Discovery of Broad‐Spectrum Repurposed Drug Combinations Against Carbapenem‐Resistant<i>Enterobacteriaceae</i>(CRE) Through Artificial Intelligence (AI)‐Driven Platform

Li, Ming; You, Kui; Wang, Peter; Hooi, Lissa; Chen, Yahua; Siah, Anqi; Tan, Shi‐Bei; Teo, Jeanette; Ng, Oon‐Tek; Marimuthu, Kalisvar; Venkatachalam, Indumathi; Blasiak, Agata; Chow, Edward Kai‐Hua; Ho, Dean; Gan, Yunn‐Hwen

doi:10.1002/adtp.202300332

Cited by 4 publications

References 55 publications

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3D Bioprinting and Artificial Intelligence‐Assisted Biofabrication of Personalized Oral Soft Tissue Constructs

Dai,

Wang,

Mishra

et al. 2024

Adv Healthcare Materials

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Regeneration of oral soft tissue defects, including mucogingival defects associated with the recession or loss of gingival and/or mucosal tissues around teeth and implants, is crucial for restoring oral tissue form, function, and health. This study presents a novel approach using three‐dimensional (3D) bioprinting to fabricate individualized grafts with precise size, shape, and layer‐by‐layer cellular organization. A multicomponent polysaccharide/fibrinogen‐based bioink is developed, and bioprinting parameters are optimized to create shape‐controlled oral soft tissue (gingival) constructs. Rheological, printability, and shape‐fidelity assays, demonstrated the influence of thickener concentration and print parameters on print resolution and shape fidelity. Artificial intelligence (AI)‐derived tool enabled streamline the iterative bioprinting parameter optimization and analysis of the interaction between the bioprinting parameters. The cell‐laden polysaccharide/fibrinogen‐based bioinks exhibited excellent cellular viability and shape fidelity of shape‐controlled, full‐thickness gingival tissue constructs over the 18‐day culture period. While variations in thickener concentrations within the bioink minimally impact the cellular organization and morphogenesis (gingival epithelial, connective tissue, and basement membrane markers), they influence the shape fidelity of the bioprinted constructs. This study represents a significant step toward the biofabrication of personalized soft tissue grafts, offering potential applications in the repair and regeneration of mucogingival defects associated with periodontal disease and dental implants.

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3D Bioprinting and Artificial Intelligence‐Assisted Biofabrication of Personalized Oral Soft Tissue Constructs

Dai,

Wang,

Mishra

et al. 2024

Adv Healthcare Materials

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Determining sex differences in drug combinations targeting aortic valve myofibroblast activation using an artificial intelligence derived platform

Vogt,

Wang,

Chavez

et al. 2024

Preprint

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Aortic valve stenosis (AVS) is a sexually dimorphic disease where aortic valve leaflets develop fibrosis and calcification, leading to heart failure if untreated. Sex differences in AVS progression depend on valvular interstitial cells (VICs) activating to myofibroblasts that drive aberrant extracellular matrix remodeling. To date, no treatment strategies have leveraged cellular sex differences to determine drug combinations that effectively target VIC myofibroblast activation. Here, we harnessed IDentif.AI, an artificial intelligence (AI)-derived drug optimization platform, to optimize sex-specific synergistic drug combinations that may prevent and reverse VIC myofibroblast activation on hydrogel biomaterials. The results reveal that anti-fibrotic drug efficacy and combinatorial interactions are dependent on cell sex. This study provides a framework for developing clinically relevant AVS treatment strategies through the integration of high-throughput hydrogel cell culture platforms and AI-driven drug optimization. The workflow towards designing targeted AVS drug combinations may help accelerate AVS drug development for male and female patients and address health disparities in AVS treatment outcomes.

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Efficacy of lyophilized Lactobacillus sakei as a potential candidate for preventing carbapenem-resistant Klebsiella infection

Tajdozian,

Seo,

Jeong

et al. 2024

Ann Microbiol

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Background Antimicrobial resistance is considered one of the greatest threats to human health, according to the World Health Organization (WHO). Gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE), have become a significant concern in antimicrobial-resistant bacteria’s global emergence and spread. Among CRE pathogens, carbapenem-resistant Klebsiella pneumoniae (CRKP) has recently been reported as a highly infectious strain associated with high mortality and morbidity in adults and immunocompromised patients. Additionally, CRKP-related infections are challenging to treat, as carbapenems are the last resort of antibiotics. Therefore, developing novel drugs with different mechanisms of action from existing drugs is urgently required to defeat this lethal menace. Under such circumstances, probiotics can be therapeutic candidates for inhibiting pathogens. Thus, our research team has been focusing on probiotics for a long time to develop potential anti-CRKP drug agents. Methods After extensive efforts, we finally found a novel probiotic strain, Lactobacillus sakei PMC104, suitable for treating CRKP infection. It was isolated from kimchi. As part of our expansion into therapeutic development, we evaluated the L. sakei strain effect against CRKP pathogens in both in vitro and in vivo experiments. Moreover, we conducted media optimization at food grade and then established a scale-up process on a pilot scale. Subsequently, a lyophilizate was obtained and used in a mouse model infected with CRKP. Results Data demonstrated that the L. sakei strain has an inhibitory effect against CRKP infection both in in vitro and in vivo experiments and also increases the level of short-chain fatty acids in the feces of mice after receiving L. sakei strain treatment for 10 days. Furthermore, treatment with L. sakei powder remarkably diminished body weight loss, mortality, and illness severity in CRKP-infected mice, showing a preventive effect of our PMC 104 against CRKP infection. Discussion Our results demonstrate the potential therapeutic effect of our candidate probiotic strain against CRKP, suggesting that L. sakei PMC 104 could be considered an antimicrobial candidate for treating CRKP infections. However, extensive studies, including additional toxicity tests and clinical trials, are still essential to develop it as a new anti-CRKP therapeutic agent.

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Discovery of Broad‐Spectrum Repurposed Drug Combinations Against Carbapenem‐ResistantEnterobacteriaceae(CRE) Through Artificial Intelligence (AI)‐Driven Platform

Cited by 4 publications

References 55 publications

3D Bioprinting and Artificial Intelligence‐Assisted Biofabrication of Personalized Oral Soft Tissue Constructs

3D Bioprinting and Artificial Intelligence‐Assisted Biofabrication of Personalized Oral Soft Tissue Constructs

Determining sex differences in drug combinations targeting aortic valve myofibroblast activation using an artificial intelligence derived platform

Efficacy of lyophilized Lactobacillus sakei as a potential candidate for preventing carbapenem-resistant Klebsiella infection

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