
Chloe Morozoff, Euripide Avokpaho, Saravanakumar Puthupalayam Kaliappan, James Simwanza, Samuel Paul Gideon, Wongani Lungu, Parfait Houngbegnon, Katya Galactionova, Maitreyi Sahu, Khumbo Kalua, Adrian J. F. Luty, Moudachirou Ibikounle, Robin Bailey, Rachel Pullan, Sitara Swarna Rao Ajjampur, Judd Walson, Arianna Rubin Means
Summary: This study compared the costs of community-wide mass drug administration (cMDA) and school-based deworming (SBD). The results showed that cMDA was generally more expensive than SBD, and the costs were sensitive to the number of treatments administered.
Review
Pharmacology & Pharmacy
Charlotte A. Hoogstraten, Jonathan J. Lyon, Jan A. M. Smeitink, Frans G. M. Russel, Tom J. J. Schirris
Summary: An increasing number of commonly prescribed drugs are known to interfere with mitochondrial function and can lead to various adverse effects. Historically, the lack of sensitive assays to identify the mechanisms underlying mitochondrial toxicity has been a challenge in drug development. However, recent advancements in network-based and structure-based systems pharmacology have paved the way for a tiered approach to detect and understand drug-induced mitochondrial dysfunction. This approach includes phenotypic characterization, metabolic profiling, mechanistic studies, and in vitro and in vivo investigations, which can help identify off-target mechanisms and optimize drug candidates to minimize mitochondrial activity.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Toxicology
Damian Roelofsen, Hedwig van Hove, Vera Bukkems, Frans Russel, Gaby Eliesen, Rick Greupink
Summary: This study explores a physiological approach to predict fetal exposure to xenobiotics by analyzing ex vivo placenta perfusion data. The results show that the PBMP model accurately describes the perfusion data and the p-PBPK model can be used to predict the concentration of xenobiotics in the fetal blood at steady-state.
TOXICOLOGY IN VITRO
(2022)
Article
Toxicology
Charlotte A. Hoogstraten, Maaike M. E. Jacobs, Guido de Boer, Melissa A. E. van de Wal, Werner J. H. Koopman, Jan A. M. Smeitink, Frans G. M. Russel, Tom J. J. Schirris
Summary: Mitochondrial dysfunction plays a pivotal role in drug-induced acute kidney injury (AKI) and the transport protein AAC is an important potential drug off-target. In this study, AAC3 deficiency led to reduced mitochondrial function and mass in human renal proximal tubular cells, particularly affecting metabolic spare capacity under galactose conditions.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Infectious Diseases
Carlijn H. C. Litjens, Laurens F. M. Verscheijden, Elin M. Svensson, Petra H. H. van den Broek, Hedwig van Hove, Jan B. Koenderink, Frans G. M. Russel, Rob E. Aarnoutse, Lindsey H. M. te Brake
Summary: This study developed a PBPK model to predict the concentration of linezolid in cranial cerebrospinal fluid (CSF) and assess its pharmacodynamic (PD) thresholds attainment in adults and children with tuberculous meningitis. The results showed that a dose of 1200 mg per day in adults and similar to 10 mg/kg BID in children could achieve reasonable target attainment in cranial CSF.
Review
Cardiac & Cardiovascular Systems
Tim Somers, Sailay Siddiqi, Wim J. Morshuis, Frans G. M. Russel, Tom J. J. Schirris
Summary: Statins, as the cornerstone of lipid-lowering treatment, have significant effects in reducing cardiovascular morbidity and mortality. However, musculoskeletal symptoms are observed in a certain percentage of users. This review discusses the adverse and beneficial effects of statins on the heart, exploring their mechanism of action and potential side effects in cardiac and skeletal muscle, and emphasizes the importance of personalized treatment strategies.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2023)
Meeting Abstract
Pharmacology & Pharmacy
K. van der Pol, J. Koenderink, J. van den Heuvel, P. van den Broek, J. Pertijs, F. Russel, J. Koldenhof, T. Schirris, A. van der Meer, G. Rongen
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Toxicology
Charlotte A. Hoogstraten, Jan A. M. Smeitink, Frans G. M. Russel, Tom J. J. Schirris
Summary: Between 14% and 26% of hospitalized cases of acute kidney injury are caused by drug-induced toxicity, highlighting the need for proper assessment of renal toxicity in pre-clinical stages. The widely used MTT assay, though effective in measuring cell viability, may not accurately assess the cytotoxicity of compounds that reduce mitochondrial function without affecting cell viability. This study suggests that an approach independent of cellular metabolism, such as a fluorescent assay for plasma membrane permeability, is preferable for evaluating cytotoxicity of compounds that induce metabolic dysfunction. Combining both assays during drug development allows for differentiation between compounds with direct or indirect mitochondrial toxic potential.
FRONTIERS IN TOXICOLOGY
(2022)