Use of Drug Sensitisers to Improve Therapeutic Index in Cancer.

The clinical management of malignant tumours is challenging, often leading to severe adverse effects and death. Drug resistance (DR) antagonises the effectiveness of treatments, and increasing drug dosage can worsen the therapeutic index (TI). Current efforts to overcome DR predominantly involve the use of drug combinations, including applying multiple anti-cancerous drugs, employing drug sensitisers, which are chemical agents that enhance pharmacokinetics (PK), including the targeting of cellular pathways and regulating pertinent membrane transporters. While combining multiple compounds may lead to drug-drug interactions (DDI) or polypharmacy effect, the use of drug sensitisers permits rapid attainment of effective treatment dosages at the disease site to prevent early DR and minimise side effects and will reduce the chance of DDI as lower drug doses are required. This review highlights the essential use of TI in evaluating drug dosage for cancer treatment and discusses the lack of a unified standard for TI within the field. Commonly used benefit-risk assessment criteria are summarised, and the critical exploration of the current use of TI in the pharmaceutical industrial sector is included. Specifically, this review leads to the discussion of drug sensitisers to facilitate improved ratios of effective dose to toxic dose directly in humans. The combination of drug and sensitiser molecules might see additional benefits to rekindle those drugs that failed late-stage clinical trials by the removal of detrimental off-target activities through the use of lower drug doses. Drug combinations and employing drug sensitisers are potential means to combat DR. The evolution of drug combinations and polypharmacy on TI are reviewed. Notably, the novel binary weapon approach is introduced as a new opportunity to improve TI. This review emphasises the urgent need for a criterion to systematically evaluate drug safety and efficiency for practical implementation in the field.

Deep Attention Fusion Hashing (DAFH) Model for Medical Image Retrieval.

In medical image retrieval, accurately retrieving relevant images significantly impacts clinical decision making and diagnostics. Traditional image-retrieval systems primarily rely on single-dimensional image data, while current deep-hashing methods are capable of learning complex feature representations. However, retrieval accuracy and efficiency are hindered by diverse modalities and limited sample sizes. OBJECTIVE: To address this, we propose a novel deep learning-based hashing model, the Deep Attention Fusion Hashing (DAFH) model, which integrates advanced attention mechanisms with medical imaging data. METHODS: The DAFH model enhances retrieval performance by integrating multi-modality medical imaging data and employing attention mechanisms to optimize the feature extraction process. Utilizing multimodal medical image data from the Cancer Imaging Archive (TCIA), this study constructed and trained a deep hashing network that achieves high-precision classification of various cancer types. RESULTS: At hash code lengths of 16, 32, and 48 bits, the model respectively attained Mean Average Precision (MAP@10) values of 0.711, 0.754, and 0.762, highlighting the potential and advantage of the DAFH model in medical image retrieval. CONCLUSIONS: The DAFH model demonstrates significant improvements in the efficiency and accuracy of medical image retrieval, proving to be a valuable tool in clinical settings.

BioKA: a curated and integrated biomarker knowledgebase for animals.

Biomarkers play an important role in various area such as personalized medicine, drug development, clinical care, and molecule breeding. However, existing animals' biomarker resources predominantly focus on human diseases, leaving a significant gap in non-human animal disease understanding and breeding research. To address this limitation, we present BioKA (Biomarker Knowledgebase for Animals, https://ngdc.cncb.ac.cn/bioka), a curated and integrated knowledgebase encompassing multiple animal species, diseases/traits, and annotated resources. Currently, BioKA houses 16 296 biomarkers associated with 951 mapped diseases/traits across 31 species from 4747 references, including 11 925 gene/protein biomarkers, 1784 miRNA biomarkers, 1043 mutation biomarkers, 773 metabolic biomarkers, 357 circRNA biomarkers and 127 lncRNA biomarkers. Furthermore, BioKA integrates various annotations such as GOs, protein structures, protein-protein interaction networks, miRNA targets and so on, and constructs an interactive knowledge network of biomarkers including circRNA-miRNA-mRNA associations, lncRNA-miRNA associations and protein-protein associations, which is convenient for efficient data exploration. Moreover, BioKA provides detailed information on 308 breeds/strains of 13 species, and homologous annotations for 8784 biomarkers across 16 species, and offers three online application tools. The comprehensive knowledge provided by BioKA not only advances human disease research but also contributes to a deeper understanding of animal diseases and supports livestock breeding.

OBIA: An Open Biomedical Imaging Archive.

With the development of artificial intelligence (AI) technologies, biomedical imaging data play an important role in scientific research and clinical application, but the available resources are limited. Here we present Open Biomedical Imaging Archive (OBIA), a repository for archiving biomedical imaging and related clinical data. OBIA adopts five data objects (Collection, Individual, Study, Series, and Image) for data organization, and accepts the submission of biomedical images of multiple modalities, organs, and diseases. In order to protect personal privacy, OBIA has formulated a unified de-identification and quality control process. In addition, OBIA provides friendly and intuitive web interfaces for data submission, browsing, and retrieval, as well as image retrieval. As of September 2023, OBIA has housed data for a total of 937 individuals, 4136 studies, 24,701 series, and 1,938,309 images covering 9 modalities and 30 anatomical sites. Collectively, OBIA provides a reliable platform for biomedical imaging data management and offers free open access to all publicly available data to support research activities throughout the world. OBIA can be accessed at https://ngdc.cncb.ac.cn/obia.

RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variant Monitoring, and Risk Pre-warning.

The Resource for Coronavirus 2019 (RCoV19) is an open-access information resource dedicated to providing valuable data on the genomes, mutations, and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this updated implementation of RCoV19, we have made significant improvements and advancements over the previous version. Firstly, we have implemented a highly refined genome data curation model. This model now features an automated integration pipeline and optimized curation rules, enabling efficient daily updates of data in RCoV19. Secondly, we have developed a global and regional lineage evolution monitoring platform, alongside an outbreak risk pre-warning system. These additions provide a comprehensive understanding of SARS-CoV-2 evolution and transmission patterns, enabling better preparedness and response strategies. Thirdly, we have developed a powerful interactive mutation spectrum comparison module. This module allows users to compare and analyze mutation patterns, assisting in the detection of potential new lineages. Furthermore, we have incorporated a comprehensive knowledgebase on mutation effects. This knowledgebase serves as a valuable resource for retrieving information on the functional implications of specific mutations. In summary, RCoV19 serves as a vital scientific resource, providing access to valuable data, relevant information, and technical support in the global fight against COVID-19. The complete contents of RCoV19 are available to the public at https://ngdc.cncb.ac.cn/ncov/.

Evaluation of the antioxidant effects of four main theaflavin derivatives through chemiluminescence and DNA damage analyses.

Theaflavins (TFs) are the dimers of a couple of epimerized catechins, which are specially formed during black tea fermentation. To explore the differences among four main TF derivatives (theaflavin (TF(1)), theaflavin-3-gallate (TF(2)A), theaflavin-3'-gallate (TF(2)B), and theaflavin-3,3'-digallate (TF(3))) in scavenging reactive oxygen species (ROS) in vitro, their properties of inhibiting superoxide, singlet oxygen, hydrogen peroxide, and the hydroxyl radical, and their effects on hydroxyl radical-induced DNA oxidative damage were systematically analyzed in the present study. The results show that, compared with (-)-epigallocatechin gallate (EGCG), TF derivatives were good antioxidants for scavenging ROS and preventing the hydroxyl radical-induced DNA damage in vitro. TF(3) was the most positive in scavenging hydrogen peroxide and hydroxyl radical, and TF(1) suppressed superoxide. Positive antioxidant capacities of TF(2)B on singlet oxygen, hydrogen peroxide, hydroxyl radical, and the hydroxyl radical-induced DNA damage in vitro were found. The differences between the antioxidant capacities of four main TF derivatives in relation to their chemical structures were also discussed. We suggest that these activity differences among TF derivatives would be beneficial to scavenge different ROS with therapeutic potential.