Exploring the Potential of Large Language models in Traditional Korean Medicine: A Foundation Model Approach to Culturally-Adapted Healthcare

Introduction: Traditional Korean medicine (TKM) emphasizes individualized diagnosis and treatment, making AI modeling difficult due to limited data and implicit processes. GPT-3.5 and GPT-4, large language models, have shown impressive medical knowledge despite lacking medicine-specific training. This study aimed to assess the capabilities of GPT-3.5 and GPT-4 for TKM using the Korean National Licensing Examination for Korean Medicine Doctors. Methods: GPT-3.5 (February 2023) and GPT-4 (March 2023) models answered 340 questions from the 2022 examination across 12 subjects. Each question was independently evaluated five times in an initialized session. Results: GPT-3.5 and GPT-4 achieved 42.06% and 57.29% accuracy, respectively, with GPT-4 nearing passing performance. There were significant differences in accuracy by subjects, with 83.75% accuracy for neuropsychiatry compared to 28.75% for internal medicine (2). Both models showed high accuracy in recall-based and diagnosis-based questions but struggled with intervention-based ones. The accuracy for questions that require TKM-specialized knowledge was relatively lower than the accuracy for questions that do not GPT-4 showed high accuracy for table-based questions, and both models demonstrated consistent responses. A positive correlation between consistency and accuracy was observed. Conclusion: Models in this study showed near-passing performance in decision-making for TKM without domain-specific training. However, limits were also observed that were believed to be caused by culturally-biased learning. Our study suggests that foundation models have potential in culturally-adapted medicine, specifically TKM, for clinical assistance, medical education, and medical research.Comment: 31 pages, 6 figure

Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans

Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C.elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.X1144sciescopu

A System-Level Mechanism of Anmyungambi Decoction for Obesity: A Network Pharmacological Approach

Obesity is a low-grade systemic inflammatory disease involving adipocytokines. As though Anmyungambi decoction (AMGB) showed significant improvement on obesity in a clinical trial, the molecular mechanism of AMGB in obesity remains unknown. Therefore, we explored the potential mechanisms of action of AMGB on obesity through network pharmacological approaches. We revealed that targets of AMGB are significantly associated with obesity-related and adipocyte-elevated genes. Evodiamine, berberine, genipin, palmitic acid, genistein, and quercetin were shown to regulate adipocytokine signaling pathway proteins which mainly involved tumor necrosis factor receptor 1, leptin receptor. In terms of the regulatory pathway of lipolysis in adipocytes, norephedrine, pseudoephedrine, quercetin, and limonin were shown to affect adrenergic receptor-beta, protein kinase A, etc. We also found that AMGB has the potentials to enhance the insulin signaling pathway thereby preventing type II diabetes mellitus. Additionally, AMGB was discovered to be able to control not only insulin-related proteins but also inflammatory mediators and apoptotic regulators and caspases, hence reducing hepatocyte injury in nonalcoholic fatty liver disease. Our findings help develop a better understanding of how AMGB controls obesity

A System-Level Mechanism of Anmyungambi Decoction for Obesity: A Network Pharmacological Approach

Obesity is a low-grade systemic inflammatory disease involving adipocytokines. As though Anmyungambi decoction (AMGB) showed significant improvement on obesity in a clinical trial, the molecular mechanism of AMGB in obesity remains unknown. Therefore, we explored the potential mechanisms of action of AMGB on obesity through network pharmacological approaches. We revealed that targets of AMGB are significantly associated with obesity-related and adipocyte-elevated genes. Evodiamine, berberine, genipin, palmitic acid, genistein, and quercetin were shown to regulate adipocytokine signaling pathway proteins which mainly involved tumor necrosis factor receptor 1, leptin receptor. In terms of the regulatory pathway of lipolysis in adipocytes, norephedrine, pseudoephedrine, quercetin, and limonin were shown to affect adrenergic receptor-beta, protein kinase A, etc. We also found that AMGB has the potentials to enhance the insulin signaling pathway thereby preventing type II diabetes mellitus. Additionally, AMGB was discovered to be able to control not only insulin-related proteins but also inflammatory mediators and apoptotic regulators and caspases, hence reducing hepatocyte injury in nonalcoholic fatty liver disease. Our findings help develop a better understanding of how AMGB controls obesity

Laser Acupuncture Exerts Neuroprotective Effects via Regulation of Creb

Acupuncture has a positive effect on cognitive deficits. However, the effects of laser acupuncture (LA) on cognitive function and its mechanisms of action are unclear. The present study aimed to evaluate the effects of LA on middle cerebral artery occlusion- (MCAO-) induced cognitive impairment and its mechanisms of action. Transient focal cerebral ischemia was modeled in adult Sprague-Dawley rats by MCAO. After LA or manual-acupuncture (MA) treatment at the GV20 and HT7 for 2 weeks, hippocampal-dependent memory was evaluated using the Morris water maze (MWM) test. The hippocampus was dissected to analyze choline acetyltransferase (ChAT) immunoreactivity and Creb, Bdnf, Bcl-2, and Bax gene expressions. MWM test demonstrated a significant improvement in hippocampal-dependent memory in the MCAO rats after LA treatment. LA treatment significantly reversed the postischemic decrease in ChAT immunoreactivity in the hippocampal CA1 region. LA treatment significantly normalized gene expression in the hippocampus which had been altered by MCAO, especially upregulating gene expression of Creb, Bdnf, and Bcl-2 and downregulating gene expression of Bax. This study suggests that LA treatment could improve cognitive impairment in MCAO rats to enhance the cholinergic system in the hippocampal CA1 region and to exert a neuroprotective effect by regulating Creb, Bdnf, Bcl-2, and Bax gene expressions

Network Pharmacological Analysis on the Herbal Combinations for Mitigating Inflammation in Respiratory Tracts and Experimental Evaluation

The regulation of inflammatory mediators, such as TNF-α, IL-6, IL-1β, and leukotriene B4, could play a crucial role in suppressing inflammatory diseases such as COVID-19. In this study, we investigated the potential mechanisms of drug combinations comprising Ephedrae Herba, Schisandra Fructus, Platycodonis Radix, and Ginseng Radix; validated the anti-inflammatory effects of these drugs; and determined the optimal dose of the drug combinations. By constructing a herb-compound-target network, associations were identified between the herbs and tissues (such as bronchial epithelial cells and lung) and pathways (such as the TNF, NF-κB, and calcium signaling pathways). The drug combinations exerted anti-inflammatory effects in the RAW264.7 cell line treated with lipopolysaccharide by inhibiting the production of nitric oxide and inflammatory mediators, including TNF-α, IL-6, IL-1β, and leukotriene B4. Notably, the drug combinations inhibited PMA-induced MUC5AC mRNA expression in NCI-H292 cells. A design space analysis was carried out to determine the optimal herbal medicine combinations using the design of experiments and synergy score calculation. Consequently, a combination study of the herbal preparations confirmed their mitigating effect on inflammation in COVID-19

Toward Sustaining Bioplastics: Add a Pinch of Seasoning

Modern society can no longer sustain accumulating plastic pollution without intervention; plastic waste has even found its way into the food that we consume. Unfortunately, biodegradable alternatives lack sound commercial and economic distinctiveness because mechanical strength and biodegradability are typically mutually exclusive. Inspired by fine cuisine, we introduce a novel synthetic method, referred to as "seasoning", which consists of adding a minimal amount of a biobased multifunctional monomer to pinch the amorphous domains of poly(butylene succinate). Seasoning with only 0.03 mol % of a biobased monomer led to a significantly improved oxygen barrier, high strength (86 MPa), and excellent elongation at break (654%). To the best of our knowledge, this "seasoning" approach with the significant property improvement provided is unique in the bioplastics research field. The proposed approach is highly scalable, relies on existing industrial production, and has the potential to expand current biodegradable plastic applications through its simplicity