BMC Med Ethics. 2023 Jul 6;24(1):48. doi: 10.1186/s12910-023-00929-6.

ABSTRACT

BACKGROUND: Healthcare providers have to make ethically complex clinical decisions which may be a source of stress. Researchers have recently introduced Artificial Intelligence (AI)-based applications to assist in clinical ethical decision-making. However, the use of such tools is controversial. This review aims to provide a comprehensive overview of the reasons given in the academic literature for and against their use.

METHODS: PubMed, Web of Science, Philpapers.org and Google Scholar were searched for all relevant publications. The resulting set of publications was title and abstract screened according to defined inclusion and exclusion criteria, resulting in 44 papers whose full texts were analysed using the Kuckartz method of qualitative text analysis.

RESULTS: Artificial Intelligence might increase patient autonomy by improving the accuracy of predictions and allowing patients to receive their preferred treatment. It is thought to increase beneficence by providing reliable information, thereby, supporting surrogate decision-making. Some authors fear that reducing ethical decision-making to statistical correlations may limit autonomy. Others argue that AI may not be able to replicate the process of ethical deliberation because it lacks human characteristics. Concerns have been raised about issues of justice, as AI may replicate existing biases in the decision-making process.

CONCLUSIONS: The prospective benefits of using AI in clinical ethical decision-making are manifold, but its development and use should be undertaken carefully to avoid ethical pitfalls. Several issues that are central to the discussion of Clinical Decision Support Systems, such as justice, explicability or human-machine interaction, have been neglected in the debate on AI for clinical ethics so far.

TRIAL REGISTRATION: This review is registered at Open Science Framework ( https://osf.io/wvcs9 ).

PMID:37415172 | DOI:10.1186/s12910-023-00929-6

Nat Biotechnol. 2023 Jul 6. doi: 10.1038/s41587-023-01863-z. Online ahead of print.

ABSTRACT

Characterization of somatic mutations at single-cell resolution is essential to study cancer evolution, clonal mosaicism and cell plasticity. Here, we describe SComatic, an algorithm designed for the detection of somatic mutations in single-cell transcriptomic and ATAC-seq (assay for transposase-accessible chromatin sequence) data sets directly without requiring matched bulk or single-cell DNA sequencing data. SComatic distinguishes somatic mutations from polymorphisms, RNA-editing events and artefacts using filters and statistical tests parameterized on non-neoplastic samples. Using >2.6 million single cells from 688 single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) data sets spanning cancer and non-neoplastic samples, we show that SComatic detects mutations in single cells accurately, even in differentiated cells from polyclonal tissues that are not amenable to mutation detection using existing methods. Validated against matched genome sequencing and scRNA-seq data, SComatic achieves F1 scores between 0.6 and 0.7 across diverse data sets, in comparison to 0.2-0.4 for the second-best performing method. In summary, SComatic permits de novo mutational signature analysis, and the study of clonal heterogeneity and mutational burdens at single-cell resolution.

PMID:37414936 | DOI:10.1038/s41587-023-01863-z

Sci Rep. 2023 Jul 6;13(1):10969. doi: 10.1038/s41598-023-37966-5.

ABSTRACT

Increased use of cross-sectional imaging has resulted in frequent detection of incidental cystic pancreatic lesions. Serous cystadenomas (SCAs) are benign cysts that do not require surgical intervention unless symptomatic. Unfortunately, up to half of SCAs do not have typical imaging findings ("atypical SCAs"), overlap with potentially malignant precursor lesions, and thus pose a diagnostic challenge. We tested whether the analysis of circulating extracellular vesicle (EV) biomarkers using a digital EV screening technology (DEST) could enhance the discrimination of cystic pancreatic lesions and avoid unnecessary surgical intervention in these atypical SCAs. Analysis of 25 different protein biomarkers in plasma EV from 68 patients identified a putative biomarker signature of Das-1, Vimentin, Chromogranin A, and CAIX with high discriminatory power (AUC of 0.99). Analysis of plasma EV for multiplexed markers may thus be helpful in clinical decision-making.

PMID:37414831 | DOI:10.1038/s41598-023-37966-5

Nat Commun. 2023 Jul 6;14(1):3993. doi: 10.1038/s41467-023-39443-z.

ABSTRACT

A lingering question in developmental biology has centered on how transcription factors with widespread distribution in vertebrate embryos can perform tissue-specific functions. Here, using the murine hindlimb as a model, we investigate the elusive mechanisms whereby PBX TALE homeoproteins, viewed primarily as HOX cofactors, attain context-specific developmental roles despite ubiquitous presence in the embryo. We first demonstrate that mesenchymal-specific loss of PBX1/2 or the transcriptional regulator HAND2 generates similar limb phenotypes. By combining tissue-specific and temporally controlled mutagenesis with multi-omics approaches, we reconstruct a gene regulatory network (GRN) at organismal-level resolution that is collaboratively directed by PBX1/2 and HAND2 interactions in subsets of posterior hindlimb mesenchymal cells. Genome-wide profiling of PBX1 binding across multiple embryonic tissues further reveals that HAND2 interacts with subsets of PBX-bound regions to regulate limb-specific GRNs. Our research elucidates fundamental principles by which promiscuous transcription factors cooperate with cofactors that display domain-restricted localization to instruct tissue-specific developmental programs.

PMID:37414772 | DOI:10.1038/s41467-023-39443-z

Nat Commun. 2023 Jul 6;14(1):3999. doi: 10.1038/s41467-023-39709-6.

ABSTRACT

SARS-CoV-2 nsp3 is essential for viral replication and host responses. The SARS-unique domain (SUD) of nsp3 exerts its function through binding to viral and host proteins and RNAs. Herein, we show that SARS-CoV-2 SUD is highly flexible in solution. The intramolecular disulfide bond of SARS-CoV SUD is absent in SARS-CoV-2 SUD. Incorporating this bond in SARS-CoV-2 SUD allowed crystal structure determination to 1.35 Å resolution. However, introducing this bond in SARS-CoV-2 genome was lethal for the virus. Using biolayer interferometry, we screened compounds directly binding to SARS-CoV-2 SUD and identified theaflavin 3,3'-digallate (TF3) as a potent binder, Kd 2.8 µM. TF3 disrupted the SUD-guanine quadruplex interactions and exhibited anti-SARS-CoV-2 activity in Vero E6-TMPRSS2 cells with an EC50 of 5.9 µM and CC50 of 98.5 µM. In this work, we provide evidence that SARS-CoV-2 SUD harbors druggable sites for antiviral development.

PMID:37414753 | DOI:10.1038/s41467-023-39709-6

Methods Mol Biol. 2023;2684:59-99. doi: 10.1007/978-1-0716-3291-8_4.

ABSTRACT

Delivering better care for patients with bladder cancer (BC) necessitates the development of novel therapeutic strategies that address both the high disease heterogeneity and the limitations of the current therapeutic modalities, such as drug low efficacy and patient resistance acquisition. Drug repurposing is a cost-effective strategy that targets the reuse of existing drugs for new therapeutic purposes. Such a strategy could open new avenues toward more effective BC treatment. BC patients' multi-omics signatures can be used to guide the investigation of existing drugs that show an effective therapeutic potential through drug repurposing. In this book chapter, we present an integrated multilayer approach that includes cross-omics analyses from publicly available transcriptomics and proteomics data derived from BC tissues and cell lines that were investigated for the development of disease-specific signatures. These signatures are subsequently used as input for a signature-based repurposing approach using the Connectivity Map (CMap) tool. We further explain the steps that may be followed to identify and select existing drugs of increased potential for repurposing in BC patients.

PMID:37410228 | DOI:10.1007/978-1-0716-3291-8_4

Front Bioinform. 2023 Jun 20;3:1199675. doi: 10.3389/fbinf.2023.1199675. eCollection 2023.

ABSTRACT

The soybean cyst nematode (SCN) [Heterodera glycines Ichinohe] is a devastating pathogen of soybean [Glycine max (L.) Merr.] that is rapidly becoming a global economic issue. Two loci conferring SCN resistance have been identified in soybean, Rhg1 and Rhg4; however, they offer declining protection. Therefore, it is imperative that we identify additional mechanisms for SCN resistance. In this paper, we develop a bioinformatics pipeline to identify protein-protein interactions related to SCN resistance by data mining massive-scale datasets. The pipeline combines two leading sequence-based protein-protein interaction predictors, the Protein-protein Interaction Prediction Engine (PIPE), PIPE4, and Scoring PRotein INTeractions (SPRINT) to predict high-confidence interactomes. First, we predicted the top soy interacting protein partners of the Rhg1 and Rhg4 proteins. Both PIPE4 and SPRINT overlap in their predictions with 58 soybean interacting partners, 19 of which had GO terms related to defense. Beginning with the top predicted interactors of Rhg1 and Rhg4, we implement a "guilt by association" in silico proteome-wide approach to identify novel soybean genes that may be involved in SCN resistance. This pipeline identified 1,082 candidate genes whose local interactomes overlap significantly with the Rhg1 and Rhg4 interactomes. Using GO enrichment tools, we highlighted many important genes including five genes with GO terms related to response to the nematode (GO:0009624), namely, Glyma.18G029000, Glyma.11G228300, Glyma.08G120500, Glyma.17G152300, and Glyma.08G265700. This study is the first of its kind to predict interacting partners of known resistance proteins Rhg1 and Rhg4, forming an analysis pipeline that enables researchers to focus their search on high-confidence targets to identify novel SCN resistance genes in soybean.

PMID:37409347 | PMC:PMC10319130 | DOI:10.3389/fbinf.2023.1199675

iScience. 2023 Jun 15;26(7):107109. doi: 10.1016/j.isci.2023.107109. eCollection 2023 Jul 21.

ABSTRACT

Phenotypic plasticity is the ability of individual genotypes to produce different phenotypes in response to environmental perturbations. We previously postulated how conformational noise emanating from conformational dynamics of intrinsically disordered proteins (IDPs) which is distinct from transcriptional noise, can contribute to phenotypic switching by rewiring the cellular protein interaction network. Since most transcription factors are IDPs, we posited that conformational noise is an integral component of transcriptional noise implying that IDPs may amplify total noise in the system either stochastically or in response to environmental changes. Here, we review progress in elucidating the details of the hypothesis. We highlight empirical evidence supporting the hypothesis, discuss conceptual advances that underscore its fundamental importance and implications, and identify areas for future investigations.

PMID:37408690 | PMC:PMC10319216 | DOI:10.1016/j.isci.2023.107109

Cells. 2023 May 13;12(10):1379. doi: 10.3390/cells12101379.

ABSTRACT

The metabolism of the model microalgae Chlamydomonas reinhardtii under nitrogen deprivation is of special interest due to its resulting increment of triacylglycerols (TAGs), that can be applied in biotechnological applications. However, this same condition impairs cell growth, which may limit the microalgae's large applications. Several studies have identified significant physiological and molecular changes that occur during the transition from an abundant to a low or absent nitrogen supply, explaining in detail the differences in the proteome, metabolome and transcriptome of the cells that may be responsible for and responsive to this condition. However, there are still some intriguing questions that reside in the core of the regulation of these cellular responses that make this process even more interesting and complex. In this scenario, we reviewed the main metabolic pathways that are involved in the response, mining and exploring, through a reanalysis of omics data from previously published datasets, the commonalities among the responses and unraveling unexplained or non-explored mechanisms of the possible regulatory aspects of the response. Proteomics, metabolomics and transcriptomics data were reanalysed using a common strategy, and an in silico gene promoter motif analysis was performed. Together, these results identified and suggested a strong association between the metabolism of amino acids, especially arginine, glutamate and ornithine pathways to the production of TAGs, via the de novo synthesis of lipids. Furthermore, our analysis and data mining indicate that signalling cascades orchestrated with the indirect participation of phosphorylation, nitrosylation and peroxidation events may be essential to the process. The amino acid pathways and the amount of arginine and ornithine available in the cells, at least transiently during nitrogen deprivation, may be in the core of the post-transcriptional, metabolic regulation of this complex phenomenon. Their further exploration is important to the discovery of novel advances in the understanding of microalgae lipids' production.

PMID:37408213 | DOI:10.3390/cells12101379

Cells. 2023 May 10;12(10):1357. doi: 10.3390/cells12101357.

ABSTRACT

Architectural proteins are essential epigenetic regulators that play a critical role in organizing chromatin and controlling gene expression. CTCF (CCCTC-binding factor) is a key architectural protein responsible for maintaining the intricate 3D structure of chromatin. Because of its multivalent properties and plasticity to bind various sequences, CTCF is similar to a Swiss knife for genome organization. Despite the importance of this protein, its mechanisms of action are not fully elucidated. It has been hypothesized that its versatility is achieved through interaction with multiple partners, forming a complex network that regulates chromatin folding within the nucleus. In this review, we delve into CTCF's interactions with other molecules involved in epigenetic processes, particularly histone and DNA demethylases, as well as several long non-coding RNAs (lncRNAs) that are able to recruit CTCF. Our review highlights the importance of CTCF partners to shed light on chromatin regulation and pave the way for future exploration of the mechanisms that enable the finely-tuned role of CTCF as a master regulator of chromatin.

PMID:37408191 | DOI:10.3390/cells12101357

Cells. 2023 May 9;12(10):1346. doi: 10.3390/cells12101346.

ABSTRACT

The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts returning from space shuttle missions or from the International Space Station have been diagnosed with various health problems, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance, including impaired visual acuity, altered metabolic and nutritional status, and immune system dysregulation. Microgravity has profound effects also on reproductive functions. Female astronauts, in fact, suppress their cycles during space travels, and effects at the cellular level in the early embryo development and on female gamete maturation have also been observed. The opportunities to use space flights to study the effects of gravity variations are limited because of the high costs and lack of repeatability of the experiments. For these reasons, the use of microgravity simulators for studying, at the cellular level, the effects, such as those, obtained during/after a spatial trip, are developed to confirm that these models can be used in the study of body responses under conditions different from those found in a unitary Gravity environment (1 g). In view of this, this study aimed to investigate in vitro the effects of simulated microgravity on the ultrastructural features of human metaphase II oocytes using a Random Positioning Machine (RPM). We demonstrated for the first time, by Transmission Electron Microscopy analysis, that microgravity might compromise oocyte quality by affecting not only the localization of mitochondria and cortical granules due to a possible alteration of the cytoskeleton but also the function of mitochondria and endoplasmic reticulum since in RPM oocytes we observed a switch in the morphology of smooth endoplasmic reticulum (SER) and associated mitochondria from mitochondria-SER aggregates to mitochondria-vesicle complexes. We concluded that microgravity might negatively affect oocyte quality by interfering in vitro with the normal sequence of morphodynamic events essential for acquiring and maintaining a proper competence to fertilization in human oocytes.

PMID:37408181 | DOI:10.3390/cells12101346

Curr Opin Chem Biol. 2023 Jul 3;76:102357. doi: 10.1016/j.cbpa.2023.102357. Online ahead of print.

ABSTRACT

Elucidating protein-protein interaction (PPI) networks and their structural features within cells is central to understanding fundamental biology and associations of cell phenotypes with human pathologies. Owing to technological advancements during the last decade, cross-linking mass spectrometry (XL-MS) has become an enabling technology for delineating interaction landscapes of proteomes as they exist in living systems. XL-MS is unique due to its capability to simultaneously capture PPIs from native environments and uncover interaction contacts though identification of cross-linked peptides, thereby permitting the determination of both identity and connectivity of PPIs in cells. In combination with high resolution structural tools such as cryo-electron microscopy and AI-assisted prediction, XL-MS has contributed significantly to elucidating architectures of large protein assemblies. This review highlights the latest developments in XL-MS technologies and their applications in proteome-wide analysis to advance structural systems biology.

PMID:37406423 | DOI:10.1016/j.cbpa.2023.102357

Trials. 2023 Jul 5;24(1):442. doi: 10.1186/s13063-023-07481-z.

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has been shown to affect nutritional recommendations. Some functional foods have been demonstrated to be useful in the treatment of people with COVID-19. However, little is known about the impact of combining functional foods on disease control. This study aimed to investigate the effects of functional foods mixture on serum levels of inflammatory cytokines and biochemical findings in patients with COVID-19.

METHODS: A randomized double-blind controlled trial was conducted in Baqiyatallah Al-Azam hospital in Tehran, Iran. Sixty patients were randomly assigned to receive either a soup containing functional foods (n = 30) or a usual soup (control group) (n = 30). Participants' sociodemographic information was gathered using a general questionnaire. Blood levels of inflammatory markers and biochemical findings were assessed using standard protocols.

RESULTS: The results showed that soup containing functional foods was more effective in controlling serum levels of D-dimer, blood urea nitrogen, and creatinine than the control group (P < 0.05). Also, more significant improvement was found in the intervention group vs control group in terms of interleukin (IL)-1β, IL-6, IL-17, IL-10, and tumor necrose factor-α (P < 0.05). In contrast, the control intervention more efficiently controlled potassium levels and reduced quantitative C-reactive protein than the intervention group (P < 0.05).

CONCLUSIONS: This study indicates a soup containing functional foods could alleviate biomarkers of inflammation in patients with COVID-19. However, its effectiveness on biochemical findings remained inconclusive which warranted further research.

TRIAL REGISTRATION: IRCT, IRCT20180201038585N11. Registered 23 August 2021, https://www.irct.ir/trial/57338.

PMID:37408032 | DOI:10.1186/s13063-023-07481-z

Sci Rep. 2023 Jul 5;13(1):10895. doi: 10.1038/s41598-023-37721-w.

ABSTRACT

Diaphorina citri Kuwayama, also known as the Asian citrus psyllid (ACP), can vector the bacterium Candidatus Liberibacter asiaticus (CLas), agent of Huanglongbing (HLB): an incurable disease affecting citrus trees worldwide. In citrus growing regions where ACP and HLB are absent, such as Australia, the risk of an incursion and consequent economic damage to citrus industries make this psyllid one of the top-priority pests. Due to ACP's small dimensions and the generally poorly studied native psylloid fauna worldwide, morphological identification of this insect to distinguish it from harmless species is challenging, especially in the field, and with immature, partial or damaged specimens. To allow rapid and efficient detection of ACP in the field, we designed and optimised a new Loop-mediated isothermal amplification (LAMP) assay for the detection of D. citri based on the mitochondrial 16S locus. The optimised ACP 16S LAMP assay produced amplification from D. citri samples within 13.3 ± 3.6 min, with an anneal derivative of ~ 78.5 °C. A synthetic gBlock gene fragment was also developed to be used as positive control for the new LAMP assay with a different anneal derivative of ~ 83 °C. An existing commercially available LAMP assay for detection of the bacterium CLas was also tested in this study on ACP DNA. The ACP 16S LAMP assay we developed and tested here provides a valuable new in-field compatible tool that can allow early detections of ACP, enabling a quick biosecurity response, and could potentially be adopted by a wide range of users, from farmers to agronomists and from researchers to industry.

PMID:37407637 | DOI:10.1038/s41598-023-37721-w

Nat Commun. 2023 Jul 5;14(1):3966. doi: 10.1038/s41467-023-39591-2.

ABSTRACT

KRAS is a frequent driver in lung cancer. To identify KRAS-specific vulnerabilities in lung cancer, we performed RNAi screens in primary spheroids derived from a Kras mutant mouse lung cancer model and discovered an epigenetic regulator Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). In human lung cancer models UHRF1 knock-out selectively impaired growth and induced apoptosis only in KRAS mutant cells. Genome-wide methylation and gene expression analysis of UHRF1-depleted KRAS mutant cells revealed global DNA hypomethylation leading to upregulation of tumor suppressor genes (TSGs). A focused CRISPR/Cas9 screen validated several of these TSGs as mediators of UHRF1-driven tumorigenesis. In vivo, UHRF1 knock-out inhibited tumor growth of KRAS-driven mouse lung cancer models. Finally, in lung cancer patients high UHRF1 expression is anti-correlated with TSG expression and predicts worse outcomes for patients with KRAS mutant tumors. These results nominate UHRF1 as a KRAS-specific vulnerability and potential target for therapeutic intervention.

PMID:37407562 | DOI:10.1038/s41467-023-39591-2

Dev Biol. 2023 Jul 3:S0012-1606(23)00109-4. doi: 10.1016/j.ydbio.2023.06.010. Online ahead of print.

NO ABSTRACT

PMID:37407371 | DOI:10.1016/j.ydbio.2023.06.010

Mol Biol Evol. 2023 Jul 5;40(7):msad141. doi: 10.1093/molbev/msad141.

ABSTRACT

Angiosperms have a complex history of whole-genome duplications (WGDs), with varying numbers and ages of WGD events across clades. These WGDs have greatly affected the composition of plant genomes due to the biased retention of genes belonging to certain functional categories following their duplication. In particular, regulatory genes and genes encoding proteins that act in multiprotein complexes have been retained in excess following WGD. Here, we inferred protein-protein interaction (PPI) networks and gene regulatory networks (GRNs) for seven well-characterized angiosperm species and explored the impact of both WGD and small-scale duplications (SSDs) in network topology by analyzing changes in frequency of network motifs. We found that PPI networks are enriched in WGD-derived genes associated with dosage-sensitive intricate systems, and strong selection pressures constrain the divergence of WGD-derived genes at the sequence and PPI levels. WGD-derived genes in network motifs are mostly associated with dosage-sensitive processes, such as regulation of transcription and cell cycle, translation, photosynthesis, and carbon metabolism, whereas SSD-derived genes in motifs are associated with response to biotic and abiotic stress. Recent polyploids have higher motif frequencies than ancient polyploids, whereas WGD-derived network motifs tend to be disrupted on the longer term. Our findings demonstrate that both WGD and SSD have contributed to the evolution of angiosperm GRNs, but in different ways, with WGD events likely having a more significant impact on the short-term evolution of polyploids.

PMID:37405949 | DOI:10.1093/molbev/msad141

STAR Protoc. 2023 Jul 4;4(3):102401. doi: 10.1016/j.xpro.2023.102401. Online ahead of print.

ABSTRACT

RNA-binding proteins (RBPs) can bind and mediate RNA-RNA contacts. However, identifying specific RBP-organized RNA-RNA contacts remains challenging. Here, we present a capture RIC-seq (CRIC-seq) technique to map specific RBP-associated RNA-RNA contacts globally. We describe steps for formaldehyde cross-linking to fix RNA in situ conformation, pCp-biotin labeling to mark RNA juncture, and in situ proximity ligation to join proximal RNAs. We then detail immunoprecipitation to isolate specific RBP-associated RNA-RNA contacts, biotin-streptavidin selection to enrich chimeric RNAs, and library construction for paired-end sequencing. For complete information on the generation and use of this protocol, please refer to Ye et al.1.

PMID:37405924 | DOI:10.1016/j.xpro.2023.102401

Front Mol Biosci. 2023 Jun 19;10:1164220. doi: 10.3389/fmolb.2023.1164220. eCollection 2023.

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) has become a global pandemic and poses a serious threat to human health. Many studies have shown that pre-existing nonalcoholic steatohepatitis (NASH) can worsen the clinical symptoms in patients suffering from COVID-19. However, the potential molecular mechanisms between NASH and COVID-19 remain unclear. To this end, key molecules and pathways between COVID-19 and NASH were herein explored by bioinformatic analysis. Methods: The common differentially expressed genes (DEGs) between NASH and COVID-19 were obtained by differential gene analysis. Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out using the obtained common DEGs. The key modules and hub genes in PPI network were obtained by using the plug-in of Cytoscape software. Subsequently, the hub genes were verified using datasets of NASH (GSE180882) and COVID-19 (GSE150316), and further evaluated by principal component analysis (PCA) and receiver operating characteristic (ROC). Finally, the verified hub genes were analyzed by single-sample gene set enrichment analysis (ssGSEA) and NetworkAnalyst was used for the analysis of transcription factor (TF)-gene interactions, TF-microRNAs (miRNA) coregulatory network, and Protein-chemical Interactions. Results: A total of 120 DEGs between NASH and COVID-19 datasets were obtained, and the PPI network was constructed. Two key modules were obtained via the PPI network, and enrichment analysis of the key modules revealed the common association between NASH and COVID-19. In total, 16 hub genes were obtained by five algorithms, and six of them, namely, Kruppel-like factor 6 (KLF6), early growth response 1 (EGR1), growth arrest and DNA-damage-inducible 45 beta (GADD45B), JUNB, FOS, and FOS-like antigen 1 (FOSL1) were confirmed to be closely related to NASH and COVID-19. Finally, the relationship between hub genes and related pathways was analyzed, and the interaction network of six hub genes was constructed with TFs, miRNAs, and compounds. Conclusion: This study identified six hub genes related to COVID-19 and NASH, providing a new perspective for disease diagnosis and drug development.

PMID:37405258 | PMC:PMC10315682 | DOI:10.3389/fmolb.2023.1164220

Drug Des Devel Ther. 2023 Jun 28;17:1933-1943. doi: 10.2147/DDDT.S417563. eCollection 2023.

ABSTRACT

Moving a new drug from bench to bedside is a long and arduous process. The tactic of drug repurposing, which solves "new" diseases with "old" existing drugs, is more efficient and economical than conventional ab-initio way for drug development. Information technology has dramatically changed the paradigm of biomedical research in the new century, and drug repurposing studies have been significantly accelerated by implementing informatics techniques related to genomics, systems biology and biophysics during the past few years. A series of remarkable achievements in this field comes with the practical applications of in silico approaches including transcriptomic signature matching, gene-connection-based scanning, and simulated structure docking in repositioning drug therapies against breast cancer. In this review, we systematically curated these impressive accomplishments with summarization of the main findings on potentially repurposable drugs, and provide our insights into the current issues as well as future directions of the field. With the prospective improvement in reliability, the computer-assisted repurposing strategy will play a more critical role in drug research and development.

PMID:37405253 | PMC:PMC10315146 | DOI:10.2147/DDDT.S417563