A publicly available toxicogenomics capability for supporting predictive toxicology and meta-analysis depends on availability of gene expression data for chemical treatment scenarios, the ability to locate and aggregate such information by chemical, and broad data coverage within chemical, genomics, and toxicological information domains. This capability also depends on common genomics standards, protocol description, and functional linkages of diverse public Internet data resources. We present a survey of public genomics resources from these vantage points and conclude that, despite progress in many areas, the current state of the majority of public microarray databases is inadequate for supporting these objectives, particularly with regard to chemical indexing. To begin to address these inadequacies, we focus chemical annotation efforts on experimental content contained in the two primary public genomic resources: ArrayExpress and Gene Expression Omnibus. Automated scripts and extensive manual review were employed to transform free-text experiment descriptions into a standardized, chemically indexed inventory of experiments in both resources. These files, which include top-level summary annotations, allow for identification of current chemical-associated experimental content, as well as chemical-exposure-related (or "Treatment") content of greatest potential value to toxicogenomics investigation. With these chemical-index files, it is possible for the first time to assess the breadth and overlap of chemical study space represented in these databases, and to begin to assess the sufficiency of data with shared protocols for chemical similarity inferences. Chemical indexing of public genomics databases is a first important step toward integrating chemical, toxicological and genomics data into predictive toxicology.
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Biomed Pharmacother
January 2025
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:
Gestational 25-hydroxyvitamin D (25[OH]D) is important in fetal lung development and may influence offspring respiratory outcomes, making accurate exposure assessment essential to understand clinical associations. Therefore, we used the combined data from two large RCTs investigating prenatal vitamin D supplementation, which included early and late prenatal 25(OH)D measurements, to refine a population pharmacokinetic model of vitamin D-25(OH)D and estimate individual area under the curve (AUC) Z-scores. The primary outcome was physician-diagnosed offspring asthma/wheezing at ages 3 and 6 years, and lung function, as a secondary outcome, was evaluated by spirometry at the ages 6 and 8 years.
View Article and Find Full Text PDFNat Prod Res
January 2025
Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy, Al-Azhar University (Boys), Cairo, Egypt.
The herbal extracts of four traditional plants; namely leaves, fruits leaves, and seeds, were identified for their main constituents using UHPLC/QTOF-MS/MS. Then, a pharmacology-based analysis and molecular docking verification were established targeting the evaluation of each individual herbal extract for their antidiabetic/anti-obesity potential besides their safety. Streptozotocin-induced diabetic rats were used to evaluate antiobesity and insulinotropic effects against insulin (10 U/Kg, IP) and metformin (100 mg/Kg, per oral) as standard regimens.
View Article and Find Full Text PDFBiomater Transl
November 2024
Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong Province, China.
Cardiovascular diseases are a leading cause of death worldwide, and effective treatment for cardiac disease has been a research focal point. Although the development of new drugs and strategies has never ceased, the existing drug development process relies primarily on rodent models such as mice, which have significant shortcomings in predicting human responses. Therefore, human-based in vitro cardiac tissue models are considered to simulate physiological and functional characteristics more effectively, advancing disease treatment and drug development.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
NovaMechanics Ltd, Nicosia 1070, Cyprus.
The CompSafeNano project, a Research and Innovation Staff Exchange (RISE) project funded under the European Union's Horizon 2020 program, aims to advance the safety and innovation potential of nanomaterials (NMs) by integrating cutting-edge nanoinformatics, computational modelling, and predictive toxicology to enable design of safer NMs at the earliest stage of materials development. The project leverages Safe-by-Design (SbD) principles to ensure the development of inherently safer NMs, enhancing both regulatory compliance and international collaboration. By building on established nanoinformatics frameworks, such as those developed in the H2020-funded projects NanoSolveIT and NanoCommons, CompSafeNano addresses critical challenges in nanosafety through development and integration of innovative methodologies, including advanced models, approaches including machine learning (ML) and artificial intelligence (AI)-driven predictive models and 1st-principles computational modelling of NMs properties, interactions and effects on living systems.
View Article and Find Full Text PDFCurr Gene Ther
January 2025
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
The evolution of genetic exploration tools, from laborious methods like radiationinduced mutations to the transformative CRISPR-Cas9 system, has fundamentally reshaped genetic research and gene editing capabilities. This journey, initiated by foundational techniques such as ZFNs and TALENs and culminating in the groundbreaking work of Doudna and Charpentier in 2012, has ushered in an era of precise DNA alteration and profound insights into gene functions. The CRISPR/Cas9 system uses the Cas9 enzyme and guides RNA (gRNA) to precisely target and cleave DNA, with subsequent repair via error-prone NHEJ or precise HDR, enabling versatile gene editing.
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