- by Zhang, J., Yu, X., Zheng, S., Qiao, G., Zhang, C., Tang, S., Gao, X., Wang, Y., Yu, Y., Cheng, J., Lei, M., Li, P., Yang, Y., Zhang, C., Yuan, Q.DICAR-JP, a functional domainof DICAR, is a potent cardiocyte protective RNA via regulating protein degradation or translation in diabetic cardiomyopathy (DCM). Using AGEs to found the cell impairment model in vivo. Using SPR to investigate the binding interaction between DICAR-JP and the binding protein nascent polypeptide-associated complex (NAC). DICAR-JP is demonstrated the functional domain that interacts with NAC to regulate OGDHL nascent peptide expression. DICAR-JP facilitated the translocation of OGDHL nascent peptides from the cytoplasm to the mitochondria using in […]
- by Xiang, J., Herold, K. F., Platholi, J., Hemmings, H. C.Neuronal voltage-gated sodium channels (Nav) are major targets for the neurophysiological actions of general anesthetics. In the adult brain, cell type-specific effects on synaptic transmission are attributed to the differential sensitivity to volatile anesthetics of specific Nav subtypes preferentially expressed in mature neurons (Nav1.1, Nav1.2, Nav1.6). Compared to mature neurons, neurons in the developing CNS are more excitable. Since the subtype-selective effects of volatile anesthetics on Nav during early development are unknown, we determined volatile anesthetic effects on Na+ currents […]
- ArcDFI: Attention Regularization guided by CYP450 Interactions for Predicting Drug-Food Interactionsby Gim, M., Kang, J., Park, D., Jeon, M.CYP450 isoenzymes are known to be deeply involved in the formation of drug-food interactions (DFI). Previously introduced computational approaches for predicting DFIs do not take drug-CYP450 interactions (DCI) into account and have limited generalizability in handling compounds unseen during model training. We introduce ArcDFI, a model that utilizes attention regularization guided by CYP450 interactions to predict drug-food interactions. Experimental results demonstrate ArcDFIs ability to predict DFIs when given unseen food or drug compounds as input. Analysis of its attention mechanism […]
- by Lelliott, P. M., Lindley, M., Vidallon, M., Hobro, A., Eliason, A. D., Moreno-Caceres, S., Samandra, S., Harrison, T., Harper, R., Trepout, S., Devineau, S., Clarke, B., Smith, N. I., Wang, X., Marciano, D., Pinto, A. R.The environmental fragmentation of plastic waste leads to the formation of micro- and nanoplastics (MNPs), which pose serious ecological and human health concerns. Despite increasing interest in their biological effects, many studies rely on artificial, uniform particles that fail to mimic the diverse physical and chemical characteristics of real-world MNPs. To address this limitation, we developed the Accelerated Plastic Aging in Suspension (APAS) system–a scalable, reproducible method that mimics natural aging processes by combining ultraviolet (UV) radiation, thermal stress, and […]
- by Mickols, E., Primpas, L., Oredsson, S., Karlgren, M.3D cultures of primary human hepatocytes (3D PHH) are successfully used to reduce and replace the use of animal experiments in biomedical research. Yet, the initial formation of 3D PHH is highly dependent on the supplementation with fetal bovine serum (FBS). However, the molecular composition of FBS and its effects on cultured cells are poorly understood. Moreover, FBS is prone to batch-to-batch variation, immunogenic risk and lack of adherence to the replacement, refinement, and reduction (3Rs) of animal experiments. Here, […]
- by Effinger, D., Schalk, S. S., King, J. L., Strong, J. R., O'Connell, C. K., Calderon, J. R., McCorvy, J., Thompson, S. M.Microdosing, the prolonged ingestion of psychedelics at sub-hallucinogenic doses, has gained popularity for its perceived cognitive and emotional benefits. Psychedelics have high affinity for 5-HT2B receptors, which cause heart disease with strong chronic activation. We investigated the effects of microdosed psychedelics on cardiovascular health in mice using electrocardiography after chronically administering either serotonin as a positive control or lysergic acid diethylamide (LSD) at two sub-hallucinogenic doses. Serotonin produced significant ventricular thickening at 4- and 8-weeks. No significant changes were observed […]
- by He, R., Zheng, W., Slof, T., Wardell, E., Mansson-Broberg, A., Norgren, S., Zhao, Y., Hassan, M.The alkylating agent cyclophosphamide (Cy) is one of the important corner stones in cancer treatment. Cy is used also as a part of conditioning regimens prior to hematopoietic cell transplantation and as a prophylactic treatment post transplantation in graft-versus-host disease. Existing evidence showed that high doses of Cy are associated with a number of side effects, including damage on arterial endothelium, which might contribute to late cardiovascular disorders. Oxidative stress has been characterized in such pathogenesis and is an exploitable […]
- by He, R., Zheng, W., Rozing, K., Moro, C. F., Li, X., Yin, Y., Zhou, W., Andaloussi, S. E., Norgren, S., Zhao, Y., Hassan, M.Graft-versus-host disease (GvHD) remains one of the major complications following allogeneic hematopoietic cell transplantation (allo-HCT), resulting in reduced quality of life, morbidity, and mortality in transplanted patients. Clinical strategies to prevent GvHD are frequently associated with off-target effects and dose-related toxicity. Given that oxidative stress is elevated in allo-HCT recipients and contributes to the pathogenesis of GvHD, the current study aims to characterize the role of N-acetylcysteine amide (NACA), a novel antioxidant, as the prophylactic treatment for acute GvHD. Using […]
- by Kruse, P. M., Ring, C. L.This paper presents the treecompareR package for R, which provides tools for reproducible visualizations of data through the use of taxonomies. The package builds on developments from ggplot2 and ggtree to provide visualizations tailored for use with taxonomic classification data. Additionally, it provides tools that leverage developments in network analysis to compare data sets. While designed specifically for chemical classification objectives using ClassyFire (http://classyfire.wishartlab.com/), treecompareR also provides tools for use with more general taxonomies. treecompareR is available from GitHub at […]
- by Lu, N., Li, Q., Duan, L.-h., Xu, R., Li, Y.-p., Shi, F.-l., Zhou, Z.-y., Gan, Y.-q., Hu, B., Li, J.-h., He, X.-h., Ouyang, D.-y., Zha, Q.-b.Andrographolide (Andro), a natural product extracted from the Chinese traditional medicine herb Andrographis paniculata, has been applied for the treatment of diverse inflammatory diseases. However, its effects on necroptosis, a lytic form of cell death implicated in various inflammatory diseases, remain uncharacterized. In the current research, we investigate whether Andro and its derivatives can suppress necroptosis. The results demonstrate that Andro notably inhibits the necroptosis in in vitro cellular models induced by either lipopolysaccharide (LPS) plus IDN-6556 or a combination […]
- by Liu, H., Morgan, R. A.Hemophilia B gene therapy treatments currently have not addressed the need for predictable, durable, active, and redosable factor IX (FIX). Unlike conventional gene therapy, engineered B Cell Medicines (BCMs) are durable, redosable, and titratable, and thus have the potential to address significant unmet needs in the Hemophilia B treatment paradigm. BE-101 is an autologous BCM comprised of expanded and differentiated B lymphocyte lineage cells genetically engineered ex vivo to secrete FIX-Padua. CRISPR/Cas9 mediated gene editing at the C-C chemokine receptor […]
- by Madugula, S. S., Jayasinghe-Arachchige, V. M., Norgan Radler, C., Wang, S., Liu, J.The CRISPR/Cas9 system is a powerful gene-editing tool. Its specificity and stability rely on complex allosteric regulation. Understanding these allosteric regulations is essential for developing high-fidelity Cas9 variants with reduced off-target effects. Here, we introduce a novel structure-based machine learning (ML) approach to systematically identify long-range allosteric networks in Cas9. Our ML model was trained using all available Cas9 structures, ensuring a comprehensive representation of Cas9s structural landscape. We then applied this model to Streptococcus pyogenes Cas9 (SpCas9) to demonstrate […]
- by Riley, S., Vy Nguyen, V., Bhattacharjeec, R., Ng, P. Q., Ritchie, T. C., Fisk, I., Gecz, J., Kumar, R., Searle, I. R.{beta}-Cyano-L-alanine (BCA) and {gamma}-glutamyl-{beta}-cyano-L-alanine (GBCA) are the primary antinutritional compounds present within the seeds of the high protein and drought tolerant orphan legume Vicia sativa. Evidence of neurotoxicity is limited to symptom analysis from animal feed trials whilst the molecular mechanisms underlying suspected neurotoxicity in monogastric animals are largely unknown. In this study, we first optimised an in vitro cell-based assay for rapid testing of BCA and GBCA toxicity in the retinoic acid differentiated SH-SY5Y human neuroblastoma cells. Using this […]
- by Kruse, P. M., Ring, C. L.The U.S. Environmental Protection Agencys Biosolids Screening Tool can predict potential human and ecological exposures to chemical contaminants in treated sewage sludge biosolids, but large quantities of chemical-specific physico-chemical data are required to parameterize the model. Here, an R workflow is presented that leverages publicly-available databases of chemical information to prepare data for model simulations using the Biosolids Screening Tool. The automated Biosolids Screening Tool workflow (autoBST) reduces the time to gather data necessary to screen hundreds of chemicals from […]
- by Myakala, K., Wang, X. X., Shults, N. V., Hughes, E., Ribeiro, P. d. C., Penjweini, R., Link, K., Barton, K., Jones, B. A., Krawczyk, E., Clarkson-Paredes, C., Popratiloff, A., Knutson, J. R., cowart, l. a., Levi, M.Mineralocorticoid receptor (MR) overactivation plays a crucial role in the pathogenesis of chronic kidney disease, as well as several cardiovascular and arterial diseases. Current studies determined the mechanisms of the beneficial kidney effects of the non-steroidal MR antagonist finerenone (FN) in a mouse model of western diet-induced obesity and insulin resistance. 10-week-old male C57BL/6J mice were fed a low fat (LF) or western diet (WD) for 12 weeks followed by treatment with either vehicle or finerenone (FN) for another 14 […]
- by Anderson, L. L., Kahlig, K. M., Barker-Haliski, M. L., Hannigan, B., Toop, H., Matthews, L. G., French, J., White, H. S., Souza, M., Petrou, S.ABSTRACT/SUMMARYO_ST_ABSObjectiveC_ST_ABSCentral to the development of novel antiseizure medications (ASMs) is testing of anticonvulsant activity in preclinical models. While various well-established models exist, their predictive validity across the spectrum of clinical epilepsies has been less clear. We sought to establish the translational concordance of commonly used preclinical models to define models with the highest predictive clinical validity for focal onset seizures (FOS). MethodsThe Praxis Analysis of Concordance (PAC) framework was implemented to assess the translational concordance between preclinical and clinical ASM […]
- by Anca, E., Pavel, I. O., Licarete, E., Rosioru, C., Dobre, C., Banciu, M.Doxorubicin is a member of the anthracycline class of chemotherapeutic agents and is among the most effective treatments available up to date. However, its clinical use is significantly limited by severe cardiotoxic effects. The purpose of this study is to investigate the transcriptomic alterations that occur in a rat model of doxorubicin-induced cardiotoxicity. Our results reveal significant dysregulations of cardiac metabolism and provide insights into the molecular mechanisms underlying cardiac damage produced by this treatment. Our analysis revealed that heart […]
- by Itokazu, Y., Beck, W. D., Terry, A. V.The prevalence of neurodegenerative diseases and mental health disorders has been increasing over the past few decades. While genetic and lifestyle factors are important to the etiology of these illnesses, the pathogenic role of environmental factors, especially toxicants such as pesticides encountered over the life span, is receiving increased attention. As an environmental factor, organophosphates pose a constant threat to human health due to their widespread use as pesticides, their deployment by rogue militaries, and their use in terrorist attacks. […]
- by Chokheli, V. A., Butenko, E. V., Pokudina, I. O., Firsova, I. M., Azarov, A. S., Belyaev, M. O., Tsymerskaia, C. A., Sushkova, S. N.The study of aqueous and alcoholic phytoextracts of medicinal plants of the Rostov region: wormwood (Artemisia absinthium), thyme (Thymus dimorphus) and sage (Salvia officinalis) for pathogenic strains of Staphylococcus aureus, Klebsiella sp. and Escherichia coli. Various plant organs, such as flower, stem, leaf, and root, were used as phytoextracts. The antibacterial effect was provided by aqueous extracts from the leaves of A. absinthium in relation to S. aureus, as well as extracts of S. officinalis on Klebsiella sp strains. Alcohol […]
- by Li, D., Zhao, Y., Guo, X., Li, C., Sun, Y., Wang, Y., Chang, L., Wang, X., Wang, Y., Schwarz, S., Du, X.-D.The global spread of the New Delhi metallo-{beta}-lactamase (NDM) -producing carbapenem-resistant Enterobacteriaceae pose a serious threat to public health, as NDM and its variants enzymes efficiently hydrolyze almost {beta}-lactam antibiotics. The development of novel antibiotics or antibiotic adjuvants capable of eradicating antibiotic-resistance bacteria through multiple mechanisms represents a promising strategy for reversing antibiotic resistance and preventing the emergence of new resistance. In this study, we utilized high-performance liquid chromatography (HPLC) to demonstrate that N-acetylcysteine (NAC) is a prominent reducing metabolite […]
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